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M-YC and R-ZL designed the research. PL reviewed HE-stained slides, analyzed the data, and wrote the manuscript. YL reviewed HE-stained slides. CZ performed follow-up of patients after surgery. Y-HL and J-TJ acquired clinicopathological data. J-PY reviewed the manuscript. All authors contributed to the article and approved the submitted version.
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For RT-PCR assay, 3 ml of an overnight broth culture of VPS02, 5HP, and XN87 was subjected to total RNA extraction using the TRIzol reagent (Invitrogen), and the RNA obtained was then treated with DNase I (Fermentas) to eliminate contaminating DNA. DNase-treated RNA (400 to 800 ng) was used as the template in RT-PCR mixtures containing 0.2 μM each primer targeting pirABVp or other putative virulence genes (the primers are listed in Table 2), 1 μl of SuperScript one-step reverse transcriptase-Platinum Taq mix (Invitrogen), and 1× reaction buffer in a 25-μl volume. RT reactions were carried out at 50°C for 30 min. After the subsequent denaturation step of 94°C for 2 min, the reactions proceeded into PCR thermocycling, as described above under “PCR amplification methods,” except that the extension time at 72°C was adjusted to 1 min/kb. Additionally, the template RNA was subjected to PCR analysis using an established pirABVp duplex PCR protocol (10) to ensure that the RNA used did not contain any contaminating DNA for the targeted toxins.
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Conglutinate color information was recorded for gravid female mussels during sampling. Due to the time of year when samples were collected, gravid female mussels were observed only when sampling the populations from the Ozark and Ouachita regions. Of the 180 samples that were collected, conglutinate color was observed for 53 individuals (29.4%). Of these, 21 individuals (39.6%) had red conglutinates, and 32 (60.4%) had brown conglutinates. No white conglutinates were observed during our sampling. 20 of the 21 females with red conglutinates were placed in clade A, and 31 of the 32 females with brown conglutinates were placed in clade B. Based on the Yule's Q contingency coefficient, mussel conglutinate colors and the mtDNA lineages (A vs. B) were strongly correlated (Q = 0.997). Analysis of the ND1 sequences for evidence of deviation from neutrality using Tajima's D statistic (D = 3.10, P < 0.001) and the codon based Z‐test (Z = −11.22, P < 0.001) both rejected the null hypothesis of neutrality.
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Для макроаденом (размер опухоли >1 см) часто характерен экстраселлярный рост. Опухоль может иметь супраселлярный, инфраселлярный, ретроселлярный, антеселлярный, латероселлярный рост и их сочетания. МРТ позволяет определить взаимоотношение опухоли с окружающими структурами: зрительными нервами, хиазмой, кавернозными синусами, ВСА, дном третьего желудочка, что важно при планировании хирургических доступов. Большинство макроаденом гипофиза имеют гипоинтенсивный сигнал в Т1-режиме и гиперинтенсивный сигнал в Т2-взвешенном режиме (рис. 9, 10). Кроме того, они могут иметь как гомогенную, так и гетерогенную структуру, а также содержать кистозный компонент. Введение контрастного вещества помогает дифференцировать ткань опухоли, для которой характерно менее интенсивное накопление контрастного вещества, от нормальной ткани гипофиза. В случаях больших аденом ткань гипофиза бывает настолько сдавлена, что может не определяться на МРТ.
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Another interesting point concerning the duplicate feature values can be seen in Figure 3, in which the deviation of the individual duplicate glass transition temperature values (all belonging to one feature vector) from their median value is depicted. As noted above, such duplicated values originate because the same substance was actually measured multiple times or because the feature representation of different substances is the same. For the Functional Group Mode (Figure 3A) as well as the SMILES Mode (Figure 3B), the data obey a normal distribution centered around the zero value, most likely due to the fact that most of the values are doublets. Often, these doublets come from the same research groups which measured a substance twice and/or reported the identical value in two different articles published a few years apart from each other. The distributions shown in Figure 3 thus support the procedure described above of using the median Tg value for such doublets.
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Several neuropsychological assessments were performed before surgery, and patients were divided into two groups; namely, the normal and preoperative deficit groups according to the results of neuropsychological assessments for every function (Fig. 1). Following that, they classified it into five subgroups (A to E) according to their postoperative course. Figure 2 shows the overlap map of resection cavities of all patients (n = 18). The right superior frontal gyrus was the greatest overlap of resection cavity in cortical level (n = 10). In subcortical level, the greatest overlap of the region was equivalent to the course of the cingulum and superior longitudinal fascicles (SLF) I and II.Figure 1Five groups which were formed depending on the deficit and clinical course. Patients were assigned to the five groups according to each function (processing speed, fluency, spatial working memory, emotion, ToM and social cognition, visuospatial cognition). Groups A and B: deficits were observed preoperatively; A, deficit recovered within 3 months; B, deficit remaining until the chronic phase. Groups C, D, and E: no deficits were observed during the preoperative phase; C, normal at the chronic phase; D, deficits occurred just after surgery, but recovered by the chronic phase; E, deficits occurred after surgery and had not recovered within 3 months. Figure 2Overlap map of the resection cavity. Overlap map of resection cavities shows that the right superior frontal gyrus was the region with the greatest overlap (n = 10). As for subcortical level, the greatest overlap region was equivalent to the course of the cingulum and SLFs I and II.
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A ESCT é uma técnica efetiva para o tratamento de hemangiomas3,15, porém não há protocolos específicos13. O agente esclerosante pode ser um derivado do ácido oleico, com propriedades hemostáticas. Sua ação ocorre mediante uma resposta inflamatória, envolvendo a troca do componente vascular por um tecido fibroso3,15. O oleoato de menoetanolamina 5% mostrou resultados satisfatórios, com boa regressão da lesão, mínima morbidade e efeitos adversos.
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Foram consideradas inadequadas as prescrições que não atenderam às razões médicas aceitáveis para a prescrição de fórmula infantil acrescidas de outras condições/patologias com potencial de dificultar o aleitamento materno, como a escabiose, a mastite, a pouca aceitação do aleitamento materno, o relato de baixa produção de leite, o óbito materno e/ou a impossibili-dade de convivência com a mãe. A adequação e a inadequação das prescrições foram avaliadas em dois momentos distintos: no ato do encaminhamento ao CEAE e durante o acompanhamento no centro. Considerou-se adequada a prescrição de fórmulas hipercalóricas apenas nos casos de patologias do lactente com necessi-dade de restrição hídrica.
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Human pluripotent stem cells (hPSCs) are mainly consisted of human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs), and have the capability to differentiate into almost any proliferative somatic cells.19 Previous studies suggested that hPSC-derived cardiomyocytes (hPSC-CMs) can be produced by simulating some developmental signaling cues.46 Indeed, hESCs are able to differentiate into functional cardiomyocytes following a mature cardiac differentiation protocol,47–49 and transplantation of hESCs-derived cardiomyocytes (hESC-CMs) and hiPSCs-derived cardiomyocytes (hiPSC-CMs) in vivo can promote the regeneration of the damaged heart and improve cardiac functions.20,50 Thus, hPSC-CMs have broad prospects in cardiac regeneration after injury. It has been reported that ESC-derived cardiomyocytes (ESC-CMs) express genes that play critical roles in cardiac development, and the electrophysiological and contractional phenotypes of the heart.51,52 Moreover, ESC-CMs transplanted into the infarcted heart can survive and improve cardiac functions.53 Nevertheless, transplantation of ESCs resulted in severe teratomas in the implanted area, which are attributed to the immune response and the accumulation of undifferentiated ESCs.54–56 IPSCs have unlimited proliferation capacity and can differentiate into cardiomyocytes.46,57 Cardiac systolic function in MI hearts was significantly improved at 4 and 12 weeks after transplantation of iPSC-derived cardiomyocytes (iPSC-CMs).58 However, as expected, the immaturity of iPSC-CMS in transplanted animals often leads to ventricular tachycardia. At the same time, iPSC-CMs trigger an immune response mediated by natural killer cells (NKCs), resulting in a low engrafting.59 Currently, attempts have been made to improve the implantation of pluripotent stem cell-based therapy and inhibit the occurrence of tumors and arrhythmias by obtaining high purity and mature iPSC-CMs (Table 1)19,46,48,49,60,61. Enrichment of cardiomyocytes by vascular cell adhesion molecule 1 (VCAMI)-coupled magnetic dynabeads62 and hydrogel63 or cell sheet holder64 have been shown to improve therapeutic effects. However, more investigations are required to determine the safety and effectiveness of pluripotent stem cell therapies, especially in clinical stage.Table 1Small molecules mediate the differentiation of human pluripotent stem cells into cardiomyocytesCell typeSmall moleculesDescriptionRef.hiPSCs/hESCsGsk3 inhibitor CHIR99021, IWP2/IWP4Activition of Wnt/catenin signal promotes hPSCs differentiation.46hESCsSB203580 (a specific p38 MAP kinase inhibitor)A specific p38 MAP kinase inhibitor can improve the efficiency of hESCs differentiation into CMs.48hESCsPGI2, SB203580Optimizing the concentration of PGI2 in serum-free medium or adding SB203580 can promote the differentiation of hESCs into CMs.49hiPSCsGsk3 inhibitor CHIR99021, Wnt-C59Optimized chemically determined medium contributes to the production of high-purity cardiac troponin T (TNNT2)+ cells.60hiPSCsXAV939 (a tankyrase inhibitor),IWP2 (a porcupine inhibitor)Combination therapy of XAV939 and IWP2 results in higher efficiency in cardiac differentiation.61CMs cardiomyocytes, Gsk3 glycogen synthase kinase 3, hPSCs human pluripotent stem cells, hESCs human embryonic stem cells, hiPSCs human-induced pluripotent stem cells, IWP2 inhibitor of Wnt production-2, IWP4 inhibitor of Wnt production-4, PGI2 prostaglandin I2
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Die in unseren bisherigen Forschungen herausgestellte Bedeutung verschiedener menschlicher und nicht-menschlicher Akteur*innen zeigt auch, wie unangemessen der Blick auf die professionellen Fachkräfte als exklusive Akteur*innen der Handlungspraxis für die Forschung ist. Wenn wir mit B. Latour (Latour 2010) davon ausgehen, dass sich professionelles Handeln in einem Netzwerk verschiedener (menschlicher wie nicht-menschlicher) Akteur*innen vollzieht (Bastian und Posmek 2020), die auch am Ergebnis einer Handlung beteiligt sind, lohnt es, diesen neuen „Player“ Coronavirus näher als „Mithandelnden“ in den Blick zu nehmen. Mit diesem – so die Vermutung – werden weitere neue Akteur*innen in das Urteilsnetzwerk eingeführt, bzw. die Mittlerfunktion einiger Akteur*innen gestärkt. Das könnten vor allem digitale Akteur*innen sein, wenn etwa Hilfeplanverfahren und Beratungen nicht mehr als Präsenztermin, sondern digital durchgeführt werden müssen.
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So far, the network has published more than 20 scientific papers and contributed to the validation of state-of-the-art assessment tools and to the training of many researchers from all the involved centers. Furthermore, in the last decade, the network contributions have led to an improvement in knowledge about main determinants of functioning and, therefore, of clinical recovery in subjects with schizophrenia. Despite the introduction of innovative pharmacological and psychosocial treatments that facilitate symptomatic remission, the impairment in different areas of real-life functioning still represent an unmet need in the care of people suffering from schizophrenia, thus causing a huge burden on patients, their families, and health care systems (31–35, 37, 39–41). The strengths of the two main network studies, with respect to previous studies, include the analysis of a greater number of variables, some of which had never been examined before; the use of state-of-the-art instruments for the assessment of each variable included; and appropriate data analysis methods, in order to explore the complex relationship between possible predictors, mediators, and functional outcome measures. Finally, the implementation of the longitudinal study allowed us to overcome the limitations of the cross-sectional design that prevented inferences about the direction of causality.
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As previously mentioned, the band of PL emission in the range from 1.3 eV to 1.7 eV is attributed by several authors to the effect of quantum confinement in Si-ncs or silicon Si-ncls ; however, in this theory, the size of the nanocrystal determines the color of the emission. In larger nanocrystals, the emission tends to lower energies, and as we can see from the results, the Si-ncs and Si-ncls are of a size that would correspond to a blue emission. These results make us take into account what is reported by other authors who suggest that the intense emission around 1.5 eV is caused by small, oxidized silicon grains (1 nm or 2 nm). According to a model of molecular type emitters at the Si/SiO2 interface in the work of Guerra and Ossicini , the importance of oxidation in nanocrystals for emission is shown, and it is corroborated that those mostly oxidized have a high photoluminescence. This could be compared with that obtained for porous silicon oxidized by Wolking et al. . In their report it is corroborated that for clusters greater than 3 nm the behavior attributed to quantum confinement (QC) is fulfilled and that when the cluster size is smaller the emission intensity results are greater. In this, case the emission process is attributed to the recombination of the free excitons. For clusters between 2 and 3 nm, the previous behavior is still satisfied but not to the same rate in which it is fulfilled in QC. Here, the recombination is related to a free hole and a trapped electron, and finally, for clusters less than 2 nm, an emission redshift occurs and the recombination processes are attributed to trapped excitons.
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We expressed the relative uncertainty for each ACS estimate by following US Census Bureau guidelines for calculating its coefficient of variation (CV) and margin of error.22 The margin of error for unemployment status was calculated using guidelines for derived proportions. The measure of educational attainment and female lone-parent families required multiple numerators or denominators to build the proportions. For these, the numerators and denominators were aggregated within the equation for calculating the margin of error for the derived estimate. Median household income and poverty status did not require further calculation because these estimates are published as percentages or monetary values. We used an adjustment factor by multiplying the margin of error for each estimate or its numerator or denominator by a factor equal to 1.960 or 1.64 to derive the SE for each estimate with 95% confidence.
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Die Finanzierung von Forschungsaktivitäten erfolgt im Vereinigten Königreich durch Drittmittel und durch eine leistungsorientierte Mittelzuweisung an Universitäten. Das Research Excellence Framework (REF) ist das Bewertungssystem, mit dem die Regierung die Qualität und Güte der Forschung beurteilt, die in wissenschaftlichen Einrichtungen durchgeführt wird . Seit 2014 fordert das REF narrative Fallstudien ein, in denen beschrieben werden soll, wie sich die durchgeführten Forschungsprojekte jenseits des akademischen Bereichs auswirkten. Die Ergebnisse des REF werden verwendet, um die Höhe der öffentlichen Forschungsgelder zu ermitteln, die jede britische Hochschule für den Zeitraum bis zum nächsten REF (in der Regel 5–7 Jahre) erhält. Der Betrag hängt davon ab, wie die jeweilige Forschung durch das REF eingestuft wird. Im REF 2014 wurden 25 % der Gesamtpunktzahl von dem beschriebenen Forschungsimpact abgeleitet. Im nächsten REF, das Ende 2021 fällig ist, sind es fast 30 % der Punktzahl.
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Finally, we assessed whether MICAL-L1 is required for EHD1 recruitment and SE fission (Fig 8). As noted, unlike Rabenosyn-5 and Syndapin2, MICAL-L1 bound only to EHD1 and not EHD4 (Fig 5). Nonetheless, upon MICAL-L1 knock-down (validated by immunoblotting in Fig 8M), significantly less EHD1 was recruited to endosomal membranes (compare Fig 8H and 8K and 8B and 8E; quantified in O). Furthermore, EEA1-labeled SE size was enhanced in the MICAL-L1 knock-down cells compared to mock-treated cells (compare Fig 8G and 8J to 8A and 8D; quantified in 8N). Despite the inability of EHD4 to interact with MICAL-L1, these findings may result from the tight interaction between MICAL-L1 and Syndapin2, since degradation of either protein occurs in the absence of its binding partner . Nonetheless, these data indicate that despite being unable to interact directly with EHD4, MICAL-L1 also serves as a potential docking/recruiting site for EHD dimers at the SE membrane.
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O processo de treinamento inclui a apresentação de imagens que são divididas aleatoriamente em três grupos: treinamento, validação e verificação. O grupo de treinamento é usado para ajustar o peso das redes conectadas. O grupo de validação é utilizado para determinar o melhor momento para finalizar o treinamento, e, então, o grupo de verificação é aplicado, definindo o desempenho do algoritmo.( 3 )
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The extant Brown Pelican Pelecanus occidentalis californicus (MVZ 66500 and 125367) has tarsometatarsi approximately the same distal width, but slightly shorter than the fossil (Table 1). The dorsal proximal pneumatic opening for the proximal foramina is proximodistally elongate, and it has a distal extension on the medial side (absent in MVZ 125367). The length of the inner medial ridge of the extensor retinaculum varies with it longer than the state in the fossil in MVZ 66500 and shorter in MVZ 125367 (not reaching the proximodistal midpoint of the opening). The plantar opening of the distal foramen is rounded. The medial side of trochlea II lacks the plantar concave area present in Pelecanus tirarensis. The proximal face of the medial hypotarsal crest lacks the concave area, adjacent ridge, and foramina present in the fossil. There is a smaller plantar medial squared off projection (in proximal view) than that in Pelecanus erythrorhynchos (see above and Figure 3). The plantar opening of the medial proximal foramen is closer in size to the state in the fossil. The medial hypotarsal crest is parallel to the tarsometatarsal shaft. There are pneumatic foramina near proximal margin of the dorsal pneumatic opening for the proximal foramina (that are absent in the Indian fossil). There is a small pneumatic foramen proximal to the plantar opening of the medial proximal foramen. The plantar opening of the medial proximal foramen is large in MVZ 125367, and it extends distal to the medial hypotarsal crest (unlike the Siwalik specimen).
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The diagnostic criteria for ILD were the presence of bilateral reticulation and consolidation or ground-glass attenuation on high-resolution computed tomography (HRCT). The HRCT pattern was classified according to the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association (ATS/ERS/JRS/ALAT) clinical practice guideline of IPF. It was classified as usual interstitial pneumonia (UIP) pattern, probable UIP pattern, indeterminate UIP pattern, and alternative diagnosis20.
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Die Patientin berichtet davon, sich die rechte Hand zwischen einer Türklinke und der Wand eingequetscht zu haben. Der Hausarzt beschreibt eine pulslose A. radialis sowie A. ulnaris, bei einer ausreichend perfundierten und seitengleich warmen Extremität. Zur weiteren Abklärung erfolgt eine Verlegung auf die Abteilung für Angiologie.
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Genome binning was performed according to the steps described by Albertsen et al. and in our previous studies [23, 34]. The contigs belonging to different taxa were separated based on the genome coverage, GC content, tetranucleotide frequency, and taxonomic information. The taxonomic information for the contigs was obtained by searching against the NCBI-Nr database with blastp (e-value <1e−07) using a set of conserved single-copy protein-encoding genes as queries, followed by importation of the blast results into MEGAN 5.0 . To exclude potential contig contamination from our genome bins, the extracted contigs could be checked by searching a local database consisting of reported genomes belonging to the same phyla. Here, we constructed a small database comprising the ORFs of seven previously reported complete Nitrospirae genomes [21, 35–37]. The ORFs in the genome bin of the present study were searched against this database with blastp (e-value <1e−07). To further assess the completeness and purity of the genome bin, single-copy protein-coding genes were also compared. In this way, we could determine whether the duplication of single-copy protein-coding genes was caused by contig contamination or incorrect hybridization.
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Trebuie luate în discuție alți factori de risc independent cum ar fi existent unor fracturi anterioare care duc la apariția instabilității funcționale. De asemenea, recomăndam monitorizarea markerilor biochimici ai turn-over osos (CTX urinar și osteocalcină plasmatică) fiind cunoscut faptul că se produce o revenire la valorile patologice ale ratelor de resorbție osoasă crescută, anterioare tratamentului, asociate cu osteoporoza din perioada de postmenopauză.
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CD8+ T-cells play a major role in controlling fungal infections , however, direct killing is still not well understood. Currently, it has been shown that CD8+ T cells use granulysin, a pore-forming antimicrobial molecule, to kill C. neoformans . In addition, yeast specific CD8+ T cells show a non-classical expression of granulysin and granzyme K instead of the classical perforin and granzyme B cytotoxic granule profile . The mechanics of the granule-mediated cytotoxic activity by CD8+ T cells against fungal targets has not been explored. However, there may be similarities to the CD8+ T cell granule-mediated anti-tumor mechanism. The granule-mediated cytotoxicity is activated through two main receptors, T-cell receptor (TCR), and toll-like receptor (TLR)/scavenger receptor . While TCR is the main receptor involved in the whole activation and degranulation signaling cascade, TLRs augment the activation through dendritic cell cross-presenting fungal antigens. While TCR is important for CD8+ T cells in antigen recognition of fungal pathogens, TLRs are used by CD8+ T cells in augmenting its activation during antigen cross-presentation . Sensing of RNA via TLR3 promotes cross presentation by dendritic cells to class I-restricted CD8+ T cells. This is made evident by TLR3-/- mice, which are more susceptible to Aspergillus infection compared to control mice . The significance of TLRs in CD8+ T cell recognition and activation is further exemplified when patients with deleterious mutations in TLR3 and TLR4 were more susceptible to various fungal infections . Like NK cells, CD8+ T cells deliver their cytotoxic granule contents into the tumor IS after trafficking to the synapse with the help of microtubules and various motor proteins. Here, kinesins and dyneins are responsible for plus- (away from the MTOC) and minus- (toward the MTOC) end directed movement along microtubule tracks and aids in the MTOC polarization . Dynein is responsible for minus end directed movement that pulls the MTOC toward the IS for successful degranulation at the IS . Kinesins play an important role in plus-end directed movement of granules on the microtubules . Specifically, terminal transport of lytic granules to the tumor IS is mediated by the kinesin-1/Slp3/Rab27a complex where kinesin-1 is essential for the final terminal movement of granules toward the IS . Kinesin-4 was found to be important in regulating microtubule growth to allow for rapid remodeling and polarization of the microtubules when CD8+ T cells are in contact with antigen presenting cells . However, the role of kinesin-4 is unclear in CD8+ T cell cytotoxic mechanisms. As for granule exocytosis at the IS, syntaxin-11 plays the same role as in NK cells during cytotoxic events.
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Equine and hamster IgG Abs were evaluated with the hemagglutination inhibition (HI) test on kaolin-adsorbed sera according to the technique of Clarke, et al.32, adapted to microtiter plates and following the procedures described in the document Técnicas de laboratorio para el diagnóstico y la caracterización de los virus del dengue33. The test was conducted for EEEV, WEEV, and VEEV, and nine hamsters were also evaluated for YFV. We used the same antigens donated by the CDC. A shortage of antigens did not allow testing other arboviruses or more hamsters for YFV. An HI titer of 1:20 or higher inhibiting hemagglutination produced by four antigen units was considered positive. Hamsters 5-7 (table S1) were analyzed before and after their exposure at the sampling site 34. After exposure, hamsters were euthanized and their tissues (brain, heart, lungs, kidneys, liver, spleen, and skeletal muscle) were processed for IC inoculation in suckling mice Balb/C4 and analyzed by RT-PCR.
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FFM will be measured using foot-to-foot BIA, which is a safe measure of body composition and useful to complement weight and BMI data. The heels of the foot are placed on 2 plates and the toes placed on the other 2 plates while the electrical current is carried via the anterior plate, and the voltage drop is measured over the posterior electrode . The foot-to-foot technique has been demonstrated to be safe and effective in estimating FFM in cancer patients . BIA will be measured on a commercially available device (Tanita Inc, Tokyo, Japan; model TI SC 330S). For each participant, total FFM (kg) will be calculated at each time point, and then, the change in FFM between time points will be calculated. A clinically significant difference in FFM between time points will be defined as 0.5-1.0 kg, which is based on previous studies of cancer patients .
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Kececioglu has introduced a graph-theoretical model for the classical primary sequence alignment problem. In the authors present a first extension of this model to RNA structures and propose a branch-and-cut approach based on an integer linear programming formulation. Based on this formulation and inspired by the successful application of Lagrangian relaxation by Lancia and Caprara to the related contact map overlap problem, in the authors switch from branch-and-cut to the Lagrangian relaxation technique. They are able to solve instances a magnitude larger by simultaneously reducing the running time significantly. In the authors give a graph-theoretic model for the computation of multiple sequence alignments with arbitrary gap costs. In the next section we will combine the formulations given in and , resulting in a novel graph-based formulation for sequence-structure alignment with arbitrary gap costs.
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Selected protease genes showed a similar expression pattern to that of auxin transporter and AUX/IAA genes during the 3 week LD treatment, but the differences between intact plants and those lacking buds were more variable (Fig. 5C). Three of the selected protease genes (Potri.009G002200, Potri.009G055900, and Potri.012G105500) were expressed at much greater levels throughout the 3 week regrowth period in intact plants compared with plants lacking buds. Expression of Potri.004G215400 and Potri.010G149400 was initially greater in plants lacking buds after 1 and 2 weeks, but after 3 weeks of growth bark expression in intact plants was significantly greater than in plants with buds removed. A putative cysteine protease (Potri.011G066900) showed a different pattern, with greater expression in plants lacking buds compared with intact plants during the LD treatment.
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The sensitivity, specificity, and accuracy for the detection of residual DCIS at the time before surgery was 88.0%, 38.8%, and 59.8% for mammography, respectively, 82.0%, 40.3%, and 58.1% for ultrasound, respectively, and 68.0%, 70.1%, and 62.9% for MRI, respectively. Fig 1 shows ROC curve analysis for detecting ypTis. AUC of mammography, ultrasound, and MRI was 0.63 (95% confidence interval [CI], 0.53–0.73), 0.61 (95% CI, 0.51–0.71), and 0.69 (95% CI, 0.59–0.79), respectively.
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The gel point or more precisely, the percolation threshold for multivalent polymers can be estimated by analytical methods, one of which is based on Flory-Stockmayer theories. Here, the important parameters are the number of interacting modules within the polymers, V, and the fraction of bound modules, x. For a specific multivalent protein that is incorporated into a pre-formed network, the average number of additional proteins recruited into the network is denoted as ε and is expressed as: ε = (V – 1)x. In a system with two types of multivalent proteins a and b, such as the poly-SH3 and poly-PRM system, the average number of proteins that are recruited into a pre-formed network of multivalent proteins and their ligands can be expressed as: ε = εaεb = (Va – 1)xa(Vb – 1)xb.
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In interdisziplinärer Zusammenarbeit der medizinischen Kliniken, Psychologischen, Biologischen und Biometrischen Fakultäten sowie des Ethik-Instituts wurden erste Schritte unternommen und Projekte begonnen, um langfristig eine Zwillingskohorte für biomedizinische Projekte und Fragestellungen aufzubauen, die weit über den Raum Tübingen und Zeithorizont der beteiligten Wissenschaftlerinnen und Wissenschaftler hinaus reichen soll.
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These two species show bathymetric and temperature preferences (see also above and Figs 7 and 8). The species diagnosed here as O. rhachophora is distributed on the outer continental shelf (50–200 m) with temperature preferences of 10–20°C, whereas O. kokusai is predominantly distributed on the upper continental slope (300–500 m) with lower temperature preferences (generally below 10°C, not higher than 15°C). Bathymetric outliers tend to have atypical temperature profiles (Fig 7). For example, in the northern part of the range of O. rhachophora, off central Honshū, the mean annual temperatures above 10°C occur considerably shallower (100–200 m) than in the southern part of the range (compare Figs 7B, 7D, 8B and 8D). Moreover, in the southernmost part of the range of O. rhachophora, the mean annual temperatures, even at 300 m, are still very high (16–17°C) (Fig 7D) and O. kokusai was not found in collections from these localities. The two species do overlap in a narrow bathymetric zone (ca. 250–300 m depth) in the northern part of their geographic range, which corresponds to the lower and upper limits of the thermal tolerance of each species (Fig 8C and 8D). Thus, the bathymetric differentiation is more correlated with mean annual temperatures than water column pressure alone. This example of bathymetric and thermal divergence between two common species in a biogeographically important transition region between tropical, temperate and arctic waters [69–71] could be used in future monitoring of global climate changes or other causes of species range shifts.
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J. Mair ist Mitglied des Nukleus der Arbeitsgruppe „Angeborene und erworbene Herzfehler“ der Österreichischen Kardiologischen GesellschaftG.-P. Diller ist Sprecher der Arbeitsgruppe „Kongenitale Herzfehler im Erwachsenenalter“ der Deutschen Gesellschaft für KardiologieH. Geiger ist Leiter der Arbeitsgruppe „Angeborene und erworbene Herzfehler“ der Österreichischen Kardiologischen GesellschaftM. Greutmann ist Past-President der Arbeitsgruppe für „Erwachsene und Teenager mit angeborenen Herzfehlern“ der Schweizerischen Gesellschaft für KardiologieD. Tobler ist Mitglied der Arbeitsgruppe für „Erwachsene und Teenager mit angeborenen Herzfehlern“ der Schweizerischen Gesellschaft für Kardiologie
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Die diagnostische Abklärung von Long COVID im Kindesalter sollte sich wie bei Erwachsenen an den beschriebenen Beschwerden und dem Ausschluss anderer Differenzialdiagnosen orientieren (s. dazu Kap. 8 und 9). Die diagnostische Abklärung kann sich dabei an den einzelnen Kapiteln dieser Leitlinie orientieren, wobei auf die pädiatrischen Gegebenheiten Rücksicht genommen werden muss. Neben der Abklärung anderer organischer Differentialdiagnosen ist eine Berücksichtigung psychischer Ursachen von essenzieller Bedeutung.
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Jedoch muss an dieser Stelle auch betont werden, dass Ferienstudien über Situationen berichten, die kaum mit der gleichzeitigen Betroffenheit von Eltern und Kindern durch die deutschlandweiten Schulschließungen zu vergleichen sind. Schulferien sind Bestandteil einer auf Dauer gestellten, wiederkehrenden und letztlich normalen Situation, die sich von dem hier fokussierten disruptiven Ereignis mit kollektivem Bezug unterscheidet. Entsprechend lässt sich aktuell auch nicht abschließend beurteilen, inwiefern die Verarbeitungsmuster und -strategien unterschiedlicher Elterngruppen in derartigen Situationen weitere Anpassungen vorhandener theoretischer Modelle (wie dem FSM) notwendig machen. Dabei ist vor allem zu beachten, dass Ereignisse mit kollektivem Bezug, wie etwa auch Lowe et al. (2012) zeigen konnten, zu einer Veränderung in den Rahmenbedingungen führen können, was etwa die Vulnerabilität der Familie reduzieren kann. Um Verknüpfungen zu den in diesem Feld ebenfalls wichtigen Diskussionen über die Relevanz familiärer Resilienz (Walsh 2016) als Schutz- und Bewältigungsfaktor herzustellen, wäre es jedoch notwendig, die Familien insgesamt in den Blick zu nehmen, was im Rahmen der hier vorgestellten Studie so nicht möglich war. Die besondere Relevanz der hier berichteten Befunde liegt jedoch auch in der belastbaren Aussagekraft der Daten im Gegensatz zu anderen aktuellen Studien, die sich mit Zusammenhängen zwischen der Pandemiesituation und familialen Verarbeitungsmechanismen auseinandersetzen (etwa Daks et al. 2020).
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Este é um estudo descritivo retrospectivo não randomizado. Foram obtidas 81 amostras de tecido fetal de mulheres que tiveram aborto espontâneo de janeiro de 2012 a dezembro de 2017. As amostras de produtos da concepção foram enviadas ao laboratório de genética, para esclarecimento da causa do aborto por citogenética clássica ou CMA. A escolha do teste a ser realizado não foi randomizada, mas clinicamente indicada. As amostras foram enviadas para o laboratório em frasco estéril contendo meio de cultura (citogenética clássica) ou solução conservante (CMA) fornecida pelo laboratório. Os médicos receberam um folheto de orientação sobre o material que deveria ser depositado nos frascos para análise.
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To confirm the consistency between CitRKD1 allelic genotypes and embryonic phenotypes, the genotypes of 95 traditional and breeding varieties from Japanese breeding programs were investigated for MITE insertion allelism. A pair of primers was newly designed using the conserved sequences among CitRKD1 alleles of 14 ancestral varieties from Japanese breeding programs (Table 1) . In allelic genotyping PCR using the new primer set, approximately 0.7 and 1.0 kbp fragments corresponded to monoembryonic alleles (M) and polyembryonic alleles (P), respectively (Fig. 10). Among the 14 ancestral varieties, Duncan grapefruit, Dancy tangerine (C. tangerina hort. ex Tanaka), sweet orange, satsuma mandarin, ponkan mandarin, Mediterranean mandarin (C. deliciosa Ten.), king mandarin (C. nobilis Lour.) and ‘Murcott’ showed approximately 0.7 and 1.0 kbp fragments, indicating M/P genotype, while clementine mandarin, ‘Mukaku-kishu’ (C. kinokuni hort. ex Tanaka), Mato buntan pumelo, hassaku (C. hassaku hort. ex Tanaka), hyuga-natsu (C. tamurana hort. ex Tanaka) and iyo-kan (C. iyo hort. ex Tanaka) had single fragments of approximately 0.7 kbp, indicating M/M genotype. Based on the fragment patterns of the allelic genotyping PCR, allelic genotyping of CitRKD1 was performed for the remaining 81 varieties. The genotypes of 52 varieties were M/M and those of 27 pedigrees were M/P. Only ‘Seminole’ and ‘Saga’ mandarin had P/P genotype, with single fragments of approximately 1.0 kbp in allelic genotyping PCR. The embryonic types of the 95 varieties were perfectly consistent with their allelic genotypes, with M/M varieties having monoembryonic seeds and M/P or P/P varieties having polyembryonic seeds. This allelic genotype and embryonic type information is summarized in Table 1.Table 1Embryonic phenotype and allelic genotype of CitRDK1 for 95 traditional and breeding varieties in Japanese breeding programCodeVarietyAcademic nameParental combinationEmbryounic phenotypeAllelic genotype1grapefruit C. paradisi Macfad.C. paradisi Macfad.C. paradisi Macfad. Ancestral varietypolyembryonicM/P2dancy tangerine C. tangerina hort. ex TanakaC. tangerina hort. ex TanakaC. tangerina hort. ex Tanaka Ancestral varietypolyembryonicM/P3clementine mandarin C. clementina hort. ex TanakaC. clementina hort. ex TanakaC. clementina hort. ex Tanaka Ancestral varietymonoembryonicM/M4Mukaku-kishu C. kinokuni hort. ex TanakaC. kinokuni hort. ex TanakaC. kinokuni hort. ex Tanaka Ancestral varietymonoembryonicaM/M5Tanigawa-buntan C.grandis OsbeckC.grandis OsbeckC.grandis Osbeck Ancestral varietymonoembryonicM/M6hassaku C. hassaku hort. ex TanakaC. hassaku hort. ex TanakaC. hassaku hort. ex Tanaka Ancestral varietymonoembryonicM/M7hyuga-natsu C. tamurana hort. ex TanakaC. tamurana hort. ex TanakaC. tamurana hort. ex Tanaka Ancestral varietymonoembryonicM/M8sweet orange C. sinensis (L.) OsbeckC. sinensis (L.) OsbeckC. sinensis (L.) Osbeck Ancestral varietypolyembryonicM/P9Iyo-kan C. iyo hort. ex TanakaC. iyo hort. ex TanakaC. iyo hort. ex Tanaka Ancestral varietymonoembryonicM/M10satsuma mandarin C. unshiu Marc.C. unshiu Marc.C. unshiu Marc. Ancestral varietypolyembryonicM/P11ponkan mandarin C. reticulata BlancoC. reticulata BlancoC. reticulata Blanco Ancestral varietypolyembryonicM/P12mediterranean mandarin C. deliciosa Ten.C. deliciosa Ten.C. deliciosa Ten. Ancestral varietypolyembryonicM/P13king mandarinC. nobilis Lour.C. nobilis Lour.C. nobilis Lour.Ancestral varietypolyembryonicM/P14Murcott – Ancestral varietypolyembryonicM/P15Seminole – 1 × 2polyembryonicP/P16Minneola – 1 × 2polyembryonicM/P17Orlando – 1 × 2polyembryonicM/P18Fortune – 3 × 17monoembryonicM/M19Southern yellow – 5 × 4monoembryonicaM/M20Nankou – 10 × 3monoembryonicM/M21Ariake – 8 × 3monoembryonicM/M22Sweet spring – 10 × 6monoembryonicM/M23JHG – 10 × 7monoembryonicM/M24Awa orange – 7 × 8polyembryonicM/P25Kiyomi – 10 × 8monoembryonicM/M26Aki tangor – 10 × 8monoembryonicM/M27HF9 – 10 × 8monoembryonicM/M28Kankitsu chukanbohon Nou 6 gou – 13 × 4polyembryonicaM/P29Hayaka – 10 × 11polyembryonicM/P30Kara mandarin – 10 × 13polyembryonicM/P31Encore – 13 × 12monoembryonicM/M32Wilking – 13 × 12monoembryonicM/M33Page – 3 × 16polyembryonicM/P34Robinson – 3 × 17monoembryonicM/M35Lee – 3 × 17monoembryonicM/M36Fairchild – 3 × 17polyembryonicM/P37Nova – 3 × 17polyembryonicM/P38Osceola tangerine – 3 × 17polyembryonicM/P39Seihou – 10 × 16polyembryonicM/P40Akemi – 10 × 15polyembryonicM/P41A7 – 22 × 8monoembryonicM/M42Okitsu 46 gou – 22 × 8monoembryonicM/M43Nishino kaori – 25 × 8monoembryonicM/M44KyOw No.21 – 25 × 10monoembryonicM/M45KyOw14 – 25 × 10monoembryonicM/M46Tsunokaori – 25 × 10polyembryonicM/P47Shiranui – 25 × 11polyembryonicM/P48Youkou – 25 × 11polyembryonicM/P49Harumi – 25 × 11polyembryonicM/P50Setomi – 25 × 11polyembryonicM/P51EnOw21 – 31 × 10monoembryonicM/M52Kuchinotsu 39 gou – 31 × 10polyembryonicM/P53Mihokoru – 10 × 31polyembryonicM/P54KyEn No.4 – 25 × 31monoembryonicM/M55Tsunonozomi – 25 × 31monoembryonicM/M56Amaka – 25 × 31monoembryonicM/M57Okitsu 45 gou – 25 × 32monoembryonicM/M58Tamami – 25 × 32monoembryonicM/M59Benibae – 27 × 31monoembryonicM/M60Hareyaka – 31 × 11polyembryonicM/P61Amakusa – 45 × 33polyembryonicM/P62Kuchinotsu 38 gou – 44 × 34monoembryonicM/M63Saga mandarin – 10 × 36polyembryonicP/P64Kankitsu chukanbohon Nou 5 gou – 35 × 4monoembryonicaM/M65E-647 – 25 × 38monoembryonicM/M66Southern Red – 30 × 38monoembryonicM/M67KyOw No.21·D No.4KyOw No.21·D No.4KyOw No.21·D No.4 – 44 × 2monoembryonicM/M68Kuchinotsu 28 gou – 44 × 2monoembryonicM/M69Haruhi – 42 × 24polyembryonicM/P702700·Oiy-252,700·Oiy-252,700·Oiy-25 – 43 × 9monoembryonicM/M71No.1408 – 51 × (25 × 9)monoembryonicM/M72Kuchinotsu 18 gou – 44 × 31monoembryonicM/M73Kuchinotsu 35 gou – 44 × 31monoembryonicM/M74Kanpei – 43 × 11polyembryonicM/P75Okitsu 57 gou – 42 × 49monoembryonicM/M76Asumi – 42 × 49monoembryonicM/M77Asuki – 42 × 49monoembryonicM/M78Seinannohikari – 51 × 48polyembryonicM/P79Kuchinotsu 27 gou – 51 × 48monoembryonicM/M80Okitsu 59 gou – 41 × (25 × 32)41 × (25 × 32)monoembryonicM/M81Kuchinotsu 33 gou – 45 × 31monoembryonicM/M82Tsunokagayaki – 45 × 31monoembryonicM/M83Setoka – 54 × 14polyembryonicM/P84Kuchinotsu 36 gou – ? × 14monoembryonicM/M85Reikou – ? × 14polyembryonicM/P86Ehime kashi No. 28 gou – 20 × 61monoembryonicM/M87Kuchinotsu 49 gou – (KO21 ‘ ROb16) ‘ 71(KO21 ‘ ROb16) ‘ 71monoembryonicM/M88Okitsu 56 gou – 57 × 64monoembryonicM/M89No.1011 – 20 × 70monoembryonicM/M90Kuchinotsu 51 gou – (? × 2) × 79(? × 2) × 79monoembryonicM/M91Harehime – 65 × 10monoembryonicM/M92Okitsu 63 gou – 65 × 11polyembryonicM/P93Kuchinotsu 52 gou – 82 × 21monoembryonicM/M94Mihaya – 55 × 71monoembryonicM/M95Okitsu 67 gou – 91 × 88monoembryonicM/MM monoembryonic allele, P polyemrbyonic allelea: Phenotype is not visually confimed due to seedless but is determined based on the phenotypes of pedigrees in the cross hybrid testsFig. 10Allelic genotyping PCR of CitRDK1 alleles for 95 traditional and breeding varieties in Japanese breeding programs using the P/M marker. The upper fragment is derived from the polyembryonic allele and the lower fragment is derived from the monoembryonic allele. ‘Seminole’ (15) and ‘Saga’ mandarin (63) possess homozygous polyembryonic alleles in their genomes
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Die KKH hat bereits mehrfach in Pressemitteilungen Ergebnisse aus ihren Abrechnungsdaten vorgestellt und berichtet den prozentualen Anstieg an KKH-Versicherten mit rheumatoider Arthritis (RA) im Vergleich zu Daten von vor 10 Jahren, zuletzt bezogen auf 2009 und 2019. Hier wurde ein Anstieg um bundesweit 36 % mit dem höchsten Anstieg in Baden-Württemberg (+59 %) und in Sachsen (+54 %) berichtet . In einem 2018 veröffentlichten Vergleich der Daten von 2007 und 2017 war die beschriebene Zunahme in Mecklenburg-Vorpommern mit 62 % am höchsten . Die KKH hat ca. 1,6 Mio. Versicherte, entsprechend ca. 2 % der gesetzlich Krankenversicherten in Deutschland. Welche Abrechnungsdiagnosen für die Identifizierung einer RA verwendet wurden und wie viele Versicherte betroffen sind, wurde nicht angegeben.
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得益于CRISPR/Cas9技术在基因编辑方面的高效性，在同一个细胞系中在基因组规模上，同时进行多个基因的编辑成为了可能。因此，研究人员们可以在基因组规模上，筛选出细胞内的哪些基因和研究者们感兴趣的表型相关。利用慢病毒转导的方式可以同时向细胞内转导入成千上万个靶向不同基因的sgRNA。最近，多篇文章的发表，证实了这种筛选方式在人类细胞中阴性和阳性的筛选能力。以往在基因组规模上进行这种功能缺失的筛选都是应用的RNAi的方法，但是这种方法仅仅能够让基因的表达水平下调，并且有着较为严重的脱靶效应。相反，Cas9介导的sgRNA文库筛选系统已经被证实具有更高的筛选敏感性，而且几乎可以靶向调节任何一段DNA序列。在将来利用sgRNA筛选文库可能会扩展到对非编码基因序列的筛选中。
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Des différences de fréquence, d'âge, d'étiologie voire même de pronostic des hémorragies digestives hautes (HDH), entre les hommes et les femmes, ont été citées dans différentes études. Ces différents paramètres sont très hétérogènes et différemment appréciés d'une étude à une autre, d'autant plus que peu de publications ont cherché les particularités des HDH selon le sexe. Dans ce travail, nous avons essayé de déceler les différences démographiques, cliniques, étiologiques et évolutives des HDH liées au genre.
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dN/dt is the focal species' rate of population change; dE/dt is the rate of environmental change; n is the size of the competitor's gene network; sf is the topology (e.g., scale-free) of the competitor's network; μ is the competitor's mutation rate; r is the competitor's recombination rate; and these abbreviations are combined for brevity in some model descriptions.
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Tecidos embebidos em parafina (enxertos no 3°, 14° e 28° dias) foram processados, e foram retiradas seções de 3 μm ao longo do enxerto; exceto pelas regiões imediatamente adjacentes às mangas da anastomose. Depois da desparafinização, o antígeno foi recuperado com tampão citrato por 20 minutos em temperatura e pressão altas, depois desativado com peroxidase endógena H2O2 a 3% for 20 minutos, e bloqueio de peroxidase endógena com albumina sérica bovina a 5% por 10 minutos. As seções foram tratadas durante a noite a 4°C com anticorpo monoclonal anti-PCNA (D3H8P; Cell Signaling), anticorpo anti-VCAM1 (ab134047; Abcam, diluição 1:500), e anticorpo anti-ICAM1 (ab119871; Abcam, diluição 1:200). Três seções separadas por enxerto foram analisadas em relação a todos os marcadores. Os cortes foram lavados várias vezes. Foram adicionadas aos cortes a solução funcional de anticorpo secundário biotinilado, e de solução funcional de estreptavidina conjugada com horseradish peroxidase. Os cortes foram lavados em PBS (pH 7.2) por 5 minutos. Foi utilizada a diaminobenzidina tetrahidrocloreto (DAB) para a visualização, e a hematoxilina foi utilizada para contracoloração. Por último, os cortes foram desidratados, e em seguida foram montadas e seladas. Todas as imagens foram capturadas por aquisição de sinal de imagem e sistema de análise (Leica-DM2000, Hefei, China). O índice de PCNA foi utilizado para descrever o nível de expressão de PCNA (índice de PCNA = número de células com PCNA positivo/número total de células). A densidade ótica média foi utilizada para descrever o padrão de expressões de VCAM-1 e ICAM-1 (densidade ótica média = densidade ótica integral/área).
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Ustawa z dnia 29 lipca 2005 r. o ofercie publicznej i warunkach wprowadzania instrumentów finansowych do zorganizowanego systemu obrotu oraz o spółkach publicznych (t.j. Dz. U. z 2019 r. poz. 623, ze zm.) [Act on Public Offering and Publicly Listed Companies]
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Predicted target human genes of abundant plant miRNAs. The predicted miR2910, miR2916 and miR2018 targets through miRTar are illustrated in this figure. The pink diamond shape nodes represent plant miRNAs while the round blue nodes represent human genes
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Cells were irradiated with UV light at 150 mJ/cm2 and lysed in buffer containing 50 mM Tris-HCl, pH 7.4, 100 mM NaCl, 1% NP-40, 0.1% SDS, 0.5% sodium deoxycholate, and protease inhibitor cocktail. RNAs were partially fragmented using RNase A (QIAGEN). After centrifuging at 10,000g for 10 minutes, an aliquot (10%) of supernatant was removed and served as input. The remaining supernatant was immunoprecipitated with either rabbit IgG or anti–YB-1 antibody immobilized on Protein G Dynabeads. The bound RNAs were washed extensively and isolated using TRIzol (Invitrogen) followed by RT-qPCR.
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LPS (E. coli 0127:B8 endotoxin; Sigma-Aldrich, St. Louis, MO, USA), as mentioned above, was used to induce monomicrobial sepsis and liver injury . Mice were randomly allocated to the sham, SEM, CP, LPS, LSEM, and LCP groups. As mentioned above, at 2 h after LPS or NS administration, the first dose of the peptide (SEM18 or CP, 0.3 mg/kg, i.p.) was administered, followed by three supplemental doses of the peptide (SEM18 or CP, 0.15 mg/kg, every 2 h, i.p.). The timing of administration of the peptides was decided on the basis of previous data from healthy volunteers showing that circulating TNF-α concentrations peaked at approximately 60–90 min after endotoxin . Three supplemental doses were administered considering the short in vivo half-life of the peptides . The first dose of SEM18 peptide was determined according to our preliminary data that 0.3 mg/kg was the lowest effective dose of SEM18 peptide that could mitigate increases in biomarkers of liver injury (i.e., plasma concentrations of AST and ALT) in mice, as measured at 6 h after LPS.
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пациентки женского пола паспортного возраста <40 лет, находящиеся в состоянии аменореи длительностью не менее 5 лет; подтвержденный медицинской документацией факт получения ГЗТ в дозе эстрогенового компонента 2 мг в течение не менее 5 лет. Все пациентки подписывали информированное согласие на проведение обследования и консультирование.
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Lastly, the saving system is responsible for saving and loading the game (context: place). The save menu, accessed via the game menu, contains three slots that are initially empty. If a player clicks the save button next to a slot, a game instance is saved and the slot is occupied with the main characters stats, like health, mana and experience points, gold, active quests etc. (Fig. 6).
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A database search was performed with XTandem Sledgehammer 2013.09.01.1 (http://www.thegpm.org/TANDEM/) via the X!tandem pipeline available at http://pappso.inra.fr/bioinfo/xtandempipeline/. Enzymatic cleavage was declared as a trypsin digestion with one possible miscleavage event. Fixed modifications of cysteine residues by iodoacetamide as well as oxidized methionins were considered. Precursor mass and fragment mass tolerance were set at 5 ppm and 0.8Da, respectively. Identified proteins were filtered according to the following specifications: at least two peptides in the same band with an E value below 0.01 and a protein E value below 10–4. Two sets of data were generated, one for the outer pericarp obtained by combining the results from the three sequential protein extracts, and one for the intermediate layers obtained by combining the results from three enriched Golgi fractions. To take redundancy into account, in each set, proteins with at least one peptide in common were grouped. The number of identified proteins given in this report corresponds to the number of protein groups. In some groups, sub-groups of proteins were defined. The proteins in these sub-groups shared some peptides with the other proteins of the group but were distinguished by at least one specific peptide.
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Toutes les données collectées ont été saisies et analysées par les logiciels Epi-info version 6.04d. et SPSS (Statistical Package for Social Sciences) version 8. Les variables quantitatives ont été exprimées en moyenne avec leur écart-type, les données qualitatives en pourcentage et leur intervalle de confiance à 95%.
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The FDR strategy’s BH (Benjamini and Hochberg) approach was utilized to further adjust the P-value of the multiple tests and obtain the adj. P-value. Finally, the differences of protein were screened out based on the differences between the multiple and the adj. P-value. Criteria for significant differences in expression are shown as follows: when the comparison group’s adj. P-value ≤0.05 and the fold change ≥1.5 (upregulation of expression) or fold change ≤0.67 (downregulation of expression), the expression is considered as a significant variety. Figure 3B depicted the volcano plots of proteins retrieved from healthy volunteers and DR+DN patients in HGECs treated with SExos. Results showed that after the treatment with 50 mM SExos from DR+DN patients for 48 h, a total of 185 differentially expressed proteins were identified in HGECs with 87 proteins upregulated (red dots) and 98 proteins downregulated (blue dots). The significant differences of expressed proteins between the groups were observed in the hierarchical clustering heat map as shown in Figure 3C . Figure 3D showed the proteins associated with endothelial dysfunction of the profile. Among the differentially expressed proteins, fibrinogen alpha chain (FGA) was the highest elevated (fold change: 4.024). Transforming growth factors beta 1 (TGFβ1) and Collagen Type I Alpha 1 Chain (COL1A1) have been linked to the diabetic endothelial-to-mesenchymal transition and have been shown to worsen diabetic glomerulosclerosis (44, 45). Circulating ICAM-1 levels are positively connected with albuminuria in individuals with type 1 diabetes (T1D) and T2D (46, 47). ICAM-1 is an endothelial damage protein marker (46). S100A6 is an important component of the PPP5C-FKBP51 axis, which protects the endothelium barrier from calcium entry-induced disruption (48).
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In the included studies, two types of data were applied to report the QOL changes on KPS score. First, the number of patients who reported QOL improvement (KPS score 10 points higher after treatment). And second, the mean ± standard deviation (SD) of the KPS score before and after treatment. As shown in Figure 6, the number of patients with improved QOL based on the KPS score were reported in 14 studies (RR: 2.03, 95% CI: 1.70–2.43, P < 0.00001, I2 = 0%); and the mean ± SD of KPS score were reported in other six studies (MD: 12.39, 95% CI: 5.48–19.30, P = 0.0004, I2 = 95%) (Figure 7). Taken together, compared with PBC, the study results showed that Astragalus-containing TCM plus PBC significantly improved QOL.
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Three clinicians suggested that closed‐loop systems should ‘theoretically … free up time’ (1/PR/Obs/6) because algorithmic insulin delivery would allow users to achieve improved control with less need for intensive clinical input: ‘it will certainly reduce the workload of … medical teams in terms of managing diabetes and the outcome will be spectacularly better for patients’ (1/PR/Nurs/7). Others raised the possibility that the improved glycaemic control offered by closed‐loop systems might help users to avoid future complications, which in turn would reduce the clinical effort needed to treat them. One midwife framed this possibility in terms of healthcare spending, suggesting that ‘when you think of the complications, it would be a lot cheaper to [use closed‐loop systems than not]’ (2/PR/Midw/7).
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For computational efficiency, we set f0 = 0.2 Hz and defined the external stimulus function (i.e., auditory stimuli with Gaussian noise), FAS (θ, t), as4\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{F}}}_{{\rm{AS}}}\left(\theta ,\,t\right)={A}_{AS}\sin \left(2\pi {f}_{AS}t+\xi \left(\mu ,\,{\sigma }^{2}\right)-\theta \right),$$\end{document}FASθ,t=AASsin2πfASt+ξμ,σ2−θ,where AAS and fAS are the amplitude and frequency of the auditory stimuli and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\xi \left(\mu ,\,{\sigma }^{2}\right)$$\end{document}ξμ,σ2 is the Gaussian noise with the expectation value μ and the variance σ2. Next, we defined the optogenetic input, FOS (θ, t), as5\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{F}}}_{{\rm{OS}}}\left(\theta ,\,t\right)={A}_{OS}\sin \left(2\pi {f}_{OS}\left(t+{\tau }_{lag}+\tau \right)-\theta \right),$$\end{document}FOSθ,t=AOSsin2πfOSt+τlag+τ−θ,where AOS and fOS are the amplitude and frequency of the optogenetic stimuli, τlag is the synaptic time delay from the BF to the cortex and τ denotes the latency of optogenetic stimulation with respect to sound onset. All parameter values used in the model are described in Table 3. By combining (Eqs. 2–5), Eq. (2) becomes6\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\begin{array}{llll}\frac{d{\theta }_{i}}{dt} & = & {\omega }_{i}+\frac{1}{N}\mathop{\sum }\limits_{j}^{N} & \frac{{k}_{max}}{\sqrt{{\left({\left({\dot{\theta }}_{j}\right)}^{2}-{\omega }_{0}^{2}\right)}^{2}+1}}\sin \left({\theta }_{i}-{\theta }_{j}\right)\\ & & & +{A}_{AS}\sin \left(2\pi {f}_{AS}t+\xi \left(\mu ,\,{\sigma }^{2}\right)-{\theta }_{i}\right)\\ & & & +{A}_{OS}\sin \left(2\pi {f}_{OS}\left(t+{\tau }_{lag}+\tau \right)-{\theta }_{i}\right),\end{array}$$\end{document}dθidt=ωi+1N∑jNkmaxθ˙j2−ω022+1sinθi−θj+AASsin2πfASt+ξμ,σ2−θi+AOSsin2πfOSt+τlag+τ−θi,for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\rm{i}}=1,\ldots ,{\rm{N}}$$\end{document}i=1,…,N. To describe the synchronization, the order parameter \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r\left(t\right),\psi \left(t\right)$$\end{document}rt,ψt is defined by7\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{re}}}^{i\psi }\equiv \frac{1}{N}\mathop{\sum }\limits_{j=1}^{N}{e}^{i{\theta }_{j}}.$$\end{document}reiψ≡1N∑j=1Neiθj.here, r(t) represents the magnitude of the mean field, which represents the degree of synchronization between cortical neurons, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\psi (t)$$\end{document}ψ(t) is the phase of the mean field. In this case, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi \left(t\right)=r\left(t\right)\sin \psi \left(t\right)$$\end{document}ϕt=rtsinψt resembles the LFP signal.Table 3The parameter values used in the model.ConditionNkmaxf0AASAOSfASfOSτlagτSound only10000.80.20.3·0.2···Advanced10000.80.20.30.090.20.2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{1}{12{f}_{0}}$$\end{document}112f0\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$-\frac{{\rm{\pi }}}{2}$$\end{document}−π2Out of phase10000.80.20.30.090.20.2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{1}{12{f}_{0}}$$\end{document}112f0πωi was selected from normal distribution with μ = 0 and σ = 0.5,θi(0) was selected from normal distribution with μ = 0 and σ = 20,(μ: an average of the normal distribution, σ: a standard deviation of the normal distribution.
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Deledalle et al. have put forward the ENLNLRB calculation method based on NL-SAR estimate and it is a good indication of quality evaluation for PolSAR filtering. For the center pixel x, the ENLNLRB can be computed as follows:(20) ENLNLRB(x)=ENLNLM(x)(1−b)2+(b2+2b(1−b)∑x′ω(x,x′))ENLNLM(x) where ENLNLM(·) is the ENL calculated by the NLM method .
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The originating influences refer to aspects associated with organisational characteristics and different aspects of management and regulation that make up the environment within which safety measures are (or not) favoured and not directly related to accidents in the short-term but are essential for explaining the long-term causes;
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In this study, we found that miR-23a expression was frequently downregulated in the radioresistant NPC tissues, restoration of miR-23a expression increased NPC radiosensitivity both in vitro and in vivo, and reduced miR-23a increased NPC radioesistance by activating IL-8/Stat3 signaling. Our study for the first time shows the role and mechanism of miR-23a in tumor radioresistance, which highlights the radiosensitizing potential of miR-23a/IL-8/Stat3 signaling axis in NPC and perhaps in other cancers.
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There is variation in the reporting of the baseline characteristics of the participants across the studies. While two of the studies specifically focus on women with mental illness, three of the studies include women across a number of classifications of mental illness and do not provide data on baseline characteristics stratified by type of mental illness. Age of the mother may play a significant role in preterm birth, and whilst all of the studies collected data relating to the age of participants, only two studies provided details that related to the specific population of patients with personality disorder , with one study only providing age data relating to the population of patients with personality disorder and not control group . Where data was available , women with personality disorder tended to be younger in age than the women in the control group. Only two of the studies took note of race/ethnicity of the participants. This is of concern, as there is significant evidence, that race/ethnic group of the mother is associated with poorer birth outcomes, particularly, Black-African women . All of the studies took account of smoking status/tobacco use, and alcohol drug misuse although only one study reported clearly on this for women with personality disorder, and in this study women with personality disorder tended to use alcohol, tobacco, and drugs more commonly than their counterparts in the control group.
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No obstante los logros alcanzados, es necesario avanzar en el diseño de intervenciones innovadoras basadas en evidencias científicas que permitan superar las barreras identificadas y que promuevan, en la población adolescente, las condiciones para el ejercicio de una sexualidad saludable y protegida. Para ello, es necesario examinar con mayor profundidad los factores sociales, cognitivos y emocionales que influyen en el comportamiento sexual y reproductivo de los y las adolescentes, en particular el papel que desempeñan las familias y los pares en la toma de decisiones (19), la necesaria interfaz entre el sistema educativo y el sistema de salud para prevenir los embarazos no intencionales (20), el involucramiento de los adolescentes varones (21) y el papel de los entornos virtuales en la socialización sexual (22). A ello contribuirá el diseño de intervenciones relacionadas con la educación sexual y la atención en salud sexual y reproductiva que tomen en cuenta los nuevos escenarios, como el que impone la pandemia por COVID-19.
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SOX9 is upregulated in DDP-resistant cervical cancer and a direct target of miR-361-3p. (A, B) SOX9 mRNA (A) and protein (B) expression in original Caski and HeLa cells and DDP-resistant Caski/DDP and HeLa/DDP cells was determined using qRT-PCR and Western blot assays. (C) SOX9 expression in DDP-sensitive and DDP-resistant cervical cancer tissues (n = 50) was determined using qRT-PCR. (D) Correlation of SOX9 expression with the survival probability of patients with cervical cancer was analyzed using the online tool Kaplan–Meier plotter based on TCGA data from Pan-Cancer Atlas. (E, F) DDP-resistant cervical cancer cells were transfected with miR-361-3p mimics or inhibitor and examined for SOX9 mRNA (E) and protein (F) expression by qRT-PCR and Western blot assays. (G) Wild- and mutant-type SOX9 luciferase reporter vectors were constructed by cloning SOX9 3’-UTR to psiCheck-2 vector or inducing mutation to the predicted miR-361-3p binding site. (H) Wild- and mutant-type SOX9 luciferase reporter vectors were co-transfected to 293T cells with miR-361-3p mimics or inhibitor. The luciferase activity was determined using Dual-luciferase Reporter Assay System. **p < 0.01, ## p < 0.01.
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Cyclic dinucleotides including cGAMP have been tested as candidate adjuvants in experimental models of parenteral or mucosal adult immunization (32–49). In the present work, mice were immunized by the intramuscular route as it is commonly employed for pediatric vaccines: a new formulation specific for intramuscular injection may fit easily with other vaccines in the pediatric vaccination schedule, while intranasal immunization against influenza virus, for example, is currently not recommended by the CDC (67). We found that free cGAMP, simply injected together with the model antigen, is much less effective in newborn than in adult mice at increasing antigen-specific antibody titers. Remarkably, cGAMP formulated with alum induces relatively high titers of antigen-specific IgG2a/c compared to alum or cGAMP alone, especially in newborn mice immunized with prime/boost or single dose schedules. The explanation for this might be that about 60% of cGAMP adsorbs onto alum in vitro, which also suggests that there is still the possibility of further optimizing this formulation and increasing the percentage of adsorbed cGAMP by modification of the adsorption pH, buffer, and alum to cGAMP ratio. Interestingly, it has already been reported that CDNs tend to diffuse in the bloodstream after injection, while their nanoparticle formulations deliver CDNs to the dLNs (40). It is tempting to speculate that the same phenomenon might explain the differences in the efficacy between cGAMP and (cGAMP + alum). In addition, it will be interesting to compare the effect of optimized (cGAMP + alum) and nanoparticle-based cGAMP formulations in our early life immunization model.
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En el caso de los antidiabéticos, la tasa de prescripción de metformina encontrada en el estudio fue baja (entre 27,86 % y 67,63%), a pesar de ser el medicamento de primera línea para la mayoría de los pacientes diabéticos (21-23). Entre las sulfonilureas, la gliclazida o la glipizida constituyen las mejores alternativas ya que no producen metabolitos activos y el sistema enzimático del citocromo no interviene en su metabolización (38). Lo anterior se contrasta con que en tres de las cinco instituciones evaluadas (H1, H2 y S2), la glimepirida o la glibenclamida se prescribieron más que la metformina (57% vs 34% en promedio, respectivamente), lo que sugiere un patrón invertido de prescripción racional, con mayor riesgo de hipoglucemia e interacciones medicamentosas en el tratamiento de los pacientes diabéticos polimedicados. Solo dos instituciones (H2 y S3) reportaron una prescripción muy baja (0,4%) de medicamentos que no cuentan con evidencia de alta calidad que demuestre su efectividad y potencial prevención de complicaciones. En los casos en que es necesario incorporar al tratamiento insulina, las formas NPH y cristalina constituyen las de primera elección ya que el uso de análogos de la insulina no ha demostrado ser costo-efectivo (29). En nuestro estudio se observó que en cuatro instituciones (H1, H2, S1, S2) se prefiere el uso de las primeras por encima del 75%, mientras que en una de ellas (S3), 6 de cada 10 pacientes reciben análogos de la insulina de acción corta y prolongada, lo que constituye una estrategia no costo-efectiva (6, 29).
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Our results strongly suggest that: Lay people are strongly opposed to outright lying.The majority support partial disclosure when it may benefit the patient.There is strong support for physicians fully disclosing the fact that no active treatment exists for a particular condition.
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The goal of glycemic control for GDM after lifestyle modifications was as follows: FBG < 5.3 mmol/L and either 1-hour blood glucose post 75 g oral glucose load < 7.8 mmol/L or 2-hour blood glucose post 75 g oral glucose load < 6.7 mmol/L . If the above criteria are met, these pregnant women are classified under the GDM1 group, and if not, they are classified under the GDM2 group. The women in the latter group were treated with insulin or hypoglycemic drugs to achieve acceptable glycemic levels.
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a Schematic illustration of the force sensor constructs MFS-H57, and MFS-IEk/MCC, the control construct MFSC-H57, and the unlabeled constructs MFS0-H57 and MFS0-IEk/MCC. b Exertion of forces stretches the spring core module, which reduces FRET yields for the molecular force sensor (here: MFS-H57) but not for the control force sensor (here: MFSC-H57). c Representative images illustrating FRET efficiencies determined on a pixel-by-pixel basis via DRAAP on gel-phase (DPPC) and fluid-phase (POPC) SLBs with the use of the MFS or the MFSC construct (bottom row), and the corresponding transmission light microcopy images (top row). d Statistical analysis of ensemble FRET measurements. Each data point corresponds to a single DRAAP experiment of up to three cells in the field of view; boxes indicate the interquartile range (first quartile to third quartile), whiskers extend 1.5 times the interquartile range from the first and third quartile, the line indicates the median. A significant reduction in FRET efficiency (ΔEbulk) was only observed for MFS on gel-phase SLBs (n.s., not significant; two-sample Mann–Whitney U test). n = 68 cells for MFS on gel-phase SLBs, n = 24 for MFS on fluid-phase SLBs, n = 27 for MFSC on gel-phase SLBs, n = 21 for MFSC on fluid-phase SLBs. e Representative single-molecule signals and time traces. The left panel depicts the fluorescence signals prior to and after photobleaching of the FRET acceptor. The middle panel shows single-molecule brightness values of the FRET donor, the FRET signal itself and the FRET acceptor. Bleaching of the acceptor could be observed as a correlated step-wise decrease of FRET and FRET acceptor intensities and an increase in FRET donor intensity. The right panel shows the stoichiometry and FRET efficiency. Scale bars: 5 µm (panel c), 1 µm (panel e).
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Principal components were identified using singular value decomposition . The projection of a transcript on a principal component was considered significant for enrichment analyses if its value was at least one standard deviation from the mean projection value of all transcripts in the dataset. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify Gene Ontology (GO) terms, biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Swiss-Prot keywords associated with co-expressed gene sets identified in our analysis . To minimize the prevalence of redundant GO terms, the functional clustering tool in DAVID was used to group GO terms with overlapping membership, using the “medium” setting; the most significant GO term in each group was then chosen to represent each functional cluster. GO terms and Swiss-Prot keywords were considered significant if the p-value was <0.05 after Benjamini correction for multiple testing. NextBio software and database (http://nextbio.com) were used to identify cell types and other array datasets associated with genes in our analysis and to establish corresponding p-values . Significance Analysis of Microarrays (SAM) was used to identify genes associated with differences between patient groups, or between patient groups and healthy controls . Correlations between relative gene expression levels and clinical parameters were calculated using perl-based scripts; the significance of Pearson correlation coefficients was calculated after deriving a null distribution through permutation of sample labels . Potential differences in clinical parameters and median expression of specific gene sets were tested using the Wilcoxon rank sum test and STATA v.10 (STATA, College Station, TX).
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TLS polymerase activity is also modulated by phosphorylation. Pol η is phosphorylated at a number of sites in the C-terminus by protein kinases including ATR, CDK2 and PKC. Following DNA damage, ATR-mediated phosphorylation of Pol η on serine 601 (114) releases it from sequestration by Pol δ-interacting protein of 38 kDa (PDIP38), freeing Pol η to bind to monoubiquitinated PCNA (115). This links ATR activation by replication arrest-induced single-stranded DNA, with recruitment of TLS polymerases to the arrested fork (115). Pol η is additionally phosphorylated by PKC on S587 and T617 (129), and on serine 687 by CDK2, which increases the stability of the polymerase in late-S and G2/M (125).
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The gentamicin‐only group exhibited decreased SOD and GPX, signifying oxidative stress. The G. glabra‐only group exhibited increased levels of GPX only, while the group cotreated with gentamycin and G. glabra exhibited only small changes in SOD and GPX, suggesting a restorative effect of G. glabra (see Table 3).
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The grazing trials were conducted at the Experimental Station of the Faculty of Agronomy of the UFRGS, in Southern Brazil (30°05”22' S latitude, 51°39”09'W longitude and 46 m above sea level), with a subtropical humid “Cfa” climate with an average annual temperature of 18°C. Italian ryegrass pastures were established on April 20th in 2017 and May 23th in 2018, through conventional soil preparation (plowing and disking), mechanical spreading of 35 kg of seed per hectare and 250 kg of the formula (NPK, 5-30-15) per hectare at seeding and 200 kg of nitrogen (urea) 30 days later.
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For the subset of 30 noncoding SNPs singled-out by a PIP > 0.6, we examined the potential for transcription factor (TF) binding site disruption (summarised in Supplementary Data 11 and presented in full Supplementary Data 12). Two TFs whose binding strengths were predicted to be significantly altered at the most sites (7 out of the 30 investigated sites) were REST and RXRA (Table 2). Chance expectations for such results were estimated to be 9.7% and 7.34%, for REST and RXRA, respectively (Supplementary Note 5). Notably, amongst the seven loci with a prioritised causal variant predicted to affect REST binding affinity, FNDC3, RXRA-COL5A1, and FOXO1 are keratoconus loci and ADAMTS8 and COL6A1, were recently suggested to be11.Table 2Prioritised CRF causal candidate variants with potential to disrupt a REST or RXRA binding site.TFvariantRef/AltAltered motifMotif sourceaStronger bind (P value)Stronger bind CRF associationMMAnnot LocusRESTrs3132302A/GggcggagtgagcAgENCODE REST_disc8G (3.4 × 10−4)Decreasing0.9315intergenic RXRA-COL5A168rs58933977T/GTgtgcacacaatggENCODE REST_disc8G (1.7 × 10−4)Decreasing0.9472intergenic MEG8-DIO3OS102rs7635832T/GctcagcacatttTttENCODE REST_disc1G (4.8 × 10−4)Decreasing0.7364intronic FNDC331rs79126727G/AGgccctgtENCODE REST_disc6A (6.1 × 10−5)Decreasing0.9297intronic FTCD135rs182804464C/GcttctCctcagcttgctgtENCODE REST_known3G (4.3 × 10−4)Decreasing0.6829intronic COL6A1135rs74948688aC/TccatCacacccagcENCODE REST_disc9C (2.3 × 10−4)aIncreasing0.9108intronic and 3’FOXO196rs2875238T/CgccactggttcTggtENCODE REST_disc1T (2 × 10−4)Increasing0.7685intronic and 5’ ADAMTS884RXRArs2035835G/CcGccatctENCODE RXRA_disc5G (3 × 10−5)Decreasing0.9832intronic OTOP2121rs34869aG/CaagggtcggaggaGatgENCODE RXRA_known6C (1 × 10−4)aIncreasing0.72475’ CDO145rs10868299C/AgggtaCcttagagaccaENCODE RXRA_known8A (1.2 × 10−4)Increasing0.8288intergenic C9orf135-MAMDC265rs74948688aC/TtttccatCacENCODE RXRA_disc4T (4.1 × 10−4)aDecreasing0.9043intronic and 3’FOXO196rs143038218T/AcgTgagtaaaENCODE RXRA_disc3T (3 × 10−4)Increasing0.9395intergenic UBIAD1-PTCHD21rs6081765A/GcaAgttcaENCODE RXRA_known4A (1.7 × 10−4)Increasing0.98899Intergenic PDYN-STK35130rs7863424aG/AagagccagagGggaSwissRegulonG (2.3 × 10−4)aDecreasing0.7977intronic GLIS363In silico prediction of significant differential binding for reference (Ref) and alternate (Alt) allele at fine-mapped prioritised SNPs was computed using transcription factor motif weight matrices from various sources (Motif Source) using MotifBreakR.MM motif match as percentage of perfect match.aDenotes a corresponding transcription factor occupancy peak in the ENCODE 3 ChIP-seq data survey of 338 factors in 130 cell types.
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In our study, long-term incubation of Candida cells in water (Figure 2(a,b)) lacking any nutrients or on plastic surfaces, similar to material found in hospital settings (Figure 2(c)) revealed a remarkable ability of C. auris to survive harsh environmental conditions over several days or even weeks – in contrast to all other tested Candida species, except the other majorly hospital-environmental species C. parapsilosis , which is in agreement with previous studies on C. auris and C. parapsilosis . Thus, we have shown and confirmed that C. auris can survive and persist for long periods outside of the human host, and that nosocomial C. auris infections can therefore originate from environmental sources, such as contaminated medical devices or hands of health care workers, without prior colonization of the infected host . This increases the risk of transmission in healthcare settings and explains why hospital outbreaks are described for C. auris and C. parapsilosis rather than for the other Candida species .
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肺癌是目前世界上最常见的恶性肿瘤。迄今，用于肺癌早期诊断和筛查的有效和廉价的方法较少。虽然组织学和细胞学检查是诊断肺癌的金标准，但确诊时患者往往处于晚期。因此，迫切需要新的诊断方法来提高早期诊断率，提高确诊率，降低死亡率。SHOX2基因甲基化分析被认为是一个具有广泛临床应用前景的诊断方法。SHOX2基因甲基化检测，与组织学、细胞学检测及影像诊断相结合可提高肺癌的确诊率，并有可能成为早期诊断的有效工具。SHOX2是同源框基因家族的一员，该家族编码含有60个氨基酸残基的蛋白。同源异型盒基因作为转录调节因子广泛存在于无脊椎动物和脊椎动物中。近年来，越来越多的研究关注SHOX2基因启动子甲基化在肺癌早期诊断中的价值。然而，SHOX2基因启动子甲基化在肺癌发生、发展中的生物学意义目前仍未完全阐明。大多数研究[20, 21]认为，SHOX2基因被证实是多种癌症信号通路的调控子或效应子，可促进肿瘤的发生和发展。SHOX2基因甲基化检测在肺癌的发生、发展、转移、耐药和复发过程中起重要作用。SHOX2基因甲基化检测联合影像学等其他诊断学方法被认为是筛查和监测肺癌的一种很好的方法，具有较高的敏感性和特异性。
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– The specificity of the effects was not fully established. Reviewers suggest control analyses that would address whether indeed what was seen in the hippocampus is something that is unique to the hippocampus, or whether it was a general effect of pharmacology in BOLD signal that was not observed elsewhere.
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Genomic DNA was extracted for all members of the Kilifi Genetic Birth Cohort Study from capillary blood samples collected into EDTA within 7 days of their recruitment using an ABI PRISM 6100 Nucleic AcidPrepStation™ (Applied Biosystems). For the current study, β‐globin gene sequencing was conducted on selected participants using samples that had been stored at −80°C. We sequenced amplicons derived by PCR using HBB primers using an ABI 3730xl sequencer and the BigDye Terminators cycle Sequencing Kit (Applied Biosystems), as described in detail previously (Clark & Thein, 2004). In brief, our sequencing method covered a 1.8kb region that included the 5ʹ promoter, 5ʹ and 3ʹ untranslated regions, exons 1–3, and the intervening sequence I and II regions flanking exons 2 and 3.
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Overall, the midwives found the MAMAACT intervention to be very relevant, indicating that the leaflet and app were an acceptable approach to attempt to increase response to pregnancy symptoms. However, while midwives found the usability of the leaflet and app to be high, they found the training course to lack information on how to communicate the MAMAACT material. These findings suggest that training in cultural competence may need to be supplemented with more practical communication tools. Although the midwives introduced the leaflet and app at the first midwifery visit, almost none of the midwives followed up on the use of the material during the following visits due to competing tasks or forgetting to do so. Lack of follow up affected the overall compliance with the intervention. In addition, while most midwives used the MAMAACT material to guide their communication, a few midwives introduced this material as a research project, indicating that training in how to introduce the MAMAACT material may have been needed instead of allowing midwives the flexibility to introduce the material as they preferred. This may also have negatively impacted women’s motivation to use the MAMACT intervention, as an incentive to participate in research can be driven by perceptions of personal relevance and gain . Finally, difficulties with the electronic booking system meant that an extension of the first midwifery visit was not possible. Nevertheless, all participating midwives introduced the MAMAACT material during the first visit, suggesting that the intervention was largely feasible under real-world conditions at the local antenatal care facilities included in the study.
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The detrainment observed in experiments suggests that some plume fluid reaches its neutral buoyancy height at intermediate heights. The assumption of top hat profiles across the width of the plume rules out this possibility in the model. So, we relax the top hat profile assumption and instead consider linear profiles for vertical velocity and density. Linear profiles allow parts of the plume to peel off at intermediate heights where the density in the plume matches that in the environment, as shown in Fig. 11. This peeling plume model was developed by Hogg et al. to look at the flow of rivers into lakes. In this section we present their model, but extend it from a line source to a full wall source, which has different governing equations (10) from those used by Hogg et al. .Fig. 11In the peeling plume model, density and vertical velocity vary linearly across the width of the plume, so parts of the plume can peel into the ambient at intermediate heights
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We used the LBA, a variant of race model that provides a simple characterization of noise in the drift process and a closed-form likelihood function for choices and RT that is computationally efficient (Brown and Heathcote, 2008). The model has been previously applied to a range of binary or multiple-choice decisions, including value-based (Trueblood et al., 2014; Rodriguez et al., 2015) and memory-informed choices (Hawkins et al., 2016). Following previous studies (Brown and Heathcote, 2008; Forstmann et al., 2008; Forstmann et al., 2010), our LBA model represents a choice between cued and uncued snack items as a race between two independent signals, each for one snack item, that linearly and deterministically accumulate evidence until one accumulator reaches a threshold.
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Depressive Störungen gehören weltweit zu den häufigsten psychischen Erkrankungen und treten in unterschiedlichen Lebensphasen (z. B. Altersdepression, postnatale Depression) und Zusammenhängen (z. B. Arbeitsplatz, posttraumatische Belastung) auf. In Deutschland erkrankt etwa ein Fünftel einmal im Leben daran und etwa 5,3 Mio. Erwachsene sind damit diagnostiziert . Etwa 6 % berichteten von einer ärztlich oder psychotherapeutisch diagnostizierten Depression (12-Monats-Diagnosen), wobei nicht alle Formen chronisch verlaufen . Neben Medikamenten und Psychotherapie haben auch Bewegung, Ernährung, Entspannung, Psychoedukation sowie die soziale Unterstützung durch Angehörige Einfluss auf den Behandlungserfolg von Depressionen in verschiedenen Altersgruppen [29–32].
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TEM analysis of silver nanoparticles was carried out using the FEI Tecnai F20 X-Twin TEM microscope, at 100 kV. The sample containing dried nanoparticles was diluted with sterile, double distilled water, applied on carbon-coated cooper TEM grids (400 µm mesh size) and then dried in room temperature prior to measurements. The obtained data were evaluated by Statistica Software (StatSoft, USA).
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The control dimension of authority is different from warmth when seen from the victims’ perspective. When the communication with the teacher is about the ongoing bullying, the victims may feel humiliated if the teacher profiles control towards them. The control dimension is, however, interesting when related to the safety of the victim, and we suggest calling this ‘perceived protective control’. By this, we mean whether the victim realizes that the teacher is willing to stop the bullying and/or capable of stopping the bullying. Again, it is interesting to disclose how the victims of long-lasting bullying discuss this.
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Com as alterações ocasionadas pelas transições demográficas e epidemiológicas, a população idosa vem crescendo de forma acelerada no país1,2. Em 2018, segundo o Instituto Brasileiro de Geografia e Estatística (IBGE), a expectativa de vida do brasileiro passou para 76,3 anos de idade e os idosos chegaram a representar 9,2% da população3. Devido a essas alterações, torna-se necessária a realização de políticas públicas e de saúde que atendam adequadamente à demanda dessa população4.
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Bringing together multi-disciplinary evidence from environmental, social and cognitive psychology, political science, tourism, behavioral and public health literature, this study develops and proposes a new conceptual framework to critically examine how residents’ place confinement can serve as a positive pathway to make them become more place attached through their engagement in pro-social and household pro-environmental behaviors. The model is developed adopting a coherent and integrated approach to advance knowledge and contribute to real life impacts. This paper critically examines the context of place confinement and its likely influence on residents’ pro-social behavior and pro-environmental behavior. The model further proposes that promoting pro-social and pro-environmental behaviors among residents positively influence their place attachment with their home and community’s environmental settings which is fundamental to their wellbeing and nature’s protection. This is the first study to explore the interplay of relationships between place confinement, pro-social behavior, household pro-environmental behaviors, place attachment as a multi-dimensional construct (with sub-dimensions of place dependence, place identity, place affect and place social bonding) and presenting their relationships to residents’ wellbeing. The proposed single integrative model makes an important contribution to place confinement and place attachment literature, pro-social, pro-environmental behavior and wellbeing literature.
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Nesse contexto pandêmico, as recomendações chinesas incluem o apoio presencial para lidar com a carga psicológica e a oferta de serviços de telessaúde.(29) Portanto, além da melhoria das condições de trabalho, há ganhos ao se organizarem equipes que ofereçam acolhimento, suporte e intervenções coletivas e individuais aos trabalhadores.(6,31) Podem ser desenvolvidas estratégias para minimizar o medo diante do risco de adoecer ou de infectar conhecidos, o convívio com a dor e a morte de pacientes e colegas de trabalho e outras questões que causam desgastes, como as condições precárias do trabalho ilustradas nos resultados desta pesquisa. É importante que tais ações sejam implantadas em caráter preventivo a todos os trabalhadores e institucionalizadas enquanto política organizacional permanente de saúde e segurança no trabalho.
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The vast majority of included studies were based in the USA (54·1% of full articles and 70·9% of the abstracts), 26·1% of the full articles were from Europe and 19·8% from the rest of the world. Of all the European papers eligible for inclusion in this study 29 were UK based, 14 of which were abstracts and 15 full articles. All of the UK based research focused on single types of neurological condition with epilepsy/seizure being the most commonly researched (seven papers), followed by Parkinson’s disease (four papers) and MS (four papers) showing a broadly similar trend to that seen in the whole body of eligible studies. However, we did not find a large enough number of UK based studies to do a full mapping review on this subset of research.
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Since SARS-CoV-2 (COVID-19) emerged, the demand for eHealth has gone viral. The novel coronavirus has swept across communities forcing a new normal that requires social distancing. Governments strongly suggest enforcing medical distancing to minimize physical contact between patients and healthcare providers. As a result, hospitals and other healthcare organizations have rapidly adopted digital alternatives to deliver healthcare services. Telehealth applications facilitate clinical benefits for patients such as consultation, diagnoses, treatment, and prevention from a distance overcoming the geographical barrier. They can also support non-clinical services for healthcare providers, such as training, meetings, and education . Furthermore, eHealth applications also provide real-time health monitoring using various devices and sensors . In 2020, remote healthcare applications shifted from a previously slow adoption rate to a record pace of uptake. The searches for online consultations have sky rocked by 350%. Whereas in 2021, the global eHealth market is expected to witness a 37.1% increase . It is further predicted to rise to USD 310.09 billion by 2027, according to Data Bridge Market Research .
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Despite the stress experienced by the majority of trainees, those that had worked in high–risk areas during the pandemic, such as critical care, COVID-19 positive wards, or care home facilities perceived a positive side to the situation: “I can tell a story that actually I did my last year of nursing during a pandemic, that’s a story and an achievement in itself” (102FNursW).
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Based on clinically frequently observed RNR-mediated G resistance and looking for potential therapeutic molecular targets, we evaluated, in a next step, the basal expression status of the RNR subunits (RRM1 and RRM2) in ACC patient samples. Our analysis of both an available dataset (Figure 4A,B) and our own patient adrenal tissue samples (Table 1, Figure 4C,D) revealed significantly elevated expression levels of RRM2 (p < 0.001), but not RRM1 gene expression in ACC (n = 33 and 30, respectively), compared to normal adrenals (n = 10 and 21) and ACA (n = 22 and 20). Moreover, in our cohort of adrenal tumors (ACA and ACC together), higher RRM2 expression positively correlated with larger tumor size (p = 0.019; R = 0.33, Figure 4G). Finally, in our ACC cohort, patients with high RRM2 expression levels at the tumor level showed a strong tendency towards poorer overall survival compared to the others (median survival 36 vs. 124 months, p = 0.05, HR 5.11, 95%CI 1.26–20.82; Figure 4F), while no such effect was detectable for RRM1 (Figure 4E; p = 0.177). Higher RRM2 expression in our patient cohort was furthermore correlated with larger tumor size (p = 0.019; Figure 4G).
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The atACS sequence shares considerable similarity with ACS sequences from a range of diverse biological phyla (Sofeo et al., 2019), and these occur in 10 conserved motifs (A1 to A10) that are distributed evenly throughout the length of these sequences (Gulick, 2009). Three of these motifs (A3, A4, and A5) contain conserved residues that determine the carboxylate substrate specificity of this class of enzymes (Marahiel et al., 1997; Gulick et al., 2003; Starai and Escalante-Semerena, 2004). Motif A10 contains a highly conserved lysine residue (at position 622 of the Arabidopsis enzyme) (Figure 1). Based on studies of homologous proteins, this lysine residue of the Arabidopsis enzyme may be a target for reversible acetylation, a mechanism that regulates the catalytic capability of these enzymes (Starai et al., 2002).
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Zwar wird in den Ansprachen Merkels auch auf die Gefahr der Virusausbreitung durch zu viel Mobilität hingewiesen, eine Schuldzuweisung an eine bestimmte soziale Gruppe wird jedoch nicht formuliert. Dies erfolgt jedoch nicht im Rahmen der Situationsbewertung, sondern im Kontext der Erläuterung und Darstellung der Maßnahmen in Regierungserklärungen im Deutschen Bundestag (vgl. Belege 10 und 11).(10)Die Kontaktbeschränkungen beziehen sich vor allen Dingen auf private Kontakte. In der Öffentlichkeit soll es in Zukunft nur noch die Begegnung von zwei Hausständen, maximal zehn Personen, geben. Private Kontakte sind insgesamt auf ein absolut notwendiges Minimum zu reduzieren. Auf nicht notwendige private Reisen ist zu verzichten, auch im Falle von Besuch bei Verwandten. (Merkel 2020h, 29.10.2020)(11)Private Reisen und Besuche, auch von Verwandten, sind weiter zu unterlassen, und das Arbeiten im Homeoffice muss, wo immer möglich, durchgesetzt werden. (Merkel 2021c, 11.2.2021)
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To investigate the flow behaviour of the high-strength low-alloy (HSLA) HX220 steel, the miniaturised tensile test specimens shown in Figure 1a were used, as in . The specimens were taken from a 1.2 mm thick sheet metal at 0°, 45°, and 90° to the rolling direction using water-jet cutting. Uniaxial tensile tests were carried out at elevated temperatures on a DIL 805A/D+T quenching(TA Instruments; New Castle; PA; USA) and forming dilatometer from TA Instruments. The test equipment of the forming dilatometer is shown in Figure 1b. Before testing, a stochastic pattern was applied, and a thermocouple was welded onto the specimen to regulate the temperature. It was then placed in the dilatometer, heated to the respective forming temperature via a heating coil with an integrated cooling system, and held for 20 s. Afterwards, the forming force was applied via the hydraulic system until failure of the specimen occurred. During the forming of the specimen, the change in length and width of the test area was measured with an ARAMIS (GOM GmbH, 38122 Braunschweig, Germany) optical measuring system from GOM GmbH. The forming temperature was investigated at 20 °C, 250 °C, and 500 °C, and the strain rate at 0.01 s−1, 0.1 s−1, and 1 s−1. Every parameter combination was performed five times to ensure statistical coverage. The occurring force and the measured length change were transferred into uniaxial flow curves according to the state of the art . Further, temperature-dependent anisotropy coefficients were derived for the strain rate of 0.01 s−1 according to the common procedure .
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GPCR: G protein-coupled receptor; Tre1: Trapped in endoderm-1; TM: Transmembrane; MD: Molecular dynamics; POPE: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine; GPCR-ITASSER: GPCR-Iterative Threading ASSEmbly Refinement; VTMC: Voronoi Tesselation and Monte Carlo integration method; RMSD: Root mean squared deviation; RMSF: Root mean squared fluctuation.
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Se revisaron los depósitos artificiales tales como tanques de almacenamiento de agua de las viviendas, llantas, canecas o baldes, recipientes diversos (desechos de alimentos, botellas, tapas, etc.), y depósitos naturales como las axilas de plantas y los huecos en árboles.
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Bees were first trained to associate one clear chip with reward in a small flight arena for two days which allowed bees to get used to the environment in the arena, the artificial chips and reward levels. On day three, three groups of bees with different colour learning were collected at different times after training (0-hour Control, 0-hour Learning and 4-hour Learning). Bees in the 0-hour Control group were trained on one clear chip and were collected immediately after training; bees in the 0-hour Learning group were trained on one yellow chip (novel colour learning) and were collected immediately after training; bees in the 4-hour Learning group were trained in the same way as the 0-hour Learning group, but were collected 4 hours after training. The 0-hour Control served as a control for the 0-hour Learning, which afforded us the opportunity to investigate genes involved in novel colour learning. Our training procedures limited the effect of the clear chip-reward association on the transcriptome changes and excluded the effects of many other factors, such as the reward level, which allowed us to be confident that the changes seen in gene expression were due to the novel yellow colour. The 4-hour Learning served as a control for the effects of time for the 0-hour Learning, i.e. this combination of groups permitted us to determine the persistence of the effects resulting from novel colour learning. Differences in gene expression patterns were expected at these two time points, i.e. we hypothesized that different sets of genes may regulate memory formation at different times shortly after learning.
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Zur einfacheren Passage wird der Muskel leicht inzidiert. Die Klappe wird nun unter direkter Kontrolle mittels transösophagealer Echokardiographie und Fluoroskopie im Bereich der Mitralklappe positioniert und ausgerichtet (Abb. 3). Nach Erreichen der optimalen Position wird mit dem Öffnen der Klappe begonnen, die schließlich im Anulus der Mitralklappe zu liegen kommt. Die Klappe selbst hat eine D‑Form und ist somit ideal an den Anulus angepasst. Nun wird überprüft, ob die neue Klappe gut arbeitet und ob eine paravalvuläre Undichtigkeit besteht. In weiterer Folge wird auch der Gradient im linksventrikulären Ausflusstrakt hämodynamisch vermessen, um eine Stenose des Ausflusstrakts durch die Klappe auszuschließen. Wenn die optimale Lage bestätigt werden kann, wird nun das Delivery-System entfernt, wobei stets ein Zug auf der Klappe über den Aufhängungsfaden der Klappe gehalten wird (Abb. 4). Nun wird dieser Faden mit einer Scheibe verbunden, die von außen an der Herzspitze herangeführt wird und durch einen vordefinierten Haltedruck die Klappe im Anulus stabilisiert. Der Vorteil dieser Methode ist zum einen eine gute Tonisierung des meist schon geschwächten Ventrikels und zum anderen eine exzellente Hämostase, da sich Blutungen oft durch den Druck der Scheibe selbst tamponieren. Nach erfolgreicher Implantation wird der Thorax mit einer Drainage versorgt und verschlossen.
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All pigs were necropsied at 7 DPC, PRRSV-induced pneumonia lung lesions were evaluated according to a previously described method40. For the macroscopic lung lesion score, the lungs were scored to estimate the percentage of the lung affected by pneumonia. Each lung lobe was assigned a number to reflect the approximate percentage of the volume of the entire lung, and the percentage volume of each lobe was added to the entire lung score (ranging from 0 to 100% of the affected lung).
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Soluția de sulfat de condroitină/amestec hialuronat de sodiu prezintă nu numai proprietăţi vâscoelastice dar evidenţiază şi uşor comportament reopectic (de exemplu, vâscozitate crește cu timpul, la viteza de forfecare constantă). Atât sulfatul de condroitină cât şi hialuronatul sunt molecule elicoidale cu lanțuri drepte, în medii extrem de vâscoase la temperaturi reduse, ambele molecule au o mobilitate mai scăzută în alinierea grupărilor N-acetilamină pentru interacțiunea reciprocă, interacțiune care are loc într-un ritm foarte lent. Creşterea temperaturii conduce la intensificarea interacțiunii reciproce ca urmare a creșterii ratei cinetice și o mai bună mobilitate a moleculelor în a-şi alinia grupurile N-acetilamină pentru legături de hidrogen. Când amestecul este supus la o viteză mare de forfecare, moleculele sunt aliniate sau orientate pentru interacțiune-lipire, astfel că vâscozitatea creşte când amestecul este supus la viteză mare de forfecare, și/ sau creșterea temperaturii, rezultând un compus modificat, cu o greutate moleculară mare.
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The existence of disease suppressive soils is living proof that microbial communities cannot just promote plant growth (Chaparro et al., 2012; Van Der Heijden et al., 2008) but also provide protection against plant pathogens (Alabouvette, 1986; Andrivon, 1994; Shiomi et al., 1999). Disease suppression can be due to competition with native soil fauna (general suppression) or to the presence of specific subsets of microbes (specific suppression). These soil protection strategies are comparable to immunity strategies of animals (Raaijmakers and Mazzola, 2016). As common to all complex ecosystems, general suppression is also common to all soils. Specific suppression, in turn, is removed by soil pasteurization and can be transferred to other soils via soil transplants. Soils can lose their suppressiveness if non-host plants are grown and can be recovered if the susceptible host and pathogen are grown back in them (Wiseman et al., 1996; Berendsen et al., 2012; Raaijmakers and Mazzola, 2016).
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Verder werd een gezonder voedselaanbod in supermarkten als mogelijkheid aangegeven voor een gezondere samenleving:‘Als de supermarkten de overbodige zoete en zoute en bewerkte producten uit de schappen zou halen waren alle Nederlanders op slag gezonder!’‘Als er meer gezonde producten in winkels komen, bijvoorbeeld zoutarme kant-en-klaarmaaltijden en vleesvervangers, enzovoort, dan zou het makkelijker zijn om dingen die je lekker vindt op een verantwoorde manier te eten.’
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We first study a within-host model based on target cell limitation. The model, which has been used for other viruses (21, 48), keeps track of the total numbers of target cells (T), cells in the eclipse phase of infection (E) (i.e., infected cells not yet producing virus), productively infected cells (I), and viruses measured in swab samples (V). The ordinary differential equations (ODEs) describing the model aredTdt=−βVTdEdt=βVT−kEdIdt=kE−δIdVdt=πI−cV.
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In this first section, we describe systems that have been specifically designed for HE students. The characteristics of each system are presented, while also addressing the level of evidence provided for each system to date. CALM (http://www.ucc.ie/en/wellbeing/calm/) Computer Aided Lifestyle Management (CALM) is an online multimedia system using interactive self-help tools to educate users about issues such as anxiety, depression, insomnia, stress, and substance misuse. The system was originally introduced at University College Cork (UCC), but is now available at other UK HEIs, including UCL and Newcastle University. The system comprises five programmes dealing with depression, anxiety, stress, sleep disorders, and substance abuse. Within each programme, there is an assessment unit to identify and track symptoms, a personal programme using CCBT, relaxation, mindfulness, and visualization techniques, and a psychoeducational unit. Although in use at several HEIs, there is currently no research published about the effectiveness of this system. MePlusMe (http://www.meplusme.com —not yet live online) MePlusMe is an online support system currently being developed by iConcipio Ltd. of which the authors of this paper form part of the research group. It is designed to support mild to moderate mental health difficulties (as shown by presenting symptoms of anxiety and depression) and study skills in HE students. Students with more severe difficulties are referred to the appropriate services for more intensive support via several filters throughout the system, including a “panic button”. A board of academics in UK HEIs and NHS clinicians oversaw the development of the system, ensuring it met the needs of current HE students.MePlusMe can be accessed on a computer or mobile device. Users can follow two routes to receive a customised package suited to their specific needs: a symptoms-route (Questionnaire) or a techniques-route (Library). The questionnaire statements were developed from validated questionnaires widely used in clinical settings [Hospital Anxiety and Depression Scale (HADS); 7-item Generalised Anxiety Disorder Scale (GAD-7); Patient Health Questionnaire (PHQ-9)] and a formal interview [Mini International Neuropsychiatric Interview (MINI)]. The results of this assessment inform the selection of techniques to address the symptoms faced by the user. Alternatively, the users can assemble their own packages with the help of an online ‘library’. Students can access and practice the techniques in their package in their own space and time, and over time use a rating system to monitor their progress. Throughout this process, MePlusMe provides optional support via emails to encourage continued use and engagement.The techniques used in MePlusMe are based on CBT, mindfulness, and educational practices, presented in an animated video format using either a male or a female character. Although the system is aimed at students with mild to moderate mental health and academic difficulties, it could also be used by the general student population. As well as individual and personalised packages, the system offers a built-in moderated social network, “Thoughtwall”, which aims to enhance the feeling of belonging to a student community with similar difficulties.MePlusMe is still in development, and research to support the system is ongoing. Initially, a small survey of 61 students was conducted to determine their opinions of online support systems (Goozee et al. submitted). This indicated that the majority of students would use such a system. They also specified that it should be interactive and personal, with techniques to support time and money management, relaxation, and social skills. A proof-of-concept study was subsequently conducted, to support the conceptual and practical value of the system among students at five UK HEIs . Students were largely positive in response to the system, but the study highlighted areas for improvement, which were incorporated into the subsequent development of the system.A feasibility study will commence in September 2017. The study will evaluate the feasibility, acceptability, and potential effects of the online tailored interventions offered in MePlusMe to address mild to moderate psychological and study skills difficulties in HE students, as well as its content. For the purpose of the study, 200 students will be recruited to a within-subjects, repeated measures study conducted over 8 weeks. A more in-depth feasibility study and a subsequent randomised controlled trial (RCT) are then planned. Mindful Kiwi (http://www.mindful-kiwi.com) Mindful Kiwi offers an 8-week programme, based on techniques from Mindfulness-Based Stress Reduction (MBSR) that are adapted to focus on the needs of HE students and healthcare professionals. There are two programs: (i) Mindfulness-Based Coping with University Life, which aims to support university students, and (ii) Mindfulness for Therapists, which was designed for therapists and other healthcare professionals.Mindfulness-Based Coping with University Life focuses on four areas: managing stress, academic performance, health and wellbeing, and communication and relationships. Mindfulness for Therapists aims to improve healthcare professionals’ wellbeing. The training is delivered either face-to-face or online, synchronously and asynchronously. Both versions provide access to a group forum and users of the synchronous delivery option can also communicate with a group facilitator. One study has investigated the approach used by Mindful Kiwi . The study was a non-randomised pilot evaluation, using a waiting list as a control group, in students from a UK HEI. Ten students used Mindful Kiwi across eight weeks, while six controls were placed on a waiting list. The results suggested that the programme is easy to implement and that students receiving the active intervention showed reductions in negative mood and anxiety, but no changes in biological indicators of stress (cortisol). However, there were no significant intergroup differences at follow-up in measures of anxiety, depression, or perceived stress. PLUS (not yet live) Personality and Living of University Students (PLUS) was designed by researchers at King’s College London and aims to tackle symptoms of anxiety and depression, and to improve self-esteem of HE students. Interventions target personality traits known to be risk factors for common mental disorders, namely Neuroticism, Concern over Mistakes, Doubts about Actions, and Hopelessness. Techniques are based on CBT and are presented as text-based exercises. Users are first guided through nine questionnaires to identify their strengths and weaknesses, with assessment of alcohol and drug use, eating disorders, self-esteem, personality traits, quality of life, depression, anxiety, and phobias. Following a general introduction to the principles of CBT, PLUS then offers the following modules to support the student: ‘anxiety, worry and panic’, ‘dealing with difficult emotions’, ‘self-esteem’, and ‘perfectionism’. These can be completed in any order, and consist of text-based information with photographs and illustrations.PLUS has been investigated in a randomized controlled trial of 1047 students from two London universities . The personality traits of students were assessed at baseline and the students were divided into groups of high and low risk for mental disorders. They were then randomised to receive the online trait-focused CBT (PLUS) or a control intervention (online information about accommodation, finances, and study skills). Anxiety and depression (PHQ9 and GAD7), alongside secondary outcomes, were assessed at baseline, 6 and 12 weeks. There was a high attrition rate, with 401 students completing the 12 weeks’ assessments. However, high-risk students were not more likely to drop out and the dropout rate (61.7%) was not greatly higher than for other web interventions. The authors reported decreased anxiety and depression at 12 weeks in high-risk students completing PLUS. They also assessed user satisfaction, with students reporting that the site was easy to use, they liked the design, and they found reminders useful. Students Against Depression (studentsagainstdepression.org) Students Against Depression is a website offering information and advice about depression, anxiety, and suicidal thoughts for students in higher education. The website was established by and is now run by Student Minds (a student-led UK mental health charity) working with the Charlie Waller Memorial Trust. Students Against Depression provides information about the mental health problems it addresses, as well as tools and strategies for self-help, such as planning a daily routine. These techniques are theoretically grounded in CBT. Users can also complete a blog and share their story.The website does not offer users access to clinicians, but does encourage students to contact counsellors and doctors. In the autumn of 2014, Student Minds and Students Against Depression collaborated to produce Positive Minds, a 6-week offline course designed to give students the skills they need to fight depression and anxiety. The Positive Minds course launched on three campuses in the UK in 2014. Since then it has been re-launched and expanded to encompass eight campuses in 2016, including Bath, Bath Spa, Bournemouth, KCL, Nottingham, Oxford, Oxford Brookes, and Southampton. The course is run by student facilitators trained by Student Minds. The site has not yet been subjected to empirical research. theDesk (http://www.thedesk.org.au) TheDesk is an Australian support system designed for HE students, but can be used by anyone registered with the website. The system provides help for various issues, from academic study skills to depression, substance abuse, and issues with sexual orientation.After a self-assessment of wellbeing through quizzes, the website recommends one (or more) of four different modules (Getting things done, Staying calm, Staying connected, and Feeling good). Each module contains videos and tips for effective time management, management of emotions, tips to avoid procrastination, breaking down problems, etc. Throughout, the users are asked to list and evaluate their own strategies for coping with different problems, as well as to assess themselves.If the results of the self-assessment suggest that professional help is needed, the website redirects the user to a Get Help link, providing professional helplines. For emergency situations (suicidal thoughts or self-harm), a suicide prevention helpline is listed. The website also provides recommendations of several apps that can increase wellbeing. The site has not yet been subjected to empirical research.
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The per cent correlation as a function of for bats (blue dashed), birds (green dashed-dot) and fish (red solid) with (thin line) and without (thick line) acceleration limits applied to the DRCA optimal velocity; markers indicate values that appear in figures 9 and 11. The x-axis is scaled by the standard deviation for each species, which is 2 m s−1 for the flying species and 0.04 m s−1 for the fish.
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After removal of the diseased tissue (fasciectomy), additional procedures might be necessary to correct capsular joint contractures (PIP joint capsulolysis) or to reconstruct a skin defect (local skinflap or graft). Postoperative splinting of the hand may not improve medium-term outcome . Complications of open surgery include delayed wound healing, skin flap necrosis, digital nerve and vessel injury, joint stiffness, hematoma and pain issues . Complex regional pain syndrome (CRPS) can be a devastating complication of surgery prolonging recovery and requiring long-term hand therapy support and chronic pain treatments .
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