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4,900 | Cell surface effects of human immunodeficiency virus | Cell killing by human immunodeficiency virus (HIV) is thought to contribute to many of the defects of the acquired immunodeficiency syndrome (AIDS). Two types of cytopathology are observed in HIV-infected cultured cells: cell-cell fusion and killing of single cells. Both killing processes appear to involve cell surface effects of HIV. A model is proposed for the HIV-mediated cell surface processes which could result in cell-cell fusion and single cell killing. The purpose of this model is to define the potential roles of individual viral envelope and cell surface molecules in cell killing processes and to identify alternative routes to the establishment of persistently-infected cells. Elucidation of HIV-induced cell surface effects may provide the basis for a rational approach to the design of antiviral agents which are selective for HIV-infected cells. |
4,901 | Time evolution of non-lethal infectious diseases: a semi-continuous approach | A model describing the dynamics related to the spreading of non-lethal infectious diseases in a fixed-size population is proposed. The model consists of a non-linear delay-differential equation describing the time evolution of the increment in the number of infectious individuals and depends upon a limited number of parameters. Predictions are in good qualitative agreement with data on influenza, which is taken to be a representative type of non-lethal infectious disease. |
4,902 | Large Context Problems and Their Applications to Education: Some Contemporary Examples | Some 35 years ago, Gerard K. O’Neill used the large context of space travel with his undergraduate physics students. A Canadian physics teacher, Art Stinner, independently arrived at a similar notion in a more limited but, therefore, more generally useful sense, which he referred to as the “large context problem” approach. At a slightly earlier time the large context problem type of approach had already been used in the study of medicine, pioneered by McMaster Medical School. And the Faculty of Education at the University of Calgary currently uses a large context problem method to deliver its entire curriculum. These approaches are four distinct ways of presenting large context problems to students. This paper will discuss these approaches historically, look at their grounds and their applications, weigh their successes and characterize their limitations. It will try to see what they take most deeply for granted as viable approaches to teaching science, both theoretical and applied. Finally, it will relate these approaches to the constructivist prejudices of our own time, suggesting their relation to earlier forms of philosophical idealism. |
4,903 | Tracing “Fearbola”: Psychological Predictors of Anxious Responding to the Threat of Ebola | Serious illnesses such as Ebola are often highly publicized in the mass media and can be associated with varying levels of anxiety and compensatory safety behavior (e.g., avoidance of air travel). The present study investigated psychological processes associated with Ebola-related anxiety and safety behaviors during the outbreak in late 2014. Between October 30 and December 3, 2014, which encompassed the peak of concerns and of the media’s attention to this particular outbreak, 107 university students completed a battery of measures assessing fear of Ebola, performance of safety behaviors, factual knowledge of the virus, and psychological variables hypothesized to predict Ebola-related fear. We found that while our sample was generally not very fearful of contracting Ebola, the fear of this disease was correlated with general distress, contamination cognitions, disgust sensitivity, body vigilance, and anxiety sensitivity-related physical concerns. Regression analyses further indicated that anxiety sensitivity related to physical concerns and the tendency to overestimate the severity of contamination were unique predictors of both Ebola fear and associated safety behaviors. Implications for how concerns over serious illness outbreaks can be conceptualized and clinically managed are discussed. |
4,904 | Comparison of six methods for detecting human rotavirus in stools | The following six methods for detecting rotavirus in human faecal samples were compared: electron microscopy, immune electron microscopy, immunofluorescence in cell culture, two enzyme immunoassays (Rotazyme, Enzygnost) and a latex agglutination test (Rotalex). Specimens were collected from 112 children with diarrhoea. The relative sensitivities of the different assays for human rotavirus were as follows: electron microscopy, 84%; immunofluorescence, 86%; Rotalex, 88%; Rotazyme, 89%; immune electron microscopy, 93%; Enzygnost, 98%. According to our findings Enzygnost is the most sensitive method, but Rotalex is more valuable for screening a small number of faecal samples. No false-positive results were observed in the two enzyme immunoassays or in Rotalex. |
4,905 | Isolation and study of the properties of an interferon-like inhibitor of viruses from normal human blood serum | A protein with a molecular weight of 17,400 daltons and an isoelectric point at pH 4.9 has been isolated from the blood serum of healthy donors by successive ion-exchange chromatography of QAE-Sephadex A-50, affinity chromatography on DNA-cellulose, and polyacrylamide gel electrophoresis, in the presence of sodium dodecyl sulfate. The protein isolated, like interferon, suppresses the development of the cytopathogenic action of the viruses of vesicular stomatitis and murine ecephalomyocarditis in cultures of human cells of the L-41 and M-19 lines. The amino acid composition of the protein isolated differs from those of various fractions of human interferons. |
4,906 | Privileged heterocycles: bioactivity and synthesis of 1,9-diazaspiro[5.5]undecane-containing compounds | This review discusses the biological activity and synthesis of 1,9-diazaspiro[5.5]undecanes, including those ring-fused with arenes and heteroarenes and/or containing a carbonyl group at position 2. These compounds could be used for the treatment of obesity, pain, as well as various immune system, cell signaling, cardiovascular, and psychotic disorders. |
4,907 | Estimating residue evolutionary conservation by introducing von Neumann entropy and a novel gap-treating approach | Evolutionary conservation derived from a multiple sequence alignment is a powerful indicator of the functional significance of a residue, and it can help to predict active sites, ligand-binding sites, and protein interaction interfaces. The results of the existing algorithms in identifying the residue’s conservation strongly depend on the sequence alignment, making the results highly variable. Here, by introducing the amino acid similarity matrix, we propose a novel gap-treating approach by combining the evolutionary information and von Neumann entropies to compute the residue conservation scores. It is indicated through a series of tested results that the new approach is quite encouraging and promising and may become a useful tool in complementing the existing methods. |
4,908 | Potential Inoculum Sources of Phaeomoniellachlamydospora in South African Grapevine Nurseries | Petri disease of grapevine is primarily caused by Phaeomoniella chlamydospora. This pathogen affects mostly young grapevines, but is also implicated in esca disease of older grapevines. Little is known about the disease cycle of this fungus. Infected propagation material was identified as a major means of dissemination of the pathogen. Recently, the pathogen was also detected from soil in South Africa and airborne conidia have been found in vineyards. The aim of this study was to use a molecular detection technique to test different samples collected from nurseries in South Africa at different nursery stages for the presence of P. chlamydospora. A one-tube nested-PCR technique was optimised for detecting P. chlamydospora in DNA extracted from soil, water, callusing medium and grapevine wood. The one-tube nested-PCR was sensitive enough to detect as little as 1 fg of P. chlamydospora genomic DNA from water and 10 fg from wood, callusing medium and soil. PCR analyses of the different nursery samples revealed the presence of several putative 360 bp P. chlamydospora specific bands. Subsequent sequence analyses and/or restriction enzyme digestions of all 360 bp PCR bands confirmed that all bands were P. chlamydospora specific, except for five bands obtained from callusing media and one from water. Phaeomoniella chlamydospora was positively detected in 25% of rootstock cane sections collected from mother blocks, 42% of rootstock cuttings and 16% of scion cuttings collected during grafting, 40% of water samples collected after pre-storage hydration, 67% of water samples collected during grafting, 8% of callusing medium samples and 17% of soil samples collected from mother blocks. These media can therefore be considered as possible inoculum sources of the pathogen during the nursery stages. |
4,909 | The long arm of climate change: societal teleconnections and the future of climate change impacts studies | “Societal teleconnections” – analogous to physical teleconnections such as El Niño – are human-created linkages that link activities, trends, and disruptions across large distances, such that locations spatially separated from the locus of an event can experience a variety of impacts from it nevertheless. In the climate change context, such societal teleconnections add a layer of risk that is currently neither fully appreciated in most impacts or vulnerability assessments nor in on-the-ground adaptation planning. Conceptually, societal teleconnections arise from the interactions among actors, and the institutions that guide their actions, affecting the movement of various substances through different structures and processes. Empirically, they arise out of societal interactions, including globalization, to create, amplify, and sometimes attenuate climate change vulnerabilities and impacts in regions far from those where a climatic extreme or change occurs. This paper introduces a simple but systematic way to conceptualize societal teleconnections and then highlights and explores eight unique but interrelated types of societal teleconnections with selected examples: (1) trade and economic exchange, (2) insurance and reinsurance, (3) energy systems, (4) food systems; (5) human health, (6) population migration, (7) communication, and (8) strategic alliances and military interactions. The paper encourages further research to better understand the causal chains behind socially teleconnected impacts, and to identify ways to routinely integrate their consideration in impacts/vulnerability assessment and adaptation planning to limit the risk of costly impacts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10584-015-1328-z) contains supplementary material, which is available to authorized users. |
4,910 | Lack of evidence of paratuberculosis in wild canids from Southwestern Europe | Wild carnivores are at the top of the trophic chain. They are predators and carrion consumers, and thus, prone to come in contact with disease agents contaminating the environment or infecting live or dead animals. We hypothesized that wild canids could be used as sentinels for the detection of regions with higher Mycobacterium avium paratuberculosis (MAP) prevalence in wild and domestic animals. To test this hypothesis, we set up an ELISA to test 262 wolf (Canis lupus) and fox (Vulpes vulpes) sera for MAP-specific antibodies and processed a subset of samples for culture (n = 61), MAP-specific PCR (15) and histopathology (14). In wolves, the optical density (OD) values in the ELISA were continuously distributed. Ten fox sera (4%) had OD readings of over twice the mean, suggesting contact with mycobacteria. However, all samples tested by PCR were negative for both IS900 and ISMAP02 sequences, and samples cultured for MAP yielded no growth. No visible paratuberculosis or tuberculosis-compatible lesions were recorded. On histopathological examination, no lesions compatible with mycobacterial diseases were observed. These results suggest that wild canids show little or no evidence of paratuberculosis and are unlikely to be useful sentinels for the detection of MAP in Southwestern Europe. |
4,911 | Clinical aspects of virus/immune myocarditis | Although a cause-and-effect relationship between viral infection and myocarditis remains inferential, two distinct clinical syndromes can be identified. During the early viral phase, the cardiac manifestations emerge while the symptoms of active viral infection are also present. During the chronic phase, symptoms of the viral infection may be remote or nonexistent, and identification of active myocarditis is contingent upon an aggressive diagnostic approach with endomyocardial biopsy and gallium 67 imaging. The exact incidence of myocarditis in patients with heart failure of unknown cause is unclear due to lack of standardization of histologic parameters. There are no other clinical clues to the presence of myocarditis in those patients presenting with cardiomyopathy or ventricular arrhythmia. For further clarification of the incidence and various presentations of myocarditis a large multi-center trial is necessary. |
4,912 | Prediction of mutations engineered by randomness in H5N1 neuraminidases from influenza A virus | In this proof-of-concept study, we attempt to determine whether the cause-mutation relationship defined by randomness is protein dependent by predicting mutations in H5N1 neuraminidases from influenza A virus, because we have recently conducted several concept-initiated studies on the prediction of mutations in hemagglutinins from influenza A virus. In our concept-initiated studies, we defined the randomness as a cause for mutation, upon which we built a cause-mutation relationship, which is then switched into the classification problem because the occurrence and non-occurrence of mutations can be classified as unity and zero. Thereafter, we used the logistic regression and neural network to solve this classification problem to predict the mutation positions in hemagglutinins, and then used the amino acid mutating probability to predict the would-be-mutated amino acids. As the previous results were promising, we extend this approach to other proteins, such as H5N1 neuraminidase in this study, and further address various issues raised during the development of this approach. The result of this study confirms that we can use this cause-mutation relationship to predict the mutations in H5N1 neuraminidases. |
4,913 | Gender influence on health and risk behavior in primary prevention: a systematic review | AIM: Prevention plays a crucial part in healthcare systems and is greatly influenced by the health and risk behavior of the population. The extent to which special tailoring to the addressed subjects would be helpful in improving the effectiveness of prevention measures is unknown. Therefore, the goal of this systematic review is to assess gender-specific differences in primary prevention actions. SUBJECT AND METHODS: A systematic review was conducted in 2015 by searching the PubMed (Medline) and Cochrane Library databases as well as adding additional studies by cross-referencing. The search focused on studies with an analysis of gender differences in health and risk behavior concerning primary prevention. Therefore, major exclusion criteria were single-gender studies, underage (<18 years) study collectives and secondary or tertiary prevention measures. RESULTS: In total, 23 studies from 13 different countries were included in the qualitative evaluation. The studies covered 11 different subtopics of primary prevention, but were too diverse in content and type to draw many fundamental conclusions. A meta-analysis was not possible. Generally a tendency for females to be more health-conscious and engaged in preventive behavior could be seen in most subgroups. CONCLUSION: The importance of gender-specific prevention measures for the healthcare system is being increasingly stressed, but only a few studies specifically analyzing the influence of gender on preventive behavior could be identified. To implement appropriate primary prevention measures tailored to gender-specific needs, more details and studies on gender differences are needed. |
4,914 | In vitro plant tissue culture: means for production of biological active compounds | Plant tissue culture as an important tool for the continuous production of active compounds including secondary metabolites and engineered molecules. Novel methods (gene editing, abiotic stress) can improve the technique. Humans have a long history of reliance on plants for a supply of food, shelter and, most importantly, medicine. Current-day pharmaceuticals are typically based on plant-derived metabolites, with new products being discovered constantly. Nevertheless, the consistent and uniform supply of plant pharmaceuticals has often been compromised. One alternative for the production of important plant active compounds is in vitro plant tissue culture, as it assures independence from geographical conditions by eliminating the need to rely on wild plants. Plant transformation also allows the further use of plants for the production of engineered compounds, such as vaccines and multiple pharmaceuticals. This review summarizes the important bioactive compounds currently produced by plant tissue culture and the fundamental methods and plants employed for their production. |
4,915 | Neurovirulence of herpes simplex virus types 1 and 2 isolates in diseases of the central nervous system | Herpes simplex virus (HSV) isolates derived from the central nervous system of ten patients with HSV-1-induced encephalitis, one patient with multiple sclerosis, and 14 patients with HSV-2-induced meningitis were investigated for neurovirulence by assaying the LD(50) after nose and intracerebral (i.c.) inoculation of mice. HSV-1 encephalitis strains were significantly more virulent after nose inoculation (i.e. neuroinvasive) when compared with HSV-1 isolates from patients with oral lesions only, whereas HSV-2 meningitis strains were significantly more virulent after i.c. inoculation when compared with HSV-2 isolates from patients with genital lesions only. No correlation between high neurovirulence (defined as low LD(50) for both routes of infection) and replication in cell cultures of neuronal and non-neuronal cell lines was found, but the weakly neurovirulent HSV-1 strain isolated from a patient with multiple sclerosis gave low replication yields. After nose inoculation, a highly neuroinvasive HSV-1 laboratory reference strain replicated to high titers in nose tissue, the trigeminal ganglia and brainstem, while a strain with low neuroinvasiveness but high i.c. virulence replicated less well in the brainstem. Neuroinvasiveness of the virus strain might be one factor of relevance in the pathogenesis of HSV-1 encephalitis in man. |
4,916 | Unraveling the role of membrane microdomains during microbial infections | Infectious diseases pose major socioeconomic and health-related threats to millions of people across the globe. Strategies to combat infectious diseases derive from our understanding of the complex interactions between the host and specific bacterial, viral, and fungal pathogens. Lipid rafts are membrane microdomains that play important role in life cycle of microbes. Interaction of microbial pathogens with host membrane rafts influences not only their initial colonization but also their spread and the induction of inflammation. Therefore, intervention strategies aimed at modulating the assembly of membrane rafts and/or regulating raft-directed signaling pathways are attractive approaches for the. management of infectious diseases. The current review discusses the latest advances in terms of techniques used to study the role of membrane microdomains in various pathological conditions and provides updated information regarding the role of membrane rafts during bacterial, viral and fungal infections. |
4,917 | Identification of the site of translational frameshifting required for production of the transposase encoded by insertion sequence IS 1 | Previous genetic analyses indicated that translational frameshifting in the −1 direction occurs within the run of six adenines in the sequence 5′-TTAAAAAACTC-3′ at nucleotide positions 305–315 in IS 1, where the two out-of-phase reading frames insA and B′-insB overlap, to produce transposase with a polypeptide segment Leu-Lys-Lys-Leu at residues 84–87. IS 1 mutants with a 1 by insertion, which encode mutant transposases with an amino acid substitution within the polypeptide segment at residues 84–87, did not efficiently mediate cointegration, except for an IS 1 mutant which encodes a mutant transposase with a Leu-Arg-Lys-Leu segment instead of Leu-LysLys-Leu. An IS 1 mutant with the DNA segment 5′-CTTAAAAACTC-3′ at positions 305–315 carrying the termination codon TAA in the B′-insB reading frame could still mediate cointegration, indicating that codon AAA for Lys corresponding to second, third and fourth positions in the run of adenines is the site of frameshifting. The β-galactosidase activity specified by several IS 1- lacZ fusion plasmids, in which B′-insB is in-frame with lacZ, showed that the region 292–377 is sufficient for frameshifting. The protein produced by frameshifting from the IS 1-lacZ plasmid in fact contained the polypeptide segment Leu - Lys - Lys - Leu encoded by the DNA segment 5′-TTAAAAAACTC-3′, indicating that −1 frameshifting does occur within the run of adenines. |
4,918 | Complete Nucleotide Sequence of Ryegrass Mottle Virus : A New Species of the Genus Sobemovirus | The genome of Ryegrass mottle virus (RGMoV) comprises 4210 nucleotides. The genomic RNA contains four open reading frames (ORFs). The largest ORF 2 encodes a polyprotein of 947 amino acids (103.6 kDa), which codes for a serine protease and an RNA-dependent RNA polymerase. The viral coat protein is encoded on ORF 4 present at the 3′-proximal region. Other ORFs 1 and 3 encode the predicted 14.6 kDa and 19.8 kDa proteins of unknown function. The consensus signal for frameshifting, heptanucleotide UUUAAAC and a stem-loop structure just downstream is in front of the AUG codon of ORF 3. Analysis of the in vitro translation products of RGMoV RNA suggests that the 68 kDa protein may represent a fusion protein of ORF 2-ORF 3 produced by frameshifting. The protease region of the polyprotein and coat protein have a low similarity with that of the sobemoviruses (approximately 25% amino acid identity), while the RNA-dependent RNA polymerase region has particularly strong similarity (54 to 60% of more than 350 amino acid residues). The sequence similarities of RGMoV to the sobemoviruses, together with the characteristic genome organization indicate that RGMoV is a new species of the genus Sobemovirus. |
4,919 | Acute respiratory infection due to Mycoplasma pneumoniae: current status of diagnostic methods | Because of the absence of well-standardized both in-house and FDA-approved commercially available diagnostic tests, the reliable diagnosis of respiratory infection due to Mycoplasma pneumoniae remains difficult. In addition, no formal external quality assessment schemes which would allow to conclude about the performance of M. pneumoniae diagnostic tests exist. In this review, the current state of knowledge of M. pneumoniae-associated respiratory infections in the context of epidemiological studies published during the past 5 years is discussed, with particular emphasis on the diagnostic strategies used and their impact on results. The role of M. pneumoniae as a cause of respiratory tract infections (RTIs) differs from study to study due to geographical and epidemiological differences, as well as to the application of different diagnostic techniques and criteria used. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10096-010-0975-2) contains supplementary material, which is available to authorized users. |
4,920 | Human melanoma invasion and metastasis enhancement by high expression of aminopeptidase N/CD13 | Aminopeptidase N/CD13 is a Zn(2+)-dependent exoprotease present on the cell surface as a transmembrane protein. Our previous studies using aminopeptidase inhibitors and antibodies demonstrated that aminopeptidase N is involved in the degradation and invasion of the extracellular matrix (ECM) by metastatic tumor cells. In the present study we transfected human A375M melanoma cells with eukaryotic plasmid expression vectors that contained full length cDNA of aminopeptidase N/CD13 and examined their characteristics. The transfectants that expressed extremely high levels of aminopeptidase N/CD13 degraded type IV collagen and invaded ECM more actively than the parental and control vector-transfected cells. Furthermore, the aminopeptidase N/CD13-transfected A375M cells had significantly augmented lung colonizing potential in nude mice. The results show that the aminopeptidase N/CD13 plays an active role in degradation and invasion of ECM and may be involved in the molecular mechanisms of blood-borne metastasis. |
4,921 | High-Mannose Specific Lectin and Its Recombinants from a Carrageenophyta Kappaphycus alvarezii Represent a Potent Anti-HIV Activity Through High-Affinity Binding to the Viral Envelope Glycoprotein gp120 | We previously reported that a high-mannose binding lectin KAA-2 from the red alga Kappaphycus alvarezii, which is an economically important species and widely cultivated as a source of carrageenans, had a potent anti-influenza virus activity. In this study, the full-length sequences of two KAA isoforms, KAA-1 and KAA-2, were elucidated by a combination of peptide mapping and complementary DNA (cDNA) cloning. They consisted of four internal tandem-repeated domains, which are conserved in high-mannose specific lectins from lower organisms, including a cyanobacterium Oscillatoria agardhii and a red alga Eucheuma serra. Using an Escherichia coli expression system, an active recombinant form of KAA-1 (His-tagged rKAA-1) was successfully generated in the yield of 115 mg per liter of culture. In a detailed oligosaccharide binding analysis by a centrifugal ultrafiltration-HPLC method with 27 pyridylaminated oligosaccharides, His-tagged rKAA-1 and rKAA-1 specifically bound to high-mannose N-glycans with an exposed α1-3 mannose in the D2 arm as the native lectin did. Predicted from oligosaccharide binding specificity, a surface plasmon resonance analysis revealed that the recombinants exhibit strong interaction with gp120, a heavily glycosylated envelope glycoprotein of HIV with high association constants (1.48 − 1.61 × 10(9) M(−1)). Native KAAs and the recombinants inhibited the HIV-1 entry at IC(50)s of low nanomolar levels (7.3–12.9 nM). Thus, the recombinant proteins would be useful as antiviral reagents targeting the viral surface glycoproteins with high-mannose N-glycans, and the cultivated alga K. alvarezii could also be a good source of not only carrageenans but also this functional lectin(s). |
4,922 | International health in a globalized development perspective | Eleven issues highlight the relation between globalization and health: 1. Globalization endangers health. Risks are spreading. AIDS and SARS are examples. 2. Global alliances are emerging to protect health, especially fighting AIDS, malaria and tuberculosis. 3. In many millennium declarations, health was declared a worldwide development goal. 4. The international development cooperation for health is ailing everywhere despite three good reasons to make health a priority. 5. Good health supports good politics and national security. 6. The lack of security in health is an essential trap of poverty and increases population growth. 7. Health has essential macroeconomic benefits. Leading economists have made this clear. 8. Thus, health and education are true keys to social and economic development. Brains and bodies are the most essential factors of production. 9. “Empowerment in security creates opportunities”. This new motto underlines the strategic importance of health literacy and social health insurance. 10. International or global health is a leitmotiv of this decade of development. 11. Globalization requires powerful ethics to gain a human face. Professional ethics and a rebellious civil society ought to be allies. Current globalization is both a threat and a positive challenge, indeed. |
4,923 | Biobanking and public health: is a human rights approach the tie that binds? | Ethical principles guiding public health and genomic medicine are often at odds: whereas public health practice adopts collectivist principles that emphasize population-based benefits, recent advances in genomic and personalized medicine are grounded in an individualist ethic that privileges informed consent, and the balancing of individual risk and benefit. Indeed, the attraction of personalized medicine is the promise it holds out to help individuals get the “right medicine for the right problem at the right time.” Research biobanks are an effective tool in the genomic medicine toolbox. Biobanking in public health presents a unique case study to unpack some of these issues in more detail. For example, there is a long history of using banked tissue obtained under clinical diagnostic conditions for later public health uses. But despite the collectivist approach of public health, the principles applied to the ethical challenges of biobanking (e.g. informed consent, autonomy, privacy) remain individualist. We demonstrate the value of using human rights as a public health ethics framework to address this tension in biobanking by applying it to two illustrative cases. |
4,924 | GeoWeb and crisis management: issues and perspectives of volunteered geographic information | Mapping, and more generally geopositioning, has become ubiquitous on the Internet. This democratization of geomatics through the GeoWeb results in the emergence of a new form of mapping based on Web 2.0 technologies. Described as Web-mapping 2.0, it is especially characterized by high interactivity and geolocation-based contents generated by users. A series of recent events (hurricanes, earthquakes, pandemics) have urged the development of numerous mapping Web applications intended to provide information to the public, and encourage their contribution to support crisis management. This new way to produce and spread geographic information in times of crisis brings up many questions and new potentials with regard to urgency services, Non Governmental Organisations (NGO), as well as individuals. This paper aims at putting into perspective the development of GeoWeb, both in terms of technologies and applications, against crisis management processes. |
4,925 | Exhaustive exercise reduces TNF-α and IFN-α production in response to R-848 via toll-like receptor 7 in mice | Stressful exercise results in temporary immune depression. However, the impact of exercise on the immune responses via toll-like receptor (TLR) 7, which recognizes the common viral genomic feature, single-stranded RNA, remains unclear. To clarify the effect of stressful exercise on immune function in response to viral infection, we measured the changes in the plasma concentration of tumor necrosis factor (TNF)-α and interferon (IFN)-α, which are induced downstream from the TLR–ligand interaction, in exhaustive-exercised mice immediately after treatment with the imidazoquinoline R-848, which can bind to and activate TLR7. Both exhaustive-exercised (EX) and non-exercised (N-EX) male C3H/HeN mice were injected with R-848 (5 mg kg(−1)), and blood samples were collected. In addition, RAW264 cells, which are mouse macrophage cells, were cultured 30 min after epinephrine (10 μM) or norepinephrine (10 μM) treatments, and were then stimulated with R-848 (10 μg ml(−1)). In addition, the effect of propranolol (10 mg kg(−1)) as blockade of β-adrenergic receptors on R-848-induced TNF-α and IFN-α production in the exercised mice was examined. Both the TNF-α and IFN-α concentrations in the plasma of EX were significantly lower than those in the plasma of N-EX after R-848 injection (P < 0.05 and P < 0.01, respectively), although the R-848 treatment increased the plasma TNF-α and IFN-α concentrations in both groups (P < 0.01, respectively). The R-848-induced TNF-α production in RAW264 cells was significantly inhibited by epinephrine and norepinephrine pre-treatment, although IFN-α was not detected. The propranolol treatment completely inhibited exercise-induced TNF-α and IFN-α suppression in response to R-848 in the mice. These data suggest that EX induces a reduction in TNF-α and IFN-α production in response to R-848, and that these phenomena might be regulated by an exercise-induced elevation of the systemic catecholamines. |
4,926 | Community-acquired methicillin-resistant Staphylococcus aureus: community transmission, pathogenesis, and drug resistance | Methicillin-resistant Staphylococcus aureus (MRSA) is able to persist not only in hospitals (with a high level of antimicrobial agent use) but also in the community (with a low level of antimicrobial agent use). The former is called hospital-acquired MRSA (HA-MRSA) and the latter community-acquired MRSA (CA-MRSA). It is believed MRSA clones are generated from S. aureus through insertion of the staphylococcal cassette chromosome mec (SCCmec), and outbreaks occur as they spread. Several worldwide and regional clones have been identified, and their epidemiological, clinical, and genetic characteristics have been described. CA-MRSA is likely able to survive in the community because of suitable SCCmec types (type IV or V), a clone-specific colonization/infection nature, toxin profiles (including Pantone-Valentine leucocidin, PVL), and narrow drug resistance patterns. CA-MRSA infections are generally seen in healthy children or young athletes, with unexpected cases of diseases, and also in elderly inpatients, occasionally surprising clinicians used to HA-MRSA infections. CA-MRSA spreads within families and close-contact groups or even through public transport, demonstrating transmission cores. Re-infection (including multifocal infection) frequently occurs, if the cores are not sought out and properly eradicated. Recently, attention has been given to CA-MRSA (USA300), which originated in the US, and is growing as HA-MRSA and also as a worldwide clone. CA-MRSA infection in influenza season has increasingly been noted as well. MRSA is also found in farm and companion animals, and has occasionally transferred to humans. As such, the epidemiological, clinical, and genetic behavior of CA-MRSA, a growing threat, is focused on in this study. |
4,927 | Import of West Nile Virus Infection in the Czech Republic | We report West Nile virus infection of the central nervous system in a 69-year-old man, residing in North Moravia (Czech Republic), who visited the USA from 6 July to 31 August 2002. He developed fever with fatigue at the end of his US stay, and was hospitalized in Ostrava after his return on 3 September with fever (up to 39.5 °C), fatigue, anorexia, moderate laryngotracheitis, dizziness, insomnia, blurred speech, and a marked bradypsychism. EEG demonstrated a slow bifrontal theta–delta activity, and CT of the brain a slight hydrocephalus. A significant increase of antibodies neutralizing West Nile virus was detected between the first (1:16) and second (1:256) blood serum sample. The patient recovered gradually and was released from hospital on 16 September. This is the first recorded human case of West Nile fever (WNF) imported to the Czech Republic. Nine similar cases of WNF import from the USA have already been reported in other European countries – France, Denmark, the Netherlands, and Germany. |
4,928 | Experimental Biology for the Identification of Causal Pathways in Atherosclerosis | More than 60 genomic loci have been implicated by genome-wide association studies (GWAS) and exome-wide association studies as conferring an increased risk of myocardial infarction and coronary artery disease (CAD). However, the causal gene and variant is often unclear. Using the functional analysis of genetic variants in experimental animal models, we anticipate understanding which candidate gene at a specific locus is associated with atherosclerosis and revealing the underlying molecular and cellular mechanisms, ultimately leading to the identification of causal pathways in atherosclerosis and may provide novel therapeutic targets for the treatment of atherosclerotic cardiovascular disease. |
4,929 | The need for European professional standards and the challenges facing clinical microbiology | Microorganisms spread across national boundaries and the professional activities of clinical (medical) microbiologists are critical in minimising their impact. Clinical microbiologists participate in many activities, e.g. diagnosis, antibiotic therapy, and there is a need for a set of professional standards for Europe with a common curriculum, to build upon the current strengths of the specialty and to facilitate the free movement of specialists within the European Union. Such standards will also better highlight the important contribution of clinical microbiologists to healthcare. There is a move to larger centralised microbiology laboratories often located off-site from an acute hospital, driven by the concentration of resources, amalgamation of services, outsourcing of diagnostics, automation, an explosion in the range of staff competencies and accreditation. Large off-site centralised microbiology laboratories are often distant to the patient and may not facilitate the early detection of microbial spread. Ultimately, the needs of patients and the public are paramount in deciding on the future direction of clinical microbiology. Potential conflicts between integration on an acute hospital site and centralisation can be resolved by a common set of professional standards and a team-based approach that puts patients first. |
4,930 | DNA sequences required for translational frameshifting in production of the transposase encoded by IS 1 | The transposase encoded by insertion sequence IS 1 is produced from two out-of-phase reading frames (insA and B′-insB) by translational frameshifting, which occurs within a run of six adenines in the −1 direction. To determine the sequence essential for frameshifting, substitution mutations were introduced within the region containing the run of adenines and were examined for their effects on frameshifting. Substitutions at each of three (2nd, 3rd and 4th) adenine residues in the run, which are recognized by tRNA(Lys) reading insA, caused serious defects in frameshifting, showing that the three adenine residues are essential for frameshifting. The effects of substitution mutations introduced in the region flanking the run of adenines and in the secondary structures located downstream were, however, small, indicating that such a region and structures are not essential for frameshifting. Deletion of a region containing the termination codon of insA caused a decrease in β-galactosidase activity specified by the lacZ fusion plasmid in frame with B′-insB. Exchange of the wild-type termination codon of insA for a different one or introduction of an additional termination codon in the region upstream of the native termination codon caused an increase in β-galactosidase activity, indicating that the termination codon in insA affects the efficiency of frameshifting. |
4,931 | Reinvention of interorganizational systems: A case analysis of the diffusion of a bio-terror surveillance system | Innovation diffusion theory proposed that adopters—whether individuals or organizations—sometimes reinvent an innovation as they gain experience using it. Reinvention can enhance (or impede) the likelihood of an IS innovation’s acceptance and further diffusion. This paper reports on a case study of BioSense, an interorganizational system that was designed as an early detection tool for bio-terror attacks and subsequently modified to better serve this need as well as to operate as a public health system for pinpointing geographic clusters of dangerous/acute disease outbreaks. By examining the interplay among the political and organizational dynamics and technical properties of the BioSense system, we shed light on processes affecting reinvention in an interorganizational context. We discuss our findings in light of theories of the diffusion and reinvention of innovations. We use Rogers’ (1995) list of factors supporting reinvention to structure the discussion of the fidelity and uniformity of the innovation within the processes it supports in adopting health services organizations. |
4,932 | Human Health, Well-Being, and Global Ecological Scenarios | This article categorizes four kinds of adverse effects to human health caused by ecosystem change: direct, mediated, modulated, and systems failure. The effects are categorized on their scale, complexity, and lag-time. Some but not all of these can be classified as resulting from reduced ecosystem services. The articles also explores the impacts that different socioeconomic–ecologic scenarios are likely to have on human health and how changes to human health may, in turn, influence the unfolding of four different plausible future scenarios. We provide examples to show that our categorization is a useful taxonomy for understanding the complex relationships between ecosystems and human well-being and for predicting how future ecosystem changes may affect human health. |
4,933 | Progress in the development of pandemic influenza vaccines and their production technologies | This article analyzes the current situation in the field of construction and production of pandemic influenza vaccines. The main task of protecting the population against influenza pandemics requires state-of-the-art approaches to the construction of influenza vaccines to be based on reassortment and genetic engineering techniques, including the analysis of primary structures of influenza viral genes, synthesis and cloning of the main viral genes, reverse genetics techniques, and banks of plasmids bearing basic viral genes. Reassortant technologies are now giving way to new approaches for objective reasons. The state-of-the-art technologies provide safety not only at the laboratories where vaccine viruses are constructed but also make the production process wholly safe. We are using the following approaches to the development of industrial production: use of nanoparticles and nanoemulsions as functional adjuvants, construction of totally-safe strains for live attenuated influenza vaccines with deletions of molecular determinants of pathogenicity, application of protein and chemical chaperones to provide self-assembly of haemagglutinin molecules of the H1N1v-2009 virus, and impregnation of whole-virion preparations with nanoparticles to enhance antigenicity. |
4,934 | Effect of Asymptomatic Natural Infections due to Common Mouse Pathogens on the Metastatic Progression of B16 Murine Melanoma in C57BL/6 Mice | To investigate whether the presence of infections in C57BL/6 mice influences the metastatic ability of B16 melanoma (B16M) cells, we compared the susceptibility to metastasis development of pathogen-free mice with that of mice from a colony endemically infected with several mouse pathogens. We found that, compared to seronegative controls, mice that were seropositive at least to Mouse Hepatitis Virus (MHV) and Mycoplasma pulmonis: (i) exhibited a higher interindividual variability in all the parameters quantifying metastatic progression; (ii) had elevated serum levels of proinflammatory cytokines both before and at the end of the experiment; (iii) were more susceptible to hepatic metastasis. Interestingly, final levels of tumor necrosis factor (TNF)-α and interleukin (IL)-18 correlated with the extent of hepatic colonization by the melanoma cells. To confirm the metastasis-enhancing effect of MHV and M. pulmonis we measured the ability of B16M cells to metastasize in pathogen-free animals housed for increasing time-intervals in the vicinity of MHV(+) animals. Notably, susceptibility to metastasis was lower in animals seronegative to MHV than in MHV(+) mice, whereas the latter were less susceptible to metastasis than MHV(+) M. pulmonis(+) mice. Seropositive animals had increased levels of TNF-α and IL-18 suggesting that MHV and M. pulmonis enhance the metastatic ability of melanoma cells by inducing the release of proinflammatory cytokines. While our results highlight the importance of using pathogen-free animals in metastasis studies, they emphasize the need for a comprehensive health monitoring of the mice used in such studies, particularly in case of using facilities lacking appropriate containment measures. |
4,935 | A random walk model for infection on graphs: spread of epidemics & rumours with mobile agents | We address the question of understanding the effect of the underlying network topology on the spread of a virus and the dissemination of information when users are mobile performing independent random walks on a graph. To this end, we propose a simple model of infection that enables to study the coincidence time of two random walkers on an arbitrary graph. By studying the coincidence time of a susceptible and an infected individual both moving in the graph we obtain estimates of the infection probability. The main result of this paper is to pinpoint the impact of the network topology on the infection probability. More precisely, we prove that for homogeneous graphs including regular graphs and the classical Erdős–Rényi model, the coincidence time is inversely proportional to the number of nodes in the graph. We then study the model on power-law graphs, that exhibit heterogeneous connectivity patterns, and show the existence of a phase transition for the coincidence time depending on the parameter of the power-law of the degree distribution. We finally undertake a preliminary analysis for the case with k random walkers and provide upper bounds on the convergence time for both the complete graph and regular graphs. |
4,936 | A Pragmatic Evaluation of the Theory of Information Ethics | It has been argued that moral problems in relation to Information Technology (IT) require new theories of ethics. In recent years, an interesting new theory to address such concerns has been proposed, namely the theory of Information Ethics (IE). Despite the promise of IE, the theory has not enjoyed public discussion. The aim of this paper is to initiate such discussion by critically evaluating the theory of IE. |
4,937 | Pathogenesis of rotavirus-induced diarrhea: Preliminary studies in miniature swine piglet | The pathogenesis of diarrhea caused by rotavirus infection was studied in miniature swine piglets. The animals were inoculated orally with 2×10(7) plaque-forming units of porcine rotavirus (OSU strain). During the height of diarrhea, intestinal function was investigated byin vivo perfusion of a 30-cm segment of proximal jejunum and a 30-cm segment of distal ileum. Absorption of Na(+) and water decreased and 3-O-methylglucose transport was markedly reduced,P<0.01 compared to control animals. Mucosal lactase and sucrase levels were depressed in both the jejunum and ileum,P<0.001. Na(+), K(+)-ATPase activity was significantly depressed only in the ileum,P<0.001. These changes were associated with a marked reduction in villous height, suggesting that the diarrhea could be an osmotic diarrhea due to nutrient (carbohydrate) malabsorption. Fresh stool samples were obtained and analyzed immediately for NA(+),K(+), osmolarity, glucose, and lactose; the osmotic gap was also determined. Stool osmolarity continually increased from 248±20 mosm/liter prior to inoculation to 348±20 mosm/liter at 75±1 hr postinoculation (P<0.005); the majority of the fecal osmotic gap could be accounted for by the amount of lactose present in the stools. Stool sodium increased from 34±6 mM prior to inoculation to a maximum of 65±4 mM at 53±1 hr postinoculation,P<0.001. There was no significant change in potassium concentration. The present investigation suggests that rotavirus-induced diarrhea is due to virus destruction of enterocytes lining the intestinal villi, thus reducing the mucosal surface area and important digestive enzymes. This destruction leads to an osmotic diarrhea due to nutrient (primarily carbohydrate) malabsorption. A possible contributing role of unopposed secretion from the crypt cannot be excluded from this study. |
4,938 | Extended expression of B-class MADS-box genes in the paleoherb Asarum caudigerum | Asarum caudigerum (Aristolochiaceae) is a paleoherb species that is important for research in origin and evolution of angiosperm flowers due to its basal position in the angiosperm phylogeny. In this study, a subtracted floral cDNA library from floral buds of A. caudigerum was constructed and cDNA arrays by suppression subtractive hybridization were generated. cDNAs of floral buds at different stages before flower opening and of leaves at the seedling stage were used. The macroarray analyses of expression profiles of isolated floral genes showed that 157 genes out of the 612 unique ESTs tested revealed higher transcript abundance in the floral buds and uppermost leaves. Among them, 78 genes were determined to be differentially expressed in the perianth, 62 in the stamens, and 100 genes in the carpels. Quantitative real-time PCR of selected genes validated the macroarray results. Remarkably, APETALA3 (AP3) B-class genes isolated from A. caudigerum were upregulated in the perianth, stamens and carpels, implying that the expression domain of B-class genes in this basal angiosperm was broader than those in their eudicot counterparts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00425-009-1048-6) contains supplementary material, which is available to authorized users. |
4,939 | Network immunization and virus propagation in email networks: experimental evaluation and analysis | Network immunization strategies have emerged as possible solutions to the challenges of virus propagation. In this paper, an existing interactive model is introduced and then improved in order to better characterize the way a virus spreads in email networks with different topologies. The model is used to demonstrate the effects of a number of key factors, notably nodes’ degree and betweenness. Experiments are then performed to examine how the structure of a network and human dynamics affects virus propagation. The experimental results have revealed that a virus spreads in two distinct phases and shown that the most efficient immunization strategy is the node-betweenness strategy. Moreover, those results have also explained why old virus can survive in networks nowadays from the aspects of human dynamics. |
4,940 | Modeling the Economic Impact of Pandemic Influenza: A Case Study in Turkey | Influenza pandemics have occurred intermittently throughout the 20th century and killed millions of people worldwide. It is expected that influenza pandemics will continue to occur in the near future. Huge number of deaths and cases is the most troublesome aspect of the influenza pandemics, but the other important trouble is the economic impact of the influenza pandemics to the countries. In this study, we try to detect the cost of a possible influenza pandemic under different scenarios and attack rates. We include the vaccination and antiviral treatment cost for direct cost and we add the work absenteeism cost to the calculations for indirect cost of influenza pandemics. As a case study, we calculate the economic impact of pandemic influenza for Turkey under three different scenarios and three different attack rates. Our optimistic estimation shows that the economic impact of pandemic influenza will be between 1.364 billion dollars and 2.687 billions dollars to Turkish economy depending on the vaccination strategies. |
4,941 | Simple Semantics in Topic Detection and Tracking | Topic Detection and Tracking (TDT) is a research initiative that aims at techniques to organize news documents in terms of news events. We propose a method that incorporates simple semantics into TDT by splitting the term space into groups of terms that have the meaning of the same type. Such a group can be associated with an external ontology. This ontology is used to determine the similarity of two terms in the given group. We extract proper names, locations, temporal expressions and normal terms into distinct sub-vectors of the document representation. Measuring the similarity of two documents is conducted by comparing a pair of their corresponding sub-vectors at a time. We use a simple perceptron to optimize the relative emphasis of each semantic class in the tracking and detection decisions. The results suggest that the spatial and the temporal similarity measures need to be improved. Especially the vagueness of spatial and temporal terms needs to be addressed. |
4,942 | Susceptibility of human retinal pigment epithelial cells to different viruses | • BACKGROUND: Different viruses have been reported to be involved in retinal diseases in animalsystems. In humans, herpes simplex virus and cytomegalovirus have been found to cause retinal disease. Most of the studied viruses are neurotropic. In this study, the in vitro susceptibility of human retinal pigment epithelial cells (RPEC) to representative members of different groups of human pathogenic viruses was investigated. • METHODS: Early cultures of RPE C — after two or three passages — were infected with the following viruses: herpes simplex virus (HSV) type 1, human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus types 1 and 7, measles virus, parainfluenza virus and coxsackie virus B3. • RESULTS: Cultures of RPE C could be infected with neurotropic viruses like HSV or measles virus as well as with typical respiratory viruses like parainfluenza or adenoviruses. Coxsackievirus, an enterovirus, replicated as well as human CMV whereas EBV and HHV-6, two lymphotropic viruses, failed to infect RPE. • CONCLUSION: These findings suggest that a variety of viruses, including those causing rather common illnesses, might be capable of inducing retinal lesions under certain circumstances due to haematogenous spread during the course of viraemia. |
4,943 | Recent developments in therapeutic protein expression technologies in plants | Infectious diseases and cancers are some of the commonest causes of deaths throughout the world. The previous two decades have witnessed a combined endeavor across various biological sciences to address this issue in novel ways. The advent of recombinant DNA technologies has provided the tools for producing recombinant proteins that can be used as therapeutic agents. A number of expression systems have been developed for the production of pharmaceutical products. Recently, advances have been made using plants as bioreactors to produce therapeutic proteins directed against infectious diseases and cancers. This review highlights the recent progress in therapeutic protein expression in plants (stable and transient), the factors affecting heterologous protein expression, vector systems and recent developments in existing technologies and steps towards the industrial production of plant-made vaccines, antibodies, and biopharmaceuticals. |
4,944 | Immunizations in the elderly: do they live up to their promise? | In the 21st century, public health is not only challenged by newly emerging and re-emerging infectious diseases but also by demographic developments that are taking place in many countries. Importantly, infections in the elderly are more frequent, more severe and have distinct features with respect to clinical presentation and treatment. This is due to a decline in the functions of the immune system referred to as immunosenescence. The most important age-related changes affect the T cell system. Although this derogates the protective effect of some vaccines, vaccinations are still considered the most cost-effective medical procedure for preventing morbidity and mortality caused by infectious diseases. The present article aims at outlining the impact of infectious diseases on the elderly and summarizing the progress made in the field of vaccinations of the elderly and how age-related changes within the immune system contribute to the decreased efficacy of vaccines. |
4,945 | Dynamic features of cells expressing macrophage properties in tissue cultures of dissociated cerebral cortex from the rat | Two previously identified forms of macrophage were investigated in primary cultures of cerebral cortical cells. Dynamic features were revealed through time-lapse video recording and aspects of macrophage function were assessed. The two cell forms were shown to be different pre-mitotic stages of a single cell type. The cell cycle for these cells involved an initial large, flat, quiescent cell which retracted to yield a slightly rounded form with numerous processes. This latter form lost processes and developed profuse filopodia as it became very rounded just prior to division; both resulting daughter cells then regained the initial large flat appearance. These cells possessed several properties of macrophages, including phagocytosis, nucleoside diphosphatase enzyme, and CR3 receptors. These properties were transient, expressed just before and after mitosis, but subsequently down-regulated in the flat daughter cells. Because of this feature, it was difficult to determine the exact size of this cell population; however, the observed rate of proliferation suggests it may be substantial. It is suggested that these cells correspond to non-microglial macrophages of brain tissue and, because of their significant down-regulation, they may be difficult to detect. This may be important in studies of brain accessory immune cells in tissue culture. |
4,946 | Ebola virus disease: any risk for oral and maxillo-facial surgery? An overview | The 2014–2015 outbreak of the Ebola virus disease (EVD) in West Africa has been considered a major global health emergency by the WHO. Implications for health care providers including oral and maxillo-facial surgeons have been published by the WHO, the Centers for Disease Control and Prevention (USA), and other medical societies and public health organizations. While the risk of infection with the Ebola virus seems to be rather small in Europe, maxillo-facial and plastic surgeons often travel to Africa to treat patients with facial burns, cleft-lip and palate, and noma. The likelihood of an encounter with patients infected by Ebola virus in subsaharan and West Africa, therefore, has increased during the last 2 years. The purpose of this short overview was to summarize the virology of the Ebola virus, transmission, epidemiology, clinical features, oral manifestations, treatment, and possible implications for maxillo-facial surgeons of EDV. |
4,947 | The Integrated Information Architecture: A Pilot Study Approach to Leveraging Logistics Management with Regard to Influenza Preparedness | Pandemic influenza is considered catastrophic to global health, with severe economic and social effects. Consequently, a strategy for the rapid deployment of essential medical supplies used for the prevention of influenza transmission and to alleviate public panic caused by the expected shortage of such supplies needs to be developed. Therefore, we employ integrated information concepts to develop a simulated influenza medical material supply system to facilitate a rapid response to such a crisis. Various scenarios are analyzed to estimate the appropriate inventory policy needed under different pandemic influenza outbreaks, and to establish a mechanism to evaluate the necessary stockpiles of medications and other requirements in the different phases of the pandemic. This study constructed a web-based decision support system framework prototype that displayed transparent data related to medical stockpiles in each district and integrated expert opinion about the best distribution of these supplies in the influenza pandemic scenarios. A data collection system was also designed to gather information through a daily VPN transmitted into one central repository for reporting and distribution purposes. This study provides timely and transparent medical supplies distribution information that can help decision makers to make the appropriate decisions under different pandemic influenza outbreaks, and also attempts to establish a mechanism of evaluating the stockpiles and requirements in the different phases of the pandemic. |
4,948 | Possible linkages between lignite aquifers, pathogenic microbes, and renal pelvic cancer in northwestern Louisiana, USA | In May and September, 2002, 14 private residential drinking water wells, one dewatering well at a lignite mine, eight surface water sites, and lignite from an active coal mine were sampled in five Parishes of northwestern Louisiana, USA. Using a geographic information system (GIS), wells were selected that were likely to draw water that had been in contact with lignite; control wells were located in areas devoid of lignite deposits. Well water samples were analyzed for pH, conductivity, organic compounds, and nutrient and anion concentrations. All samples were further tested for presence of fungi (cultures maintained for up to 28 days and colonies counted and identified microscopically) and for metal and trace element concentration by inductively-coupled plasma mass spectrometry and atomic emission spectrometry. Surface water samples were tested for dissolved oxygen and presence of pathogenic leptospiral bacteria. The Spearman correlation method was used to assess the association between the endpoints for these field/laboratory analyses and incidence of cancer of the renal pelvis (RPC) based on data obtained from the Louisiana Tumor Registry for the five Parishes included in the study. Significant associations were revealed between the cancer rate and the presence in drinking water of organic compounds, the fungi Zygomycetes, the nutrients PO(4) and NH(3), and 13 chemical elements. Presence of human pathogenic leptospires was detected in four out of eight (50%) of the surface water sites sampled. The present study of a stable rural population examined possible linkages between aquifers containing chemically reactive lignite deposits, hydrologic conditions favorable to the␣leaching and transport of toxic organic compounds from the lignite into the groundwater, possible microbial contamination, and RPC risk. |
4,949 | Codetection of Respiratory Syncytial Virus in Habituated Wild Western Lowland Gorillas and Humans During a Respiratory Disease Outbreak | Pneumoviruses have been identified as causative agents in several respiratory disease outbreaks in habituated wild great apes. Based on phylogenetic evidence, transmission from humans is likely. However, the pathogens have never been detected in the local human population prior to or at the same time as an outbreak. Here, we report the first simultaneous detection of a human respiratory syncytial virus (HRSV) infection in western lowland gorillas (Gorilla gorilla gorilla) and in the local human population at a field program in the Central African Republic. A total of 15 gorilla and 15 human fecal samples and 80 human throat swabs were tested for HRSV, human metapneumovirus, and other respiratory viruses. We were able to obtain identical sequences for HRSV A from four gorillas and four humans. In contrast, we did not detect HRSV or any other classic human respiratory virus in gorilla fecal samples in two other outbreaks in the same field program. Enterovirus sequences were detected but the implication of these viruses in the etiology of these outbreaks remains speculative. Our findings of HRSV in wild but human-habituated gorillas underline, once again, the risk of interspecies transmission from humans to endangered great apes. |
4,950 | Bacteriophage T7 morphogenesis and gene 10 frameshifting in Escherichia coli showing different degrees of ribosomal fidelity | Bacteriophage T7 infection has been studied in Escherichia coli strains showing both increased and decreased ribosome fidelity and in the presence of streptomycin, which stimulates translational misreading, in an effort to determine effects on the apparent programmed translational frameshift that occurs during synthesis of the gene 10 capsid protein. Quantitation of the protein bands from SDS-PAGE failed to detect any significant effects on the amounts of the shifted 10B protein relative to the in-frame 10A protein under all fidelity conditions tested. However, any changes in fidelity conditions led to inhibition of phage morphogenesis in single-step growth experiments, which could not be accounted for by reduced amounts of phage protein synthesis, nor, at least in the case of decreased accuracy, by reduced amounts of phage DNA synthesis. Reduction in phage DNA synthesis did appear to account for a substantial proportion of the reduction in phage yield seen under conditions of increased accuracy. Similar effects of varying ribosomal fidelity on growth were also seen with phage T3, and to a lesser extent with phage T4. The absence of change in the high-frequency T7 gene 10 frameshift differs from earlier reports that ribosomal fidelity affects low-frequency frameshift errors. |
4,951 | Methods for counting particles in microfluidic applications | Microfluidic particle counters are important tools in biomedical diagnostic applications such as flow cytometry analysis. Major methods of counting particles in microfluidic devices are reviewed in this paper. The microfluidic resistive pulse sensor advances in sensitivity over the traditional Coulter counter by improving signal amplification and noise reduction techniques. Nanopore-based methods are used for single DNA molecule analysis and the capacitance counter is useful in liquids of low electrical conductivity and in sensing the changes of cell contents. Light-scattering and light-blocking counters are better for detecting larger particles or concentrated particles. Methods of using fluorescence detection have the capability for differentiating particles of similar sizes but different types that are labeled with different fluorescent dyes. The micro particle image velocimetry method has also been used for detecting and analyzing particles in a flow field. The general limitation of microfluidic particle counters is the low throughput which needs to be improved in the future. The integration of two or more existing microfluidic particle counting techniques is required for many practical on-chip applications. |
4,952 | Mitochondrial mutations restricting spontaneous translational frameshift suppression in the yeast Saccharomyces cerevisiae | The +1 frameshift mutation, M5631, which is located in the gene (oxi1) for cytochrome c oxidase II (COXII) of the yeast mitochondrial genome, is suppressed spontaneously to a remarkably high extent (20%–30%). The full-length wild-type COXII produced as a result of suppression allows the mutant strain to grow with a “leaky” phenotype on non-fermentable medium. In order to elucidate the factors and interactions involved in this translational suppression, the strain with the frameshift mutation was mutated by MnCl(2) treatment and a large number of mutants showing restriction of the suppression were isolated. Of 20 mutants exhibiting a strong, restricted, respiration-deficient (RD) phenotype, 6 were identified as having mutations in the mitochondrial genome. Furthermore, genetic analyses mapped one mutation to the vicinity of the gene for tRNA(Pro) and two others to a region of the tRNA cluster where two-thirds of all mitochondrial tRNA genes are encoded. The degree of restriction of the spontaneous frameshift suppression was characterized at the translational level by in vivo (35)S-labeling of the mitochondrial translational products and immunoblotting. These results showed that in some of these mutant strains the frameshift suppression product is synthesized to the same extent as in the leaky parent strain. It is suggested that more than one +1 frame-shifted product is made as a result of suppression in these strains: one is as functional as the wild-type COXII, the other(s) is (are) non-functional and prevent leaky growth on non-fermentable medium. A possible mechanism for this heterogenous frameshift suppression is discussed. |
4,953 | Prediction of mutations engineered by randomness in H5N1 hemagglutinins of influenza A virus | This is the continuation of our studies on the prediction of mutation engineered by randomness in proteins from influenza A virus. In our previous studies, we have demonstrated that randomness plays a role in engineering mutations because the measures of randomness in protein are different before and after mutations. Thus we built a cause-mutation relationship to count the mutation engineered by randomness, and conducted several concept-initiated studies to predict the mutations in proteins from influenza A virus, which demonstrated the possibility of prediction of mutations along this line of thought. On the other hand, these concept-initiated studies indicate the directions forwards the enhancement of predictability, of which we need to use the neural network instead of logistic regression that was used in those concept-initiated studies to enhance the predictability. In this proof-of-concept study, we attempt to apply the neural network to modeling the cause-mutation relationship to predict the possible mutation positions, and then we use the amino acid mutating probability to predict the would-be-mutated amino acids at predicted positions. The results confirm the possibility of use of internal cause-mutation relationship with neural network model to predict the mutation positions and use of amino acid mutating probability to predict the would-be-mutated amino acids. |
4,954 | The public perception of the value of vaccines - the case of Switzerland | AIM: In this original article, we seek to analyse the environment in which immunisation policies are adopted and, more specifically, the way the public perception of vaccines influences decision-making, by looking more closely at the case of Switzerland. SUBJECTS AND METHODS: Historical and present-day examples of attitudes towards immunisation and specific vaccines, both on the part of the public and of health-care workers, are reviewed. RESULTS: Decision-making with regard to vaccine policy implementation has been and is still most often driven by fear: fear of disease (when perceived as rampant and/or dangerous), but also fear of vaccine-associated adverse events (when the disease is less or no longer “visible”). However, methodology for introducing evidence-based immunisation policies exists and can be used by public health authorities, while vaccination information systems (such as the Swiss InfoVac) have proven their usefulness in providing trustworthy, peer-based knowledge to health-care workers. CONCLUSION: Only information based on clear, evidence-based data gathered and analysed according to solid methodological criteria coupled with adequate information of health-care workers (and thus patients) can ensure in future the implementation of scientifically coherent, publicly acceptable, and equitable immunisation policies. |
4,955 | A disposable, integrated loop-mediated isothermal amplification cassette with thermally actuated valves | An inexpensive, disposable, integrated, polymer-based cassette for loop-mediated isothermal amplification (LAMP) of target nucleic acids was designed, fabricated, and tested. The LAMP chamber was equipped with single-use, thermally actuated valves made with a composite consisting of a mixture of PDMS and expandable microspheres. The effect of the composite composition on its expansion was investigated, and the valve’s performance was evaluated. In its closed state, the valve can hold pressures as high as 200 kPa without any significant leakage. Both the LAMP chamber and the valves were actuated with thin film heaters. The utility of the cassette was demonstrated by carrying out LAMP of Escherichia coli DNA target and reverse transcribed loop meditated isothermal amplification (RT-LAMP) of RNA targets. The amplicons were detected in real time with a portable, compact detector. The system was capable of detecting as few as 10 target molecules per sample in well under 1 h. The portable, integrated cassette system described here is particularly suited for applications at the point of care and in resource-poor countries, where funds and trained personnel are in short supply. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10404-011-0788-3) contains supplementary material, which is available to authorized users. |
4,956 | An improved ELISA for the detection of antibodies againstBabesia bovis using either a native or a recombinantB. bovis antigen | Two new enzyme-linked immunosorbent assayes (ELISA) for the diagnosis ofBabesia bovis in cattle are described. The ELISA using a native antigen is more sensitive and less laborious than the assays described previously, because it does not require adsorption of sera with bovine erythrocytes. The second ELISA, using a recombinantB. bovis antigen expressed inEscherichia coli, was both sensitive and specific. It is suitable to replace the native antigen, thus avoiding large batch-to-batch variations in antigen preparations and the need to sacrifice experimental cattle. |
4,957 | Oral application of cytokines | A number of different laboratories reported on studies with orally administered interferons and cytokines. Their observations extend previous observations which showed that orally administered interferons and cytokines can exert both local and systemic effects. As difficult as it may be to understand how orally administered interferons and cytokines may exert both effects, the increasing number of laboratories that demonstrate biological effects with orally administered cytokines suggests that serious consideration be given to the possibility that orally administered interferons and cytokines can indeed exert effects. They also raise the possibility that these effects may have biological relevance for the treatment of human disease. Moreover, they may indicate that the nasal/oral region is a window on the environment. It is most important, however, to assure that these experiments are performed with special care to avoid presenting preliminary data that is not properly controlled. It is essential to carry out these studies with sufficient animals or patients to ascertain their significance; and to plan the studies as double-blind evaluations to avoid misinterpretations when subjective tests are used. Nevertheless, the overall data presented give one the impression of an area that should be pursued. |
4,958 | Identification of a new susceptibility variant for multiple sclerosis in OAS1 by population genetics analysis | Contrasting results have been reported concerning the association of a splice-site polymorphism (rs10774671) in OAS1 with multiple sclerosis (MS). We analysed two OAS1 regions encompassing alternatively spliced exons. While the region carrying the splice-site variant is neutrally evolving, a signature of long-standing balancing selection was observed across an alternative exon 7. Analysis of variants in this exon identified an insertion/deletion polymorphism (rs11352835, A/−) that originates predicted products with distinct C termini. This variant is located along the major branch of the haplotype genealogy, suggesting that it may represent the selection target. A case/control study for MS indicated that rs11352835 is associated with disease susceptibility (for an allelic model with the deleted allele predisposing to MS, OR 1.27, 95% CI 1.072–1.513, p = 0.010). No association was found between rs10774671 and MS. As the two SNPs are in linkage disequilibrium in Europeans, the previously reported association between rs10774671 and MS susceptibility might be driven by rs11352835, possibly explaining the contrasting results previously observed for the splice-site polymorphism. Thus, we describe a novel susceptibility variant for MS in OAS1 and show that population genetic analyses can be instrumental to the identification of selection targets and, consequently, of functional polymorphisms with an effect on phenotypic traits. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-011-1053-2) contains supplementary material, which is available to authorized users. |
4,959 | Travelling Companions: Emerging Diseases of People, Animals and Plants Along the Malawi-Mozambique Border | Humans, animals and plants suffer from similar types of diseases (e.g., fungal, viral etc.). These can “emerge” as new diseases by expanding their geographical range or by jumping species (from plants to plants, or from animals to humans). Emerging diseases place an additional burden on developing countries which are often struggling to manage the diseases they already have. New diseases spread through weather, insects or other vectors, or by the movement of people, animals or goods. This study examines the role of cross-border travel in the spread of diseases. A survey of travelers and of residents along the Malawi-Mozambique border found that most cross it frequently and that they rarely travel empty-handed, often taking plants and animals with them. People also cross borders seeking medical attention. Attempting to limit travel would hamper an already struggling economy, where many people make a living by producing, processing or transporting plants and animals for food. Cross border travel per se may pose slight danger for the spread of diseases, if governments can collaborate on sharing information about the status of diseases within their border. |
4,960 | An update on swine-origin influenza virus A/H1N1: a review | Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. The recent flu pandemic caused by a swine-origin influenza virus A/H1N1 (S-OIV) presents an opportunity to examine virulence factors, the spread of the infection and to prepare for major influenza outbreaks in the future. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it probably arose through reassortment of two viruses of swine origin. Specific markers for virulence can be evaluated in the viral genome, PB1-F2 is a molecular marker of pathogenicity but is not present in the new S-OIV. While attention was focused on a threat of an avian influenza H5N1 pandemic emerging from Asia, a novel influenza virus of swine origin emerged in North America, and is now spreading worldwide. However, S-OIV demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. There are concerns that this virus may mutate or reassort with existing influenza viruses giving rise to more transmissible or more pathogenic viruses. The 1918 Spanish flu pandemic virus was relatively mild in its first wave and acquired more virulence when it returned in the winter. Thus preparedness on a global scale against a potential more virulent strain is highly recommended. Most isolates of the new S-OIVs are susceptible to neuraminidase inhibitors, and currently a vaccine against the pandemic strain is being manufactured and will be available this fall. This review summarizes the current information on the new pandemic swine-origin influenza virus A/H1N1. |
4,961 | Synthesis of a-secomethylenamino- and substituted amidoximotriterpenoids | Development of the functionalization of triterpenoids to A-secoamidoximes, A-secomethylenamines, and branched 3-(3-aminopropylamino)-3-(3-aminopropoxy)amidoximes is illustrated by the betulonic acid ketoxime. An effective way to get of the derivatives of 20,29-dihydrolupanes using diborane is suggested. The antiviral and antituberculosis activity data of some compounds are presented. |
4,962 | Pattern formation of an epidemic model with diffusion | One subject of spatial epidemiology is spatial variation in disease risk or incidence. The spread of epidemics can result in strong spatial patterns of such risk or incidence: for example, pathogen dispersal might be highly localized, vectors or reservoirs for pathogens might be spatially restricted, or susceptible hosts might be clumped. Here, spatial pattern of an epidemic model with nonlinear incidence rates is investigated. The conditions for Hopf bifurcation and Turing bifurcation are gained and, in particular, exact Turing domain is found in the two parameters space. Furthermore, numerical results show that force of infection, namely β, plays an important role in the spatial pattern. More specifically, different patterns emerge as β increases. The mathematical analysis and numerical results well extend the finding of pattern formation in the epidemic models and may well explain the field observed in some areas. |
4,963 | Viral lower urinary tract infections | Lower urinary tract infections (UTIs) are common among the general population and are most often caused by bacterial pathogens. Viruses are an uncommon cause of UTIs in an immunocompetent host; however, viruses are increasingly recognized as the cause of lower UTI, especially hemorrhagic cystitis, among immunocompromised patients. BK virus, adenovirus, and cytomegalovirus are predominant pathogens involved in hemorrhagic cystitis after stem cell and solid organ transplantation, and their early diagnosis and treatment may prevent significant morbidity of hemorrhagic cystitis. The diagnosis of viral lower UTI is based on molecular techniques, and real-time polymerase chain reaction is often the method of choice because it allows for quantification of viral load. Cidofovir is becoming a drug of choice in viral UTIs because it is active against the most common viral pathogens. This review discusses the epidemiology, pitfalls in diagnosis, and current treatment of viral UTIs. |
4,964 | Molecular evolution of novel swine-origin A/H1N1 influenza viruses among and before human | We find that the novel A/H1N1 influenza viruses exhibit very low genetic divergence and suffer strong purifying selection among human population and confirm that they originated from the reassortment of previous triple-reassortant swine influenza viruses including genomic segments from both avian and human lineages with North American and Eurasian swine lineages. The longer phylogenetic branch length to their nearest genetic neighbors indicates that the origin of the novel A/H1N1 is unlikely to be a very recent event. Seventy-six new unique mutations are found to be monomorphically fixed in the novel A/H1N1 virus lineages, suggesting a role of selective sweep in the early evolution of this virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-009-0393-7) contains supplementary material, which is available to authorized users. |
4,965 | Relevant Cytokines in the Management of Community-Acquired Pneumonia | Community-acquired pneumonia (CAP) is the leading cause of infectious death in the world. Immune dysregulation during acute lung infection plays a role in lung injury and the systemic inflammatory response. Cytokines seem to be major players in severe lung infection cases. Here, we present a review of published papers in the last 3 years regarding this topic. The cytokine response during pneumonia is different in bacterial vs viral infections; some of these cytokines correlate with clinical severity scales such as CURB65 or SOFA. Treatment focused in the cytokine environment is an interesting area that could impact the prognosis of CAP. Some of the agents that have been studied as co-adjuvant therapy are corticosteroids, macrolides, and linezolid, but anyone of those have shown a clear or proven efficacy or have been recommended as a part of the standard of care for CAP. More studies designed to define the role of immunomodulatory agents, such as co-adjuvant therapy in pneumonia, are needed. |
4,966 | Prospective study of avian influenza H9 infection in commercial poultry farms of Punjab Province and Islamabad Capital Territory, Pakistan | A prospective study was conducted from November 2013 to February 2014 to estimate the spatial clustering; cumulative incidence and risk factors associated with avian influenza (AI) subtype H9 infection on commercial poultry farms of Pakistan. A total of 400 farms were enrolled and followed during the study period. Among these, 109 farms submitted samples suspected for AI to the laboratory, and only 47 farms were confirmed positive by hemagglutinin inhibition (HI) test. Data was collected from these 109 farms about their demography, management, and biosecurity practices. The cumulative incidence of H9N2 was 11.75 % (95 % confidence interval (CI) 8.76–15.23). The highest number of cases (40.42 %) was reported in January. One most likely cluster (p = 0.009, radius = 4.61 km) occurred in the Kasur district. Multivariable logistic regression analyses showed that the presence of wild birds on the farms (odds ratio (OR) = 16.18; 95 % CI 3.94–66.45) was independently associated with H9N2 infection. Cleaning of cages before delivery on farm (OR = 0.16; 95 % CI = 0.06–0.47), presence of a footbath at the entrance of farm (OR = 0.24; 95 % CI 0.08–0.79), and changing of gloves (OR = 0.33; 95 % CI 0.11–0.99) were protective factors against H9N2 infection. Reducing the exposure to risk factors and adapting biosecurity measures may reduce the risk of AI H9N2 infection on commercial poultry farms in Pakistan. |
4,967 | Heptad-repeat sequences in the glycoprotein of rhabdoviruses | Two or three regions containing three or more successive newly defined heptads of a–d hydrophobic amino acid repeats have been located in the cDNA-derived amino acid sequences of glycoprotein G of all rhabdoviruses examined (rabies, vesicular stomatitis, fish, and plant rhabdoviruses) by computer search. These new heptad-repeats differ from those previously reported in other viruses because of the presence of all the hydrophobic amino acids in positions a or d, and because they are not predicted to form coiled coils by current methods and thus they have not been detected previously in any rhabdoviruses. The two or three heptad-repeat regions were the only parts of the glycoprotein with at least three successive heptad-repeats in all the rhabdoviral sequences studied and had low sequence variability among the members of each of the rhabdoviral genus but show no sequence similarity among the different genus. All these newly detected heptad repeats were in the vicinity of some of the higher hydrophobic regions in each of the rhabdovirus genera studied and were found mostly, but not always, outside the extra amino acid sequences that occur in the longer insect or plant rhabdovirus glycoprotein G. The correspondence of position and structure of these heptad-repeats among all the rhabdoviruses suggests its participation in common function(s), most probably related to viral fusion with cellular membranes. |
4,968 | QSAR for RNases and theoretic–experimental study of molecular diversity on peptide mass fingerprints of a new Leishmania infantum protein | The toxicity and low success of current treatments for Leishmaniosis determines the search of new peptide drugs and/or molecular targets in Leishmania pathogen species (L. infantum and L. major). For example, Ribonucleases (RNases) are enzymes relevant to several biologic processes; then, theoretical and experimental study of the molecular diversity of Peptide Mass Fingerprints (PMFs) of RNases is useful for drug design. This study introduces a methodology that combines QSAR models, 2D-Electrophoresis (2D-E), MALDI-TOF Mass Spectroscopy (MS), BLAST alignment, and Molecular Dynamics (MD) to explore PMFs of RNases. We illustrate this approach by investigating for the first time the PMFs of a new protein of L. infantum. Here we report and compare new versus old predictive models for RNases based on Topological Indices (TIs) of Markov Pseudo-Folding Lattices. These group of indices called Pseudo-folding Lattice 2D-TIs include: Spectral moments π (k)(x,y), Mean Electrostatic potentials ξ (k)(x,y), and Entropy measures θ (k)(x,y). The accuracy of the models (training/cross-validation) was as follows: ξ (k)(x,y)-model (96.0%/91.7%)>π (k)(x,y)-model (84.7/83.3) > θ (k)(x,y)-model (66.0/66.7). We also carried out a 2D-E analysis of biological samples of L. infantum promastigotes focusing on a 2D-E gel spot of one unknown protein with M<20, 100 and pI <7. MASCOT search identified 20 proteins with Mowse score >30, but not one >52 (threshold value), the higher value of 42 was for a probable DNA-directed RNA polymerase. However, we determined experimentally the sequence of more than 140 peptides. We used QSAR models to predict RNase scores for these peptides and BLAST alignment to confirm some results. We also calculated 3D-folding TIs based on MD experiments and compared 2D versus 3D-TIs on molecular phylogenetic analysis of the molecular diversity of these peptides. This combined strategy may be of interest in drug development or target identification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11030-009-9178-0) contains supplementary material, which is available to authorized users. |
4,969 | An insight into the potentially old-wonder molecule—quercetin: the perspectives in foresee | Use of phyto-medicine and digitalization of phyto-compounds has been fallen enthralling field of science in recent years. Quercetin, a flavonoid with brilliant citron yellow pigment, is typically found in fruits and leafy vegetables in reasonable amount. Quercetin’s potentials as an antioxidant, immune-modulator, antiinflammatory, anti-cancer, and others have been the subject of interest in this review. Although, profiling the insights in to the molecular characterization of quercetin with various targets provided the loop-holes in understanding the knowledge for the aforementioned mechanisms, still necessitates research globally to unearth it completely. Thus, the available science on the synthesis and significant role played by the old molecule - quercetin which does wonders even now have been vividly explained in the present review to benefit the scientific community. |
4,970 | A nondisposable microplate for use with organic solvents | A nondisposable, or “hard”, multiwell microplate is described for use with small volumes of biological solutions containing organic solvents. The design of this teflon-coated, aluminum device resembles the 96-well layout of the disposable variety of tissue culture microplates. The reusable, hard microplate has been specifically developed to hold and evaporate volatile organic solvents from aliquots of crude sample extractions or partitions intended for testing in various in vitro biological screening assays. This device is a valuable adjunct for converting numerous small volumes of nonpolar or nonaqueous dissolved compounds into reconstituted solutions containing acceptable assay solvents. |
4,971 | Treatment of acute bronchitis in adults without underlying lung disease | OBJECTIVE: To determine whether antibiotic and bronchodilator treatment of acute bronchitis in patients without lung disease is efficacious. DESIGN: A MEDLINE search of the literature from 1966 to 1995 was done, using “Bronchitis” as the key word. Papers addressing acute bronchitis in adults were used as well as several citations emphasizing pediatric infections. A manual search of papers addressing the microorganisms causing acute bronchitis was also done. Data were extracted manually from relevant publications. SETTING: All published reports were reviewed. Papers dealing with exacerbations of chronic bronchitis were excluded in this review. RESULTS: Although acute bronchitis has multiple causes, the large majority of cases are of viral etiology.Mycoplasma pneumoniae, Chlamydia pneumoniae, andBordetella pertussis are the only bacteria identified as contributing to the cause of acute bronchitis in otherwise healthy adults. Nine double-blind, placebo-controlled trials were reviewed. Four studies showed no advantage for doxycycline and one study showed no advantage for erythromycin. One study using erythromycin and one study using trimethoprim and sulfamethoxazole showed that these antibiotics were slightly better than placebo. Two other studies showed an impressive superiority for liquid or inhaled albuterol when compared with erythromycin. CONCLUSIONS: Most studies showed no significant difference between drug and placebo, and the two studies that did showed only small clinical differences. Albuterol had an impressive advantage over erythromycin. Antibiotics should not be used in the treatment of acute bronchitis in healthy persons unless convincing evidence of a bacterial infection is present. |
4,972 | Supreme Emergencies Without the Bad Guys | This paper discusses the application of the supreme emergency doctrine from just-war theory to non-antagonistic threats. Two versions of the doctrine are considered: Michael Walzer’s communitarian version and Brian Orend’s prudential one. I investigate first whether the doctrines are applicable to non-antagonistic threats, and second whether they are defensible. I argue that a version of Walzer’s doctrine seems to be applicable to non-antagonistic threats, but that it is very doubtful whether the doctrine is defensible. I also argue that Orend’s version of the doctrine is applicable to non-antagonistic threats, but that his account is not defensible, regardless of whether the threats are antagonistic or not. |
4,973 | Expression of recombinant herpes simplex virus type 2 glycoprotein D by high-density cell culture of Spodoptera frugiperda | Herpes simplex virus type 2 (HSV-2) is the major cause of genital herpes in humans. The glycoprotein D of HSV-2 (gD2) is a promising subunit vaccine candidate for the treatment of genital herpes. The aim of the present study was to express a biologically active recombinant gD2 in eukaryotic baculovirus system in quantities sufficient for further studies. Human cDNA encoding a gD2 protein with 393 amino acids was subcloned into the pFastBac HTb vector and the recombinant protein was expressed in Spodoptera frugiperda (Sf9) cells by high-density cell culture. In a stirred bioreactor, the key limiting factors including glucose concentration, glutamine concentration and dissolved oxygen (DO) were optimized for high-density cell growth. The Sf9 cell density could reach 9.6×10(6) cells/mL and the yield of recombinant gD2 protein was up to 192 mg/L in cell culture under the optimal conditions of 15 mM glucose, 0.4 g/L glutamine and 40% DO. Production of significant amounts of pure, full-length gD2 opened up the possibility to investigate novel functions of gD2. Moreover, the purified recombinant gD2 protein revealed a partial prophylactic immune function in genital herpes of guinea pigs infected with HSV-2. |
4,974 | The use of loop-mediated isothermal DNA amplification for the detection and identification of the anthrax pathogen | The results of detection and identification of Bacillus anthracis strains in loop-mediated isothermal DNA amplification (LAMP) reaction performed under optimized conditions with original primers and thermostable DNA polymerase are presented. Reproducible LAMP-based detection of chromosomal and plasmid DNA targets specific for B. anthracis strains has been demonstrated. No cross reactions with DNA from bacterial strains of other species of the B. cereus group were detected. The development of tests for anthrax-pathogen detection based on the optimized reaction of loop isothermal DNA amplification is planned. These tests will be convenient for clinical studies and field diagnostics due to the absence of requirements for sophisticated equipment. |
4,975 | Hepatitis C virus NS4A inhibits cap-dependent and the viral IRES-mediated translation through interacting with eukaryotic elongation factor 1A | The genomic RNA of hepatitis C virus (HCV) encodes the viral polyprotein precursor that undergoes proteolytic cleavage into structural and nonstructural proteins by cellular and the viral NS3 and NS2-3 proteases. Nonstructural protein 4A (NS4A) is a cofactor of the NS3 serine protease and has been demonstrated to inhibit protein synthesis. In this study, GST pull-down assay was performed to examine potential cellular factors that interact with the NS4A protein and are involved in the pathogenesis of HCV. A trypsin digestion followed by LC-MS/MS analysis revealed that one of the GST-NS4A-interacting proteins to be eukaryotic elongation factor 1A (eEF1A). Both the N-terminal domain of NS4A from amino acid residues 1–20, and the central domain from residues 21–34 interacted with eEF1A, but the central domain was the key player involved in the NS4A-mediated translation inhibition. NS4A(21–34) diminished both cap-dependent and HCV IRES-mediated translation in a dose-dependent manner. The translation inhibitory effect of NS4A(21–34) was relieved by the addition of purified recombinant eEF1A in an in vitro translation system. Taken together, NS4A inhibits host and viral translation through interacting with eEF1A, implying a possible mechanism by which NS4A is involved in the pathogenesis and chronic infection of HCV. |
4,976 | Global stressors and the global decline of amphibians: tipping the stress immunocompetency axis | There is a widespread consensus that the earth is experiencing a mass extinction event and at the forefront are amphibians, the most threatened of all vertebrate taxa. A recent assessment found that nearly one-third (32%, 1,856 species) of the world’s amphibian species are threatened. Amphibians have existed on the earth for over 300 million years, yet in just the last two decades there have been an alarming number of extinctions, nearly 168 species are believed to have gone extinct and at least 2,469 (43%) more have populations that are declining. Infectious diseases have been recognized as one major cause of worldwide amphibian population declines. This could be the result of the appearance of novel pathogens, or it could be that exposure to environmental stressors is increasing the susceptibility of amphibians to opportunistic pathogens. Here I review the potential effects of stressors on disease susceptibility in amphibians and relate this to disease emergence in human and other wildlife populations. I will present a series of case studies that illustrate the role of stress in disease outbreaks that have resulted in amphibian declines. First, I will examine how elevated sea-surface temperatures in the tropical Pacific since the mid-1970s have affected climate over much of the world and could be setting the stage for pathogen-mediated amphibian declines in many regions. Finally, I will discuss how the apparently rapid increase in the prevalence of amphibian limb deformities is linked to the synergistic effects of trematode infection and exposure to chemical contaminants. |
4,977 | How to deal with partially analyzable acts? | In some situations, a decision is best represented by an incompletely analyzed act: conditionally on a given event A, the consequences of the decision on sub-events are perfectly known and uncertainty becomes probabilizable, whereas the plausibility of this event itself remains vague and the decision outcome on the complementary event [Formula: see text] is imprecisely known. In this framework, we study an axiomatic decision model and prove a representation theorem. Resulting decision criteria aggregate partial evaluations consisting of (i) the conditional expected utility associated with the analyzed part of the decision, and (ii) the best and worst consequences of its non-analyzed part. The representation theorem is consistent with a wide variety of decision criteria, which allows for expressing various degrees of knowledge on ([Formula: see text]) and various types of attitude toward ambiguity and uncertainty. This diversity is taken into account by specific models already existing in the literature. We exploit this fact and propose some particular forms of our model incorporating these models as sub-models and moreover expressing various types of beliefs concerning the relative plausibility of the analyzed and the non-analyzed events ranging from probabilities to complete ignorance that include capacities. |
4,978 | Sero-prevalences of selected cattle diseases in the Kafue flats of Zambia | Sera from five traditionally managed herds grazing in the Kafue flats were tested for antibodies to bovine viral diarrhoea-mucosal disease (BVD-MD), parainfluenza 3 (PI3), infectious bovine rhinotracheitis-infectious pustular vulvovaginitis (IBR-IPV), bovine adenovirus 3 (BAV3) and Bluetongue (BT). The sero-prevalences of the first four diseases were respectively 76.2, 94.4, 42.1 and 87.4%. Five samples (2.3%) gave doubtful reactions for BT. Prevalences of 28.5% for brucellosis, 14% for Rift Valley fever (RFV), 0.9% for Q fever and 11.2% for chlamydiosis were also recorded. Significantly higher values for BVD-MD (p<0.005), IBR-IPV (p<0.01) and brucellosis (p<0.05) were found in animals over 1 year of age. No differences were recorded between herds or between male and female animals. The high concentration of wild and domestic ruminants grazing together in the flood plains during the dry season may be a major determinant of the high values observed. Traditional farmers, slaughterhouse workers and other people involved in livestock production are particularly at risk of contracting brucellosis and RVF because of the high prevalences in cattle and local habits favourable to their transmission. |
4,979 | Viral evolution and insects as a possible virologic turning table | Three lines of observation demonstrate the role of arthropods in transmission and evolution of viruses. a) Recent outbreaks of viruses from their niches took place and insects have played a major role in propagating the viruses. b) Examination of the list of viral families and their hosts shows that many infect invertebrates (I) and vertebrates (V) or (I) and plants (P) or all kingdoms (VIPs). This notion holds true irrespective of the genome type. At first glance the argument seems to be weak in the case of enveloped and non-enveloped RNA viruses with single-stranded (ss) segmented or non-segmented genomes of positive (+) or negative polarity. Here, there are several families infecting V or P only; no systematic relation to arthropods is found. c) In the non-enveloped plant viruses with ss RNA genomes there is a strong tendency for segmentation and individual packaging of the genome pieces. This is in contrast to ss+ RNA animal viruses and can only be explained by massive transmission by seed or insects or both, because individual packaging necessitates a multihit infection. Comparisons demonstrate relationships in the nonstructural proteins of double-stranded and ss+ RNA viruses irrespective of host range, segmentation, and envelope. Similar conclusions apply for the negative-stranded RNA viruses. Thus, viral supergroups can be created that infect V or P and exploit arthropods for infection or transmission or both. Examples of such relationships and explanations for viral evolution are reviewed and the arthropod orders important for cell culture are given. |
4,980 | Complex dynamic behavior in a viral model with state feedback control strategies | With the consideration of mechanism of prevention and control for the spread of viral diseases, in this paper, we propose two novel virus dynamics models where state feedback control strategies are introduced. The first model incorporates the density of infected cells (or free virus) as control threshold value; we analytically show the existence and orbit stability of positive periodic solution. Theoretical results imply that the density of infected cells (or free virus) can be controlled within an adequate level. The other model determines the control strategies by monitoring the density of uninfected cells when it reaches a risk threshold value. We analytically prove the existence and orbit stability of semi-trivial periodic solution, which show that the viral disease dies out. Numerical simulations are carried out to illustrate the main results. |
4,981 | Identification of a 37 kDa plant protein that interacts with the turnip mosaic potyvirus capsid protein using anti-idiotypic-antibodies | Experimental data are provided for the presence of a plant protein that interacts with the capsid protein (CP) of turnip mosaic potyvirus (TuMV). The receptor-like protein was identified by exploiting the molecular mimicry potential of anti-idiotypic antibodies. A single-chain Fv molecule derived from the monoclonal antibody 7A (Mab-7A), which recognizes the CP of TuMV, was produced in Escherichia coli and the recombinant protein was used to raise rabbit antibodies. The immune serum reacted with Mab-7A but not with a monoclonal antibody of the same isotype, indicating that anti-idiotypic antibodies were produced. These anti-idiotypic antibodies recognized a 37 kDa protein from Lactuca sativa. Complex formation between the anti-idiotypic antibodies and the plant protein was inhibited by the CP of TuMV which indicates that the plant protein interacts with the viral protein. The 37 kDa protein was localized in chloroplasts and was detected in other plant species. |
4,982 | Neutralizing immunogenicity of transgenic carrot (Daucus carota L.)-derived measles virus hemagglutinin | Although edible vaccines seem to be feasible, antigens of human pathogens have mostly been expressed in plants that are not attractive for human consumption (such as potatoes) unless they are cooked. Boiling may reduce the immunogenicity of many antigens. More recently, the technology to transform fruit and vegetable plants have become perfected. We transformed carrot plants with Agrobacterium tumefaciens to generate plants (which can be eaten raw) transgenic for an immunodominant antigen of the measles virus, a major pathogen in man. The hemagglutinin (H) glycoprotein is the principle target of neutralizing and protective antibodies against measles. Copy numbers of the H transgene were verified by Southern blot and specific transcription was confirmed by RT-PCR. The H protein was detected by western blot in the membrane fraction of transformed carrot plants. The recombinant protein seemed to have a 8% lower molecular weight than the viral protein. Although this suggests a different glycosylation pattern, proper folding of the transgenic protein was confirmed by conformational-dependent monoclonal antibodies. Immunization of mice with leaf or root extracts induced high titres of IgG1 and IgG2a antibodies that cross-reacted strongly with the measles virus and neutralized the virus in vitro. These results demonstrate that transgenic carrot plants can be used as an efficient expression system to produce highly immunogenic viral antigens. Our study may pave the way towards an edible vaccine against measles which could be complementary to the current live-attenuated vaccine. |
4,983 | Demyelination and remyelination in the dorsal funiculus of the rat spinal cord after heat injury | Part of the dorsal funiculus of the adult male rat (Wistar) spinal cord was treated for l h at the thoracolumbar level by running hot water, at approximately 48–50 ° C, through a polyethylene tube 2 mm in diameter in contact with the dura. Animals were fixed 1 day to 4 weeks later and the spinal cords were examined by light and electron microscopy. The affected area in the dorsal funiculus was approximately 1 mm long and less than 1 mm wide at the dorsal surface, and varied from 0.4 to 0.7 mm in depth. Within 3 days after treatment, almost all the myelin sheaths in the affected area were degraded, leaving the axons denuded, and at the same time astrocyte endfeet at the glial limiting membrane were swollen and partly destroyed. Almost all the denuded axons remained intact, exhibiting no noticeable morphological changes. There was evidence of a moderate vasogenic oedema, but minimal signs of haemorrhage in the lesion. Seven days after treatment, many immature Schwann cells but no oligodendrocytes were found between the denuded axons. By 2 weeks many of the denuded axons were remyelinated, and by 4 weeks almost all of those axons located near the pial and perivascular surfaces had been remyelinated by Schwann cells, while most of those located in the deep and marginal zones bordering the adjoining intact areas were remyelinated by oligodendrocytes. Longitudinal sections revealed that at nodes of Ranvier PNS-type myelin sheaths were apposed by either intact or newly formed CNS-type myelin sheaths. A typical glial limiting membrane was not reformed beneath the pial surface, but an inconspicuous one was found between the PNS- and CNS-type fibre areas. |
4,984 | Bovine Chlamydophila spp. infection: Do we underestimate the impact on fertility? | Classical methods for detection of Chlamydophila species, and of antibodies against these agents, have indicated that these bacteria are highly prevalent in cattle and associated with numerous disease conditions. These methods demonstrated acute Chlamydophila-induced diseases such as epizootic bovine abortion, as well as worldwide variable, but generally high, Chlamydophila seroprevalence. However, it was impossible to consistently detect the low levels of these organisms which were suspected to be present in endemic infections. Application of highly sensitive real-time PCR and ELISA methods for detection of Chlamydophila spp. DNA and of antibodies against Chlamydophila spp., respectively, in a series of prospective cohort studies revealed a high prevalence of Chlamydophila spp. genital infections in female calves (61%) and adult heifers (53%). These infections were acquired by extragenital transmission in the first weeks of life, and infection frequency was increased by crowding of the animals. A challenge study demonstrated that infection with C. abortus resulted in decreased fertility of heifers. The experimental use of a C. abortus vaccine provided evidence for immunoprotection against C. abortus-induced suppression of bovine fertility. The results of these investigations suggest that bovine Chlamydophila infection should be viewed more as pervasive, low-level infection of cattle than as rare, severe disease. Such infections proceed without apparent disease or with only subtle expressions of disease, but potentially have a large impact on bovine herd health and fertility. |
4,985 | Frequency of group A rotavirus in diarrhoeic calves in Brazilian cattle herds, 1998–2002 | The frequency of group A bovine rotavirus (gpA BRV) in calves from 1998 to 2002 was determined by the polyacrylamide gel electrophoresis technique in 2177 faecal samples, of which 1898 samples were diarrhoeic and 279 were of normal consistency (control group) that were collected from asymptomatic calves for comparative purposes. The animals were from beef and dairy cattle herds (n = 321) from 158 counties in seven States (Paraná, São Paulo, Minas Gerais, Mato Grosso do Sul, Mato Grosso, Goiás and Rondônia) and four Brazilian geographical regions (south, south-east, centre-west, and north). GpA BRV was detected in 19.4% (369/1898; p = 0.0001) of the samples collected in calves with diarrhoea and in only 2.2% (6/279; p = 0.0001) of the faeces with normal consistency. The proportion of positive samples collected from beef and dairy cattle herds was 22.8% (205/899; p = 0.0001) and 16.4% (169/999; p = 0.0005), respectively. In relation to age, a higher prevalence of infections was found in calves up to 30 days old, where 33.0% (189/573; p = 0.0001) and 20.2% (138/683; p = 0.0001) of the diarrhoeic faecal samples from beef and dairy cattle herds, respectively, were positive for gpA BRV. These results show the possible importance of inclusion of gpA BRV in the management of neonatal calf diarrhoea in Brazilian cattle herds. |
4,986 | Prokaryote phylogeny based on ribosomal proteins and aminoacyl tRNA synthetases by using the compositional distance approach | In order to show that the newly developed K-string composition distance method, based on counting oligopeptide frequencies, for inferring phylogenetic relations of prokaryotes works equally well without requiring the whole proteome data, we used all ribosomal proteins and the set of aminoacyl tRNA synthetases for each species. The latter group has been known to yield inconsistent trees if used individually. Our trees are obtained without making any sequence alignment. Altogether 16 Archaea, 105 Bacteria and 2 Eucarya are represented on the tree. Most of the lower branchings agree well with the latest, 2003, Outline of the second edition of the Bergey’s Manual of Systematic Bacteriology and the trees also suggest some relationships among higher taxa. |
4,987 | Mutation patterns in human α-galactosidase A | A way to study the mutation pattern is to convert a 20-letter protein sequence into a scalar protein sequence, because the 20-letter protein sequence is neither vector nor scalar while a promising way to study patterns is in numerical domain. In this study, we use the amino-acid pair predictability to convert α-galactosidase A with its 137 mutations into scalar sequences, and analyse which amino-acid pairs are more sensitive to mutation. Our results show that the unpredictable amino-acid pairs are more sensitive to mutation, and the mutation trend is to narrow the difference between predicted and actual frequency of amino-acid pairs. |
4,988 | Expression of anti-tumor recombinant IgG- and IgE-like genes in eukaryotic cells | The tandem of humanized variable VL and VH genes (ScFv fragment 4D5) possessing a high affinity to the HER-2/neu oncogene (the epidermal growth factor receptor expressed in many types of human tumors) was attached through a flexible linker to the second exon of human antibodies of IgG or IgE isotypes constant gene. The humanized construct of IgE isotype was generated for the first time. Genes of the recombinant antibodies were cloned into the pCl-neo vector under the control of universal cytomegalovirus (CMV) promoter. Transfected HEK-293 cells efficiently produced antibodies of the corresponding isotypes IgE and IgG1. The results of Western blotting confirmed homogeneity of the expressed antibodies, which had the predicted molecular weight and specifically interacted with the HER-2/neu. The attachment of leader peptide to the 5′-end of the gene resulted in the preferential accumulation of recombinant antibodies in the cultural medium. These results indicate that de novo constructed humanized immunoglobulin genes express functionally active, single-chain recombinant antibodies in eukaryotic cells. |
4,989 | Synthesis and biological activity of water-soluble polymer complexes of arbidol | We have synthesized water-soluble complexes between the antiviral drug arbidol and polymer compounds with molecular masses of 19–31 kDa representing copolymers of acrylamide (AA) and 2-acrylamido-2-methylpropanesulfonic acid (AAMPS). The complexes are less toxic than arbidol and retain the high level of antiviral activity of this drug. The content of arbidol in the obtained complexes is within 26.4–32.1 mass%. The antiviral activity of the synthesized polymeric complexes against all studied viruses, including human epidemic influenza virus A (H3N2), bird highly pathogenic influenza virus A (H5N1), herpes type 1 virus (HSV-1), and adenovirus type III (AV-III) is comparable to the antiviral effect of nonmodified arbidol. The in vitro toxicity of the obtained complexes is about one order of magnitude lower than that of nonmodified arbidol; the pharmacological index, four times that of the initial low-molecular-weight drug. The synthesized water-soluble polymer complexes of arbidol can be useful in pharmacology since they can serve as the basis for new effective and safe parent antiviral substances and related formulations. |
4,990 | Mathematical Models of Memory CD8(+) T-Cell Repertoire Dynamics in Response to Viral Infections | Immunity to diseases is conferred by pathogen-specific memory cells that prevent disease reoccurrences. A broad repertoire of memory T-cells must be developed and maintained to effectively protect against viral invasions; yet, the total number of memory T-cells is constrained between infections. Thus, creating memory to new infections can require attrition of some existing memory cells. Furthermore, some viruses induce memory T-cell death early in an infection, after which surviving cells proliferate to refill the memory compartment. We develop mathematical models of cellular attrition and proliferation in order to examine how new viral infections impact existing immunity. With these probabilistic models, we qualitatively and quantitatively predict how the composition and diversity of the memory repertoire changes as a result of viral infections. In addition, we calculate how often immunity to prior diseases is lost due to new infections. Comparing our results across multiple general infection types allows us to draw conclusions about, which types of viral effects most drastically alter existing immunity. We find that early memory attrition does not permanently alter the repertoire composition, while infections that spark substantial new memory generation drastically shift the repertoire and hasten the decline of existing immunity. |
4,991 | Risk analysis for the highly pathogenic avian influenza in Mainland China using meta-modeling | A logistic model was employed to correlate the outbreak of highly pathogenic avian influenza (HPAI) with related environmental factors and the migration of birds. Based on MODIS data of the normalized difference vegetation index, environmental factors were considered in generating a probability map with the aid of logistic regression. A Bayesian maximum entropy model was employed to explore the spatial and temporal correlations of HPAI incidence. The results show that proximity to water bodies and national highways was statistically relevant to the occurrence of HPAI. Migratory birds, mainly waterfowl, were important infection sources in HPAI transmission. In addition, the HPAI outbreaks had high spatiotemporal autocorrelation. This epidemic spatial range fluctuated 45 km owing to different distribution patterns of cities and water bodies. Furthermore, two outbreaks were likely to occur with a period of 22 d. The potential risk of occurrence of HPAI in Mainland China for the period from January 23 to February 17, 2004 was simulated based on these findings, providing a useful meta-model framework for the application of environmental factors in the prediction of HPAI risk. |
4,992 | From social data mining to forecasting socio-economic crises | 1. Develop strategies to quickly increase the objective knowledge about social and economic systems. 2. Describe requirements for efficient large-scale scientific data mining of anonymized social and economic data. 3. Formulate strategies how to collect stylized facts extracted from large data set. 4. Sketch ways how to successfully build up centers for computational social science. 5. Propose plans how to create centers for risk analysis and crisis forecasting. 6. Elaborate ethical standards regarding the storage, processing, evaluation, and publication of social and economic data. |
4,993 | Group I but not Group II NPV induces antiviral effects in mammalian cells | Nucleopolyhedrovirus (NPV) is divided into Group I and Group II based on the phylogenetic analysis. It has been reported that Group I NPVs such as Autographa californica multiple NPV (AcMNPV) can transduce mammalian cells, while Group II NPVs such as Helicoverpa armigera single NPV (HaSNPV) cannot. Here we report that AcMNPV was capable of stimulating antiviral activity in human hepatoma cells (SMMC-7721) manifested by inhibition of Vesicular Stomatitis virus (VSV) replication. In contrast, the HaSNPV and the Spodoptera exigua multiple NPV (SeMNPV) of group II had no inhibitory effect on VSV. Recombinant AcMNPV was shown to induce interferons alpha/beta even in the absence of transgene expression in human SMMC-7721 cells, while it mediated transgene expression in BHK and L929 mammalian cells without an ensuing antiviral activity. |
4,994 | Sustainability science: an ecohealth perspective | Sustainability science is emerging as a transdisciplinary effort to come to grips with the much-needed symbiosis between human activity and the environment. While there is recognition that conventional economic growth must yield to policies that foster sustainable development, this has not yet occurred on any broad scale. Rather, there is clear evidence that the Earth’s ecosystems and landscapes continue to degrade as a consequence of the cumulative impact of human activities. Taking an ecohealth approach to sustainability science provides a unique perspective on both the goals and the means to achieve sustainability. The goals should be the restoration of full functionality to the Earth’s ecosystems and landscapes, as measured by the key indicators of health: resilience, organization, vitality (productivity), and the absence of ecosystem distress syndrome. The means should be the coordinated (spatially and temporally) efforts to modify human behaviors to reduce cumulative stress impacts. Achieving ecosystem health should become the cornerstone of sustainability policy—for healthy ecosystems are the essential precondition for achieving sustainable livelihoods, human health, and many other societal objectives, as reflected in the Millennium Development Goals. |
4,995 | Vulnerability, diversity and scarcity: on universal rights | This article makes a contribution to the on-going debates about universalism and cultural relativism from the perspective of sociology. We argue that bioethics has a universal range because it relates to three shared human characteristics,—human vulnerability, institutional precariousness and scarcity of resources. These three components of our argument provide support for a related notion of ‘weak foundationalism’ that emphasizes the universality and interrelatedness of human experience, rather than their cultural differences. After presenting a theoretical position on vulnerability and human rights, we draw on recent criticism of this approach in order to paint a more nuanced picture. We conclude that the dichotomy between universalism and cultural relativism has some conceptual merit, but it also has obvious limitations when we consider the political economy of health and its impact on social inequality. |
4,996 | Antiparasitic DNA vaccines in 21(st) century | Demands for effective vaccines to control parasitic diseases of humans and livestock have been recently exacerbated by the development of resistance of most pathogenic parasites to anti-parasitic drugs. Novel genomic and proteomic technologies have provided opportunities for the discovery and improvement of DNA vaccines which are relatively easy as well as cheap to fabricate and stable at room temperatures. However, their main limitation is rather poor immunogenicity, which makes it necessary to couple the antigens with adjuvant molecules. This paper review recent advances in the development of DNA vaccines to some pathogenic protozoa and helminths. Numerous studies were conducted over the past 14 years of 21(st) century, employing various administration techniques, adjuvants and new immunogenic antigens to increase efficacy of DNA vaccines. Unfortunately, the results have not been rewarding. Further research is necessary using more extensive combinations of antigens; alternate delivery systems and more efficient adjuvants based on knowledge of the immunomodulatory capacities of parasitic protozoa and helminths. |
4,997 | The Problems with Forbidding Science | Scientific research is subject to a number of regulations which impose incidental (time, place), rather than substantive (type of research), restrictions on scientific research and the knowledge created through such research. In recent years, however, the premise that scientific research and knowledge should be free from substantive regulation has increasingly been called into question. Some have suggested that the law should be used as a tool to substantively restrict research which is dual-use in nature or which raises moral objections. There are, however, some problems with using law to restrict or prohibit certain types of scientific research, including (i) the inherent imprecision of law for regulating complex and rapidly evolving scientific research; (ii) the difficulties of enforcing legal restrictions on an activity that is international in scope; (iii) the limited predictability of the consequences of restricting specific branches of scientific research; (iv) inertia in the legislative process; and (v) the susceptibility of legislators and regulators to inappropriate factors and influence. Rather than using law to restrict scientific research, it may be more appropriate and effective to use a combination of non-traditional legal tools including norms, codes of conduct, restrictions on publication, and scientist-developed voluntary standards to regulate problematic scientific research. |
4,998 | Modeling of epidemic spreading with white Gaussian noise | Motivated by the need to include the different characteristics of individuals and the damping effect in predictions of epidemic spreading, we build a model with variant coefficients and white Gaussian noise based on the traditional SIR model. The analytic and simulation results predicted by the model are presented and discussed. The simulations show that using the variant coefficients results in a higher percentage of susceptible individuals and a lower percentage of removed individuals. When the noise is included in the model, the percentage of infected individuals has a wider peak and more fluctuations than that predicted using the traditional SIR model. |
4,999 | A Fuzzy Reed–Frost Model for Epidemic Spreading | In this paper, we present a fuzzy approach to the Reed–Frost model for epidemic spreading taking into account uncertainties in the diagnostic of the infection. The heterogeneities in the infected group is based on the clinical signals of the individuals (symptoms, laboratorial exams, medical findings, etc.), which are incorporated into the dynamic of the epidemic. The infectivity level is time-varying and the classification of the individuals is performed through fuzzy relations. Simulations considering a real problem with data of the viral epidemic in a children daycare are performed and the results are compared with a stochastic Reed–Frost generalization. |
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