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Fluorescence cross-correlation spectroscopy using single wavelength laser
In this paper, we first introduced the basic principle of fluorescence cross-correlation spectroscopy (FCCS) and then established an FCCS setup using a single wavelength laser. We systematically optimized the setup, and the detection volume reached about 0.7 fL. The homebuilt setup was successfully applied for the study of the binding reaction of human immunoglobulin G with goat antihuman immunoglobulin G. Using quantum dots (745 nm emission wavelength) and Rhodamine B (580 nm emission wavelength) as labeling probes and 532 nm laser beam as an excitation source, the cross-talk effect was almost completely suppressed. The molecule numbers in a highly focused volume, the concentration, and the diffusion time and hydrodynamic radii of the reaction products can be determined by FCCS system.
5,601
P1.3 Pathologies et risques infectieux
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5,602
Effect of down-regulating VEGF on proliferation of colon carcinoma cell HT-29
We designed specific small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF) mRNA and synthesized oligo fragments, then siRNA was obtained by in vitro transcription and transfected into cultured human colon carcinoma cell line HT-29 with lipofectamine. We also analyzed the effect of the siRNA on proliferation of HT-29 cells by methyl thiazolyl tetrazolium (MTT) assay and expression level of VEGF mRNA of transfected cells by RT-PCR as well as amounts of secreted VEGF protein in the supernatant by enzyme linked immunosorbent assay (ELISA). Two groups of siRNA targeting human VEGF effectively inhibited proliferation of HT-29 cells after transfection. The secretion of VEGF protein also notably decreased, but the control scramble siRNA showed no effect.
5,603
Virus
Rond het begin van de twintigste eeuw heerste er een algemeen optimisme de mens van alle ernstige infectieziekten voor altijd te zullen kunnen bevrijden. Er bleek helaas een klasse pathogenen te zijn – die nog niemand ooit gezien had – die deze hoop ondermijnde.
5,604
Infecties en immunisatie: Een gewaarschuwd mens …
De nieuwe WIP-richtlijn heeft al veel stof doen opwaaien. Binnen alle discussies over de nieuwe richtlijn wordt echter nauwelijks gesproken over hoofdstuk 5: ‘Infecties en immunisatie’. Dit is enorm uitgebreid ten opzichte van de vorige versie en bevat wel degelijke relevante aanbevelingen. Wanneer is een medewerker bijvoorbeeld daadwerkelijk beschermd tegen hepatitis B? En hoe dient een praktijk de behandeling van een MRSA-patiënt uit te voeren? Of mag je deze eigenlijk helemaal niet behandelen? Vragen die – zoals blijkt uit onze ervaring – binnen praktijken nauwelijks aan bod komen, maar wel degelijk bijdragen aan infectiepreventie.
5,605
Epidemic Spread on One-Way Circular-Coupled Networks
Real epidemic spreading networks are often composed of several kinds of complex networks interconnected with each other, such as Lyme disease, and the interrelated networks may have different topologies and epidemic dynamics. Moreover, most human infectious diseases are derived from animals, and zoonotic infections always spread on directed interconnected networks. So, in this article, we consider the epidemic dynamics of zoonotic infections on a unidirectional circular-coupled network. Here, we construct two unidirectional three-layer circular interactive networks, one model has direct contact between interactive networks, the other model describes diseases transmitted through vectors between interactive networks, which are established by introducing the heterogeneous mean-field approach method. Then we obtain the basic reproduction numbers and stability of equilibria of the two models. Through mathematical analysis and numerical simulations, it is found that basic reproduction numbers of the models depend on the infection rates, infection periods, average degrees, and degree ratios. Numerical simulations illustrate and expand these theoretical results very well.
5,606
Heterocycle-Fused Acridines
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5,607
NMR spectroscopy of basic/aromatic amino acid clusters in membrane proteins
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5,608
Contents Page
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5,609
Contents Page
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5,610
New CLEM Method to Reveal Ultrastructural Reorganization in the Host Cell during Coronavirus Infection
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5,611
Erratum
In the 1 May 2006 issue of the Journal in the article by Poccia et al. (Poccia F, Agrati C, Castilletti C, et al. Anti–severe acute respiratory syndrome coronavirus immune responses: the role played by Vγ9Vδ2 T cells. J Infect Dis 2006; 193:1244–9), there was a deficiency in the “Financial support” footnote, at the bottom of the left-hand column of the title page (page 1244); the sources of support listed in this footnote should have included the European Commission EPISARS (contract NSP22-CT-2004-511063). The authors regret this error
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Seligman (2007; 195:609)
In the 15 February 2007 issue of the Journal, in the letter by Seligman (Seligman SJ. Evidence for quasi species in severe acute respiratory syndrome—associated coronavirus deletion mutants. J Infect Dis 2007; 195:609), it should be noted that, in accordance with Journal style, “quasi species” has been spelled as 2 words, whereas many other publications use the single-word form, “quasispecies”; readers doing a search for the term are advised to take this variant treatment into account.
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Security Issues
Cyber Terrorism, attacks on the integrity of travel documents, the use of full body scanners and issues flowing therefrom, civil unrest as they threaten the security of airports and unlawful interference with civil aviation are issues that draw the attention of the aviation community in general and the air transport industry in particular.
5,614
Clinical Virology in NICU, PICU and AICU
Viruses are significant causes of nosocomial infections, particularly in intensive care unit (ICU) where seriously ill and vulnerable patients are being cared for. Four major routes of nosocomial virus transmission in the ICU are identified, viz. respiratory, faecal–oral, exposure to blood and body fluid and direct contact with infected patients or through fomites. Different infection control measures are available according to the natural history, biology, pathogenesis, epidemiology and mode of transmission of each virus. In this chapter, we discuss some of the important viruses that could be associated with nosocomial infections in the ICU. Intensivists should work closely with microbiologists, virologists and the laboratory to diagnose such infection early, work proactively to prevent outbreaks and manage viral infections using appropriate strategies.
5,615
Climate Change
The battle lines that have been drawn between climate change believers and deniers could not be more distinct. However, outside of the halls of power and beyond diplomatic chatter there is a subtle, if imperceptible shift heralding a potentially more impactful climate awakening. Those favoring grandiose solutions to the very real challenges posed by climate change will find no victory with the advent of true market-based solutions to climate risk. These shifts in the market are brought forth without presidential decree and signing ceremonies. Rather, they are brought about the same way each economic revolution occurs—with the inexorable drive among entrepreneurs, engineers, planners and risk managers tackling the immediacy of problems, with practical solutions for which the market is willing to pay.
5,616
Distribution of Graph-Distances in Boltzmann Ensembles of RNA Secondary Structures
Large RNA molecules often carry multiple functional domains whose spatial arrangement is an important determinant of their function. Pre-mRNA splicing, furthermore, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium therefore provides useful information on the overall shape of the molecule can provide insights into the interplay of its functional domains. Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between arbitrary nucleotides can be computed in polynomial time by means of dynamic programming. A naive implementation would yield recursions with a very high time complexity of O(n (11)). Although we were able to reduce this to O(n (6)) for many practical applications a further reduction seems difficult. We conclude, therefore, that sampling approaches, which are much easier to implement, are also theoretically favorable for most real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules.
5,617
Cleavage Site Analysis Using Rule Extraction from Neural Networks
In this paper, we demonstrate that the machine learning approach of rule extraction from a trained neural network can be successfully applied to SARS-coronavirus cleavage site analysis. The extracted rules predict cleavage sites better than consensus patterns. Empirical experiments are also shown.
5,618
Electrophoresis in Microfluidic Systems
Many chemical and biochemical analysis methods involve performing a sequence of processes that can be broadly classified in terms of sample preparation, reactions, and product analysis. Since the reaction products often contain mixtures of multiple chemical species, subsequent analytical steps must be capable of separating and identifying the individual components. Electrophoresis, which relies on inducing detectable differences in migration behavior between charged species under the influence of an applied electric field, has proven to be a highly versatile analytical technique owing to a favorable combination of characteristics including relatively simple hardware design and compatibility with a wide range of analytes including biological macromolecules (e.g., DNA, proteins). More recently, there has been considerable interest in adapting electrophoresis technology to miniaturized microfluidic formats with the aim of producing portable low-cost versions of conventional benchtop-scale instrumentation. Ultimately, it is envisioned that these efforts will enable electrophoresis to become an integral component of self-contained “lab-on-a-chip” devices capable of putting the power to perform a variety of sophisticated chemical, biological, and biomedical assays directly in the hands of those who need the information most.
5,619
Antibacterial Activity of Chitosan-Based Systems
Chitosan and its derivatives can be called environmental purification functional materials as they can effectively control the growth and reproduction of hazardous bacteria and also control toxic pollutants. From the basic science to the latest developments and innovations, starting with the history of the material, this chapter presents a facile way to understand the antibacterial activity of the chitosan, together with other materials, to the reader. This chapter also summarizes the general developments in the study of antimicrobial applications. In the light of the current situation of the research and the progress in the related fields, this chapter discusses the differences among influencing factors in detail and compares the antimicrobial activity between different physical states of chitosan. Also, this chaper discusses the more recent processes and applications.
5,620
Global Strategies and Response Measures to the Influenza A (H1N1) Pandemic
As an infectious respiratory disease, influenza is prone to cause pandemics for its fast mutation, easy dissemination, susceptibility to humans, and its elusive nature in terms of treatment. Three influenza pandemics occurred in the 20th century which caused huge losses worldwide.
5,621
The Practice of Advanced Mathematics Teaching Quality Evaluation System
To integrate the mathematical history and the idea of mathematical modeling into the teaching of mathematics timely, so that students can get deeper understanding of how to get and apply the mathematics concepts and theories to real life. In order to prove the feasibility, the advanced mathematics teaching quality evaluation system is designed. And, the effectiveness of the implementation of the advanced mathematics teaching quality evaluation system in our university is verified.
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Age-associated T-cell Clonal Expansions (TCE) in vivo—Implications for Pathogen Resistance
Age-related T-cell clonal expansions (TCE) are an incompletely understood disturbance in T-cell homeostasis found frequently in old humans and experimental animals. These accumulations of CD8 T-cells have the potential to distort T-cell population balance and reduce T-cell repertoire diversity above and beyond the changes seen in the aging of T-cell pool in the absence of TCE. This chapter discusses our current knowledge of the role of these expansions in health and disease, with a special focus on their influence upon immune defense against infectious diseases.
5,623
Viruses
Viral infections are an important and often unrecognized component of disease in immunocompromised patients. The diagnosis and management of viral infections have expanded largely because of new quantitative molecular diagnostic assays. Well-recognized pathogens such as herpes simplex virus (HSV), cytomegalovirus (CMV), and respiratory viruses have been joined by newly recognized pathogens such as BK virus, human herpesvirus-6 (HHV-6), and human metapneumovirus in this highly susceptible patient population. The role of Epstein-Barr virus (EBV) and Human herpesvirus-8 (HHV-8) in lymphoproliferative diseases also continue to be clarified. As a result, the management of viral infections in patients with hematologic malignancies continues to be a growing challenge for the clinician.
5,624
Emergency Preparedness
Outbreaks of infectious diseases during peacetime or in disaster/war-related conditions, may most often need an effective crisis management in the hospital. The emergency preparedness in hospitals may vary within, and between countries, dependent on endemic and epidemic conditions, capacity, knowledge and economy. Lack of preparedness may result in a high risk of disease burden and death and cause a high economic impact on the health care.
5,625
Social Disparities in the Evolution of an Epidemiological Profile: Transition Processes in Mortality Between 1971 and 2008 in an Industrialized Middle Income Country: The Case of Hungary
The present paper seeks to understand the transformation of mortality patterns in Hungary, by which mortality inequalities by education began to appear in the early 1980s, continued to grow in the following 25 years, and now seem to be stabilising. The first part of this paper overviews the theoretical innovations of the last decades regarding the interpretation of cause-specific mortality dynamics, often referred to as epidemiological transition theories, and their relevance for the analysis of mortality inequalities. The paper then analyses the cause-specific trends of mortality for two educational classes between 1971 and 2008. The trends were corrected for changes in the coding system and divided into linear (stagnating, increasing or decreasing) periods. Causes of death were grouped according to the relationship between the sequences of these periods for the two educational classes. The 57 causes of death were finally clustered into six groups. One group, which is dominated by nutrition-related and cardiovascular diseases, is largely responsible for the onset of mortality inequalities in 1980. The results imply that the quality of nutrition has diverged for the educational classes since 1980, and this fact has left its footprint on the pattern of mortality. The history of food production and availability seems to be in line with nutrition-related mortality, and it is argued that nutrition transition theory provides a very plausible explanatory framework for the growth of mortality inequalities.
5,626
Emerging Zoonotic and Vector-Borne Viral Diseases
Many vector-borne and zoonotic diseases are considered to be emerging; since they are either newly reported to cause human disease, or are causing disease in geographical locations or species not previously documented. In the past 15 years, significant outbreaks of Severe Acute Respiratory Syndrome (or SARS) and Middle Eastern Respiratory Syndrome (or MERS), Nipah and Hendra, Ebola virus disease and Zika fever and others have been reported. In this chapter the clinical characteristics, epidemiological aspects, treatment and prevention and information related to the laboratory investigation of important zoonotic and vector-borne diseases that have emerged in the past 10 years, and how this affects children, will be discussed. Furthermore rabies, considered a neglected viral disease with the majority of victims in Africa being children, will also be addressed.
5,627
International Organizations and Their Approaches to Fostering Development
Multilateral agencies define and operationalized health and development in a variety of ways. The World Health Organization (WHO) and the World Bank are two dominant actors in health and development. Each espouses a different ideal of health as it relates to the process of development. The WHO defines health as a human right, and focuses on health outcomes as inputs to and the result of development. The World Bank’s approach to development focuses largely on macro-economic growth as input to human capabilities. The World Bank became a leading actor in international health policy in the 1990s when it operationalized health as an outcome of financial and health care systems. This chapter looks at programming efforts by the WHO and the World Bank to foster development via investment in health or through macro-economic adjustment. Results are mixed. Efforts to improve primary care were successful in improving health outcomes of children under five, but made little impact on maternal mortality. Structural adjustment programs achieved moderate success with medium- to long-term economic growth but increased health inequities. These mixed achievements resulted in an effort by the United Nations to foster a multi-sectoral approach to development espoused in the Millennium Development Goals and Sustainable Development Goals.
5,628
Bioorganometallic Chemistry and Malaria
This chapter summarizes recent developments in the design, synthesis, and structure–activity relationship studies of organometallic antimalarials. It begins with a general introduction to malaria and the biology of the parasite Plasmodium falciparum, with a focus on the heme detoxification system. Then, a number of metal complexes from the literature are reported for their antiplasmodial activity. The second half of the chapter deals with the serendipitous discovery of ferroquine, its mechanism(s) of action, and the failure to induce a resistance. Last, but not least, we suggest that the bioorganometallic approach offers the potential for the design of novel therapeutic agents.
5,629
Article 14 Prevention of Spread of Disease
Each contracting State agrees to take effective measures to prevent the spread by means of air navigation of cholera, typhus (epidemic), smallpox, yellow fever, plague, and such other communicable diseases as the contracting States shall from time to time decide to designate, and to that end contracting States will keep in close consultation with the agencies concerned with international regulations relating to sanitary measures applicable to aircraft. Such consultation shall be without prejudice to the application of any existing international convention on this subject to which the contracting States may be parties.
5,630
Integration of Instance-Based Learning and Text Mining for Identification of Potential Virus/Bacterium as Bio-terrorism Weapons
There are some viruses and bacteria that have been identified as bioterrorism weapons. However, there are a lot other viruses and bacteria that can be potential bioterrorism weapons. A system that can automatically suggest potential bioterrorism weapons will help laypeople to discover these suspicious viruses and bacteria. In this paper we apply instance-based learning & text mining approach to identify candidate viruses and bacteria as potential bio-terrorism weapons from biomedical literature. We first take text mining approach to identify topical terms of existed viruses (bacteria) from PubMed separately. Then, we use the term lists as instances to build matrices with the remaining viruses (bacteria) to discover how much the term lists describe the remaining viruses (bacteria). Next, we build a algorithm to rank all remaining viruses (bacteria). We suspect that the higher the ranking of the virus (bacterium) is, the more suspicious they will be potential bio-terrorism weapon. Our findings are intended as a guide to the virus and bacterium literature to support further studies that might then lead to appropriate defense and public health measures.
5,631
Modeling the Impact of Behavior Changes on the Spread of Pandemic Influenza
We use mathematical models to assess the impact of behavioral changes in response to an emerging epidemic. Evaluating the quantitative and qualitative impact of public health interventions on the spread of infectious diseases is a crucial public health objective. The recent avian influenza (H5N1) outbreaks and the 2009 H1N1 pandemic have raised significant global concerns about the emergence of a deadly influenza virus causing a pandemic of catastrophic proportions. Mitigation strategies based on behavior changes are some of the only options available in the early stages of an emerging epidemic when vaccines are unlikely to be available and there are only limited stockpiles of antiviral medications. Mathematical models that capture these behavior changes can quantify the relative impact of different mitigation strategies, such as closing schools, in slowing the spread of an infectious disease. Including behavior changes in mathematical models increases complexity and is often left out of the analysis. We present a simple differential equation model which allows for people changing their behavior to decrease their probability of infection. We also describe a large-scale agent-based model that can be used to analyze the impact of isolation scenarios such as school closures and fear-based home isolation during a pandemic. The agent-based model captures realistic individual-level mixing patterns and coordinated reactive changes in human behavior in order to better predict the transmission dynamics of an epidemic. Both models confirm that changes in behavior can be effective in reducing the spread of disease. For example, our model predicts that if school closures are implemented for the duration of the pandemic, the clinical attack rate could be reduced by more than 50%. We also verify that when interventions are stopped too soon, a second wave of infection can occur.
5,632
Ear, Nose, and Throat Disorders
This chapter reviews Otolaryngology conditions most commonly seen by pediatricians. Included are issues involving the ears, nose and nasopharynx, sinuses, throat, mouth and oropharynx, and the neck. The most common surgical Otolaryngological procedures will also be discussed. Many of the disease discussed can be effectively identified, diagnosed, and treated by primary care physicians. However, for certain conditions, prompt identification and timely referral to Otolaryngology are required.
5,633
Nanomaterials-Based (Bio)Sensing Systems for Safety and Security Applications
The development of new nanomaterials and nanotechnologies has ­provided many new opportunities for (bio)sensing systems. The introduction of nanomaterials, such as magnetic nanoparticles, gold nanoparticles, graphene, quantum dots, etc. is bringing advantages in terms of improving the selectivity and sensitivity of these systems. These nanomaterials also offer advantages in biosensors owing to their nanometric size, shape, composition, physical properties, ability to manipulate their surface chemistry and the property that they have in terms of adsorbing biological molecules and the change of their physical properties. In recent years, several ­bacterial pathogens, toxins, viruses, parasites and explosives have been considered as potential threats for bioterrorism, among which can find Escherichia coli, Salmonella, Bacillus anthracis, Clostridium botulinum, Botulinum Neurotoxin, Vaccinia, Plasmodium falciparum, Trinitrotoluene, etc. Bioterrorism is extremely complex to tackle but the science and technology are fundamental ­elements to reduce its threat. For this reason, monitoring systems for quick identification of biomolecules are the core of much of the basic research activities in combating bioterrorism. In this chapter we discuss the research efforts by using nanobiotechnologies with the aim of developing accurate, easy, cheap, portable and ultrasensitive assays for agents that pose a biologic threat. Some ­nanomaterial-based (bio)sensing systems used to detect agents related with bioterrorism for safety and security applications in agriculture, food, forensic, biomedical are also given.
5,634
Plant-Based Vaccines as a Global Vaccination Approach: Current Perspectives
This chapter provides a perspective on the evolution of the field of plant-based vaccine from the limitations identified in initial developments as to how this biotechnological approach has become sophisticated via the development of new technologies and has gained industry interest. Perspectives for the field at both the basic research and the industrial level are emphasized. Perspectives considered of relevance in terms of basic research include (1) advancing the development of oral formulations, (2) expanding the modalities of expression of immunogens, (3) diversifying production platforms, particularly those performed under full containment, and (4) targeting a broader number of diseases. These goals are expected to multiply the expectations for benefits derived from plant-based vaccine-production technology. On the other hand, technology transfer and regulatory issues represent a critical hurdle to this technology becoming a reality. It is also critical to achieve social acceptance as well as implement initiatives for the exploitation of the technology for humanitarian purposes and for the benefit of poor countries. This overview predicts considerable potential for plant-based vaccines to positively impact the field of vaccinology in the near future.
5,635
Application of Support Vector Machines in Viral Biology
Novel experimental and sequencing techniques have led to an exponential explosion and spiraling of data in viral genomics. To analyse such data, rapidly gain information, and transform this information to knowledge, interdisciplinary approaches involving several different types of expertise are necessary. Machine learning has been in the forefront of providing models with increasing accuracy due to development of newer paradigms with strong fundamental bases. Support Vector Machines (SVM) is one such robust tool, based rigorously on statistical learning theory. SVM provides very high quality and robust solutions to classification and regression problems. Several studies in virology employ high performance tools including SVM for identification of potentially important gene and protein functions. This is mainly due to the highly beneficial aspects of SVM. In this chapter we briefly provide lucid and easy to understand details of SVM algorithms along with applications in virology.
5,636
An Introduction to Ecoimmunology
Ecoimmunology is the study of the causes and consequences of variation in immunity. This integrative field builds on and complements comparative immunology by evaluating immunity across levels of biological organization using an evolutionary and ecological framework. One major accomplishment of ecoimmunology has been to demonstrate that immune defenses have costs, and these costs can be context-dependent. As a result, researchers assess immunity not only in terms of specific immune pathways but also as functional, emergent traits, such as resistance against and tolerance of parasites. Ecoimmunology also highlights the importance of integration across physiological systems, including the immune, endocrine, and nervous systems, in the production of immune defenses. The field has demonstrated the importance of genetics, developmental environment, and current conditions to individual variation in immune function and emphasized the traits of species, such as body size, that could be integral to immune phenotypes. Furthermore, ecoimmunological studies have shown that heterogeneity in immunity at the individual and species levels can have important consequences for disease dynamics within populations and communities as well as population cycling. Herein we discuss these key research areas in ecoimmunology as they relate to three central themes: (1) immunity in the context of the whole organism, (2) heterogeneity in immunity, and (3) the broad consequences of individual variation in immunity. We conclude by reviewing future directions for ecoimmunology, focusing on those that could have important implications for public health, conservation, and wildlife management.
5,637
Newer Insights into the Biochemical Physiology of the Renin–Angiotensin System: Role of Angiotensin-(1-7), Angiotensin Converting Enzyme 2, and Angiotensin-(1-12)
Knowledge of the mechanisms by which the rennin–angiotensin system contributes to cardiovascular pathology continues to advance at a rapid pace as newer methods and therapies uncover the nature of this complex system and its fundamental role in the regulation of blood pressure and tissue function. The characterization of the biochemical pathways and functions mediated by angiotensin-(1-7) [Ang-(1-7)], angiotensin converting enzyme 2 (ACE2), and the mas receptor has revealed a vasodepressor and antiproliferative axis that within the rennin–angiotensin system opposes the biological actions of angiotensin II (Ang II). In addition, new research expands on this knowledge by demonstrating additional mechanisms for the formation of Ang II and Ang-(1-7) through the existence of an alternate form of the angiotensinogen substrate [angiotensin-(1-12)] which generates Ang II and even Ang-(1-7) through a non-renin dependent action. Altogether, this research paves the way for a better understanding of the intracellular mechanisms involved in the synthesis of angiotensin peptides and its consequences in terms of cell function in both physiology and pathology.
5,638
Preventive, Diagnostic and Therapeutic Applications of Baculovirus Expression Vector System
Different strategies are being worked out for engineering the original baculovirus expression vector (BEV) system to produce cost-effective clinical biologics at commercial scale. To date, thousands of highly variable molecules in the form of heterologous proteins, virus-like particles, surface display proteins/antigen carriers, heterologous viral vectors and gene delivery vehicles have been produced using this system. These products are being used in vaccine production, tissue engineering, stem cell transduction, viral vector production, gene therapy, cancer treatment and development of biosensors. Recombinant proteins that are expressed and post-translationally modified using this system are also suitable for functional, crystallographic studies, microarray and drug discovery-based applications. Till now, four BEV-based commercial products (Cervarix(®), Provenge(®), Glybera(®) and Flublok(®)) have been approved for humans, and myriad of others are in different stages of preclinical or clinical trials. Five products (Porcilis(®) Pesti, BAYOVAC CSF E2(®), Circumvent(®) PCV, Ingelvac CircoFLEX(®) and Porcilis(®) PCV) got approval for veterinary use, and many more are in the pipeline. In the present chapter, we have emphasized on both approved and other baculovirus-based products produced in insect cells or larvae that are important from clinical perspective and are being developed as preventive, diagnostic or therapeutic agents. Further, the potential of recombinant adeno-associated virus (rAAV) as gene delivery vector has been described. This system, due to its relatively extended gene expression, lack of pathogenicity and the ability to transduce a wide variety of cells, gained extensive popularity just after the approval of first AAV-based gene therapy drug alipogene tiparvovec (Glybera(®)). Numerous products based on AAV which are presently in different clinical trials have also been highlighted.
5,639
Cells and Viruses
Cells are the smallest structural component of all known living organisms capable of self-maintenance and reproduction. Although cells vary greatly in their appearance or size, their structure is basically similar. Even the plant and animal cells show a significant degree of similarity in their overall organization. There are two types of cells: eukaryotic and prokaryotic. The main difference between them is the method of genetic material storage: in eukaryotic cells — in an isolated nucleus, in prokaryotic cells — directly in the cytoplasm (there is no nucleus). Prokaryotic cells are usually independent (unicellular), while eukaryotic cells are often found in multicellular organisms.
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Gene therapy for cystic fibrosis lung disease
Cystic fibrosis (CF) is characterised by respiratory and pancreatic deficiencies that stem from the loss of fully functional CFTR (CF transmembrane conductance regulator) at the membrane of epithelial cells. Current treatment modalities aim to delay the deterioration in lung function, Which is mostly responsible for the relatively short life expectancy of CF sufferers; however none have so far successfully dealt with the underlying molecular defect. Novel pharmacological approaches to ameliorate the lack of active CFTR in respiratory epithelial cells are beginning to address more of the pathophysiological defects caused by CFTR mutations. However, CFTR gene replacement by gene therapy remains the most likely option for addressing the basic defects, including ion transport and inflammatory functions of CFTR. In this chapter, We will review the latest preclinical and clinical advances in pharmacotherapy and gene therapy for CF lung disease.
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Trends and National Needs of China’s Public Health
It is widely recognized among governments and public in the world that the public health has a direct influence upon economic development and social progress of countries, and it is an important base for constructing a harmonic society. Rapid development of science and technology has exerted unprecedented influences in the field of the public health, including the life span and the quality of life, the mechanism of the human body and combat against diseases. Current status and characteristic of the public health are described below.
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Incidental Findings in TMJ Imaging
For years, the conventional imaging modalities are generally used in dental practice routine. They provide precious information about dentomaxillofacial region; they also have some limitations such as superimpositions, magnifications, distortions, and low-image quality. Because of these limitations, some pathologies, calcifications, and anatomical variations may be missed. Any findings on a radiographic image which are not related to the research areas of interest could be a description of “incidental findings.” Calcifications are one of these incidental findings. They are asymptomatic and also common in TMJ images. Although most of the calcifications require no treatment, correct identification will reduce further diagnostic assessments. Incidental findings on TMJ images were rare, while examining images for temporomandibular disorders and associated issues, it is important not only to examine the TMJ structures but also to look at the nearby anatomical features to check for evidence of incidental findings pathologies that may have mimicked signs and symptoms of TMJ disorders.
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Avida: A Software Platform for Research in Computational Evolutionary Biology
Avida(1) is a software platform for experiments with self-replicating and evolving computer programs. It provides detailed control over experimental settings and protocols, a large array of measurement tools, and sophisticated methods to analyze and post-process experimental data. This chapter explains the general principles on which Avida is built, its main components and their interactions, and gives an overview of some prior research.
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High-Throughput Carbohydrate Microarray Technology
One of our long-term interests is to explore the immunogenic sugar moieties that are important for “self-” and “nonself” discrimination and host immune responses. We have established a highthroughput platform of carbohydrate microarrays to facilitate these investigations. Using this technology, carbohydrate-containing macromolecules of distinct structural configurations, including polysaccharides, natural glycoconjugates, and mono- and oligosaccharides coupled to lipid, polyacrylamide, and protein carriers, have been tested for microarray construction without further chemical modification. Here, we discuss issues related to the establishment of this technology and areas that are highly promising for its application. We also provide an example to illustrate that the carbohydrate microarray is a discovery tool; it is particularly useful for identifying immunological sugar moieties, including differentially expressed complex carbohydrates of cancer cells and stem cells as well as sugar signatures of previously unrecognized microbial pathogens.
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Gastrointestinal Emergencies
Oropharyngeal: Neurological motility disorder: stroke; movement disorders (Parkinson’s disease, progressive supranuclear palsy); amyotrophic lateral sclerosis; multiple sclerosis; bulbar palsy; brainstem tumour; pseudobulbar palsy. Striated muscle disease: myasthenia gravis; myotonic dystrophy; polymyositis; dermatomyositis; inflammatory myopathy; muscular dystrophy. Reduced salivary flow leading to dry mouth (xerostomia): Sjogren’s syndrome; anticholinergics; antihistamines; ACE inhibitors; alpha-adrenergic blockers. Structural lesions: inflammatory: pharyngitis, tonsillar abscess; head and neck tumours; pharyngeal diverticula; ulcerative stomatitis; painful glossitis; anterior marginal cervical osteophytes (especially with diffuse idiopathic skeletal hyperostosis). Metabolic: hypothyroidism; hyperthyroidism; steroid myopathy.
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Global Variations and Changes in Patterns of Infectious Uveitis
Before 1940, most uveitis cases were supposed to be due to infectious agents, mainly syphilis or tuberculosis [1]. Progress in the understanding of intraocular inflammation led to the discovery that uveitis can be of infectious and noninfectious origin and that many pathogens can cause infectious uveitis. Theoretically, Koch postulates must be fulfilled, in order to formerly demonstrate that a disease is due to an infectious agent. However, in infectious uveitis, most often, serological evidence, molecular or histological demonstration, and treatment response are usually the only available elements to suggest the infectious origin of the uveitis. Using those evidences, a large number of infectious organisms have been demonstrated to cause infectious uveitis. Some have a global importance around the world, while others have more limited niches. Many of them have been considered as emerging pathogens.
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RNA Interference Mechanisms and Therapeutic Applications
RNA interference (RNAi) is a technology developed after the recent discovery of well-conserved cellular processes that induce posttranscriptional gene silencing triggered by small fragments of double-stranded RNA. This technique is rapidly developing into a promising tool used for functional genetics and therapeutic applications. We focus here on the aspects concerning RNAi mechanism, applications in mammals, and construct design and delivery. We summarize some therapeutic applications in general and speculate on the relevance in cardiovascular medicine.
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Infectious Mechanisms Regulating Susceptibility to Acute Exacerbations of COPD
Acute exacerbations of COPD (AECOPD) are defined by clinical criteria, outlined in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines [1]. These include an acute increase in one or more of the following cardinal symptoms, beyond day to day variability: dyspnea, increased frequency or severity of cough and increased volume or change in character of sputum, which represent an acute increase in airway inflammation. The role of infection in the pathogenesis of COPD, acute exacerbation and disease progression has been a clinical and research question for many years, and the pendulum has swung from infection as a major cause of acute exacerbation and COPD (British Hypothesis) [2], to infection as an unrelated epiphomenon in acute exacerbation [3–5], and back again to infection as integral in the development of AECOPD and likely an important contributor to COPD progression [6–19]. Upwards of 80 % of AECOPD are driven by infectious stimuli, with 40–50 % associated with bacterial infection and 30–50 % associated with acute viral infection, with some exacerbations having dual bacterial and viral causation [20]. Much of the advancement in our understanding of the role of infection is AECOPD is due to the advancement of clinical and research tools that have allowed researchers to accurately characterize the microbial pathogens, and better understand the host-pathogen interactions (Table 1).
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What Next?
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Assessing the Threat: Public Health
This chapter describes three methods for assessing the impact of transfusion-transmitted infections on public health. In order of increasing precision and labor intensity, these tools are: 1. A blueprint for a structured, qualitative inventory and report, describing the relevant characteristics of the emerging agent, which helps to make ad hoc decisions and which identifies gaps in our knowledge. 2. Two more sophisticated “off the shelf” methods for the quantitative analysis of threats to blood safety are mentioned: the Biggerstaff-Petersen model and the European Up-Front Risk Assessment Tool (EUFRAT). The Biggerstaff-Petersen model estimates the number of potentially infectious donations, while EUFRAT also takes into account the components prepared from donations and the efficacy of various mitigating interventions. 3. Finally examples of quantitative studies of specific agents are mentioned: a donor-recipient transmission study and a cost-benefit modeling study. For this kind of analysis, no standardized recipe is available.
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Nanomechanical Cantilever Array Sensors
Microfabricated cantilever sensors have attracted much interest in recent years as devices for the fast and reliable detection of small concentrations of molecules in air and solution. In addition to application of such sensors for gas and chemical-vapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. In the past few years, the cantilever-sensor concept has been extended to biochemical applications and as an analytical device for measurements of biomaterials. Because of the label-free detection principle of cantilever sensors, their small size and scalability, this kind of device is advantageous for diagnostic applications and disease monitoring, as well as for genomics or proteomics purposes. The use of microcantilever arrays enables detection of several analytes simultaneously and solves the inherent problem of thermal drift often present when using single microcantilever sensors, as some of the cantilevers can be used as sensor cantilevers for detection, and other cantilevers serve as passivated reference cantilevers that do not exhibit affinity to the molecules to be detected.
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Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications
Chitin is a linear polysaccharide of N-acetylglucosamine, which is highly abundant in nature and mainly produced by marine crustaceans. Chitosan is obtained by hydrolytic deacetylation. Both polysaccharides are renewable resources, simply and cost-effectively extracted from waste material of fish industry, mainly crab and shrimp shells. Research over the past five decades has revealed that chitosan, in particular, possesses unique and useful characteristics such as chemical versatility, polyelectrolyte properties, gel- and film-forming ability, high adsorption capacity, antimicrobial and antioxidative properties, low toxicity, and biocompatibility and biodegradability features. A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. The number of studies in this research field has exploded particularly during the last two decades. Here, we review recent advances in utilizing chitosan and chitosan derivatives in different technical, agricultural, and biomedical fields.
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Viral pathogens and epidemiology, detection, therapy and resistance
Worldwide community-acquired pneumonia (CAP) is one of the most frequent infectious diseases and a leading cause of death. Several studies have shown that a pathogen could be identified only in 50 to 60% of all patients, although in children < 6 month infectious agents can be detected in about 90%. Viral infections are most frequent in children < 2 years (80%), whereas bacterial infections increase with age. RSV, influenzaviruses, rhinoviruses, parainfluenzaviruses and adenoviruses are the most common viruses associated with CAP in children. Among adenoviruses a predominance of adenovirus 7 has been reported in several countries with emergence of highly pathogenic variants with significant lethality in young children. Many childhood respiratory infections are caused by more than one pathogen and up to 30% mixed viral / bacterial infections can be observed. CAP in immunocompetent adults is rare, whereas persons with underlaying diseases have an increased incidence of CAP. In the elderly, RSV, influenzaviruses, parainfluenzaviruses and less frequent adenoviruses are predominant viruses causing pneumonia. Less frequently associated with CAP are the newly discovered human metapneumovirus and the coronaviruses NL63 and HKU1. Hantaviruses, involved in the hantavirus pulmonary syndrome, belong to the emerging pathogens to date in North, Middle and South America. For optimum diagnosis the whole spectrum of potential respiratory viral agents should be included and multiple diagnostic techniques have to be used. In view of the high relevance of influenzavirus for CAP influenza vaccination is highly advisable for prevention of CAP, especially in high-risk groups.
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Common Viral Pneumonia
Common respiratory viruses are now recognised as true opportunistic respiratory pathogens in patients with haematological malignancies. The epidemiology of these viruses has not been extensively studied in immunocompromised hosts, but is probably closely related to viral activity in immunocompetent hosts, who constitute the virus reservoir for immunocompromised patients. In these patients, common respiratory viruses may cause severe infections with higher rates of progression to pneumonia and mortality compared to immunocompetent individuals. Prolonged high-titre viral shedding is common in patients with haematological malignancies and may enhance not only viral transmission, but also the selection of resistant strains. Influenza and respiratory syncytial virus (RSV) infections have been particularly well studied. They are associated with pneumonia rates of about one-third for influenza and 30–40% for RSV. Both viruses are responsible for mortality rates ranging from 15% to 30%. The exact mechanisms of pneumonia related to these viruses remains unknown, but bacterial and fungal co-infections are frequent and must be carefully investigated. Parainfluenza viruses (PIV) and RSV have also been linked to late airflow obstruction in haematopoietic stem cell transplant recipients. Neuraminidase inhibitor therapy has been suggested for influenza, ribavirin for RSV, and cidofovir for adenovirus infections. However, there is no evidence supporting the use of these drugs, and randomised controlled trials are urgently needed to better define the optimal management of common viral pneumonia in patients with haematological malignancies. The absence of proven effective treatments highlights the critical importance of prevention. Viral transmission may be interrupted by contact isolation with droplet precautions for infected patients and by having patients and health care workers with suspected infection, and their relatives, refrain from visits and work. Immunisation remains the cornerstone of influenza prevention and is recommended for patients with haematological malignancies, their relatives, and health care workers.
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Implications of Results
While the pursued customer network-centric valuation approach contains a variety of implications, this chapter summarizes the most relevant issues with respect to the outlined target group. First, findings relevant to managers of companies operating in software markets are presented, before implications for financial sponsors are depicted. Then, the consequences for various streams of research conclude this chapter. In this first section the most relevant implications for managers are investigated. All in all, managers should note that the outlined approach supports decision making in software markets based on a better understanding of customer networks, their topologies and their dynamics. This has implications on various aspects of management, such as strategic management, marketing and turnaround management. It is important to note that the following categories are not mutually exclusive and collectively exhaustive as some of the following implications are relevant to more than one cluster.
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Global Health Security Innovation
Heyman et al. (Global health security: the wider lessons from the west African Ebola virus disease epidemic, vol 385. May 9, 2015 www.thelancet.com, 2015:1888) argues that, “the world is ill-prepared” to handle any “sustained and threatening public-health emergency”. Disease outbreaks such as Ebola SARS, and H1N1 challenged national and global response mechanisms. The emergence of these disease outbreaks and their influence globally has sparked a renewed attention to global health security. In the Chatham House report ‘Preparing for High Impact, Low Probability Events’, Lee et al. (Preparing for high-impact, low-probability events: lessons from Eyjafjallajökull. Chatham House Report, January 2012:vii) ‘…found that governments and businesses remain unprepared for such events … the frequency of ‘high-impact, low-probability’ (HILP) events in the last decade signals the emergence of a new ‘normal’. This calls for innovation on an unprecedented level to manage such global health threats as they represent a global health security challenge. This chapter explores the foundations of the innovation space as it applies to global health security. The wicked nature of global health security points to how innovation and complexity framing go hand in hand in dealing with such global issues.
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Molecular Diagnostics
Effective and early management of diseases requires record of the history, behavioral parameters, and travel information. These are helpful for the diagnosis, prevention, and control of the disease. There have been several advancements in the methods for diagnosing infectious diseases. The wide spectrum of tests such as biochemical evaluation, microbiological tools, immunological and molecular biology techniques, etc., is available. Each type of diagnostic technique is strong and reliable in its own sense but poses certain limitations. These limitations may be complemented by using a combination of tests. Older techniques such as microscopy and culturing of organisms from clinical specimens are error-free but are very labor intensive and extremely time consuming. There is a need to develop rapid and sensitive tests that can be used in both high- and low-resource settings. Molecular diagnostics such as Western blot, ELISA, PCR, DNA, and protein microarrays are revolutionizing the clinical practice of infectious diseases. Their effects are significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes.
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Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders
Neuropsychiatric disorders and dementia represent a major cause of disability and high cost in developed societies. Most disorders of the central nervous system (CNS) share some common features, such as a genomic background in which hundreds of genes might be involved, genome-environment interactions, complex pathogenic pathways, poor therapeutic outcomes, and chronic disability. Recent advances in genomic medicine can contribute to accelerate our understanding on the pathogenesis of CNS disorders, improve diagnostic accuracy with the introduction of novel biomarkers, and personalize therapeutics with the incorporation of pharmacogenetic and pharmacogenomic procedures to drug development and clinical practice. The pharmacological treatment of CNS disorders, in general, accounts for 10–20% of direct costs, and less than 30–40% of the patients are moderate responders to conventional drugs, some of which may cause important adverse drugs reactions (ADRs). Pharmacogenetic and pharmacogenomic factors may account for 60–90% of drug variability in drug disposition and pharmacodynamics. Approximately 60–80% of CNS drugs are metabolized via enzymes of the CYP gene superfamily; 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10–20% of Caucasians are carriers of defective CYP2D6 polymorphic variants that alter the metabolism of many psychotropic agents. Other 100 genes participate in the efficacy and safety of psychotropic drugs. The incorporation of pharmacogenetic/ pharmacogenomic protocols to CNS research and clinical practice can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improving drug efficacy and safety. To achieve this goal several measures have to be taken, including: (a) educate physicians and the public on the use of genetic/ genomic screening in the daily clinical practice; (b) standardize genetic testing for major categories of drugs; (c) validate pharmacogenetic and pharmacogenomic procedures according to drug category and pathology; (d) regulate ethical, social, and economic issues; and (e) incorporate pharmacogenetic and pharmacogenomic procedures to both drugs in development and drugs in the market to optimize therapeutics.
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The Role of DUOX Isozymes in the Respiratory Tract Epithelium
Increasingly, reactive oxygen species such as superoxide and hydrogen peroxide are recognized to be intentionally generated intracellularly to serve important cellular functions. A key protein family responsible for the regulated generation of reactive oxygen species in multiple cell types is the NOX/DUOX enzyme family. Two family members, DUOX1 and DUOX2, appear to be highly expressed in tissues of endodermal origin including the thyroid, respiratory tract, and gastrointestinal tract. In this chapter, we will focus our review on DUOX proteins in the respiratory tract. We will discuss a brief history of the discovery of the DUOX isoforms, the estimated hydrogen peroxide-generating capacity of DUOX in respiratory tract epithelium, putative functions of the DUOX enzymes, and some regulatory factors responsible for DUOX gene expression and oxidase activity.
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Viral Diagnostics
This chapter discusses recent developments in diagnostics for cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), community respiratory viruses (CRVs), parvovirus, hepatitis viruses, HIV, and other viral agents of importance in solid organ and hematopoietic stem cell transplantation.
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Advances in Transfusion Safety
Although transfusion is now extremely safe, the tools of molecular biology are continually being harnessed to improve diagnosis and therapy. Viral genome testing has been introduced in the developed world for HIV and HCV, to detect donors in the infectious “window period” before sero-conversion. Pathogen inactivated fresh frozen plasma and platelets are already available, but alloimmunization has halted trials of pathogen-inactivated red cells. Development of synthetic oxygen carriers has included perflurocarbons, and crosslinked, polymerized or mutated human or bovine hemoglobin, either free or encapsulated. No perfect replacement for the human red cell is yet on the horizon.
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Soft Computing Based Epidemical Crisis Prediction
Epidemical crisis prediction is one of the most challenging examples of decision making with uncertain information. As in many other types of crises, epidemic outbreaks may pose various degrees of surprise as well as various degrees of “derivatives” of the surprise (i.e., the speed and acceleration of the surprise). Often, crises such as epidemic outbreaks are accompanied by a secondary set of crises, which might pose a more challenging prediction problem. One of the unique features of epidemic crises is the amount of fuzzy data related to the outbreak that spreads through numerous communication channels, including media and social networks. Hence, the key for improving epidemic crises prediction capabilities is in employing sound techniques for data collection, information processing, and decision making under uncertainty and exploiting the modalities and media of the spread of the fuzzy information related to the outbreak. Fuzzy logic-based techniques are some of the most promising approaches for crisis management. Furthermore, complex fuzzy graphs can be used to formalize the techniques and methods used for the data mining. Another advantage of the fuzzy-based approach is that it enables keeping account of events with perceived low possibility of occurrence via low fuzzy membership/truth-values and updating these values as information is accumulated or changed. In this chapter we introduce several soft computing based methods and tools for epidemic crises prediction. In addition to classical fuzzy techniques, the use of complex fuzzy graphs as well as incremental fuzzy clustering in the context of complex and high order fuzzy logic system is presented.
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New concepts in anti-HIV therapies
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Reticulate Evolution Everywhere
Reticulation is a recurring evolutionary pattern found in phylogenetic reconstructions of life. The pattern results from how species interact and evolve by mechanisms and processes including symbiosis; symbiogenesis; lateral gene transfer (that occurs via bacterial conjugation, transformation, transduction, Gene Transfer Agents, or the movements of transposons, retrotransposons, and other mobile genetic elements); hybridization or divergence with gene flow; and infectious heredity (induced either directly by bacteria, bacteriophages, viruses, prions, protozoa and fungi, or via vectors that transmit these pathogens). Research on reticulate evolution today takes on inter- and transdisciplinary proportions and is able to unite distinct research fields ranging from microbiology and molecular genetics to evolutionary biology and the biomedical sciences. This chapter summarizes the main principles of the diverse reticulate evolutionary mechanisms and situates them into the chapters that make up this volume.
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Anti-Histidine Antibodies as Tools for Reversible Capturing of His-Tagged Fusion Proteins for Subsequent Binding Analysis
The hexahistidine tag is one of most commonly used fusion tags in affinity purification of recombinantly expressed proteins. Real-time binding analysis using Biacore technology allows in-depth characterization of respective association and dissociation patterns of potential binders. Here we tested four commercially available anti-His antibodies for reversible capturing of His-tagged proteins as a basis for a subsequent interaction analysis with non-His-tagged proteins. Anti-penta-, anti-hexa- and anti-RGS-(His)4 antibodies from different distributors were covalently coupled to Biacore sensor chips. Parallel binding studies of 12 heterogeneously sized RGS-(His)6-tagged (Arg-Gly-Ser-(His)6) proteins revealed that the slowest dissociation rate was obtained when using an anti-RGS-(His)4 antibody. Thus in a sandwich binding assay the anti-RGS-(His)4 antibody can be utilized as an appropriate tool for stable yet reversible capturing of RGS-(His)6-tagged proteins with a non-His-tagged protein.
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Human Security in East Asia: Beyond Crises
In this globalized world, we face multiple threats to human security, a powerful supplement to national security. The introduction to this book provides both a history and a definition of human security. Enhanced connectivity in East Asia not only gives rise to serious threats but also provides the means for ensuring people’s security and opportunities for mutual learning. After explaining the three research questions that are aimed at evaluating the practice of human security—sovereignty, coordination and empowerment—the introductory chapter goes on to provide summaries of the following chapters.
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Influenza-Associated Pediatric Mortality and the Application of Multiplex Testing to Detect Respiratory Virus Coinfection—Wisconsin, October 4, 2014–February 7, 2015
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Comparative Evaluation of Diatherix Target Enriched Multiplex Polymerase Chain Reaction and BioFire FilmArray in the Detection of Viral and Bacterial Respiratory Pathogens
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Crystal Structure of Human Coronavirus NL63 Main Protease in Complex With an Inhibitor
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Modelling of potentially promising SARS protease inhibitors
In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.
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Beyond SumBasic: Task-focused summarization with sentence simplification and lexical expansion
In recent years, there has been increased interest in topic-focused multi-document summarization. In this task, automatic summaries are produced in response to a specific information request, or topic, stated by the user. The system we have designed to accomplish this task comprises four main components: a generic extractive summarization system, a topic-focusing component, sentence simplification, and lexical expansion of topic words. This paper details each of these components, together with experiments designed to quantify their individual contributions. We include an analysis of our results on two large datasets commonly used to evaluate task-focused summarization, the DUC2005 and DUC2006 datasets, using automatic metrics. Additionally, we include an analysis of our results on the DUC2006 task according to human evaluation metrics. In the human evaluation of system summaries compared to human summaries, i.e., the Pyramid method, our system ranked first out of 22 systems in terms of overall mean Pyramid score; and in the human evaluation of summary responsiveness to the topic, our system ranked third out of 35 systems.
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Papel de los receptores toll-like en las enfermedades respiratorias
There has been growing interest in the last 10 years in the study of innate immunity, in particular because of the possible role that toll-like receptors (TLR) may play in the pathogenesis of some respiratory disease such as for example, asthma, chronic obstructive pulmonary disease, and infections. TLR are a family of type 1 transmembrane proteins, responsible for recognizing molecular patterns associated with pathogens (PAMP, pathogen-associated molecular patterns), and expressed by a broad spectrum of infectious agents. This recognition leads to quick production of cytokines and chemokines which provides a long-lasting adaptive response to the pathogen. Currently, it is considered that the administration of drugs which modulate the activity of these receptors upwards or downwards may represent major therapeutic progress for handling these diseases. The aim of this review is to describe the different TLS, define their possible role in the pathogenesis of the main respiratory diseases and finally, speculate over the therapeutic possibilities which their modulation, agonist or antagonist, offers as possible therapeutic targets.
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Agudización de la EPOC
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Wichtige Zoonosen: Neuartige Coronaviren
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Neuartiges Coronavirus (SARS-CoV-2)
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Neuartiges Coronavirus (SARS-CoV-2)
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Clinical and Molecular Epidemiology of Respiratory Viruses in a Tertiary Care Center During the 2009–2014 Consecutive Winter Seasons
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Screening for Respiratory Viruses in Healthcare Workers During the Influenza Season
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Etiology Unknown: Are Less Recognized Respiratory Pathogens Associated With a Milder Course of Illness?
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Epidemiology of Respiratory Viral Infections in Pediatric Solid Organ Transplant or Hematopoietic Stem Cell Transplant Recipients
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Patterns of Viral and Bacterial Co-detection Among Otherwise Healthy Adults With Influenza-Like Illness: Utilization of a Multiplex Respiratory Pathogen Panel
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Impact of Enterovirus D68 in Children With Asthma and Other Complex Medical Conditions
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Cross-protection studies between feline infectious peritonitis and porcine transmissible gastroenteritis viruses
Cross-protection studies between the feline infectious peritonitis (FIP) and the porcine transmissible gastroenteritis (TGE) viruses were conducted in cats, pigs and pregnant gilts. Cats vaccinated with TGE virus developed neutralizing antibodies against TGE virus and low titer antibody against FIP virus detected by an indirect fluorescent antibody technique but were not protected against a virulent FIP virus challenge. Baby pigs and pregnant gilts vaccinated with FIP virus did not develop detectable antibodies to TGE virus. Nevertheless, it appeared that vaccination of swine with FIP virus conferred some immunity against TGE virus infection. Seventeen-day-old pigs vaccinated with two doses of FIP virus had a 67% survival rate following a virulent TGE virus challenge, and 75% of the 3-day-old pigs suckling either FIP or TGE-virus-vaccinated gilts survived virulent TGE virus infection in contrast to 0% survival of baby pigs suckling unvaccinated gilts.
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Contents of veterinary microbiology, volume 28
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Clinical Differences Between Respiratory Viral and Bacterial Mono- and Dual-Pathogens Detected Among Singapore Military Servicemen With Febrile Respiratory Illness
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Early Detection and Timely Reporting of Non-Mumps Etiologies of Parotitis: An Example in Developing Clinical and Public Health Partnerships
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In Vivo and In Vitro Characterization of Provodine, a Long Acting, Alcohol-Free Professional Antiseptic, Against Ebola Virus and Other Serious Viral, Bacterial and Fungal Pathogens
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Effects of ambient temperatures on clinical and immune responses of pigs infected with transmissible gastro-enteritis virus
Two- to three-months-old pigs infected with transmissible gastroenteritis (TGE) virus showed no clinical response when housed at 30°C, but comparable infected pigs exposed to temperature changes from 30°C to 4°C following infection showed typical signs of TGE. Development of TGE-specific immune responses, as measured by blastogenic response of tissue lymphocytes, occurred at 3 days post-inoculation (DPI) in pigs held at 30°C, but not until 7 DPI in infected pigs held under the adverse conditions. Immunosuppression with corticosteroids resulted in a fall in circulatory T cells, lowering of non-specific blastogenic response of circulatory lymphocytes, and clinical signs of disease when immunosuppressed pigs were infected with TGE virus and held at 30°C. It is suggested that clinical responses to TGE virus infection may be affected by the influence of ambient temperatures on the immune responses of pigs.
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Subject Index, Volumes 98-104
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Keyword index — volumes 43–47 (1995)
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Contents of veterinary microbiology, volume 31
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Author index, volumes 48–53
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Veterinary Immunology: Bruce N. Wilkie and Patricia E. Shewen (Editors) Elsevier Science Publishers, Amsterdam, 1988. 518 pp., price US$ 126.25/ Dfl. 240.00, ISBN 0-444-42917-4.
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Contents of veterinary microbiology, volume 21
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New aspects of positive-strand RNA viruses: Edited by M.A. Brinton and F.X. Heinz (1990). American Society for Microbiology, Washington, D.C. 405 pp, US$75, ISBN 1-5581-022-S.
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Proceedings of minisymposium on neonatal diarrhea in calves and pigs: Saskatoon, Sask., 3–4 May 1976. Veterinary Infectious Diseae Organization (VIDO), University of Saskatchewan, Saskatoon, University Publications Office, 1976, 155pp., $5.00, ISBN 0-88880-004-5
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Author index : Veterinary Microbiology, volumes 26–50, 1991–1996
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Contents of Veterinary Microbiology, Volume 115
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Detection of rotavirus infection by immunodiffusion
Three precipitin reactions associated with bovine rotavirus infection were demonstrable by immunodiffusion. One of the reactions has been utilized in a diagnostic test for the detection of rotavirus in faeces, or specific antibody to rotavirus group antigen in serum or faeces. The test, based on bovine materials, appeared to be group-specific and effective in demonstrating rotaviral antigen or antibody in other species of animals, including human beings. The procedure was as efficient as electron microscopy in detecting evidence of rotavirus in faeces of calves and a range of other species.