Effect of container opening area on air distribution during precooling of horticultural produce

An existing research tool was used to investigate air distribution in horticultural produce containers during forced-air precooling. This tool consisted of an instrumented produce simulator that allowed indirect measurement of surrounding air velocity at different positions inside a package. Using this new research tool for different forced-air cooling conditions, the surrounding air velocity was inferred as a function of the simulator's location in reference to the air entrance. The air pathway during the cooling process was investigated for three total package-opening areas (0.67%, 2%, 6%) at airflow rates ranging from 0.125 to 3.9 L s(-1) kg(-1). The air approach velocity at each position inside a package rose as the opening area increased More vented area also enhanced the cooling efficiency. However increasing the airflow rate resulted in a greater air pressure drop. Opening areas more than 6% of the package surface should be tested to achieve the maximum necessary vented configuration that meets the structure constraints and generates air distribution and cooling efficiency not significantly different from fully open.4762033203

Regulation of host gene expression by HIV-1 TAR microRNAs

Background: The transactivating response (TAR) element of human immunodeficiency virus type 1 (HIV-1) is the source of two functional microRNAs (miRNAs), miR-TAR-5p and miR-TAR-3p. The objective of this study was to characterize the post-transcriptional regulation of host messenger RNAs (mRNAs) relevant to HIV-1 pathogenesis by HIV-1 TAR miRNAs. Results: We demonstrated that TAR miRNAs derived from HIV-1 can incorporate into host effector Argonaute protein complexes, which is required if these miRNAs are to regulate host mRNA expression. Bioinformatic predictions and reporter gene activity assays identified regulatory elements complementary and responsive to miR-TAR-5p and miR-TAR-3p in the 3’ untranslated region (UTR) of several candidate genes involved in apoptosis and cell survival. These include Caspase 8, Aiolos, Ikaros and Nucleophosmin (NPM)/B23. Analyses of Jurkat cells that stably expressed HIV-1 TAR or contained a full-length latent HIV provirus suggested that HIV-1 TAR miRNAs could regulate the expression of genes in T cells that affect the balance between apoptosis and cell survival. Conclusions: HIV-1 TAR miRNAs may contribute to the replication cycle and pathogenesis of HIV-1, by regulating host genes involved in the intricate balance between apoptosis and infected cell, to induce conditions that promote HIV-1 propagation and survival

Demonstration of Patient-Specific Simulations to Assess Left Atrial Appendage Thrombogenesis Risk

Atrial fibrillation (AF) alters left atrial (LA) hemodynamics, which can lead to thrombosis in the left atrial appendage (LAA), systemic embolism and stroke. A personalized risk-stratification of AF patients for stroke would permit improved balancing of preventive anticoagulation therapies against bleeding risk. We investigated how LA anatomy and function impact LA and LAA hemodynamics, and explored whether patient-specific analysis by computational fluid dynamics (CFD) can predict the risk of LAA thrombosis. We analyzed 4D-CT acquisitions of LA wall motion with an in-house immersed-boundary CFD solver. We considered six patients with diverse atrial function, three with either a LAA thrombus (removed digitally before running the simulations) or a history of transient ischemic attacks (LAAT/TIA-pos), and three without a LAA thrombus or TIA (LAAT/TIA-neg). We found that blood inside the left atrial appendage of LAAT/TIA-pos patients had marked alterations in residence time and kinetic energy when compared with LAAT/TIA-neg patients. In addition, we showed how the LA conduit, reservoir and booster functions distinctly affect LA and LAA hemodynamics. Finally, fixed-wall and moving-wall simulations produced different LA hemodynamics and residence time predictions for each patient. Consequently, fixed-wall simulations risk-stratified our small cohort for LAA thrombosis worse than moving-wall simulations, particularly patients with intermediate LAA residence time. Overall, these results suggest that both wall kinetics and LAA morphology contribute to LAA blood stasis and thrombosis.This work was partially supported by the Comunidad de Madrid (Sinergias Y2018/BIO-4858 PREFI-CM), Cátedra Excelencia UC3M-Santander, Ministry of Education of Spain (Salvador de Madariaga program), the US NHLBI (NCAI-UCCAI-2017-06-6), the United States American Heart Association (AHA 20POST35200401), and the 2019 UCSD GEM Program. Computational time provided by XSEDE (Comet) and RES (Altamira) is gratefully acknowledged

Models of Somatic Hypermutation Targeting and Substitution Based on Synonymous Mutations from High-Throughput Immunoglobulin Sequencing Data

Analyses of somatic hypermutation (SHM) patterns in B cell immunoglobulin (Ig) sequences contribute to our basic understanding of adaptive immunity, and have broad applications not only for understanding the immune response to pathogens, but also to determining the role of SHM in autoimmunity and B cell cancers. Although stochastic, SHM displays intrinsic biases that can confound statistical analysis, especially when combined with the particular codon usage and base composition in Ig sequences. Analysis of B cell clonal expansion, diversification, and selection processes thus critically depends on an accurate background model for SHM micro-sequence targeting (i.e., hot/cold-spots) and nucleotide substitution. Existing models are based on small numbers of sequences/mutations, in part because they depend on data from non-coding regions or non-functional sequences to remove the confounding influences of selection. Here, we combine high-throughput Ig sequencing with new computational analysis methods to produce improved models of SHM targeting and substitution that are based only on synonymous mutations, and are thus independent of selection. The resulting “S5F” models are based on 806,860 Synonymous mutations in 5-mer motifs from 1,145,182 Functional sequences and account for dependencies on the adjacent four nucleotides (two bases upstream and downstream of the mutation). The estimated profiles can explain almost half of the variance in observed mutation patterns, and clearly show that both mutation targeting and substitution are significantly influenced by neighboring bases. While mutability and substitution profiles were highly conserved across individuals, the variability across motifs was found to be much larger than previously estimated. The model and method source code are made available at http://clip.med.yale.edu/SH

Waveshifters and Scintillators for Ionizing Radiation Detection

Scintillation and waveshifter materials have been developed for the detection of ionizing radiation in an STTR program between Ludlum Measurements, Inc. and the University of Notre Dame. Several new waveshifter materials have been developed which are comparable in efficiency and faster in fluorescence decay than the standard material Y11 (K27) used in particle physics for several decades. Additionally, new scintillation materials useful for fiber tracking have been developed which have been compared to 3HF. Lastly, work was done on developing liquid scintillators and paint-on scintillators and waveshifters for high radiation environments

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand

Endogenous DNA damage is removed mainly via base excision repair (BER), however, whether there is preferential strand repair of endogenous DNA damage is still under intense debate. We developed a highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify in vivo endogenous DNA damage. Using PADDA, we documented significantly higher levels of endogenous damage in Saccharomyces cerevisiae cells in stationary phase than in exponential phase. We also documented that yeast BER-defective cells have significantly higher levels of endogenous DNA damage than isogenic wild-type cells at any phase of growth. PADDA provided detailed fingerprint analysis at the single-nucleotide level, documenting for the first time that persistent endogenous nucleotide damage in CAN1 co-localizes with previously reported spontaneous CAN1 mutations. To quickly and reliably quantify endogenous strand-specific DNA damage in the constitutively expressed CAN1 gene, we used PADDA on a real-time PCR setting. We demonstrate that wild-type cells repair endogenous damage preferentially on the CAN1 transcribed strand. In contrast, yeast BER-defective cells accumulate endogenous damage preferentially on the CAN1 transcribed strand. These data provide the first direct evidence for preferential strand repair of endogenous DNA damage and documents the major role of BER in this process