niryuu/sni-each-converted huggingface dataset:
Providing information about single virus particles has for a long time been mainly the domain of electron microscopy. More recently, technologies have been developed-or adapted from other fields, such as nanotechnology-to allow for the real-time quantification of physical virion particles, while supplying additional information such as particle diameter concomitantly. These technologies have progressed to the stage of commercialization increasing the speed of viral titer measurements from hours to minutes, thus providing a significant advantage for many aspects of virology research and biotechnology applications. Additional advantages lie in the broad spectrum of virus species that may be measured and the possibility to determine the ratio of infectious to total particles. A series of disadvantages remain associated with these technologies, such as a low specificity for viral particles. In this review we will discuss these technologies by comparing four systems for real-time single virus particle analysis and quantification.
Output: Quantitative real-time single particle analysis of virions
Objectives: 1) To compare the 2-year completed suicide and reattempt rates in a preintervention group of Hong Kong Chinese suicide attempters (aged 65 years and older) who received standard care and a postintervention group enrolled in a regional elderly suicide prevention program (ESPP) that adopts a two-tiered multifaceted care management model and 2) to examine the trend of suicide rates in older adults aged 65 years and older in the pre-and postintervention periods. Design: The first part is an observational cohort study with baseline, follow-up, and outcome data being identified from a clinical electronic registry. The second part examines changes in suicide rates from official mortality statistics. Setting: A government-funded suicide intervention program serving catchment population (852,796 people aged 65 years and older) in Hong Kong, China. Participants: Suicide attempters (aged 65 years and older) presenting to old-age psychiatric service in the pre-and postintervention phases. Measurements: 1) Two-year rates of completed suicide and suicide reattempt and 2) changes in population suicide rates in the pre-and postintervention periods. Results: The 2-year completed suicide rate was 7.58% in the preintervention group (N = 66) and 1.99% in the ESPP group (N = 351) χ 2 = 6.192; p value: 0.028; df = 1). Reattempt rates were not different. At a population level, suicide rate dropped significantly only in women aged 85 years and older, relative to the preintervention period. Conclusions: The ESPP was associated with a reduced rate of completed suicide in old-age suicide attempters and might have contributed to a fall of suicide rate in women aged 85 years and older. (Am J Geriatr Psychiatry 2011; 19:1-12) 
Output: Outcomes of a Two-Tiered Multifaceted Elderly Suicide Prevention Program in a Two-Tiered Multifaceted ESPP
Background: Respiratory syncytial virus and other respiratory tract viruses lead to common colds in most infants, whereas a minority develop acute severe bronchiolitis often requiring hospitalization. We hypothesized that such an excessive response to respiratory tract viral infection is caused by host factors reflected in pre-existing increased bronchial responsiveness. Objective: We sought to compare bronchial responsiveness and lung function in 1-month-old neonates who later develop acute severe bronchiolitis with those who do not. Methods: We measured infant lung function (n 5 402) and bronchial responsiveness to methacholine (n 5 363) using the raised-volume rapid thoracoabdominal compression technique before any respiratory symptoms in 1-month-old neonates from the Copenhagen Prospective Study of Asthma in Childhood birth cohort born to mothers with asthma. The children were prospectively monitored for respiratory symptoms and given a diagnosis of acute severe bronchiolitis according to a fixed algorithm. Results: Thirty-four (8.5%) infants had acute severe bronchiolitis before 2 years of age, 21 (62%) were hospitalized,
Output: Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants
With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most indemand nanoparticles owing to their exponential number of uses in various sectors. The increased use of Ag-NPs-enhanced products may result in an increased level of toxicity affecting both the environment and living organisms. Several studies have used different model cell lines to exhibit the cytotoxicity of Ag-NPs, and their underlying molecular mechanisms. This review aimed to elucidate different properties of Ag-NPs that are responsible for the induction of cellular toxicity along with the critical mechanism of action and subsequent defense mechanisms observed in vitro. Our results show that the properties of Ag-NPs largely vary based on the diversified synthesis processes. The physiochemical properties of Ag-NPs (e.g., size, shape, concentration, agglomeration, or aggregation interaction with a biological system) can cause impairment of mitochondrial function prior to their penetration and accumulation in the mitochondrial membrane. Thus, Ag-NPs exhibit properties that play a central role in their use as biocides j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / j a r e along with their applicability in environmental cleaning. We herein report a current review of the synthesis, applicability, and toxicity of Ag-NPs in relation to their detailed characteristics. Ó 2017 Production and hosting by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Output: A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify smaller changes. In this study, we have used a NimbleGen tiling array for whole genome comparison of 13 BCG strains. Using this approach, in tandem with DNA resequencing, we have identified six novel large sequence polymorphisms including four deletions and two duplications in specific BCG strains. Moreover, we have uncovered various polymorphisms in the phoP-phoR locus. Importantly, these polymorphisms affect genes encoding established virulence factors including cell wall complex lipids, ESX secretion systems, and the PhoP-PhoR two-component system. Our study demonstrates that major virulence factors are different among BCG strains, which provide molecular mechanisms for important vaccine phenotypes including adverse effect profile, tuberculin reactivity and protective efficacy. These findings have important implications for the development of a new generation of vaccines.
Output: BMC Genomics Novel genome polymorphisms in BCG vaccine strains and impact on efficacy
The innate immune system possesses a multitude of pathways to sense and respond to microbial pathogens. One such family are the interferons (IFNs), a family of cytokines that are involved in several cellular functions. Type I IFNs are appreciated to be important in several viral and bacterial diseases, while the recently identified type III IFNs (IFNL1, IFNL2, IFNL3, IFNL4) have been studied primarily in the context of viral infection. Viral and bacterial infections however are not mutually exclusive, and often the presence of a viral pathogen increases the pathogenesis of bacterial infection. The role of type III IFN in bacterial and viral-bacterial co-infections has just begun to be explored. In this mini review we discuss type III IFN signaling and its role in microbial pathogenesis with an emphasis on the work that has been conducted with bacterial pathogens.
Output: Microbial pathogenesis and type III interferons
In view of the restricted knowledge on the diversity of coronaviruses in poultry other than chicken, this study aimed to investigate the genetic diversity of coronaviruses in quail, pheasant, and partridge from two regions of Northern Italy. To this end, pools of tracheal and cloacal swabs from European quail (Coturnix Coturnix) and intestinal tract from pheasants (Phasianus Colchicus) and partridge (Perdix Perdix) flocks, with or without enteric signs, were collected during 2015. Avian coronavirus (Gammacoronavirus) was detected in quail not vaccinated against Infectious Bronchitis Virus (IBV) and in pheasants vaccinated with an IBV Massachusetts serotype. Based on DNA sequences for the gene encoding the S protein, the avian coronaviruses detected in the quail and pheasant are related to the IBV 793B and Massachusetts types, respectively. However, RNA-dependent RNA polymerase (RdRp) analyses showed the susceptibility of quail also to Deltacoronaviruses, suggesting that quail and pheasant avian coronaviruses share spike genes identical to chicken IBV spike genes and quail might host Deltacoronavirus.
Output: MOLECULAR AND CELLULAR BIOLOGY Gamma and Deltacoronaviruses in quail and pheasants from Northern Italy 1
A virulent infectious bronchitis virus (IBV), designated as CK/CH/GD/QY16 (referred as QY16), was isolated from a diseased chicken farm in Guangdong province, China, in 2016. The complete genome of the strain was sequenced and analyzed. The results show that the genome of QY16 consists of 27,670 nucleotides, excluding poly (A) tail, and that its genome organization is 5' UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3' UTR-poly (A) tail. Sequence comparison among QY16 and other IBV strains was conducted and its results demonstrate that the S1 gene of QY16 has the highest nucleotide sequence identity with that of 4/91, and the other part of its genome is highly similar to that of YX10. The results of the phylogenic analysis show that the entire genome of QY16 and most of the QY16 genes are located in the same cluster as those of YX10, except for the S1 gene which is located in the same cluster with that of 4/91. It has been further confirmed by the RDP and SimPlot analysis that QY16 is a recombinant strain deriving from YX10 (as the major parental sequence) and 4/91 (as the minor parental sequence), and that the recombination occurs in a region which includes the 3'-terminal 1b sequence (85 nt) and the 5'-terminal S1 protein gene sequence (1,466 nt). The results of the vaccination-challenge test suggest that QY16 is a nephropathogenic strain of IBV and that the vaccine strains-H120 and 4/91-cannot provide effective protection against it. These results indicate that the continuing evolution of IBV strains by genetic drift and genetic recombination may lead to IBV outbreaks even among the vaccinated chickens in China.
Output: Molecular characteristic and pathogenicity analysis of a virulent recombinant avain infectious bronchitis virus isolated in China
Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK) cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the welldefined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV) by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-a/b production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs) for cytokine production, preserves the conventional dendritic cell (cDC) compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-a administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate cytokine shock and to the promotion of adaptive immunity.
Output: Natural Killer Cells Promote Early CD8 T Cell Responses against Cytomegalovirus
Ebola viruses (EBOV) are filamentous single-stranded RNA viruses of the family Filoviridae. Zaire ebolavirus (ZEBOV) causes severe haemorrhagic fever in humans, great apes and non-human primates (NHPs) with high fatality rates. In contrast, Reston ebolavirus (REBOV), the only species found outside Africa, is lethal to some NHPs but has never been linked to clinical disease in humans despite documented exposure. REBOV was isolated from pigs in the Philippines and subsequent experiments confirmed the susceptibility of pigs to both REBOV and ZEBOV with predilection for the lungs. However, only ZEBOV caused severe lung pathology in 5-6 weeks old pigs leading to respiratory distress. To further elucidate the mechanisms for lung pathology, microarray analysis of changes in gene expression was performed on lung tissue from ZEBOV-infected pigs. Furthermore, systemic effects were monitored by looking at changes in peripheral blood leukocyte subsets and systemic cytokine responses. Following oro-nasal challenge, ZEBOV replicated mainly in the respiratory tract, causing severe inflammation of the lungs and consequently rapid and difficult breathing. Neutrophils and macrophages infiltrated the lungs but only the latter were positive for ZEBOV antigen. Genes for proinflammatory cytokines, chemokines and acute phase proteins, known to attract immune cells to sites of infection, were upregulated in the lungs, causing the heavy influx of cells into this site. Systemic effects included a decline in the proportion of monocyte/dendritic and B cells and a mild proinflammatory cytokine response. Serum IgM was detected on day 5 and 6 post infection. In conclusion, a dysregulation/over-activation of the pulmonary proinflammatory response may play a crucial role in the pathogenesis of ZEBOV infection in 5-6 weeks old pigs by attracting inflammatory cells to the lungs.
Output: ): e61904. Funding: Funding was provided from Defence Research and Development Canada through the Chemical, Biological, Radiological and Nuclear (CBRN) Research and Technology Initiative (CRTI) Cluster Activity fund
Under physical or chemical stress, proteins tend to form aggregates either highly ordered (amyloid) or unordered (amorphous) causing many pathological disorders in human and loss of proteins functionality in both laboratory conditions and industries during production and storage at commercial level. We investigated the effect of increasing temperature on Conalbumin (CA) and induced aggregation at 65 • C. The enhanced Thioflavin T (ThT) and ANS (1-anilinonaphtalene 8-sulfonic acid) fluorescence intensity, show no shift on Congo red binding, additionally, transmission and scanning electron microscopy (TEM) (SEM) reveal amorphous morphology of the aggregate. Our investigation clearly demonstrated that polyols namely Glycerol (GL) and Ethylene glycol (EG) are so staunch to inhibit amorphous aggregates via restoring secondary conformation. Addition of polyols (15% GL and 35% EG) significantly decrease the turbidity, Rayleigh scattering ThT and ANS fluorescence intensity. The dynamic light scattering (DLS) data show that hydrodynamic radii (R h ) of the aggregates is ∼20 times higher than native CA while nearly similar for GL and EG protected CA due to condensation of core size with little difference.
Output: Polyols (Glycerol and Ethylene glycol) mediated amorphous aggregate inhibition and secondary structure restoration of metalloproteinase-conalbumin (ovotransferrin)
Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries on the efficiency of viral detection and virus genome coverage were compared. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces.
Output: Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent NIH Public Access
The function of Semliki Forest Virus nsP2 protease was investigated by site-directed mutagenesis. Mutations were introduced in its protease domain, Pro39, and the mutated proteins were expressed in Escherichia coli, purified and their activity in vitro was compared to that of the wild type Pro39. Mutations M781T, A662T and G577R, found in temperaturesensitive virus strains, rendered the enzyme temperature-sensitive in vitro as well. Five conserved residues were required for the proteolytic activity of Pro39. Changes affecting Cys 478 , His 548 , and Trp 549 resulted in complete inactivation of the enzyme, whereas the replacements N600D and N605D significantly impaired its activity. The importance of Trp 549 for the proteolytic cleavage specificity is discussed and a new structural motif involved in substrate recognition by cysteine proteases is proposed.
Output: Characterization of the cysteine protease domain of Semliki Forest virus replicase protein nsP2 by in vitro mutagenesis
Predicting the course of an epidemic is difficult, predicting the course of a pandemic from an emerging virus even more so. The validity of most predictive models relies on numerous parameters, involving biological and social characteristics often unknown or highly uncertain. COVID-19 pandemic brings additional factors such as population density and movements, 5 behaviours, quality of the health system. Data from the COVID-19 epidemics in China, Japan and South Korea were used to build up data-driven deterministic models. Epidemics occurring in selected European countries rapidly evolved to overtake most Chinese provinces, to overtake South Korean model for France and even Hubei in the case of Italy and Spain. This approach was applied to other European countries and provides relevant information to inform disease 10 control decision-making. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Output: Title: Chaos theory applied to the outbreak of Covid-19: an ancillary approach to decision-making in pandemic context
Understanding the complex population biology and transmission ecology of multihost parasites has been declared as one of the major challenges of biomedical sciences for the 21st century and the Neglected Zoonotic Diseases (NZDs) are perhaps the most neglected of all the Neglected Tropical Diseases (NTDs). Here we consider how multihost parasite transmission and evolutionary dynamics may affect the success of human and animal disease control programmes, particularly neglected diseases of the developing world. We review the different types of zoonotic interactions that occur, both ecological and evolutionary, their potential relevance for current human control activities, and make suggestions for the development of an empirical evidence base and theoretical framework to better understand and predict the outcome of such interactions. In particular, we consider whether preventive chemotherapy, the current mainstay of NTD control, can be successful without a One Health approach. Transmission within and between animal reservoirs and humans can have important ecological and evolutionary consequences, driving the evolution and establishment of drug resistance, as well as providing selective pressures for spill-over, host switching, hybridizations and introgressions between animal and human parasites. Our aim here is to highlight the importance of both elucidating disease ecology, including identifying key hosts and tailoring control effort accordingly, and understanding parasite evolution, such as precisely how infectious agents may respond and adapt to anthropogenic change. Both elements are essential if we are to alleviate disease risks from NZDs in humans, domestic animals and wildlife. Adamo, S., and J. P. Webster 2013. Neural parasitology: how parasites alter host behaviour. Journal of Experimental Biology 216:1-2.
Output: One health -an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases
Orange JS, Du W and Falsey AR (2015) Therapeutic immunoglobulin selected for high antibody titer to RSV also contains high antibody titers to other respiratory viruses. Specific antibodies against infections most relevant to patients with primary immunodeficiency diseases are not routinely evaluated in commercial polyclonal immunoglobulin preparations. A polyclonal immunoglobulin prepared from plasma of donors having high neutralizing antibody titers to respiratory syncytial virus (RSV) was studied for the presence of antibody titers against seven additional respiratory viruses. While donors were not selected for antibody titers other than against RSV, the immunoglobulin preparation had significantly higher titers to 6 of 7 viruses compared to those present in 10 commercially available therapeutic immunoglobulin products (p ≤ 0.01 to p ≤ 0.001). To consider this as a donor-specific attribute, 20 random donor plasma samples were studied individually and identified a significant correlation between the RSV antibody titer and other respiratory virus titers: donors with high RSV titers were more likely to have higher titers to other respiratory viruses. These findings suggest either some humoral antiviral response bias or more frequent viral exposure of certain individuals.
Output: Therapeutic immunoglobulin selected for high antibody titer to RSV also contains high antibody titers to other respiratory viruses
Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.
Output: High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non- Typeable Haemophilus influenzae
Although known that purebreed cats are more likely to develop feline infectious peritonitis (FIP), previous studies have not examined the prevalence of disease in individual breeds. All cats diagnosed with FIP at a veterinary teaching hospital over a 16-year period were identified. Breed, sex and reproductive status of affected cats were compared to the general cat population and to mixed breed cats evaluated during the same period. As with previous studies sexually intact cats and purebreed cats were significantly more likely to be diagnosed with FIP; males and young cats also had a higher prevalence of disease. Abyssinians, Bengals, Birmans, Himalayans, Ragdolls and Rexes had a significantly higher risk, whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues and Siamese cats were not at increased risk for development of FIP. Although additional factors doubtlessly influence the relative prevalence of FIP, this study provides additional guidance when prioritizing differentials in ill purebreed cats.
Output: Prevalence of feline infectious peritonitis in specific cat breeds *
Human bocavirus (HBoV) was identified as the second human parvovirus with pathogenic potential in 2005 in respiratory samples from children suffering from viral respiratory infections of unknown etiology. Since its first description, a large number of clinical studies have been performed that address the clinical significance of HBoV detection and the molecular biology of the virus. This review summarizes the most important steps taken in HBoV research to date and addresses open questions that need to be answered in the future to provide a better understanding of the role of a virus that is difficult to grow in cell culture and is suspected to be a pathogen, although it has not yet fulfilled Koch's postulates.
Output: Human Bocavirus: Lessons Learned to Date
Severe Acute Respiratory Syndrome (SARS) has become a new worldwide epidemic whose origin was until recently unknown. It is the unpredictable nature of this epidemic that makes people want answers to some important questions about what they can do to protect themselves. This study presents an inquiry into people's knowledge and self-reported changes in behavior in response to the epidemic. Respondents were drawn from seven major occupational groups in the large central city of Wuhan. Although most respondents knew of SARS, there was still 8.4% who did not know about it. Knowledge was lowest among farmers who had come to the city for temporary work. Most respondents took action to avoid being infected by SARS, including, most commonly, efforts to improve indoor ventilation, to disinfect the indoor environment and to increase handwashing frequency. Self-reported increases in hand-washing frequency were significant; however, among the seven occupational groups, reports of increased hand-washing were consistently greater among commercial service workers, students and farmers. While it seems that possible fears induced by the epidemic led to these changes, there are still about one-third of respondents who do not wash their hands as frequently as desired. There is also the challenge of devising strategies for maintaining the desired frequency of hand-washing among those who did change.
Output: Severe Acute Respiratory Syndrome epidemic and change of people's health behavior in China
Simulating epidemics in metapopulations is a challenging issue due to the large demographic and geographic scales to incorporate. Traditional epidemiologic models choose to simplify reality by ignoring both the spatial distribution of populations and possible intrapopulation heterogeneities, whereas more recent solutions based on Individual-Based Modeling (IBM) can achieve high precision but are costly to compute and analyze. We introduce here an original alternative to these two approaches, which relies on a novel hybrid modeling framework and incarnates a multiscale view of epidemics. The model relies on a technical fusion of two modeling paradigms: System Dynamics (SD) and Individual-Based Modeling. It features an aggregated representation of local outbreaks rendered in SD, and at the same time a spatially-explicit simulation of the spread between populations simulated in IBM. We first present the design of this deterministic model, show that it can reproduce the dynamics of real resurgent epidemics, and infer from the sensitivity of several spatial factors absent in compartmental models the importance of having large-scale epidemiological processes represented inside of an explicitly disaggregated metapopulation. After discussing the implications of results obtained from simulation runs and the applicability of this model, we conclude that SD-IB hybrid modeling can be an interesting choice to represent epidemics in a spatially-explicit way without necessarily taking into account individual heterogeneities, and therefore it can be considered as a valuable alternative to simple compartmental models suffering from detrimental effects of the well-mixed assumption.
Output: Impact of the topology of metapopulations on the resurgence of epidemics rendered by a new multiscale hybrid modeling approach
In this study, a high-resolution frontal area density (FAD) map that depicts the surface roughness of urban Hong Kong is produced using a mapping method that takes into account the dense urban morphology and the site wind availability of the territory. Using the MM5/CALMET model simulated wind data of Hong Kong, the FAD map of three urban zones are calculated: podium (0-15 m), building (15-60 m), and urban canopy (0-60 m). The wind tunnel test data is used to correlate the FAD understanding of the three zones. The grid sensitivity test indicates that 200 m × 200 m is the reasonable resolution for the FAD map; the test also establishes that the lower urban podium zone yields the best correlation with the experimental data. The study further establishes that the simpler two-dimensional ground coverage ratio (GCR), which is readily available in the planning circle, can be used to predict the area's average pedestrian level urban ventilation performance of the city. Working with their inhouse GIS team using available data, it allows the planners a way to understand the urban ventilation of the city for decisions related to air paths, urban permeability and site porosity.
Output: Improving the wind environment in high-density cities by understanding urban morphology and surface roughness: A study in Hong Kong
Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteriainfecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host-specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed.
Output: Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences
Parasitic agents are a common cause of diarrhea in dogs and cats and, thus, determining their prevalence is essential to establish preventive and control measures. This retrospective study examined the fecal tests records from 1111 dogs and 203 cats with diarrhea submitted to a diagnostic laboratory in the city of Medellin between January and May 2018. The detection of parasites was carried out by direct smears and simple flotation methods. Parasitic organisms were detected in feces from 464 (41.7%) dogs and 96 (47.3%) cats. In order of decreasing prevalence, the parasites detected in dogs were: Giardia intestinalis (13%), ancylostomids (12.6%), Entamoeba spp. (6.1%), coccidian oocysts (5.8%), Toxocara spp. (5.6%) and Dipylidium caninum (1.3%). In cats, the prevalence was: Giardia intestinalis (20%), coccidian oocysts (8.9%), Entamoeba spp. (7.9%), ancylostomids (6.4%), Toxocara spp. (2.5%) and Dipylidium caninum (2%). Age, but not gender, was a predisposing factor, as puppies and kittens had significantly higher infection rates that older age categories. The majority of Giardia intestinalis positive cases occurred in puppies (109/145, 75.2%) and kittens (19/36, 52.8%), making this parasite the most prevalent in amongst animals with diarrhea. Out of 117 positive infections in the adult dog population, ancylostomids accounted for 56 cases (47.9%) and was the most common parasite in this age group. In conclusion, although these results do not imply a cause and effect relationship, they are an estimate of the type of parasites that may be most commonly associated with diarrhea in dogs and cats. The lower diagnostic sensitivity of the traditional methods used here as compared to more contemporary techniques like fecal flotation with centrifugation and PCR, may have underestimated the actual prevalence and diminished the detection of coinfections. Future studies should aim to have diagnostic panels that also screen for other enteric pathogens, including bacterial and viral agents.
Output: Giardia is the most prevalent parasitic infection in dogs and cats with diarrhea in the city of Medellín, Colombia
Background: The 3C-like protease (3CL pro ) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection. Methodology/Principal Findings: To obtain a thorough understanding of substrate specificity of the protease, a substrate library of 19|8 variants was created by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer. The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high b-sheet propensity; P4 prefers small hydrophobic residues; P2 prefers hydrophobic residues without b-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. Conclusions/Significance: Our results demonstrated a strong structure-activity relationship between the 3CL pro and its substrate. The substrate specificity profiled in this study may provide insights into a rational design of peptidomimetic inhibitors.
Output: Profiling of Substrate Specificity of SARS-CoV 3CL pro
The outbreak of a new coronavirus (SARS-CoV-2) disease has become pandemic. To be more effectively controlling the disease, it is critical to set up an optimal quarantine period so that about 95% of the cases developing symptoms will be retained for isolation. At the moment, the WHO-established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases (10 and ~100, respectively), however, over 80% of adult-and 95% of child-cases were not necessary to stay in hospitals, and therefore, had not been hospitalized. Therefore, we are questioning if the current-inferred median incubation time is representative for the whole Covid-19 population, and if the current quarantine period is optimal. We compiled and analyzed the patient-level information of 2015 laboratory-confirmed Covid-19 cases including 99 children in 28 Chinese provinces. This cohort represents a wide-range spectrum of Covid-19 disease with both hospitalized and non-hospitalized cases. The full range of incubation periods of the Covid-19 cases ranged from 0 to 33 days among 2015 cases. There were 6 (0.13%) symptom-free cases including 4 females with a median age of 25.5 years and 2 males with a median age of 36 years. The median incubation period of both male and female adults was similar (7-day) but significantly shorter than that (9-day) of child cases (P=0.02). This cohort contained 4 transmission generations, and incubation periods of the cases between generations were not significantly different, suggesting that the virus has not been rapidly adapted to human beings. Interestingly, incubation periods of 233 cases (11.6%) were longer than the WHO-established quarantine period (14 days). Data modeling suggested that if adults take an extra 4-day or 7-day of isolation (i.e., a quarantine period of 18 or 21 days), 96.2% or 98.3%, respectively, of the people who are developing symptoms will be more effectively quarantined. Patients transmitted via lunch/dinner parties (i.e., gastrointestinal tract infection . CC-BY-NC 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint .
Output: Is a 14-day quarantine period optimal for effectively controlling coronavirus disease 2019 (COVID-19)?
Behavioral finance studies reveal that investor sentiment affects investment decisions and may therefore affect stock pricing. This paper examines whether the geographic proximity of information disseminated by the 2014-2016 Ebola outbreak events combined with intense media coverage affected stock prices in the U.S. We find that the Ebola outbreak event effect is the strongest for the stocks of companies with exposure of their operations to the West African countries (WAC) and the U.S. and for the events located in the WAC and the U.S. This result suggests that the information about Ebola outbreak events is more relevant for companies that are geographically closer to both the birthplace of the Ebola outbreak events and the financial markets. The results also show that the effect is more pronounced for small and more volatile stocks, stocks of specific industry, and for the stocks exposed to the intense media coverage. The event effect is also followed by the elevated perceived risk; that is, the implied volatility increases after the Ebola outbreak events.
Output: Stock prices and geographic proximity of information: Evidence from the Ebola outbreak ☆
This paper articulates the disproportionate policy perspective and uses it to mount four challenges for the new policy design orientation. First, in contrast to the new policy design thinking, disproportionate policy options may be systematically designed, and at times, successfully implemented. Second, in contrast to the new policy design thinking, there are certain conditions under which policymakers may tend to develop effective response, with cost considerations becoming only secondary in importance if at all (read, policy overreaction), or cost-conscious response, with effectiveness considerations becoming only secondary in importance if at all (read, policy underreaction). Third, in contrast to the new policy design thinking, disproportionate policy options may be designed for purposes other than implementation (e.g., to be used as signaling devices or as context-setters). Fourth, in contrast to new policy design thinking, there are certain conditions under which the emotional arena of policy may be equally, if not more, important than the substantive one. The paper concludes that so far the literature on new policy design has not responded to the emergence of the disproportionate policy perspective, but a robust research agenda awaits those answering this paper's call for action.
Output: The implications of the emerging disproportionate policy perspective for the new policy design studies
The replicase of mouse hepatitis virus strain JHM (MHV-JHM) is encoded by two overlapping open reading frames, ORF1a and ORF1b, which are translated to produce a 750-kDa precursor polyprotein. The polyprotein is proposed to be processed by viral proteinases to generate the functional replicase complex. To date, only the MHV-JHM amino-terminal proteins p28 and p72, which is processed to p65, have been identified. To further elucidate the biogenesis of the MHV-JHM replicase, we cloned and expressed five regions of ORF1a in bacteria and prepared rabbit antisera to each region. Using the immune sera to immunoprecipitate radiolabeled proteins from MHV-JHM infected cells, we determined that the MHV-JHM ORF1a is initially processed to generate p28, p72, p250, and p150. Pulse±chase analysis revealed that these intermediates are further processed to generate p65, p210, p40, p27, the MHV 3C-like proteinase, and p15. A putative replicase complex consisting of p250, p210, p40, p150, and a large protein (Ͼ300 kDa) coprecipitate from infected cells disrupted with NP-40, indicating that these proteins are closely associated even after initial proteolytic processing. Immunofluorescence studies revealed punctate labeling of ORF1a proteins in the perinuclear region of infected cells, consistent with a membrane-association of the replicase complex. Furthermore, in vitro transcription/translation studies of the MHV-JHM 3Cpro and flanking hydrophobic domains confirm that 3C protease activity is significantly enhanced in the presence of canine microsomal membranes. Overall, our results demonstrate that the MHV-JHM ORF1a polyprotein: (1) is processed into more than 10 protein intermediates and products, (2) requires membranes for efficient biogenesis, and (3) is detected in discrete membranous regions in the cytoplasm of infected cells.
Output: Processing of the Coronavirus MHV-JHM Polymerase Polyprotein: Identification of Precursors and Proteolytic Products Spanning 400 Kilodaltons of ORF1a
. Bovine monoclonal antibodies to the F5 (K99) pilus antigen of E. coli, produced by murine/bovine hybridomas. Vet. Immunol. Immunopathol., 15: 223-237. Lymph node cells from calves immunized with purified pilus antigen of K99 + enterotoxigenic E. coli (ETEC) were fused with mouse nweloma (NSO) cells, and with non-lg producing mouse/calf hybridomas or with a bovine Ig-producing mouse/calf/calf secondary hybridoma. Lines secreting bovine monoclonal IgG I specific for K99 pilus antigen in an ELISA were obtained in each case. Th~ two lines derived from xenohybridoma fusion partners have been secreting anti-K99 bovine monoclonal antibody for over one year in continual passage. None of the antibodies cross-reacted with other pilus types including K88, CFAI, CFAII, 987P or CP; they all inhibited agglutination of horse RBC (which have a K99 receptor) in the presence of K99 ~ntigen; they showed positive fluorescence in an indirect binding assay on K99 ETEC and inhibited K99-ETEC adhesion to piglet enterocytes. These antibodies have potential prophylactic and therapeutic use in control and treatment of diarrhoea.
Output: BOVINE MONOCLONAL ANTIBODIES TO THE F5 (K99) PILUS ANTIGEN OF E. COLI, PRODUCED BY MURINE/BOVINE HYBRI DOMAS
The severe acute respiratory syndrome coronavirus nucleocapsid protein (SARS-CoV N) is one of the major targets for SARS vaccine due to its high potency in triggering immune responses. In this study, we have identified a novel HLA-A*0201 restricted epitope, N220 (LALLLLDRL), of the SARS-CoV N-protein through bioinformatics analysis. The N-protein peptide N220 shows a high binding affinity towards human MHC class I in T2-cells, and is capable of activating cytotoxic T-cells in human peripheral blood mononuclear cells (PBMCs). The application of using the N220 peptide sequence with a single-chain-trimer (SCT) approach to produce a potential DNA vaccine candidate was investigated in HLA-A2.1K b transgenic mice. Cytotoxicity assay clearly showed that the T-cells obtained from the vaccinated animals were able to kill the N-protein expressing cells with a cytotoxicity level of 86% in an effector cells/target cells ratio of 81:1 one week after the last vaccination, which is significantly higher than other N-protein peptides previously described. The novel immunogenic N-protein peptide revealed in the present study provides valuable information for therapeutic SARS vaccine design.
Output: Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope