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COVID-19 is currently the top public health concern worldwide. It is estimated that approximately 97% of the world’s population is susceptible to SARS-CoV-2 . Previous studies have indicated that the overall seroprevalence varies widely across different countries and regions, with a higher seropositivity prevalence being observed in locations of early outbreaks, as well as countries with higher income levels and human development index scores .
| 3 | 0biomedical
| 0Study
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340,681 |
a Csn-B increases WFDC21P expression levels in a dose dependent manner in Huh7 and HepG2 cells. The WFDC21P expression levels were detected by RT-qPCR. b Csn-B increases the activity of the WFDC21P promoter. Luciferase assays were performed in Huh7 cells. c Csn-B inhibits the HCC cell viability. MTT assays were performed in Huh7 and HepG2 cells. d Csn-B cannot inhibit cell viability in WFDC21P knockdown cells. MTT assays were performed in Huh7 and HepG2 cells. e WFDC21P is required for the inhibitory effect of Csn-B in xenograft tumors (n = 6). The tumor growth curves, tumor weights, and Ki-67 expression levels are shown. Scale bars in xenograft images and Ki-67 staining were 1 cm and 100 μm, respectively. f Schematic diagram of the Nur77–WFDC21P–PFKP/PKM2 axis in HCC progression inhibition. Csn-B, an agonist for Nur77, stimulates the transcriptional activity of Nur77. Nur77 then activates the transcription of WFDC21P by directly binding to NBREs on the promoter of WFDC21P. On the one hand, WFDC21P interacts with PFKP to attenuate its tetramer formation, resulting in decreased PFKP activity. On the other hand, WFDC21P interacts with PKM2, which blocks its nuclear translocation and, therefore, its function as a transcriptional coactivator. As a result, WFDC21P inhibits glycolysis in HCC cells and suppresses HCC development. *p < 0.05; **p < 0.01; ***p < 0.001 and ns no significance.
| 4 | 0biomedical
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248,226 |
Evidence from this study showed mixed small‐to‐medium effects on self‐reported deradicalization measures in favour of the treatment group. Eight out of nine calculated effect sizes favoured the intervention, though six of these were statistically insignificant. One survey item favoured the comparison group: “I make friends with people from other races”. However, these results need to be interpreted with caution due to the study limitations.
| 2 | 2other
| 0Study
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105,370 |
Interactions of differentially expressed proteins. Specific interaction networks analysis of differentially expressed proteins. Network nodes represent proteins. Splice isoforms or post-translational modifications are collapsed, i.e. each node represents the protein produced by a single, protein-coding gene locus. Colored nodes represent query proteins and the first shell of interactors. White nodes represent the second shell of interactions. Small nodes are the proteins with unknown 3D structure. Large nodes are the proteins with known or predicted 3D structure. Lines represent protein-protein interactions. Known Interactions: represents from curated databases; represents experimentally determined. Predicted Interactions: represents gene neighborhood; represents gene fusions; gene co-occurrence. Others: represents textmining; represents co-expression; represents protein homology.
| 5 | 0biomedical
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147,795 |
As performing surgery on malnourished patients without careful consideration can sometimes lead to serious complications, in order to improve the prognosis of HNC surgery, it is important to have a good grasp of their nutritional status beforehand, as well as before and after HNC resection, and manage nutrition after surgery; in other words, an assessment of nutrition should be conducted before and after surgery . Continuous nutritional assessment from preoperative to postoperative status is expected to reduce the risk of postoperative malnutrition, accelerate wound healing after HNC resection, and lead to early recovery.
| 4 | 0biomedical
| 1Other
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54,811 |
For each patient in the model group, the first BV measurement occurred one hour after the patient drank the required amount of water but before each fraction was taken. Thereafter, multiple measurements might be required at regular 10-min intervals until the BV was consistent with that of the planning CT. Based on a previous report by our group, the default tolerance of BV is recommended to be within ±15% to maintain a constant BV14–16. This value might be updated after dosimetry data supporting the clinical effects are analysed.
| 4 | 0biomedical
| 0Study
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203,803 |
To investigate the possible mechanism leading to increased cellular glucose uptake, we evaluated the Pi3K/Akt/AS160-pathway, the PKD1-pathway, and the AMP-activated protein kinase (AMPK)-pathway in more detail, each well-known for their key regulatory roles in GLUT4 translocation . PE stimulation resulted in an upregulation of both the Pi3K/Akt/AS160-pathway (visualized by increased degree of phosphorylation of the Akt protein and its substrate AS160) and the PKD1-pathway (visualized by increased degree of phosphorylation of PKD at ser744 and ser916, and troponin I at ser23 and ser24 (TropI)) after 16 h, 24 h, and 48 h stimulation compared to those of control (Figure 2F–J). In contrast, PE stimulation decreased AMPK phosphorylation (Figure 2A,K) after 24 h compared to that of control, without any alterations in total AMPK protein expression (Figure 2A). Approximately in line with this, acetyl-CoA carboxylase (ACC) phosphorylation was decreased after 16 h and 24 h PE stimulation compared to that of control (Figure 2A,L), suggesting a decrease in shuttling of fatty acids into the mitochondria. Taken together, these results show that stimulation of glucose uptake correlates proportionally to upregulation of the Pi3K/Akt/AS160-pathway and the PKD1-pathway.
| 4 | 0biomedical
| 0Study
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237,669 |
The TCR proximal signaling pathway that regulate T cell function comprise a complex cascade of interactions involving numerous extracellular and intracellular proteins with unique functions. Perturbations such as polymorphisms and mutations in each contribute to a myriad of human diseases ranging from immunodeficiency to autoimmunity, and some even have significant contributions to various malignancies. Understanding the nuanced role of each molecule has allowed for the design of immunotherapies to take advantage of the significant involvement of TCR signaling and cytokine activation of T cells in cancer. The genetic alterations described throughout this review are summarized in Table 1 .
| 4 | 0biomedical
| 2Review
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8,235 |
Incubation of recombinant cytokines with RBCs. Boxplot summaries of cytokine log2 transformed raw fluorescence response data for RBC lysates collected using (a) the Bio-Plex human 27-plex panel and (b) the Bio-Plex human 21-plex panel (n = 5). Cells were incubated for 24 hours (37 °C) with or without recombinant cytokines (BP, and control, respectively). Data are statistically significantly different if p < 0.05 (*), or p < 0.001 (***).
| 4 | 0biomedical
| 0Study
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295,157 |
Allura Red AC has a high dusting potential (range 9.7–10.9 g/m3) and particle size measurement of the dust showed the presence of a fraction of small particles (see Section 3.1); therefore, users are considered as being at risk of inhalation exposure to dust from the additive. In the absence of information on the inhalation toxicity of Allura Red AC, such exposure is regarded as hazardous.
| 4 | 0biomedical
| 0Study
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208,382 |
From a functional point of view, the results suggest a clear interaction between nitrogen and sulfur cycles in both metagenomes, as some members of the genera Thermodesulfovibrio, Sulfurihydrogenibium, and Thermus have been described as important players in both biogeochemical cycles and are abundantly found in BW and MDV hot springs, as well as the sequences related with metabolic pathways involved in nitrogen and sulfur cycles.
| 4 | 0biomedical
| 0Study
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349,454 |
All interpreters spoke of the challenges created by clinicians’ questions that required they violate shared (client–interpreter) norms, particularly in relation to sensitive topics that trigger strong feelings of shame in their communities. What was felt to be challenging was that the questions could appear to be coming from the interpreter, and thus risk jeopardizing the client–interpreter relationship. Such questioning could be regarded as at best revealing cultural incompetence (“I am supposed to know. I’m supposed to know where that person is coming from, because we are from the same culture”) and, at worst, violating moral codes of conduct (“It is difficult and its rude, they take it as rude sometimes”).
| 2 | 2other
| 1Other
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359,360 |
Based on the results of study part A, the second part will consist of a multicenter, two-armed, randomized-controlled parallel group trial. Participants in the intervention group (IG), for a period of 4 weeks, will receive online workouts with video live-streaming using the appropriate software (e.g., Zoom, Zoom video communications, San Jose, California, USA; BlackBoard, Washington, DC, USA). Duration, frequency, and contents will be selected balancing (a) the needs of the population as indicated via the ASAP questionnaire and (b) scientific recommendations for exercise prescription. For example, the minimum training frequency will be once per week and minimum duration will be 10 min (21). To allow a higher degree of standardization between the countries, the instructors will be provided with modifiable demo workouts exhibiting different content-related focuses (e.g., strength, endurance, postural control/balance, cognition, relaxation), which can be individually adapted. The control group (CG) will not receive an intervention and is instructed to complete the outcome assessments (see below). Randomization (1:1 ratio) will be performed using a software algorithm of the online database used for survey delivery (Soscisurvey, Soscisurvey GmbH, Munich, Germany). To allow concealed group allocation, the participants will be automatically informed by the system about allocation upon survey completion at baseline.
| 4 | 0biomedical
| 0Study
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147,305 |
In the analyzed studies, the average age of patients suspected of foreign body aspiration who underwent rigid bronchoscopy was 3 years old, while most of them (52–81%) did not exceed 3 years old . It is believed that the third year of life carries the greatest risk of foreign body aspiration. Our study confirmed this statistical data.
| 4 | 0biomedical
| 0Study
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145,822 |
Among the HC, a total of 62 individuals filled in the swe-BIS questionnaires on two occasions, approximately 1 week between completion of the questionnaires. There was a statistically significant test-retest correlation for swe-BIS total score (r = .78; p < .001), as well as for the subscales of attentional (r = .63; p < .001), motor (r = .54; p < .001) and non-planning (r = .77; p < .001) impulsiveness. The test-retest correlations were greater within each subscale, compared to the correlations across different subscales (Table 2B).
| 4 | 0biomedical
| 0Study
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177,573 |
In the following we consider additional steps beyond the absolute, vacuum level energy referencing ability of Method 2 (Fig. 1B and C) and address the interfacial electronic structure information that becomes accessible using a condensed-matter framework and associated experimental approach. This leads us to attempt to determine EF and eΦ in both water and aqueous solutions, with the latter providing a means to differentiate between solute-induced changes of (bulk or surface) liquid electronic structure or interfacial effects. Correspondingly, we briefly explain the concepts of EF and eΦ. EF is formally equivalent to the chemical potential, μ, and at thermodynamic equilibrium is the energy at which a (potentially hypothetical) electronic state has 50% probability of being occupied at fixed temperature and any given time. The position of EF throughout matter in electrical equilibrium assumes the same thermodynamic value. This makes EF an advantageous energy reference in condensed-matter spectroscopies, especially for metallic samples, in which electrons occupy states up to EF, and which can be directly measured using photoemission. EF is conceptually connected to two additional important quantities, the electrochemical potential, , and the work function, eΦ. is the energy required to bring an electron at rest at infinity into the bulk of the material. Hence, the sum of EF and is equivalent to Ev∞ (and in a metal, the energy of with respect to EF is equivalent to the electron affinity). In contrast, eΦ is the minimum energy required to remove an electron at EF, deep inside the material, and place it at rest at a point in free space just outside the surface, thus connecting to the local vacuum level, Elocv. Elocv and eΦ are correspondingly local properties of a surface which can change widely depending on the surface conditions.||||In fact, it is possible to deliberately modify eΦ, e.g., by adsorption of molecules on the sample surface, which typically induces or alters a pre-existing surface dipole, the associated value of χd, and necessarily the value of Elocv.24,35,91 This creates or modifies the energetic barrier for the photoelectrons escaping from the sample into vacuum, and can be detected as a change in KE of the emitted electrons. For a sample with a truly uncharged, amorphous, apolar surface, we note that Ev∞ = EF + = EF + eΦ. However, if an intrinsic dipolar surface potential exists, the first equality holds, and the second generally will not. In such a case, and depending on the geometry of the liquid surface and its overlap with an ionizing light source, condensed phase VIEs or binding energies will be offset by an experimental-geometry-averaged amount with respect to Ev∞ due to the average offset of Elocv.
| 4 | 0biomedical
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161,812 |
model wait times between Poisson distributed events; i.e. it models sums of exponentially distributed random variables. Thus, it can be linked to this use case. Furthermore, this use case takes advantage of this distribution’s versatility in shape through manipulation of the shape parameters: a and b, Thus: R ∼ Gamma(aR, bR), G ∼ Gamma(aG, bG) and B ∼ Gamma(aB, bB), where the shape parameters are finite. The means and variances derived for the Normal distribution were used to derive the shape parameters of this distribution where: mean = ab and variance = ab2.
| 4 | 0biomedical
| 0Study
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397,122 |
The present study had some limitations. First, the results of this study may differ from those obtained from different age ranges, sex, races, countries, health financing systems, and socioeconomic status. Second, annual changes in the adjusted mean medical costs and dental costs for each BMI/metabolic group varied too widely to assess trends during the follow-up, especially in smaller groups. A study with a larger sample size and a longer follow-up period is needed. Third, as receipts are essentially used to claim healthcare fees, if the patient has multiple diseases, these receipts do not show the details of fees and the number of days needed for each disease. Moreover, indirect economic burdens, such as lost work productivity costs and reduced quality of life, were not available. However, such receipts are valuable for accurate knowledge of healthcare days and costs.
| 4 | 0biomedical
| 0Study
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310,014 |
The response surface test design was carried out based on the single factor test results and the results was presented in Table 2. Table 2 showed that the experimentally measured and the regression model predicted dependent variables. The comprehensive score of the degree of gelatinization and the sensory evaluation of adzuki beans is the response value of the dependent variable for the 20 combinations of three independent variables (i.e., soaking time A, microwave power B and microwave time C as independent variables). Design-Expert version 8.05 is used to analyze the data in Table 2. The results are as followed Table 3. According to Table 3, it was evident that the quadratic term coefficients (B2), and cross-product coefficients (AB, AC, BC) were not significant (p > 0.05). By performing quadratic multiple regression fitting on the data in the table, multiple regression equations between various factors and response values can be established:Y1 = −98.46 + 3.50 A + 0.07 B + 0.90 C(2) Y2 = −92.95 + 1.56 A + 0.09 B + 1.39 C − 0.013 AC − 0.09 A2 (3) Y = −15.70 + 0.31 A + 0.011 B + 0.22 C − 0.022 A2 − 1.18767 E − 003 C2 (4)Y2: Sensory evaluation Y1: Degree of gelatinization.
| 4 | 0biomedical
| 0Study
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89,101 |
The medium components (in total 1.7 L) were sterilized separately (Schinagl et al., 2016; Vrabl et al., 2016). After blending the medium components and transfer into the bioreactor under sterile conditions, the medium was inoculated with 100 mL of pre-culture (72 h, ammonium exhausted at c. 48 h and glucose excess). Two hours after the inoculation the feed pump was started. Cultures reached a steady state after four hydraulic residence times. Growth proceeded at pH 7 and μ = 0.1 h−1. Analytics of main nutrients (glucose, ammonium, and phosphate) as well as determination of biomass and extracellular organic acids were done as specified in Vrabl et al. (2012). Nitrate was determined according to Doblander and Lackner (1996).
| 4 | 0biomedical
| 0Study
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350,720 |
In each chain of PLCε, the first helix of the EF3 subdomain (E3α, residues 1284–1303, Supplementary Figs. 1 and 3) is disordered, potentially due to the absence of EF1/2. The PLC common core domains, which span the F3α helix of EF3 through the C2 domain, have a similar arrangement as observed in the PLCβ, PLCδ, and PLCγ subfamilies (Supplementary Fig. 4)23,25–27. The highly conserved active site residues within the PLCε TIM barrel are similarly configured to those of other PLC subfamilies, and weak electron density is observed for the catalytic Ca2+ in each of the four chains (Supplementary Figs. 1 and 4).
| 4 | 0biomedical
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180,372 |
Phase III RCTs reporting data on the efficacy of COVID-19 vaccines in preventing the illness were selected and included in this quantitative synthesis. The studies in which the immunization schedule, dosing, and route of administration were consistent with those approved were selected and included in the quantitative synthesis.
| 3 | 0biomedical
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48,456 |
Cell adhesion is crucial in the development of endometriosis to allow the attachment of endometrial tissue onto the mesothelial lining in the pelvic cavity following retrograde menstruation. Treatment via the transwell system was found to cause a significant increase in the adhesion of ESCendo, but it had no effect on the adhesion of ESCcyst. Conditioned medium caused a significant decrease in the adhesion of ESCcyst, but it had no effect on the adhesion of ESCendo. These results can be understood in light of the results of cell proliferation, since it is known that cells that divide rapidly are likely to be less adherent . Moreover, the results may be explained by differences between the transwell and the conditioned medium systems; there is a paracrine effect in the transwell system that is absent in the conditioned medium as described above. To our knowledge, there are no other studies in the literature that have examined the effects of MSC on the adhesion of ESCendo and ESCcyst.
| 4 | 0biomedical
| 0Study
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386,448 |
For most sessions, we recorded rats twice in an arena; before and after the lattice maze (Table 1; Fig. 5a, b). To test if home bases were stable between these arena trials, we found the nearest neighbour in the second arena trial for each home base in the first trial and compared these distances to a shuffled dataset (Fig. 5c; Materials and methods: "Home base stability"). For both arenas, nearest neighbour distances were significantly lower than chance, suggesting that rats maintained home bases in similar locations (black text Fig. 5d, e). However, multimodality in these distributions suggests that often one or more home bases were not stable (Hartigan dip test results; coloured text Fig. 5d, e). Home bases were equally stable in the platform and walled arena (t(33) = − 0.74, p = 0.46; two-sample t test).Fig. 5The stability of home bases within sessions. a Example home base maps in the platform arena; each map gives the density of stops made within home bases. Each row gives data from one rat and for one day, columns give the data for the first and second trials. b Same as a but for the walled arena. c Schematic showing the method for testing home base stability. The nearest detected home base was found in the second arena trial for each base in the first trial. Stable home bases would each have a close neighbour in the second arena. These distances were compared to a shuffled data set, where the home bases in the second trials were shuffled and randomly rotated in 90° increments. d Distribution of nearest neighbour distances when all platform arena trials are combined (blue) or for the shuffle (red) or for individual rats (triangles). Coloured text gives the result of a Hartigan’s dip test on the corresponding distribution; p ≤ 0.05 indicates unimodality while p > 0.05 indicates significant deviation from unimodality (Materials and methods: "Home base stability within sessions"). Black text gives the result of a two-sided, two-sample t test comparing the distributions. e Same as d but for the walled arena. These distributions sometimes have multiple peaks because fields were often in corners and thus nearest neighbour (NN) distances tended to be in multiples of the arena side lengths (120 cm). For instance, the right example in c shows how nearest neighbour (NN) distances of approximately 60 cm can arise
| 4 | 0biomedical
| 0Study
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308,211 |
We recently discovered changes in locomotion, USV emission, and HR in Wistar rats exposed to ultrasonic playback from a speaker . In particular, 50-kHz playback elicited abundant appetitive vocalization, increased HR, and locomotor activity. In contrast, 22-kHz playback led to an abrupt decrease in HR and locomotor activity. We wanted to establish whether prior stress affects rats’ reactions to ultrasonic playback and whether the response is dependent on the number of shocks previously received (dose-dependent). Towards this end, we fear-conditioned (FC) rats with varying numbers of shocks, encompassing the usually used range , and investigated changes in locomotion, USV emission and HR in rats exposed to 50-kHz vs. 22-kHz USV playback.
| 4 | 0biomedical
| 0Study
|
158 |
These molecules share a similar domain structure, containing six LRRs, an immunoglobulin (Ig) domain, and a fibronectin type III (FNIII) domain in the extracellular side, followed by a transmembrane domain and a cytoplasmic region that ends with PDZ domain-binding motif (Figure 1A). The PDZ domain-binding motif is present in SALMs 1–3, but not SALM4 or SALM5. In contrast to the extracellular domains of SALMs, which share high amino acid sequence identities, especially in adhesion domains, the cytoplasmic regions lack shared domains and substantially differ in length as well as amino acid sequence, suggesting that they may have distinct functions.
| 4 | 0biomedical
| 0Study
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72,729 |
A number of structural studies have been made on LN and LT, generally using congruent crystals that have been Czochralski grown (Abrahams, Reddy et al., 1966 ▸; Abrahams, Hamilton et al., 1966 ▸; Abrahams, Levinstein et al., 1966 ▸; Abrahams & Bernstein, 1967 ▸; Abrahams et al., 1967 ▸, 1973 ▸). The initial measurements of the physical properties varied between samples because they can be made with a range of Li content. LN can be made in the range of 46.4–50 mol% Li2O and LT in the range 46–50 mol% Li2O (Carruthers et al., 1971 ▸; Barns & Carruthers, 1970 ▸). Both LN and LT undergo a high-temperature phase transition to a paraelectric structure with space group , with the transition varying from 1310 to 1480 K and 780 to 965 K as the Li content increases to 50 mol% Li2O for LN and LT, respectively (Bordui et al., 1995 ▸; Barns & Carruthers, 1970 ▸).
| 4 | 2other
| 0Study
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131,420 |
Generally, MOT approaches work according to the tracking-by-detection principle and employ either some or all of the following: steps :Detection stage—input frame is analyzed and observed objects are identified within the input frame;Feature extraction/motion prediction stage—detected objects from the previous step are analyzed for their unique set of features. Motion prediction is an optional part of this step, where the algorithm predicts object’s approximate position in the next input frame;Affinity stage—features and motion predictions are used to compare presently detected objects with previously detected objects (from a previous frame or frames);Association stage—objects are associated with previously detected objects by assigning them the same ID and newly detected objects are assigned a new ID.
| 4 | 2other
| 1Other
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77,932 |
SKRC-17 and SKRC-52 were stimulated with 100 µg/ml orellanine for 2, 6 or 24 hours. Cells were washed twice with ice cold PBS before lysis. The bioactivity of caspase-3, caspase-8 and -9 was measured with a Fluorometric Assay Kit (Abcam). In brief, equal concentrations of protein lysates were incubated with the DEVD-AFC (caspase-3 substrate), IETD-AFC (caspase-8 substrate) or the caspase-9 substrate LEHD-AFC. The fluorescence of the cleaved substrates was determined at an excitation wavelength of 400 nm and an emission wavelength of 505 nm, using a fluorescence plate reader (Spectra Max Gemini XS, Molecular Devices).
| 4 | 0biomedical
| 0Study
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392,809 |
Many of Cr speciation using column have been developed such as, Solid Phase Extraction-AAS [7, 8, 9], Inductive Coupled Plasma-Mass Spectrometry (ICP-MS) [10, 11], Ionic Chromatography-ICP-MS , High Performance Liquid Chromatography (HPLC)-ICP-MS , and Reverse Phase-HPLC . Those methods are difficult to be applied because the instrument is relatively expensive and have complicated procedure analysis. AAS is one of the standard instruments that is used for metal analysis, but its instrument cannot be used for speciation analysis and does not have a good sensitivity for trace analysis. Given the aforementioned explanation, we need separation and pre concentration before the analysis using AAS to deal with the issue.
| 2 | 0biomedical
| 0Study
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286,633 |
Interesting spectral changes are observed for the samples immersed in acetone. For pure resin and its composites with PSP, the most important changes concern the intensity of the absorption bands. A significant increase is observed at about 2950 cm−1, which is responsible for the vibrations of the methylene groups, while the intensity of the characteristic vibration band of the carbonyl and the ester groups decreases. A similar observation regarding the UPR was made by Abellache et al. . Another effect observed in the infrared spectra of immersed composites is the shifting and broadening of the carbonyl band.
| 4 | 0biomedical
| 0Study
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300,955 |
Another subtype is closed-angle glaucoma, where the anterior chamber angle is closed. Despite being less prevalent worldwide, closed-angle glaucoma carries a much higher risk of blindness because narrow/closed angles can lead to very high IOP levels in a short period of time .
| 2 | 0biomedical
| 1Other
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332,544 |
Finally, we classified the 25-cancer types represented within the GDSC database into two categories: one with a higher CRISPR-derived dependency on MAPK genes and the other with lower dependency on these genes (see the “Methods” section). Again, we compared the mean dose-responses of the 28 MAPK pathway inhibitors between these two groups of cancer types. Here, we found that 14 MAPK pathway inhibitors were significantly more effective at killing cancers that had higher dependencies on MAPK pathway genes than they were at killing cancers with lower dependencies on these genes (t = 5.9, p = 1.5 × 10−51; Supplementary Fig. 7c). The MAPK inhibitors that exhibited the most significant differences in their efficacy between these two groups of cancer types were PD0325901 (t = 5.6, p = 7.6 × 10−09), selumetinib (t = 6.0, p = 2.9 × 10−08) and AZ628 (t = 5.2, p = 6.9 × 10−08; Fig. 6c). Here, the MEK1/MEK2 inhibitors all ranked in the top six (five out of the top six ranking inhibitors), revealing that cancers that were more dependent on functional MAPK pathway genes were likely to exhibit stronger responses to MEK1/MEK2 inhibitors than cancers that were less dependent on functional MAPK pathway genes. Here, none of the cancer types with a lower degree of dependency on MAPK pathway genes displayed significantly more sensitive to any of the MAPK pathway inhibitors than cancer types with higher degrees of dependency on MAPK pathway genes (Fig. 6c; Supplementary File 4). Moreover, previous studies have shown an association between drug sensitivity and both the expression levels of targeted proteins and/or the presence of alterations within these proteins21–23,53–55. Here, we also show a clear correlation between the gene dependencies and drug sensitivities of cancer cell lines.
| 4 | 0biomedical
| 0Study
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253,925 |
Other parameters that were identified as carrying higher risk for death in persons with type 2 diabetes were age 45 years and older, and male gender, in addition to comorbidities. Our study did not find Arab background to be an independent risk factor for mortality. Previous studies reported higher rates of all-cause mortality among Arabs, particular with respect to cardiovascular diseases22,23. However, combined comorbidities as defined herein were not reported in those studies.
| 3 | 0biomedical
| 0Study
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68,657 |
The model was trained with the stimuli (both veridical walking directions) rendered with a single elevation angle of 78.75 degrees, simulating illumination from above and using the data from all 4 actors and 25 body shape models with varying shape parameters. This variability in the training set prevents overfitting of individual training stimuli and makes the recognition more robust. For Experiment 1 the model was tested with all generated stimuli (in total 6600) using all 33 light source positions. To simulate Experiment 2, the training set was the same, and the test stimuli were generated from, also, 4 different actors, using only two light source positions, but rendered with 9 experimental conditions with different combinations of elements with or without intrinsic shading gradients (Fig. 4A). In total, only ~3% of the movies were used for training the model of Experiment 1 and ~10.0% of the movies were used for training the model of Experiment 2.
| 4 | 0biomedical
| 0Study
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329,556 |
Promoter organization of target genes. The sequences were derived from Vibrio cholerae El Tor C7258. The transcription/translation start sites are indicated by bent arrows. The –10 and –35 elements are enclosed in boxes. The binding sites of ToxR and TcpP identified by DNase I digestion were previously reported by Krukonis et al. (2000). The sequence protected by ToxT in the promoter DNA region of tcpA was identified by Yu and DiRita (2002) and Withey and DiRita (2006). The Fur sites are underlined with solid lines, whereas the HapR sites are underlined with broken lines.
| 5 | 0biomedical
| 0Study
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390,742 |
According to Table 5, the SHS products do not qualitatively differ from each other and contain TiB2, Al, and traces of the Al3Ti phase. The lattice parameters in all the specimens differ insignificantly. One can see a change in the phase composition and the size of the coherent scattering region with an increasing time of planetary milling. The coherent scattering region in titanium diboride and aluminum is extreme; viz. 97 and 100 nm, respectively. The coherent scattering region is a characterized region of crystallite that scatters X-rays coherently and independently of other similar regions. The CSR size is used to analyze the size of crystallites in polycrystals and is measured experimentally with the help of diffraction reflection attenuation.
| 4 | 0biomedical
| 0Study
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349,213 |
For haplotype network analysis, DnaSP561 and Arlequin ver3.562 were used to align and sort haplotypes based on the variations of MYB61 in the 232 rice accessions. PopART software63 was used to construct the Templeton, Crandall & Sing (TCS) network of the identified haplotypes to estimate the progenitor haplotype score distribution and the modern haplotype score distribution. The absence of helitron transposon in the promoter regions was identified using Delly64.
| 4 | 0biomedical
| 0Study
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231,468 |
The minimum number of sites with CAL used in the included studies was either ≥1 or ≥2 sites. A higher sensitivity from 7.4 to 21.8% resulted when CAL was assessed at ≥1 site compared to CAL at ≥2 sites. However, the use of CAL measurements at ≥2 sites is preferable in order to preclude sites with CAL due to other etiologies such as having a single isolated PPD due to endodontic involvements or root fractures.
| 4 | 0biomedical
| 0Study
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396,304 |
For example, ultraviolet and H2O2 treatment generates ceramide, which activates AMPK , while short-chain ceramides inhibit Nrf2 activation , and knock out of acid ceramidase 3 augments C18:1-ceramide levels, which alleviates early inflammation, oxidative stress, and fibrosis in a mouse model of NASH . It has also been suggested that ceramide-activated AMPK can limit nutrient-induced stress and autophagy . Altogether, these evidences could suggest an unappreciated compensatory action of ceramides upon energy metabolism in NASH or, alternatively, that non-toxic sub lethal doses of exogenous ceramide may have unappreciated effects upon energy metabolism. Finally, it could be conceivable that ceramide metabolites, and not ceramide itself, have a role in NASH pathophysiology .
| 5 | 0biomedical
| 0Study
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26,072 |
After removal of bFGF, FGF4, and EGF and addition of BDNF, GDNF, IGF-1, dbcAMP, and DAPT for at least 30 days, single cell-derived colonies on MG showed neural trilineage differentiation capacity, as evidenced by positive immunostaining for neuronal microtubule associated protein 2 (MAP2), astrocytic glial fibrillary acidic protein (GFAP; Figure 3a), and the oligodendrocyte marker galactosylceramidase (GALC; Figure 3b). Percentage of total cells (as determined by DAPI staining) was 72% for MAP2, 8.9% for GFAP and 5.7% for GALC (Figure 3c).
| 4 | 0biomedical
| 0Study
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44,422 |
Spatially, sites in which stimulation produced a selective syntactic deficit vs. a non-selective deficit during production were closely apposed, lying within only 0.9 ± 0.1 cm of each other along the coronal axis. The midpoint between paired sites lied within ±0.2 cm of the TPJ (Fig. 3b). Moreover, sites in which stimulation produced a selective vs. non-selective deficit were significantly spatially distinct within individual subjects (Kolmogorov–Smirnov test of K-means centroid, n = 24, p = 0.003). In summary, within individual subjects, sites in which stimulation produced a selective deficit in the syntactic condition were consistently closely apposed to, yet significantly spatially distinct from, sites above the TPJ which were more broadly engaged in diverse linguistic computations.
| 4 | 0biomedical
| 0Study
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140,432 |
Whitworth et al. (2015) studied AMH in relation to indoor, primarily seasonal, DDT and pyrethroid spraying for malaria prevention among women 20–30 years of age in eight rural South African villages . Women who reported indoor residual pyrethroid spraying had 25% lower AMH concentrations compared with women who reported no spraying, although there was only limited evidence for associations with DDT spraying. Prior reviews have suggested links between pesticide exposure and ovarian toxicity leading to female infertility, including premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS), menstrual problems and altered sex steroid hormone synthesis , although the effects were likely dose-dependent and agent specific , and varied with the timing of the exposure .
| 4 | 0biomedical
| 0Study
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41,418 |
(A-F) Representative sections from superior and inferior retina of non-light damaged control (control), light damage + injection of PBS (LD/Sham) and light damage + injection of g8+ cells (LD/G8+). Dying cells were labeled with TUNEL (red) and cell nuclei were stained with bisbenzimide dye (blue). The arrows at the left of D show how the thickness of the ONL (shorter arrow) and of the nuclear layers of the retina (longer arrow) was measured. Retinas without light damage showed no labeled cells with TUNEL reagents (A and D). TUNEL+ cells were mostly present in the ONL of retinas with light damage in the superior retina when injected with PBS or G8+ cells (B, C and E). TUNEL+ cells were present in the sham injected eye (E) but not present in these control and G8+ injected sections (D and F). The ONL was disorganized in the LD/Sham retina, but not in the control and LD/G8+ retinas. (G) Normalized ONL thickness for the non-light damaged) control (black line), LD/Sham (Gray line) and LD/G8+ (blue line) groups from superior to inferior areas of the retina. Error bars show SEMs. Significant difference in retinal thickness were seen between LD/Sham and LD/G8+; * p < 0.05; **p<0.01. (H) Normalised ONL thickness for control, LD/Sham and LD/G8+ groups. Error bars show SEMs. The ONL is significantly thicker in LD retinas treated with G8+ cells than those injected with PBS. No difference was seen in ONL thickness between control and LD/G8+ sections. **p<0.01. (I) Number of TUNEL+ cells in the ONL/section for the same three groups. Error bars show SEMs. Significantly more TUNEL+ cells were present in the LD retinas than control retina (asterisk p value). Fewer TUNEL+ cells were present in the retinas injected with G8+ cells than those injected with PBS (asterisk p value). (G-I: Control = 5, LD/Sham = 4, LD/G8+ = 5). ***p < 0.001; ** p < 0.01. ILM, inner limiting membrane; INL, inner nuclear layer; ONL, outer nuclear layer; OLM, outer limiting membrane.
| 4 | 0biomedical
| 0Study
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341,686 |
In the biggest pit lake studied, ST, the photosynthetic activity has a moderate effect on the concentration of DO at depth, as illustrated in Figure 5c; the DO saturation level was around 70%-80% sat. in the upper four meters in April 2010 and approached 125% three months later. However, in the smaller pit lakes, CM or HER, the photosynthetic activity often produced marked MOM where DO concentrations drastically increased to values far exceeding saturation (Figure 6). This phenomenon occurs especially in summer, when a clear oxygen supersaturation is observed at some meters below the lake surface: in CM at 4.7 m the saturation of O2 was 150% in July 2011 (Figure 6b) and in HER was 200% to 340% O2 sat. at 5 m depth in June 2010 and July 2011, respectively (Figure 6e). These saturation values corresponded to DO concentrations around 12–13 mg/L O2 in CM and up to 22–24 mg/L O2 in HER. More recently, an outstanding MOM has also been observed in the Brunita (BRU) APL in July 2019 (320% O2 sat. at 2 m below the lake surface; see Figure S3). These oxygen concentrations are, to our knowledge, among the highest reported in lakes worldwide (either natural or artificial), and clearly reflect a strong disequilibrium between O2-producing (i.e., photosynthesis) and O2-consuming (e.g., aerobic bacterial metabolisms) processes at these depths.
| 4 | 0biomedical
| 0Study
|
95,676 |
Blood group system was discovered way back by Karl Landsteiner in 1901. Later “Rhesus” system was defined by Landsteiner and Wiener in 1937. A total of 30 human blood group systems are now recognized by the International Society of Blood Transfusion which vary in their frequency of distribution among various races of mankind. Clinically, only “ABO” and “Rhesus” groups are of major importance. “ABO” system is further classified as “A,” “B,” “AB,” and “O” blood groups according to presence of corresponding antigen in plasma. “Rhesus” system is classified into “Rh +ve” and “Rh −ve” according to the presence or absence of “D” antigen . As the inheritance of dermatoglyphic patterns and ABO blood group is polygenic , the exact manner of inheritance of ABO blood group was revealed by Bernstein .
| 3 | 0biomedical
| 1Other
|
255,986 |
Ionizing radiation (IR) can directly interact with water in human bodies, and generate ROS, which could be amplified by Fenton reaction and generate an extremely reactive hydroxy radical (Ahsan et al., 2003; Yu, 2012). The hydroxy radical results in lipid peroxide and induces cell death, including ferroptosis (Kajarabille and Latunde-Dada, 2019). Radiotherapy is an essential mode for many cancers, including breast cancer, particularly those seeking breast-conserving surgery. Radiotherapy to breast conservation surgery can halve the rate of disease recurrence and reduce breast cancer mortality by about one-sixth (Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) et al., 2011). According to NCCN clinical practice guidelines in oncology, the adjuvant therapy and overall treatment pathway should be adjusted according to the level of ER expression, although in the ER-positive group (Gradishar et al., 2020). In this study, we designed a systematic study to elucidate the underlying mechanisms of radio-resistance in ER-positive breast cells and managed to improve radiation killing effect through targeted intervention of IR-induced ferroptosis.
| 4 | 0biomedical
| 0Study
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181,292 |
Compound 15: m.p. 213.4 °C (EtOH); 1H NMR (400.13 MHz, DMSO-d6) δ 10.45 (s, 1H, H1), 8.08 (dd, 3J = 8.0, 4J = 1.8 Hz, 2H, H2′–H6′), 7.56 (m, 3H, H3′–H5′, H4′), 7.29 (ddd, 3JF9 = 10.6, 3JF7 = 8.7, 4J = 2.9 Hz, 1H, H8), 7.10 (ddd, 3JF7 = 9.9, 4J = 2.9, 5JF7 = 1.8 Hz, 1H, H6), 3.61 (s, 2H, H3); 13C NMR (100.62 MHz, DMSO-d6) δ 165.8 (C2), 161.6 (C4), 157.5 (dd, 1JF = 242.0, 2JF = 14.4 Hz, C7), 153.3 (dd, 1JF = 248.3, 3JF = 14.9 Hz, C9), 142.2 (d, 3JF = 14.2 Hz, C5a), 136.5 (C1′), 131.6 (C4′), 128.8 (C3′–C5′), 127.8 (C2′–C6′), 116.1 (dd, 2JF = 13.7, 4JF = 1.9 Hz, C9a), 108.5 (dd, 2JF = 22.9, 4JF = 3.4 Hz, C6), 101.3 (dd, 2JF = 27.7, 2JF = 24.5 Hz, C8), 40.1 (C3); 15N NMR (40.54 MHz, DMSO-d6) δ–253.6 (N1), n.o. (N5); 19F NMR (376.50 MHz, DMSO-d6) δ–119.9 (ddd, 3JH8 = 10.3, 4JFF = 4.6, 5JH6 = 1.5 Hz, 1F, F9),–116.4 (td, 3JH8 δ 3JH6 δ 9.3, 4JFF = 4.9 Hz, 1F, F7); Anal. Calcd for C15H10F2N2O: C, 66.18; H, 3.70; N, 10.29. Found: C, 65.88; H, 3.66; N, 10.10.
| 5 | 0biomedical
| 0Study
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343,653 |
The mutations involved in HHT most commonly affect genes coding for the Endoglin (ENG) and Activin receptor-like kinase 1 (ACVRL1) causing HHT type 1 and type 2, respectively [9, 10]. In rare cases, HHT is caused by mutations of the SMAD4 gene leading to a phenotype with concomitant juvenile polyposis [10, 11]. The common denominator of these mutations is that they result in loss of function of receptors belonging to the transforming growth factor beta (TGFβ) superfamily, which are present in endothelial cells, involved in angiogenesis and considered to be the cause of vascular dysfunction in HHT [12, 13].
| 4 | 0biomedical
| 0Study
|
133,504 |
The leadership behavior of the female participants not only was compatible with the universities’ emergency responses, but more importantly, addressed the shortcomings of these official efforts (Majchrzak et al. 2007). Consequently, guaranteeing frontline services (for example, mental health services and extending emergency staff’s working hours), would smoothly facilitate students’ evictions and should be strengthened in universities’ organizational emergency management plans. Potential research could examine how to increase student engagement in the university emergency decision-making process to improve the official efforts in better serving students and other on-campus stakeholders.
| 2 | 2other
| 1Other
|
42,122 |
A-F: Standard chow intake, chocolate intake and total intake (the sum of chocolate and standard chow intake) relative to body weight after 240 minutes of the beginning of the AM251 test in male (A,C,E) and female offspring (B,D,F). Values are expressed as mean ± S.E.M. Open bars indicate vehicle treatment. Solid bars denote AM251 treatment. Two-way ANOVA and Bonferroni post-hoc test: */** p<0.05/0.01 vs CC vehicle group; $ p<0.05 vs PC vehicle group.
| 3 | 0biomedical
| 0Study
|
131,922 |
With the increase in the task closure rate and the gradual formation of engineers’ habits, it can be seen from the efficiency ratio of post functions and tasks that the completion habits of employees have greatly and steadily improved since September 2019. For tracking data, please refer to Fig 11.
| 1 | 2other
| 1Other
|
236,292 |
In contrast, amino-glycans were synthesized by reduction of the anomeric azides and later conjugated to the PHEAs by displacement of the PFP group. Hereinafter, polymers were assembled onto citrate-stabilized gold nanoparticles. Characterization analysis revealed that 35 nm sialyl-lactose particles were the most stable ones and were selected to perform glycan-binding assays. This study replicated a lateral flow situation using protein expressed mammalian cells (HEK) to ensure glycosylation. The assays revealed that in this system sialic acid gave the strongest response and consequently was taken forward. With the successful identification of sialic acid as a target ligand, its application as the capture unit in lateral flow was examined. It is important to highlight that the performance does not only depend on the affinity of the capture ligand but also on the flow of the particles. For this reason, “half” lateral flow assays were established to optimize the particles. The negative test line was (commercial) 2,3-silyllactose-BSA, which the nanoparticle should not bind to (to avoid false positives). The positive control was immobilized SARS-CoV-2 and the sialic acid-AuNPs 35 nm nanoparticles flowed over them. The lateral flow devices could clearly detect the virus-like particles at a concentration of 5 µg/mL protein. Sialic acid particle system had a clear preference for SARS-CoV-2, demonstrating selectivity in this glyconanoparticle system. This data supports the notion that the terminal sialic acid is the key binding motif. Therefore, this system can detect the spike glycoprotein from SARS-CoV-2 virus under 30 min, thus being interesting for the creation of rapid point-of-care diagnostics in a format which requires no infrastructure and limited training.
| 4 | 0biomedical
| 0Study
|
100,701 |
In the genetic toggle switch (Figure 3A), either gene X or gene Y is switched on due to their mutual repression. These two memory states can be flip-flopped by two different input signals. In the positive feedback circuit (Figure 3B), the expression of gene X is switched on by an input stimulus. Once activated, the ON state is self-sustaining due to positive feedback. SGNs for associative learning can be built based upon these memory circuits. Several groups have proposed such SGNs, including Lu et al. who put forward an associative learning SGN based on a toggle switch.
| 4 | 0biomedical
| 0Study
|
341,332 |
Rapid review 1 aimed to identify primary studies published from 2010 of models giving estimates of the prevalence of diabetes in adults in England or the UK. We examined how the models take account of future changes in age-specific prevalence rates and test their validity.
| 2 | 0biomedical
| 2Review
|
95,730 |
There is a clear necessity for the improvement of care for brain metastasis patients as they tend to live longer. Currently, several treatment strategies exist for brain metastasis, but data on the most effective strategy is lacking. Factors such as radiation dose, treatment timing, chemotherapy combinations among others should be evaluated in future studies in order to evaluate the most effective treatment modalities. The wide range of treatment modalities also provides a potential to strive towards more individualized patient care. In addition, evaluated outcomes should not be limited to survival or progression and should include quality of life. Indeed, currently a phase III randomized trial is being conducted to evaluate postoperative SRS versus WBRT in brain metastasis patients (NCT01372774) . Primary endpoints will be evaluation of survival and neurocognitive progression and secondary endpoints will be QOL, adverse events, and functional independence among others. Last, the use of “big data” may provide a method to evaluate these outcomes more thoroughly.
| 4 | 0biomedical
| 0Study
|
224,867 |
All analyses were performed using the Statistical Package for the Social Sciences, Version 26.0 (SPSS Inc., Chicago, IL, USA). Descriptive characteristics were presented for each gender and full sample. After verification of the normal distribution of continuous variables through the Shapiro–Wilks test and PP plot (probability–probability plot), descriptive characteristics were shown as the mean + standard deviation, while qualitative variables were presented as frequencies or medians. The chi-squared test, the t-test for independent variables (means) and Mann–Whitney U-test (medians) were performed to study differences between genders and p-value was assessed for all tests. Correlation analysis followed the assumptions of Pearson r (parametric data) or Spearman’s ρ (non-parametric data) depending on the characteristics of the correlated variables. Statistically significant correlations were expressed as r/ρ and p-value < 0.05 or < 0.01. Regression analysis of quantitative continuous dependent variables was conducted for a restricted portion of studied variables by creating regression models through a stepwise linear regression method. Independent variables were chosen from statistically significant correlated variables and by excluding multicollinearity factors or contributing factors. The qualitative regression of ordinal data was performed through multinomial logistic analysis instead. Best fitting model/models were determined automatically from the software. The confidence interval (CI) was set at 95%.
| 4 | 0biomedical
| 0Study
|
151,684 |
Macroautophagy (hereafter referred to as autophagy) is an evolutionally conserved, cell-autonomous process, delivering cytosolic material to the lysosomes for degradation by lysosomal hydrolases. Among several autophagy-related proteins, microtubule-associated proteins 1A/1B light chain 3B (LC3) and p62/SQSTM (p62) are widely used to estimate the autophagic flux . A crucial regulator of autophagy is the mechanistic target of rapamycin (mTOR), suppressing early steps in autophagy . Thereby, mTOR forms two distinct complexes, mTORC1 and mTORC2, with different sensitivities to rapamycin .
| 5 | 0biomedical
| 0Study
|
210,544 |
As most loudspeakers behave as a simple mechanical oscillator for a wide range of frequencies, they can be well approximated as a first-order mechanical oscillator, two transformers and an electrical circuit. In the case of piezoelectric loudspeakers, the usual gyrator used for the electromechanical transduction is replaced by a transfomer, and the electrical circuit is a simple capacitor. The equivalent electrical circuit of the loudspeaker detailed in is presented in Figure 1, where Rg is the output resistance of the amplifier and the resistance of the connection lines, Cp is the piezoelectric capacitance, γ is the transduction ratio of the piezoelectric layer, Rms represents the viscous losses of the mechanical oscillator, Mms is the moving mass of the loudspeaker, Cms is the compliance of the loudspeaker and Sd is the effective radiating area of the membrane.
| 3 | 2other
| 1Other
|
86,068 |
Lead (Pb) is a non-essential element that could result in serious health problems due to toxicity arising from environmental pollution1–3. The risk is significant with the World Health Organisation (WHO) reporting 853,000 deaths related to Pb toxicity in 20134. Ingesting contaminated food and water is the route of lead intoxication for the general population, while inhalation of polluted dust and fumes is more common in the occupational setting2. Accumulation of Pb in tissues induces cellular damage through oxidative stress following overproduction of reactive oxygen species (ROS) and reduction in the activities of cellular antioxidant system5–8. The metal also inhibits cellular energy production and induces apoptosis subsequent to mitochondrial impairment and DNA damage9,10. Additionally, Pb simultaneously upregulates and inhibits the production of several pro- and anti-inflammatory cytokines11,12.
| 4 | 0biomedical
| 0Study
|
51,238 |
PRI changes remained continuous even when the Photosynthetic Photon Flux Density (PPFD) changed by a factor of ten under controlled laboratory conditions (between the levels of full sunlight and complete shade) (Fig. 1): the first measured PRI value in shade equaled the last one in light, and vice versa. After the change in the light conditions, PRI approached the acclimated value \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{PRI}}_{\infty }$$\end{document}PRI∞ exponentially (Fig. 2) for at least ten first seconds. The time constants of this change calculated from the slope of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left| {{ \ln }\left( {{\text{PRI}} - {\text{PRI}}_{\infty } } \right)} \right|$$\end{document}lnPRI-PRI∞ against time were 26.5 and 16.0 s for light to shade transitions (Fig. 2a, c, respectively); for shade to light transitions, the values were 14.1 and 8.9 s (Fig. 2b, d, respectively). More scatter in Fig. 2a and c is explained by the low light (shade) conditions during the measurements. Time constants of the acclimations decreased with time, probably due to incomplete acclimation.Fig. 1Adaptation of a mat of needles to varying light conditions: PRI and light conditions indicated by the reflected radiance at 570 nm [L(570), in W m−2 nm−1 sr−1]. The letters (a, b, c, d) identify irradiation transitions plotted in Fig. 2: a, c are high → low transitions and b, d low → high transitions Fig. 2The variation of PRI directly after change in light condition. The results of fitting \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{ln Y}} = { \ln }\left| {{\text{PRI}} - {\text{PRI}}_{\infty } } \right|$$\end{document}ln Y=lnPRI-PRI∞ for t < 10 s with a linear equation are given in the figure. Subplot letters correspond to the letters in Fig. 1, the broken line connects the PRI values measured after the first ten data points used in line fitting
| 4 | 0biomedical
| 0Study
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213,337 |
The F-SIM specifications do not force the use of a specific forward link but only require that it supports certain features. In practice, the forward link is implemented with the DVB-S2 protocol, using MPE encapsulation to support the IP. Signaling is transported as multicast IP streams containing compressed Protobuf structures. DVB adaptive coding and modulation (ACM) is supported, with the following advantages:Supporting terminals with different performances, e.g., different antenna sizes;Providing high availability, by using strong DVB-S2 physical layer configurations (MODCODs) when required by weather conditions;Increase coverage up to the limits of the satellite beam;Avoiding bandwidth waste, by switching to more efficient MODCODs if the link budget permits this action.
| 1 | 2other
| 1Other
|
28,654 |
In recently reports, H19 exerted two opposite effects depending on tumor types: it functioned as an oncogene in ovarian cancer , colorectal cancer , breast cancer and glioblastoma ; whereas, it exerted tumor suppression effects in hepatocellular carcinoma , prostate cancer and Wilms’ tumor . In our previous study, we found that H19 functions as an oncogene in GBC and promoted cell proliferation by upregulating the AKT2 expression level in GBC cells, and upregulation of H19 promoted the epithelial-mesenchymal transition (EMT) [28, 29]. Based on these previous researches, our further revealed that H19/miR-343-5p/FOXM1 might be a potential ceRNA regulatory network in GBC.
| 4 | 0biomedical
| 0Study
|
277,538 |
The SPEAD method (19) however includes various steps where samples are transferred from plate to plate during the treatment steps (Table IV). In such methods, the calculation of the cumulative dilution should be done systematically. In the published procedure (19), an initial sample dilution of 1/4 in buffer followed by addition of a biotin labeled drug at a 1/1 ratio or a 1/2 further dilution, corresponding to a 1/8 cumulative dilution at this stage. At the subsequent step, 100 µL of this mixture is added to a streptavidin plate and incubated. After incubation and a series of washes, 60 µL of acid is added to dissociate. At this step, the sample is concentrated back at a ratio of 1.67-fold resulting in a cumulative dilution back to 1/4.8. The subsequent transfer of 50 µL of sample to another plate with 150 µL of a neutralizing reagent results in a fourfold dilution (cumulative dilution of 1/19.2). That sample preparation is then coated on the final surface for detection. In this example, the MRD and minimum titer reported are established as 1/19.2 and any additional sample dilution performed for determining the antibody titer (pre- or post-treatment) should be factored into that value. Although not necessary, a minor adjustment to one of the volumes of a particular step can result in a whole number if desired. For example, changing the volume of acid from 60 to 62.5 µL will result in a cumulative dilution of 1/5 at that step and a subsequent overall MRD of 1/20. Regardless of the practice of adjusting the volume or not to allow for whole number MRD values, the actual titer value should be reported.Table IVSPEAD Titer Calculation (SPEAD Indicates Solid-Phase Extraction with Acid Dissociation)StepDescriptionStep dilutionCumulative dilutionDay 1Sample predilution1/4 dilution of sample1/41/4Sample pretreatment 1Biotin-drug complex: equal volume of sample and biotin-drug1/21/8Day 2Sample pretreatment 2Streptavidin: biotin-drug complex capture (100 µL of prior step)No dilution1/8Acid dissociation (60 µL of acid (2/1); concentrated back to 1/4; 50 µL transferred)1.67/11/4.8Sample neutralization: 150 µL of base added to 50 µL of acid from prior step1/41/19.2Sample analysisCoat neutralized sample, block, enzyme-HRP drug, substrateNo dilution1/19.2For samples diluted further, add the applicable fold dilution for titer reporting, for example, 1/19.2, 1/38.4, and 1/76.8, if 1/2 scheme is followed
| 4 | 0biomedical
| 0Study
|
113,049 |
We also consider several other choices of the sample sizes in each of the two groups (case and control), and calculate the size and draw the power curves for each of the following choices of the sample sizes: r 1 = 100, r 2 = 70; r 1 = 50, r 2 = 40; and r 1 = r 2 = 50, representing reduced sample sizes and unequal sample sizes in each treatment group. Overall, from our analyses with different choices of sample size, we find that the power of our test is increasing with increase in the sample size as well as an increase in the differential connectivity of the genes with the transcription factors in the two groups. Details of the variation of the power with sample size can be found in Additional file 2 which shows the power curves for each of the above choices of the sample sizes with different choices of δ, 0 ≤ δ ≤ 1.
| 4 | 0biomedical
| 0Study
|
38,316 |
Although the CO number was obviously reduced by ~30% in the atrad51-/+ atrad51c-/+ atxrcc3-/+ triple heterozygote, no univalents were observed, consistent with a mechanism that ensures at least one CO per chromosome . If the COs were distributed among the 5 Arabidopsis bivalents randomly, they would follow the Poisson function P (k COs per bivalent) = (λke-λ)/k! where λ is the mean number of COs per bivalent. Using this function, from the analyses of 52 WT and 15 atrad51-/+ atrad51c-/+ atxrcc3-/+ triple heterozygote meiocytes, we would expect to find 36 and 19 univalents in WT and the triple mutant, respectively, but none were observed (Table 2).
| 4 | 0biomedical
| 0Study
|
242,696 |
Costly prosocial behavior measure 2: Self-sacrifice for entities. A second costly prosocial measure gauged willingness to sacrifice one’s own life to save a group of entities . Participants were asked to imagine a scenario where a ruthless dictator was about to wipe out a particular group of entities, but that if they sacrificed their own life, the entity group would be spared. Participants were then presented with four different groups of entities: “people from your hometown”, “people from Africa”, “chimpanzees”, and “redwood trees”. Participants were asked to elect on a 10-point scale how many of each entity would need to be annihilated before they would sacrifice their own life in their place (1 = 1–10, 2 = 10 to 100, 3 = 100 to 1000, 4 = 10%, 5 = 20%, 6 = 50%, 7 = 75%, 8 = 90%, 10 = I would never sacrifice myself). Individual responses regarding each entity group showed good reliability (α = .81), so an aggregate ‘self-sacrifice for entities’ measure was used for analyses.
| 3 | 2other
| 0Study
|
392,679 |
Predictive performances (MCC) of IPANEMAP, averaged over 10 runs, for the DiLCrz dataset, consisting of 16 reactivity profiles. (Pseudo) MFE and MEA structures, predicted using RNAfold (31), are included for reference. The structure was probed in presence (•) or absence (○) of Mg2 +
| 3 | 0biomedical
| 0Study
|
221,745 |
Quality measures focusing on emotional/spiritual support and effective and timely communication with patients and families have been previously proposed as specific targets for improving the quality of care at the end of life . For example, many hospitals settings have chaplains (“spiritual care practitioners”) available on-site to provide spiritual care to dying patients and their families and to accommodate religious needs. While some hospitals may be able to provide more consistent access to Protestant, Catholic and Jewish religious leaders, due to the relative proportion of religions among patient populations, absence of community leaders and supports for individuals of less common faiths in our hospital setting – for example, Islamic faith in this study – may have influenced our findings. Efforts to improve access to diverse community and religious leaders for patients and families from different ethnocultural backgrounds might lead to better clinical outcomes and improved satisfaction at the end of life.
| 4 | 0biomedical
| 0Study
|
185,675 |
The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.
| 1 | 0biomedical
| 1Other
|
308,989 |
Figure 2 summarises our results. As we can see in panels A-D, the distributions of the parameter estimates are centred around values consistent with the predicted \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta \approx 6$$\end{document}η≈6 scaling (see “Connection with the theory of ego-networks” section). Additionally, the model is able to capture individual’s nuances (panels a-d), and the fittings are, generally speaking, strikingly good (see Supplementary Information for a comprehensive set of figures, including fittings for every subject within every time window). Furthermore, we find a very high, significant correlation between the estimated parameter for each ego and the number of alters in his or her network (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\tilde{L}}$$\end{document}L~). More precisely: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta ^{T_1}\sim {\tilde{L}}^{T_1}$$\end{document}ηT1∼L~T1 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r=0.84,p<10^{-6}$$\end{document}r=0.84,p<10-6), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta ^{T_2}\sim {\tilde{L}}^{T_2}$$\end{document}ηT2∼L~T2 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r=0.52,p<10^{-3}$$\end{document}r=0.52,p<10-3), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta ^{T_3}\sim {\tilde{L}}^{T3}$$\end{document}ηT3∼L~T3 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r=0.81,p<10^{-5}$$\end{document}r=0.81,p<10-5) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta ^{T_1\cup T_2\cup T_3}\sim {\tilde{L}}^{T_1\cup T_2\cup T_3}$$\end{document}ηT1∪T2∪T3∼L~T1∪T2∪T3 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r=0.83,p<10^{-6}$$\end{document}r=0.83,p<10-6)—Pearson’s r coefficients, 2-tailed tests. This fact further endorses the claim that the amount of resource available to form relationships is a seemingly fixed quantity that individuals spread according to the maximum entropy principle12.
| 4 | 0biomedical
| 0Study
|
19,897 |
Septic shock status was considered if patients were refractory to IV fluids and needed vasopressors to maintain mean arterial pressure (MAP) > 65 mmHg. Diagnosis of PJP was based on clinical presentation, radiographic presentations of ground-glass opacities by either computed tomography (CT) or chest radiographs (CXR). There were no facilities to perform bronchoalveolar lavage (BAL). Clinical variables included CD4 count, viral load (plasma HIV RNA if available within 6 months of admission), biochemical and hematological values especially serum albumin, need for vasopressors, and mechanical ventilation, and APACHE II score was calculated. The primary outcome was survival to hospital discharge and secondary outcomes were predictors of mortality. We also measured ICU mortality in all non-HIV patients admitted to the ICU in the study period.
| 4 | 0biomedical
| 0Study
|
281,642 |
Active, topical anti-inflammatory treatment should be started at the first sign of a flare and be applied on hydrated skin, particularly when using ointments.24 Topical corticosteroids and TCIs are the anti-inflammatory medications of choice to treat AE (Table 1).68
| 3 | 0biomedical
| 1Other
|
151,201 |
Kidney tissues consist of the cortex, medulla, and pelvis, all of which have distinctive main functions. In this study, we focused on the renal cortex and medulla portions. H&E staining was implemented on frozen tissue sections to distinguish histological features by a renal pathologist, and AFADESI–MSI experiments were performed in both the positive and negative ion mode on the adjacent tissue sections to acquire molecule profiling of the metabolites. Figure 3A illustrates one representative histology-specific MSI in the positive ion mode, in which the distribution of L-carnitine matches well with its histological features. Moreover, as depicted in the figure, the ion intensities were significantly different between db/m mice and db/db mice among the cortex and medulla, respectively. In total, 509 and 507 biologically informative peaks were observed in the renal cortex and medulla, respectively, for the negative ion mode, whereas in the positive ion mode, 724 and 728 peaks were probed in the renal cortex and medulla, respectively (not shown). In order to explore the overall differentiation of metabolic molecules in the DKD, OPLS–DA was used to choose histology-specific metabolic biomarkers based on the MSI pixel point in the negative ion mode (Figure 3B) and positive ion mode (Supplementary Figure 1A). As a result, both the renal cortex and medulla parts, respectively, could be clearly distinguished between db/db and db/m mice, indicating striking separations in the metabolite profiling of not only the cortex but also the medullary portion induced by T2DM. Next, we selected discriminating metabolites with clear identification potential from the two groups, using a variable importance in projection threshold (VIP)≥1.0 generated by OPLS–DA, and p<0.05 according to one-way analysis of variance (ANOVA). Volcano plots were drawn to visualize the dysregulated metabolites in the renal cortex and medulla between the two groups (Figure 3C for negative ion mode; Supplementary Figure 1B for positive ion mode). To further identify significantly perturbated metabolic pathways that may be involved in DKD, we performed metabolic pathway matching analysis by importing the discriminating metabolites into the kyoto encyclopedia of genes and genomes (KEGG) database (Sun et al., 2019; Chen et al., 2021b). We observed that taurine and hypotaurine metabolism, arginine and proline metabolism, histidine metabolism, biosynthesis of unsaturated fatty acids, and fatty acid degradation pathways were significantly dysregulated in DKD (Figure 3D for cortex portion, Supplementary Figure 1C for medulla portion). In total, the in situ molecular profiles of the kidneys in a T2DM mouse model based on a histology-specific analysis were first presented, suggesting that several metabolic pathways were remodeled in both the cortex and the medulla portion of a diabetic kidney.
| 4 | 0biomedical
| 0Study
|
280,719 |
In this study, we derived cochleates from the bacterial membranes of S. Infantis and then efficiently encapsulated the cochleates using two different technologies, spray drying and ionotropic gelation, to develop an oral vaccine prototype. Encapsulation by ionotropic gelation was more efficient, obtaining millimeter-sized beads (1620–1950 µm) with a protein content between 1.0–2.5 mg/g (reflecting the high content of antigens). Beads containing 15% v/v cochleates were delivered orally to birds for a safety test. During the safety study, no physical or health alterations were observed in the birds. In the post-mortem examination, no pathological alterations or lesions were observed in the gastrointestinal tract or in the organs analyzed. In this study, we took the first step toward the development of a novel prototype oral vaccine against S. Infantis. It is essential to analyze the immune response of the birds and the efficiency of the vaccine in future studies.
| 4 | 0biomedical
| 0Study
|
84,627 |
With the aim of transfering functional annotation from well studied genes from model species to orthologous genes in other genomes, we first analyzed in depth orthologous relationships between monocots and dicots LRR-RLK genes in each SG. This analysis led us to define what we named the “core set” of LRR-RLK genes in angiosperms: i.e., orthologous genes which have not been completely lost in either monocots or dicots throughout the angiosperms evolutionary history. To do so, the 20 SG-specific trees were scaned to locate monocots/dicots bifurcations (Figure 2). Based on this analysis, 101 OGs containing monocots and dicots sequences (named MD OGs) were characterized and defined as the “core” set of LRR-RLK genes in angiosperms.
| 4 | 0biomedical
| 0Study
|
228,864 |
Overall Treatment Response. Waterfall plots of best overall response. Maximum percentage change in the aggregate diameter of Response Evaluation Criteria in Solid Tumors target lesions (a); maximum percentage change in the aggregate diameter of irradiated lesions (b) and maximum percentage change in aggregate diameter of unirradiated target lesions (c). Kaplan–Meier curves of 1-year overall survival (A) and progression-free survival (B). Plasma IL-6, IL-8, IL-10, and IL-17A levels before and 4 weeks after nivolumab treatment in nivolumab responders (C, n=10) and non-responders (D, n=7). P values are calculated using the paired t-test, *P < 0.05.
| 4 | 0biomedical
| 0Study
|
22,108 |
The mean RNFL of the temporal and nasal sectors was significantly thicker at 1 month (P < 0.001) and 3 months (P < 0.001, P < 0.05, resp.) after the MH surgery. The mean RNFL thickness did not differ significantly at 6, 12, and 24 months from baseline thickness.
| 4 | 0biomedical
| 0Study
|
85,699 |
Young found a range of HBC models and interventions for HIV but these were generally from small studies and the majority were based in developed countries . Since this review was published, there has been a change in the evidence with more focus on HBC in LMICs. Home-based HIV voluntary counselling and testing has been found to have the potential to increase uptake in developing countries . Nurses are an important element of HBC for HIV but have not been covered in depth in Young or any other recent review. This review assesses the effects of home-based nursing to reduce morbidity in people infected with HIV/AIDS.
| 4 | 0biomedical
| 2Review
|
367,056 |
The transcriptome data were submitted to the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (https://www.ncbi.nlm.nih.gov/sra/), with the BioProject ID, PRJNA591729. In this study, gene model annotations and reference genomes (ARS-UCD1.2/bosTau9) were accessed from UCSC (31), lncRNA model annotations were accessed from NONCODE (32), and miRNA model annotations were obtained from miRbase (33).
| 4 | 0biomedical
| 0Study
|
395,580 |
The overall Kaiser-Meier-Olkin measure of sampling adequacy (MSA) was 0.82, and MSA per item was above 0.5 for all items. Out of 62 items 6 had MSA values between 0.50 and 0.59, 8 had MSA between 0.60 and 0.69, 12 had MSA values between 0.70 and 0.79 and 36 had MSA of 0.8 and above.
| 3 | 0biomedical
| 0Study
|
298,909 |
For these reasons, several irrigation strategies have been essayed to obtain high-quality fruits without a great loss in crop yield while optimizing the water use . As the response to abiotic stress is commonly species- and cultivar-dependent, the stress impacts on fruit metabolism must be monitored individually to obtain the best performance .
| 2 | 0biomedical
| 1Other
|
8,424 |
Mammalian Y-box binding protein-1 (YB-1) is a member of the DNA/RNA-binding family of proteins that are involved in DNA repair, mRNA transcription, splicing, translation and stabilization . YB-1 is related to cell proliferation, anti-apoptosis, and epithelial-mesenchymal transition as well as castration resistance in PC . It is reported that YB-1 translocation from the cytoplasm to the nucleus stimulates transcription of a number of genes encoding proteins responsible for drug resistance, disease recurrence, metastasis and poor prognosis in various cancers [18, 19]. YB-1 acts as a biomarker for predicting the efficacy of high-dose chemotherapy in breast cancer . Increases in YB-1 protein expression have also been described for other malignant tumors, such as osteosarcoma, PC, pancreatic adenocarcinoma, colorectal carcinoma, and glioblastoma, indicating the clinical impact of YB-1 for the progression of these malignant diseases [15, 18].
| 4 | 0biomedical
| 0Study
|
242,708 |
Table 3 displays all correlations between variables included in the study. Search for meaning was positively related to happiness-pursuit measures (rs = .27-.41, ps < .001), negatively related to life satisfaction, and again negatively related to age and presence of meaning. Presence of meaning was significantly positively related to willingness to donate a kidney, but not the other two costly prosociality measures. Concerning our hypothesis, zero-order correlations revealed that costly prosociality was not significantly related to either search for meaning or happiness-pursuit variables.
| 2 | 2other
| 0Study
|
187,335 |
Standard aloin A and aloin B solutions were prepared by dissolving these drugs in a solution comprised of HPLC-grade methanol/water and methanol (90:10, v/v). As for the cloxacillin and ceftiofur standard solutions, these were prepared by a solution of HPLC-grade water/acetonitrile (50:50, v/v). Once prepared, these solutions (1 mg/ml) were stored in the dark and refrigerated at a temperature of 4 ± 2°C for <3 months.
| 3 | 0biomedical
| 0Study
|
112,713 |
Five patient groups (i.e., free of CNS cancer or tumor, CNS tumor free with systemic cancer, LMC, brain metastasis, and brain tumor other than brain metastasis) were enrolled in this study (Table 1). Each patient group underwent various therapies based on the disease, and the therapy type affected our metabolomics profiling results. For example, many of the identified metabolites or selected candidate metabolites that were identified as discriminant LMIs appeared as a chemical drug used in the treatment of patients, especially meperidine and ketobemidone (Table 2 and Supplementary Table 1). This result also supported the sensitivity of the discriminant LMI selection from the 10,905 LMIs, and indicated that the CSF metabolomics profiling results were reliable.
| 4 | 0biomedical
| 0Study
|
42,051 |
Surrogate or reduced models are based on much simpler mathematical operators than partial differential equations. For steady problems, they may consist of algebraic equations, or ordinary differential equations to capture time dependent phenomena. Such models are often called lumped parameter models, because they synthesize into a small number of coefficients the behavior of spatially dependent functions, solutions of partial differential equations, a.k.a. distributed parameter models.
| 3 | 0biomedical
| 1Other
|
212,734 |
Cases with incomplete information were removed from the corresponding analysis. Student’s t-test and one‐way analysis of variance (ANOVA) were used to test for significant differences between two groups or multiple groups, respectively. For CENPN protein expression, the chi-square test was employed. Data are presented as the mean ± standard deviation (SD) of at least three independent experiments. p < 0.05 was viewed statistically significant. All statistical tests were two-sided. R software v3.6.2. and GraphPad Prism 8 were used for the statistical analyses.
| 4 | 0biomedical
| 0Study
|
165,484 |
Perceived physical health, mental health, and poor health are measured by the following questions with the response options “__number of days”, “none”, “don’t know/not sure”, or “refused”. The items measured in days were classified as “none”, “1–5 days” or “6 days or more” in a month.
| 2 | 0biomedical
| 1Other
|
233,318 |
The testes or epididymis tissues were fixed in Bouin’s solution for hematoxylin and eosin (HE) staining or in 4% formaldehyde (PFA) in PBS for immunostaining. In brief, tissues were fixed overnight, embedded in paraffin wax, and cut to produce 5 μm-thick sections. For immunohistochemistry (IHC), the sections were dewaxed in xylene and rehydrated in serial dilutions of alcohol. Endogenous peroxidase was blocked by immersing the sections in 0.3% H2O2 in methanol for 20 min at room temperature. The sections were then blocked with 5% bovine serum albumin (BSA) and incubated with the primary antibody at 4 °C overnight, and then the secondary antibody was applied for 1 h. Staining was visualized using a DAB substrate kit according to the manufacturer’s protocol (Zhongshan Technology, Beijing, China). The negative controls were subjected to the same protocol except that PBS was used instead of the primary antibody. We use double blind strategy in tissue analysis experiment.
| 4 | 0biomedical
| 0Study
|
275,308 |
In contrast to the moderate influence of the backbone extensions on Aβ40 fibril formation and structure, the N-methylation modification of the peptide backbone causes a more severe interference with Aβ40 structure formation. N-methylation is one of the strategies to stabilize peptides against proteolysis and makes them more water soluble31,40. Likewise, methylation that interferes with intermolecular hydrogen bond formation is used for the design of amyloid-β aggregation inhibitors67,68. There are at least three identified ways how N-methylation impairs protein aggregation: (i) replacement of the amide proton cuts the hydrogen-bonding possibility between two neighboring β-strands; (ii) prevention of regular packing through steric hindrance (higher steric demand) and (iii) tertiary amides favoring trans-conformation leading to β-strand conformation, which, in this case, does not disturb the secondary structure69. Thus, the current results fit into the picture that fibrillation kinetics are either completely blocked (N-Me-F, N-Me-F/L) or greatly slowed down (N-Me-L). In the literature, examples by Meredith and co-workers, who used two times two N-methylated amino acids (2NMe(NTerm): residues 17 and 19; 2NMe(CTerm): residues 37 and 39), fibrils could still be formed, although significantly slower than in absence of the modification29. Only four N-methylated amino acids in the same peptide could prevent the fibrils from their formation. Noticeably, they could show that the β-sheet secondary structure for the respective strands is disrupted independently from each other according to their modification pattern, while N-methylation at position 17 and 19 has a higher impact on the fibril formation process, as it is true also for N-Me-F and N-Me-F/L compared to N-Me-L. However, the striking difference is that in our case N-methylation at only one (Phe19) or two residues (Phe19/Leu34), which were identified to be a critical early folding contact in fibril extension27, are sufficient to prevent from fibril formation. The protective behavior of N-Me-F, N-Me-L and N-Me-F/L counteracting cytotoxicity is expressed in the assay measuring caspase-3 activity, where they significantly decrease caspase-3 activation compared to the WT and partly to the control. This is in alignment with other N-methylated peptides in the literature70.
| 5 | 0biomedical
| 0Study
|
240,017 |
Fatigue indexes based on different fatigue algorithms come in different ranges. In order to compare the actual performance, the fatigue index signals Φt are normalized, as described in . Normalization is based on a linear regression line G60gs,Ne,fdt that is obtained from the segment 0 s<t<60 s of the reference fatigue index signal Ξ60GN,Ne,fdt originating from the 60% MVC load case. No gating (strategy GN) was utilized for the reference signals regardless of the gating strategy for the fatigue index signal Φt undergoing normalization. All other relevant parameters, such as epoch size Ne and applied fatigue index fd, are chosen to match. The offset at t=0 s and the change in the first minute of the linear regression line G60gs,Ne,fdt were used to obtain normalized fatigue index signals Φ^t, as given by Equation (7). (7)Φ^Λ,η,chcr,gs,Ne,fdt=ΦΛ,η,chcr,gs,Ne,fdt−G60gs,Ne,fd0 sG60gs,Ne,fd60 s−G60gs,Ne,fd0 s
| 4 | 0biomedical
| 0Study
|
74,770 |
The proportions of nirS, nirK, nosZI, nosZII and nifH in prokaryotic communities were significantly higher in the natural site soil than in the drained site soil (F = 70.35–460.54, p < 0.001 in all cases), whereas the proportions of archaeal amoA appeared to be fairly similar at the natural and drained sites (Supplementary Table 2).
| 3 | 0biomedical
| 0Study
|
260,948 |
Now, as ⪯d is thinner than ⪯, one could use it in order to determine new sets of comparable monomials and thus generate polar codes in a more efficient manner. Indeed, as more monomials are comparable with respect to ⪯d, they induce new chains in the poset {Mm,⪯d}. This enables us to reduce the number of non comparable elements and also the number of strongly decreasing monomial codes compared to decreasing monomial codes. These two ideas are being illustrated as possible methods for reducing the complexity of the construction algorithm, hence directing towards possible practical applications.
| 1 | 2other
| 1Other
|
37,263 |
We applied a modified social network index (SNI) to access social integration . The SNI has been used in a previous investigation of the NHANES III database . The SNI encompass four fields, and we scored one point for each of the following: (1) current in marital status, (2) more than 156 contacts with close friends and relatives in the past one year, (3) ≥ 4 church or religious activities in the past one year, and (4) participating in community groups. The total SNI score ranged from 0–4. Total scores of 2, 3, and 4 indicated good social integration, while total scores of 0 and 1 indicated social isolation (unfavorable).
| 4 | 0biomedical
| 0Study
|
257,130 |
Study participants were a diverse group of adult men who had extensive interaction with criminal legal system. The mean age of participants was 46 years and they ranged in age from 23 to 58. Forty percent of participants identified as Black, 40% as Hispanic/Latino, and 20% as White. All participants had significant experiences with incarceration; 63% experienced incarceration as a juvenile, the average number of sentences served was 6.4, and the average length of the most recent sentence was 11 years. Almost all participants (95%) had spent some time in solitary confinement, ranging from a total of 14 days to 15 years. Almost half of the participants (45%) had been diagnosed with PTSD and two or more psychiatric conditions. The men described their experiences being incarcerated in local jails, state prisons, and in federal correctional facilities.
| 2 | 2other
| 0Study
|
136,409 |
When the results are measured at multiple time points, each outcome at each time point will be analysed in a separate meta‐analysis with other comparable studies taking measurements at a similar time point. As a general guideline, these will be grouped together as follows: (a) postintervention (b) less than a year follow up, (c) 1–2 year follow up, and (d) More than 2 year follow up. However, should the studies provide viable reasons for an adjusted choice of relevant and meaningful duration intervals for the analysis of outcomes, we will adjust the grouping.
| 4 | 0biomedical
| 0Study
|
345,919 |
Policymakers should be aware that cultural groups, and those within groups, may have different beliefs about the effectiveness of treatment methods and vaccines against COVID-19. It is important to first understand these beliefs and co-design health promotion messages with local groups . Stigmatization risks entrenching hostile attitudes further . Campaigns are likely to be more successful if they rely on peer interactions with people that members of the target audience share a social identity with, e.g. by encouraging people who already follow guidelines to become peer educators in their real-life social networks. Peer intervention (e.g. on social media) can be used to refute harmful information that is liable to prevent people from following guidelines, such as the idea that COVID-19 is caused by 5G masts . Conformist social influence can be used to emphasize how others in a social environment or target audience peer group are currently complying with regulations so that others then adopt these behaviours .
| 2 | 2other
| 1Other
|
261,476 |
Full‐length FXR:RXR reporter gene assay. HeLa cells were grown in DMEM high glucose supplemented with 10 % FCS, sodium pyruvate (1 mM), penicillin (100 U/mL) and streptomycin (100 μg/mL) at 37 °C and 5 % CO2 and seeded in 96‐well plates 24 h before transfection with a density of 8000 cells per well. 3.5 h before transfection, medium was changed to DMEM high glucose, supplemented with sodium pyruvate (1 mM), penicillin (100 U/mL), streptomycin (100 μg/mL) and 0.5 % charcoal‐stripped FCS. Cells were then transiently transfected with using the calcium phosphate transfection method with pGL3basic‐BSEP[26, 27] (containing a shortened construct of the promotor of the bile salt export protein (BSEP) cloned into the SacI/NheI cleavage site in front of the luciferase gene), pcDNA3‐hFXR and pSG5‐hRXR coding for the full‐length human nuclear receptors FXR and RXRα, and pRL‐SV40 (Promega) for normalization of transfection efficiency and cell growth. 16 h after transfection, medium was changed to DMEM high glucose, supplemented with sodium pyruvate (1 mM), penicillin (100 U/mL), streptomycin (100 μg/mL) and 0.5 % charcoal‐stripped FCS. 24 h after transfection, medium was changed to DMEM without phenol red, supplemented with sodium pyruvate (1 mM), penicillin (100 U/mL), streptomycin (100 μg/mL), L‐glutamine (2 mM) and 0.5 % charcoal‐stripped FCS, now additionally containing 0.1 % DMSO and the respective test compound or 0.1 % DMSO alone as untreated control. Each sample was tested in triplicate wells and each experiment was repeated independently at least three times. Following 24 h incubation with the test compounds, cells were assayed for luciferase activity using Dual‐Glo Luciferase Assay System (Promega) according to the manufacturer's protocol. Luminescence was measured with a Tecan Spark M luminometer (Tecan). Normalization of transfection efficiency and cell growth was done by division of firefly luciferase data by Renilla luciferase data multiplied by 1000 resulting in relative light units (RLU). Fold activation was obtained by dividing the mean RLU of the tested compound at a respective concentration by the mean RLU of untreated control. EC50 and standard error of the mean values were calculated with the mean fold activation values of at least three independent experiments with SigmaPlot 10.0 (Systat Software GmbH, Erkrath, Germany) using a four‐parameter logistic regression. GW4064 (EC50 0.5±0.2 μM, 3 μM defined as 100 % activation), CDCA (EC50 18±1 μM, 88±3 % eff.) and obeticholic acid (EC50 0.16±0.02 μM, 87±3 % eff.) served as reference FXR agonists.
| 4 | 0biomedical
| 0Study
|
390,523 |
All data analyses and visualizations were prepared using Microsoft Office Professional 2016 (Microsoft Excel 2016; Microsoft Corp, Redmond, Washington, USA) and IBM SPSS Statistics version 25 for Windows (IBM Corp, Armonk, New York, USA). Intraclass correlation coefficients (ICCs) were calculated to provide results on consistency among observational ratings provided by multiple raters .
| 2 | 0biomedical
| 1Other
|
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