Miracle-dz/UniFAR-FTUs huggingface dataset:
Directed evolution of phosphotriesterase: towards the efficient detoxification of sarin and soman

Directed Evolution of Phosphotriesterase: Towards the Efficient Detoxification of Sarin and Soman. (May 2004) Karin T. Lum, A.B. , Smith College Chair of Advisory Committee: Dr. Frank M. Raushel Directed evolution studies were done with PTE for the enhancement of hydrolysis of both sarin and soman analogs. Particular attention was focused on the toxic SpRc and SpSc isomers of the soman analog, and the Sp isomer of the sarin analog. Double substitution libraries yielded several mutants that had enhanced activity for the substrates. Among them was the double mutant, H257Y-L303T, which displayed a 462-fold increase in activity for hydrolysis of the most toxic SpSc isomer of the GD analog in comparison to the wild type. Several other mutants such as the triple mutants H254R-H257A-L303T and H254R-H257SL303T had enhancements of between 150and 200-fold, and had also displayed a different order of stereoselectivity relative to the wild type. For these mutants, the order of preferential hydrolysis was such that the SpRc isomer was preferentially hydrolyzed first. In contrast, the order of preferential hydrolysis for the wild type was that the RpRc was hydrolyzed first, followed by the RpSc, SpRc, and then the SpSc isomer. The reversal of stereoselective preference was also seen with the double substitution library members for hydrolysis of the sarin analog isomers. However, there were no significant improvements for sarin analog hydrolysis in these libraries. Among the best mutants obtained were H254G-H257W, H254G-H257R, and H257Y, all of which had catalytic efficiencies on the order of 10 M s for hydrolysis of the Sp isomer. iv The toxicity for analogs of sarin, soman, and VX was evaluated using Hydra attenuata as a model organism. The toxicity of each compound was assessed quantitatively by measuring the minimal effective concentration within 92 h in H. attenuata. There was a positive correlation between the molecular hydrophobicity of the compound and its ability to cause toxicity. Results from this study indicate the potential for application of this assay in the field of organophosphate nerve agent detection, as well as for the prediction of toxicity of structurally similar organophosphate compounds. The minimal effective concentration for two of the VX analogs was 2 orders of magnitude more toxic than the analog for soman and four orders of magnitude more toxic than the analog for sarin.
Effect of Ferrous Ion on Heat-Induced Aroma Deterioration of Green Tea Infusion

Aroma deterioration is one of the biggest problems in processing tea beverages. The aroma of tea infusion deteriorates fast during heat sterilization and the presence of ferrous ion (Fe2+) aggravates it. The underlying mechanism remains unveiled. In this study, Fe2+ was verified to deteriorate the aroma quality of green tea infusion with heat treatment. Catechins were necessary for Fe2+-mediated aroma deterioration. By enhancing the degradation of catechins, Fe2+ dramatically increased the production of hydrogen peroxide (H2O2). Fe2+ and H2O2 together exacerbated the aroma of green tea infusion with heat treatment. GC-MS analysis revealed that the presence of Fe2+ enhanced the loss of green/grassy volatiles and promoted the formation of new volatiles with diversified aroma characteristics, resulting in a dull scent of green tea infusion. Our results revealed how Fe2+ induced aroma deterioration of green tea infusion with heat treatment and could help guide tea producers in attenuating the aroma deterioration of tea infusion during processing.
Ramadan Observance Is Associated with Impaired Kung-Fu-Specific Decision-Making Skills

The aim of the present study is to evaluate the effect of Ramadan observance (RAM) on decision-making in Kung-Fu athletes. Fourteen male Kung-Fu athletes (mean age = 19 ± 3 years) completed two test sessions: before Ramadan (BR) and at the end of Ramadan (ER). In the afternoon of each session (between 16:00 h and 18:00 h), participants completed: Epworth Sleepiness Scale (ESS), Profile of Mood States (POMS), and Pittsburg Sleep Quality Index (PSQI). Subjects also reported subjective fatigue, alertness, and concentration. Additionally, all participants performed video-based decision-making tasks (i.e., reaction time and decision-making). Results indicated that reaction time decreased by 30% at ER vs. BR (p < 0.01). However, decision-making decreased by 9.5% at ER vs. BR (p < 0.05). PSQI results indicated sleep quality score, sleep duration, and sleep efficiency were negatively affected at ER compared to BR (p < 0.05). ESS was higher at ER compared to BR (p < 0.05). In addition, fatigue scores, estimated by the POMS and current subjective feelings (i.e., fatigue, concentration, and alertness), were also negatively affected at ER compared to BR (p < 0.05). In conclusion, Ramadan observance was associated with an adverse effect on sleep and decision making, as well as feelings of fatigue, alertness, and concentration.
Basal Vitamin D Status and Supplement Dose Are Primary Contributors to Maternal 25-Hydroxyvitamin D Response to Prenatal and Postpartum Cholecalciferol Supplementation

ABSTRACT Background Variability in the 25-hydroxyvitamin D [25(OH)D] response to prenatal and postpartum vitamin D supplementation is an important consideration for establishing vitamin D deficiency prevention regimens. Objectives We aimed to examine interindividual variation in maternal and infant 25(OH)D following maternal vitamin D supplementation. Methods In a randomized trial of maternal vitamin D supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) received a prenatal cholecalciferol (vitamin D-3) dose of 0, 4200, 16,800, or 28,000 IU/wk from 17 to 24 wk of gestation followed by placebo to 6 mo postpartum. A fifth group received 28,000 IU cholecalciferol/wk both prenatally and postpartum. In a subset of participants, associations of 25(OH)D with hypothesized explanatory factors were estimated in women at delivery (n = 655) and 6 mo postpartum (n = 566), and in their infants at birth (n = 502) and 6 mo of age (n = 215). Base models included initial 25(OH)D and supplemental vitamin D dose. Multivariable models were extended to include other individual characteristics and specimen-related factors. The model coefficient of determination (R2) was used to express the percentage of total variance explained. Results Supplemental vitamin D intake and initial 25(OH)D accounted for the majority of variance in maternal 25(OH)D at delivery and postpartum (R2 = 70% and 79%, respectively). Additional characteristics, including BMI, contributed negligibly to remaining variance (<5% increase in R2). Variance in neonatal 25(OH)D was explained mostly by maternal delivery 25(OH)D and prenatal vitamin D intake (R2 = 82%). Variance in 25(OH)D in later infancy could only partly be explained by numerous biological, sociodemographic, and laboratory-related characteristics, including feeding practices (R2 = 43%). Conclusions Presupplementation 25(OH)D and vitamin D supplemental dose are the major determinants of the response to maternal prenatal vitamin D intake. Vitamin D dosing regimens to prevent maternal and infant vitamin D deficiency should take into consideration the mean 25(OH)D concentration of the target population.
Effects of Mutations in TSC Genes on Neurodevelopment and Synaptic Transmission

Mutations in TSC1 or TSC2 genes are linked to alterations in neuronal function which ultimately lead to the development of a complex neurological phenotype. Here we review current research on the effects that reduction in TSC1 or TSC2 can produce on the developing neural network. A crucial feature of the disease pathophysiology appears to be an early deviation from typical neurodevelopment, in the form of structural abnormalities. Epileptic seizures are one of the primary early manifestation of the disease in the CNS, followed by intellectual deficits and autism spectrum disorders (ASD). Research using mouse models suggests that morphological brain alterations might arise from the interaction of different cellular types, and hyperexcitability in the early postnatal period might be transient. Moreover, the increased excitation-to-inhibition ratio might represent a transient compensatory adjustment to stabilize the developing network rather than a primary factor for the development of ASD symptoms. The inhomogeneous results suggest region-specificity as well as an evolving picture of functional alterations along development. Furthermore, ASD symptoms and epilepsy might originate from different but potentially overlapping mechanisms, which can explain recent observations obtained in patients. Potential treatment is determined not only by the type of medicament, but also by the time point of treatment.
Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization

The ability of endocannabinoid (eCB) to change functional microglial phenotype can be explored as a possible target for therapeutic intervention. Since the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of anandamide (AEA), may provide beneficial effects in mice model of Alzheimer’s disease (AD)-like pathology, we aimed at determining whether the FAAH inhibitor URB597 might target microglia polarization and alter the cytoskeleton reorganization induced by the amyloid-β peptide (Aβ). The morphological evaluation showed that Aβ treatment increased the surface area of BV-2 cells, which acquired a flat and polygonal morphology. URB597 treatment partially rescued the control phenotype of BV-2 cells when co-incubated with Aβ. Moreover, URB597 reduced both the increase of Rho protein activation in Aβ-treated BV-2 cells and the Aβ-induced migration of BV-2 cells, while an increase of Cdc42 protein activation was observed in all samples. URB597 also increased the number of BV-2 cells involved in phagocytosis. URB597 treatment induced the polarization of microglial cells towards an anti-inflammatory phenotype, as demonstrated by the decreased expression of iNOS and pro-inflammatory cytokines along with the parallel increase of Arg-1 and anti-inflammatory cytokines. Taken together, these data suggest that FAAH inhibition promotes cytoskeleton reorganization, regulates phagocytosis and cell migration processes, thus driving microglial polarization towards an anti-inflammatory phenotype.
Genomic architecture constrained placental mammal X Chromosome evolution

Susumu Ohno proposed that the gene content of the mammalian X Chromosome should remain highly conserved due to dosage compensation. X Chromosome linkage (gene order) conservation is widespread in placental mammals but does not fall within the scope of Ohno's prediction and may be an indirect result of selection on gene content or selection against rearrangements that might disrupt X-Chromosome inactivation (XCI). Previous comparisons between the human and mouse X Chromosome sequences have suggested that although single-copy X Chromosome genes are conserved between species, most ampliconic genes were independently acquired. To better understand the evolutionary and functional constraints on X-linked gene content and linkage conservation in placental mammals, we aligned a new, high-quality, long-read X Chromosome reference assembly from the domestic cat (incorporating 19.3 Mb of targeted BAC clone sequence) to the pig, human, and mouse assemblies. A comprehensive analysis of annotated X-linked orthologs in public databases demonstrated that the majority of ampliconic gene families were present on the ancestral placental X Chromosome. We generated a domestic cat Hi-C contact map from an F1 domestic cat/Asian leopard cat hybrid and demonstrated the formation of the bipartite structure found in primate and rodent inactivated X Chromosomes. Conservation of gene order and recombination patterns is attributable to strong selective constraints on three-dimensional genomic architecture necessary for superloop formation. Species with rearranged X Chromosomes retain the ancestral order and relative spacing of loci critical for superloop formation during XCI, with compensatory inversions evolving to maintain these long-range physical interactions.
Role of Dendritic Cell in Diabetic Nephropathy

Diabetic nephropathy (DN) is one of the most significant microvascular complications in diabetic patients. DN is the leading cause of end-stage renal disease, accounting for approximately 50% of incident cases. The current treatment options, such as optimal control of hyperglycemia and elevated blood pressure, are insufficient to prevent its progression. DN has been considered as a nonimmune, metabolic, or hemodynamic glomerular disease initiated by hyperglycemia. However, recent studies suggest that DN is an inflammatory disease, and immune cells related with innate and adaptive immunity, such as macrophage and T cells, might be involved in its development and progression. Although it has been revealed that kidney dendritic cells (DCs) accumulation in the renal tissue of human and animal models of DN require activated T cells in the kidney disease, little is known about the function of DCs in DN. In this review, we describe kidney DCs and their subsets, and the role in the pathogenesis of DN. We also suggest how to improve the kidney outcomes by modulating kidney DCs optimally in the patients with DN.
Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

There is a lack of research regarding blood tests within individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and between patients and healthy controls. We aimed to compare results of routine blood tests between patients and healthy controls. Data from 149 patients diagnosed with ME/CFS based on clinical and psychiatric evaluation as well as on the DePaul Symptom Questionnaire, and data from 264 healthy controls recruited from blood donors were compared. One-way ANCOVA was conducted to examine differences between ME/CFS patients and healthy controls, adjusting for age and gender. Patients had higher sedimentation rate (mean difference: 1.38, 95% CI: 0.045 to 2.714), leukocytes (mean difference: 0.59, 95% CI: 0.248 to 0.932), lymphocytes (mean difference: 0.27, 95% CI: 0.145 to 0.395), neutrophils (mean difference: 0.34, 95% CI: 0.0 89 to 0.591), monocytes (mean difference: 0.34, 95% CI: 0.309 to 0.371), ferritin (mean difference: 28.13, 95% CI: −1.41 to 57.672), vitamin B12 (mean difference: 83.43, 95% CI: 62.89 to 124.211), calcium (mean difference: 0.02, 95% CI: −0.02 to 0.06), alanine transaminase (mean difference: 3.30, 95% CI: −1.37 to -7.971), low-density lipoproteins (mean difference: 0.45, 95% CI: 0.104 to 0.796), and total proteins (mean difference: 1.53, 95% CI: −0.945 to 4.005) than control subjects. The patients had lower potassium levels (mean difference: 0.11, 95% CI: 0.056 to 0.164), creatinine (mean difference: 2.60, 95% CI: 0.126 to 5.074) and creatine kinase (CK) (mean difference: 37.57, 95% CI: −0.282 to 75.422) compared to the healthy controls. Lower CK and creatinine levels may suggest muscle damage and metabolic abnormalities in ME/CFS patients.
Multi-Camera Vessel-Speed Enforcement by Enhancing Detection and Re-Identification Techniques †

This paper presents a camera-based vessel-speed enforcement system based on two cameras. The proposed system detects and tracks vessels per camera view and employs a re-identification (re-ID) function for linking vessels between the two cameras based on multiple bounding-box images per vessel. Newly detected vessels in one camera (query) are compared to the gallery set of all vessels detected by the other camera. To train and evaluate the proposed detection and re-ID system, a new Vessel-reID dataset is introduced. This extensive dataset has captured a total of 2474 different vessels covered in multiple images, resulting in a total of 136,888 vessel bounding-box images. Multiple CNN detector architectures are evaluated in-depth. The SSD512 detector performs best with respect to its speed (85.0% Recall@95Precision at 20.1 frames per second). For the re-ID of vessels, a large portion of the total trajectory can be covered by the successful detections of the SSD model. The re-ID experiments start with a baseline single-image evaluation obtaining a score of 55.9% Rank-1 (49.7% mAP) for the existing TriNet network, while the available MGN model obtains 68.9% Rank-1 (62.6% mAP). The performance significantly increases with 5.6% Rank-1 (5.7% mAP) for MGN by applying matching with multiple images from a single vessel. When emphasizing more fine details by selecting only the largest bounding-box images, another 2.0% Rank-1 (1.4% mAP) is added. Application-specific optimizations such as travel-time selection and applying a cross-camera matching constraint further enhance the results, leading to a final 88.9% Rank-1 and 83.5% mAP performance.
Factors Influencing Patient Compliance during Clear Aligner Therapy: A Retrospective Cohort Study

Compliance is highly relevant during clear aligner therapy (CAT). In this retrospective cohort study, we assessed compliance and associated covariates in a large cohort of CAT patients. A comprehensive sample of 2644 patients (75.0% females, 25.0% males, age range 18–64 years, median 27 years), all receiving CAT with PlusDental (Berlin, Germany) finished in 2019, was analyzed. Covariates included demographic ones (age, gender) as well as self-reported questionnaire-obtained ones (satisfaction with ones’ smile prior treatment, the experience of previous orthodontic therapy). The primary outcome was compliance: Based on patients’ consistent use of the mobile application for self-report and aligner wear time of ≥22 h, patients were classified as fully compliant, fairly compliant, or poorly compliant. Chi-square test was used to compare compliance in different subgroups. A total of 953/2644 (36.0%) of patients showed full compliance, 1012/2644 (38.3%) fair compliance, and 679/2644 (25.7%) poor compliance. Males were significantly more compliant than females (p = 0.000014), as were patients without previous orthodontic treatment (p = 0.023). Age and self-perceived satisfaction with ones’ smile prior to treatment were not sufficiently associated with compliance (p > 0.05). Our findings could be used to guide practitioners towards limitedly compliant individuals, allowing early intervention.
Demographics, Socioeconomic Status, Social Distancing, Psychosocial Factors and Psychological Well-Being among Undergraduate Students during the COVID-19 Pandemic

The COVID-19 pandemic impacted on academic routine because of the social distancing measures. This study examined the relationships of sociodemographic characteristics, social distancing aspects and psychosocial factors on psychosocial well-being among undergraduate students during the social distancing period due to COVID-19. A web-based survey was conducted of undergraduate students at a public university in Brazil (n = 620). Demographics, socioeconomic status (SES), social distancing factors, negative affectivity (DASS-21), sense of coherence (SOC-13), social support and psychosocial well-being (GHQ-12) were measured. The direct and indirect links between was variables was tested using structural equation modelling. The estimated model showed that greater social support, higher sense of coherence and lower negative affectivity were directly associated with better psychological well-being. Female gender, higher SES, not working during the social distancing period and availability of online modules were indirectly associated with psychological well-being through psychosocial factors. Working during the social distancing period and availability of online modules mediated the link of age, gender, SES with psychological well-being. Our findings suggest the need to provide psychological support, online teaching and financial aid to undergraduate students during the social distancing period due to COVID-19 pandemic to improve their psychological well-being.
Investigation into the Effect of Spinel Pigments on the Photostability and Combustion Properties of Ethylene-Norbornene Copolymer

Multicolor ethylene-norbornene (EN) composites filled with three different spinel pigments (Cobalt Green-PG50, Zinc Iron Yellow-PY 119, Praseodym Yellow-PY159) were prepared by melt mixing and characterized in terms of their stability under destructive environmental conditions. The EN films were subjected to accelerated aging by ultraviolet (UV) photooxidation for 300 h, 600 h, or 900 h. The mechanical performance of the EN composites was investigated in static and dynamic mechanical tests. The morphologies of the EN samples and their color changes during the aging process were evaluated by scanning electron microscopy (SEM) and spectrophotometric measurements. Fourier transform infrared (FTIR) spectroscopy was applied to determine the amount of carbonyl groups resulting from surface oxidation at different aging times. The effects of the spinel pigments on the thermal stability and combustion properties of the multicolor polymer composites were also assessed, and compared with a sample containing the organic Pigment Yellow 139 (PY139). The results show that the color changes (ΔE) in the spinel pigments were minor in comparison to those in the organic pigment (PY139) and the reference film. The Zinc Yellow (PY119) pigment was the most effective stabilizer of EN copolymer. Moreover, the spinel pigments had a positive effect on the flame retardancy of the EN composites. Microcombustion tests (MCC) showed that the incorporation of both the spinels and the organic pigment PY139 into the EN matrix reduced the heat release rate (HRR) and total heat release (THR) parameters.
Evaluation of a Fourth-Year Student Pharmacist Research Process at a Community Teaching Health System

Objective. To evaluate a process developed to support research by fourth-year student pharmacists enrolled in an advanced pharmacy practice experience at a health system affiliated with a school of pharmacy. Methods. In 2017, clinical, non-tenure track faculty transitioned from facilitating a fourth-year research elective to implementing a new student research process that matches students to research preceptors at the beginning of the academic year and provides training and resources to them throughout the year. This pre-post study evaluated student pharmacist research participation, dissemination, and placement into a residency or job position at the time of graduation, and then compared data for the three years before the new process was implemented to data for the three years after implementation. Results. Thirty-three fourth-year students assigned to the health system graduated from 2015 to 2017, and 31 graduated from 2018 to 2020. The percentage of students in each cohort who completed research projects increased significantly (48.5% vs 87.1%), the number of projects increased significantly (18 vs 35), the number of presentations increased significantly (29 vs 63), and the number of publications increased significantly (9 vs 20). The percentage of research students who pursued postgraduate training increased (68.8% vs 96.3%), as did their rate of placement into training programs (81.8% vs 92.3%). Of those students who did not participate in research, the percent who pursued training also increased (17.6% vs 75%), but the rate of placement remained the same (66.7%). Conclusion. Matching fourth-year student pharmacists to research preceptors at the beginning of the academic year and providing them with training and resources throughout the year was associated with increased research productivity.