A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide

The naturally occurring nucleotide 3′-deoxy-3′,4′-didehydro-cytidine-5′-triphosphate (ddhCTP) was recently found to exert potent and broad-spectrum antiviral activity. However, nucleoside 5′-triphosphates in general are not cell-permeable, which precludes the direct use of ddhCTP as a therapeutic. To harness the therapeutic potential of this endogenous antiviral nucleotide, we synthesized phosphoramidate prodrug HLB-0532247 (1) and found it to result in dramatically elevated levels of ddhCTP in cells. We compared 1 and 3′-deoxy-3′,4′-didehydro-cytidine (ddhC) and found that 1 more effectively reduces titers of Zika and West Nile viruses in cell culture with minimal nonspecific toxicity to host cells. We conclude that 1 is a promising antiviral agent based on a novel strategy of facilitating elevated levels of the endogenous ddhCTP antiviral nucleotide

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development

Complete genome characterization of two wild-type measles viruses from Vietnamese infants during the 2014 outbreak

A large measles virus outbreak occurred across Vietnam in 2014. We identified and obtained complete measles virus genomes in stool samples collected from two diarrheal pediatric patients in Dong Thap Province. These are the first complete genome sequences of circulating measles viruses in Vietnam during the 2014 measles outbreak

Continuous Earned Value Management with Singularity Functions for Comprehensive Project Performance Tracking and Forecasting

[EN] Earned value management (EVM) is a classical project monitoring technique that is widely used in construction projects. Due to its simplicity, this technique suffers from limitations due to its discrete nature ¿ activity durations, costs, and progress are gathered only at update points with no information in between. These limitations preclude EVM from being easily implemented on some project types (e.g. repetitive projects) and in conjunction with some planning techniques (e.g. linear scheduling), where information continuity is both possible and desired. Therefore, in EVM is reformulated based on singularity functions (SF). SF are a type of expressions that can be easily concatenated to model continuous inputs at the activity-level. SF are also additive so as to immediately yield project-level performance information. It is demonstrated how the complete theory of EVM is newly expressed in SF. This offers several advantages: (1) EVM metric axes can be easily swapped (allowing exact calculation of modern metrics such as Earned Schedule or the p-factor); (2) activity progress data can be inserted at any frequency as the available data allow; and (3) short-term project duration and cost forecasts are directly possible for the first time. These advantages are exemplified on a real construction project. Finally, it is discussed how the new formulation with SF produces more accurate project duration and cost estimates compared to the former discrete EVM on real construction projects.The first author was supported by Undergraduate Internship Funds, School of Engineering Executive Committee, Catholic University of America, September 28, 2020 - December 31, 2020 / January 1, 2021 - April 30, 2021 / May 16 - August 15, 2021.Ngo, KA.; Lucko, G.; Ballesteros-Pérez, P. (2022). Continuous Earned Value Management with Singularity Functions for Comprehensive Project Performance Tracking and Forecasting. Automation in Construction. 143:1-10. https://doi.org/10.1016/j.autcon.2022.10458311014

Virus Detection Protocols for West Nile Virus in Vertebrate and Mosquito Specimens

The recent outbreaks of West Nile virus (WNV) infection in the northeastern United States and other regions of the world have made it essential to develop efficient, sensitive, and rapid protocols for virus surveillance. Laboratory testing is the backbone of any surveillance program. Protocols to detect the presence of WNV have been refined since 1999 for sensitivity, speed, efficiency, and specificity. This paper presents the protocols currently used by the New York State Department of Health to handle vertebrate and mosquito specimens that have been submitted for WNV testing to the Arbovirus Laboratories of the Wadsworth Center

Symptoms and risk factors for stroke in a community-based observational sample in Viet Nam

Background: Viet Nam is experiencing a health transition from infectious to chronic disease. Data on cardiovascular diseases, including strokes, are limited. Methods: Data were randomly collected from six communities in Da Nang, Viet Nam, on participant demographics, medical history, blood pressure, anthropometrics and health behavior using World Health Organization (WHO) guidelines. Stroke symptoms were collected by self-report with the standardized Questionnaire for Verifying Stroke Free Status. Multivariate logistic regression was used to identify factors associated with the presence of stroke symptoms. Results: One thousand six hundred and twenty one adults were examined with a mean age of 52.0 years (±12.5 years), of which 56.1% were women. 27.3% of the participants were found to have hypertension, 26.2% used tobacco, and 16.1% were overweight. More than two-thirds of the participants with hypertension were unaware of their condition. Almost one fourth of the participants were identified by the questionnaire as previously experiencing at least one stroke symptom. Age, rural residence, and education were associated with the presence of stroke symptoms. Models adjusted for demographics found hypertension, high cholesterol, reported severe chest pain, former smoking, and being overweight to be associated with a higher prevalence of stroke symptoms. Conclusions: The high frequency of stroke symptoms in Da Nang calls for further evaluation and interventions to reduce hypertension and other risk factors for chronic disease in Viet Nam and other health transition countries