Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of Enzyme Kinetic Parameters of Cell Surface-displayed Organophosphorus Hydrolase and Construction of a Biosensing System for Organophosphorus Compounds

Yeast cells displaying organophosphorus hydrolase (OPH), which was anchored using a lectin-like cell-wall protein (Flo1p), were used as a biocatalyst for the detection of organophosphorus compounds (OPs). The concentration of p -nitrophenol produced by the hydrolysis of the OPs paraoxon was calculated from the absorbance change at 415 nm during a 30-min reaction. The apparent Michaelis-Menten constant ( K ′_m) for surface-displayed OPH was estimated to be approximately 50 µM, which is consistent with the value of purified OPH, and shows that cell-surface expression is a useful strategy to overcome the mass-transport resistance of substrates across the cell membrane. Notably, the long-term storage stability of the enzyme activity exceeded 40 days when cells displaying OPH were preserved at temperatures below −4°C. A fiber-optic biosensing system was also constructed using a commercial optical-fiber detection device and yeast cells with surface-displayed OPH. A linear relationship was obtained for paraoxon concentrations of up to 50 ppm (182 µM), with a detection sensitivity of 0.0043 A.U. per ppm ( R ^2 = 0.9574) and a detection limit of 5 ppm (18 µM).
GPU-Based Point Cloud Superpositioning for Structural Comparisons of Protein Binding Sites

In this paper, we present a novel approach to solve the labeled point cloud superpositioning problem for performing structural comparisons of protein binding sites. The solution is based on a parallel evolution strategy that operates on large populations and runs on GPU hardware. The proposed evolution strategy reduces the likelihood of getting stuck in a local optimum of the multimodal real-valued optimization problem represented by labeled point cloud superpositioning. The performance of the GPU-based parallel evolution strategy is compared to a previously proposed CPU-based sequential approach for labeled point cloud superpositioning, indicating that the GPU-based parallel evolution strategy leads to qualitatively better results and significantly shorter runtimes, with speed improvements of up to a factor of 1,500 for large populations. Binary classification tests based on the ATP, NADH, and FAD protein subsets of CavBase, a database containing putative binding sites, show average classification rate improvements from about 92 percent (CPU) to 96 percent (GPU). Further experiments indicate that the proposed GPU-based labeled point cloud superpositioning approach can be superior to traditional protein comparison approaches based on sequence alignments.
Activation Mapping from the Coronary Sinus May Be Limited by Anatomic Variations

The purpose of this study was to examine the anatomic relationship between the mitral annulus (MA) and the coronary sinus (CS). Fifty consecutive hearts of 31 men and 19 women, 63.5 ± 13.7 years of age, were examined at autopsy. MA was divided perpendicularly to the annular plane into an anteromedial block and a posterolateral block by sectioning from the CS ostium through the center of MA. The posterolateral block was subdivided radially into five equal sections at 36°, 72°, 108°, 144°, and 180°. The distance from the ventricular endocardium under MA to the nearest wall of CS (D) was measured in each cross‐section. D measured 9.7 ± 2.3, 10.9 ± 3.3, 10.2 ± 3.6, 9.2 ± 3.4, and 8.2 ± 2.9 mm at 36°, 72°, 108°, 144°, and 180°, respectively. D at 72 was significantly longer than at 144° and 180° (P < 0.01). Likewise, D at 108° was significantly longer than at 144° and 180° (P < 0.05). The population was divided according to the morphology into five patterns. “Type C” the pattern that separated in the middle section and then reapproximated, was more common (66%) than any other pattern. D was confirmed to be longest at the level of the 72° section, corresponding to a left posterolateral free‐wall location. The potential mapping in CS would be easily modified by this anatomic feature. When mapping activation from the CS, the electrophysiohgical data should be interpreted in light of these anatomic findings.
Clinical and Molecular Features of Decreased Chlorhexidine Susceptibility among Nosocomial Staphylococcus aureus Isolates at Texas Children's Hospital

ABSTRACT One of the strategies utilized to decrease infections in the hospital setting relies on topical antimicrobials and antiseptics. While their use is beneficial, concerns arise over the potential to develop resistance or tolerance to these agents. We examined nosocomial Staphylococcus aureus isolates from 2007 to 2013 for the presence of genes associated with tolerance to chlorhexidine. Isolates and patients were identified from an S. aureus surveillance study at Texas Children's Hospital. Nosocomial S. aureus isolates (those causing infection at ≥72 h of hospitalization) were identified and underwent PCR for the qacA or qacB (qacA/B) and smr genes associated with elevated minimum bactericidal concentrations of chlorhexidine. Molecular typing with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and agr typing and a review of the medical record were performed. Two hundred forty-seven nosocomial S. aureus infections were identified. Overall, 111 isolates carried one or both genes (44.9%); 33.1% were positive for smr, 22.7% were positive for qacA/B, and 10.9% of the isolates possessed both genes. The smr-positive isolates were more often resistant to methicillin, ciprofloxacin, and/or clindamycin. The isolates positive for qacA/B were more often associated with indwelling central venous catheters and a vancomycin MIC of ≥2 μg/ml. Isolates carrying either smr or qacA/B were associated with a diagnosis of bacteremia. The smr-positive isolates more often belonged to sequence type 8 (ST8) than the isolates that were positive for qacA/B. Mupirocin resistance was detected in 2.8% of the isolates. Antiseptic-tolerant S. aureus strains are common in our children's hospital and are associated with decreased susceptibility to other systemic antimicrobials and with bloodstream infections. Further work is needed to understand the implications that these organisms have on the hospital environment and antiseptic use in the future.
Relationship between changes in depressive symptoms and unhealthy lifestyles in late middle aged and older persons: results from the Longitudinal Aging Study Amsterdam.

BACKGROUND depressed mood is common in late life, more prevalent among the chronically diseased than in the general population, and has various health-related consequences. So far, the association between depression and unhealthy lifestyles among chronically diseased has not been examined longitudinally in older persons. PRIMARY OBJECTIVE to determine if depressed mood is associated with unhealthy lifestyles in late middle aged and older people, with or without chronic somatic diseases. METHODS in a sample of 1,280 community-dwelling people from the Netherlands, the associations between depressive symptoms and lifestyle domains were analysed cross-sectionally and longitudinally - using logistic regression analyses and multivariate analyses of variance. RESULTS after controlling for confounders, depressed people (n=176 at baseline) were more likely to be smokers (odds ratio 1.71; 95% confidence interval 1.17-2.52). A persistent depression was associated with an increase in cigarette consumption (P=0.036). Having an emerging depression (n=155) was most likely to co-occur with a person's change from being physically active to being sedentary (relative risk-ratio 1.62; 95% confidence interval 1.05-2.52), and was associated with the largest decrease in minutes of physical activity (P=0.038). This effect was not modified or confounded by chronic somatic disease. A persistent depression tended to be associated with incident excessive alcohol use (relative risk-ratio 4.04; 95% confidence interval 0.97-16.09; P=0.056). CONCLUSIONS depression is associated with smoking behaviour, and with an increase in cigarette consumption. An emerging depression is associated with becoming sedentary, irrespective of a person's disease status at baseline, and is associated with decrease in minutes of physical activity.
Physical Layer Time Interleaving for the ATSC 3.0 System

This paper presents optimized time interleaving which has been adopted for the Advanced Television System Committee 3.0 system as a physical layer tool to mitigate the effects of burst errors. The adopted time interleaver (TI) is very flexible and can have different configurations according to the number of physical layer pipes (PLPs) and service type, i.e., fixed, portable, and mobile. Notably, for single-PLP mode a sheer convolutional TI (CTI) is used, whereas for the multiple-PLP mode a hybrid TI (HTI) composed of cell interleaver, twisted block interleaver, and a convolutional delay-line is used. Optionally, the CTI and the HTI can be used in conjunction with extended time interleaving and a cell interleaver (only for HTI) to further improve robustness over long burst error lengths at the expense of latency.
[In vitro dexamethasone release from nanoparticles and its pharmacokinetics in the inner ear after administration of the drug-loaded nanoparticles via the round window].

OBJECTIVE To investigate the feasibility of local drug delivery into the inner ear using solid lipid nanoparticles (SLN) and evaluate its potential for inner ear disease treatment in terms of the pharmacokinetics of the delivered drug in the inner ear. METHODS Dexamethasone acetate (DA)-loaded SLN was prepared with Compritol 888 ATO as the matrix by means of hot dispersion-ultrasonic technique. A high-performance liquid chromatography (HPLC) was established for determining DA and dexamethasone (Dex). The pharmaceutical properties of DA-loaded SLN including the particle size, entrapment ratio and in vitro release were estimated. DA-loaded SLN was administered via intratympanic injection or intravenous injection in guinea pigs and Dex concentration in the perilymph was measured with HPLC for estimation of the pharmacokinetic parameters. RESULTS The mean diameter of the DA-loaded SLN was 106.8 nm with entrapment ratio of 83.8%, and the in vitro DA release from the nanoparticles well conformed to Weibull distribution, with sustained-release of DA from the SLN exceeding 6 days. After intravenous injection of DA-loaded SLN in guinea pigs, Dex failed to be detected in the perilymph. Compared with Dex-loaded in situ gel following intratympanic injection, the relative bioavailability of Dex in the perilymph was 504% following intratympanic injection of DA-loaded SLN, which also resulted in increased t(1/2) and mean residence time (MRT) by 0.5 and 1.9 folds respectively. CONCLUSION Nanoparticles can be a promising tympanic drug delivery system for topical drug administration in the treatment of inner ear diseases.
Delayed recall, hippocampal volume and Alzheimer neuropathology

Objective: To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. Methods: Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer’s Disease Delayed Word Recall Test administered an average of 1 year prior to death. Results: When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. Conclusions: The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.
Premelanosome Amyloid-like Fibrils Are Composed of Only Golgi-processed Forms of Pmel17 That Have Been Proteolytically Processed in Endosomes*

Melanin pigments are synthesized within specialized organelles called melanosomes and polymerize on intraluminal fibrils that form within melanosome precursors. The fibrils consist of proteolytic fragments derived from Pmel17, a pigment cell-specific integral membrane protein. The intracellular pathways by which Pmel17 accesses melanosome precursors and the identity of the Pmel17 derivatives within fibrillar melanosomes have been a matter of debate. We show here that antibodies that detect Pmel17 within fibrillar melanosomes recognize only the luminal products of proprotein convertase cleavage and not the remaining products linked to the transmembrane domain. Moreover, antibodies to the N and C termini detect only Pmel17 isoforms present in early biosynthetic compartments, which constitute a large fraction of detectable steady state Pmel17 in cell lysates because of slow early biosynthetic transport and rapid consumption by fibril formation. Using an antibody to a luminal epitope that is destroyed upon modification by O-linked oligosaccharides, we show that all post-endoplasmic reticulum Pmel17 isoforms are modified by Golgi-associated oligosaccharide transferases, and that only processed forms contribute to melanosome biogenesis. These data indicate that Pmel17 follows a single biosynthetic route from the endoplasmic reticulum through the Golgi complex and endosomes to melanosomes, and that only fragments encompassing previously described functional luminal determinants are present within the fibrils. These data have important implications for the site and mechanism of fibril formation.
Characterization of luteinizing hormone secretion in the primiparous, lactating sow: relationship to blood metabolites and return-to-estrus interval.

Lactating, primiparous Landrace x Yorkshire sows were used to characterize LH secretion during lactation in sows that experienced an early (less than 9 d; n = 14) or late (greater than 15 d; n = 9) return to estrous postweaning and to evaluate the relationship between LH secretion and blood metabolites. Twenty-three sows were fed one of nine corn-soybean meal diets to achieve a matrix of lysine (15 to 45 g/d) and energy (6.5 to 16.5 Mcal of ME/d) intakes and a range in metabolite concentrations and return-to-estrus intervals. Blood samples for LH analysis were collected every 15 min for 6 h on d 0, 7, 14, 21, and 28 of lactation. Circulating concentrations of glucose, amino acids, insulin, triglycerides, urea N, and nonesterified fatty acids also were measured on d 7 and 21. Mean LH concentrations were . 27 and . 42 ng/mL at farrowing for sows with an early and late return to estrus, respectively, but decreased (P less than .01) to . 12 ng/mL by d 7 in both early and late groups. Mean LH and number of LH peaks per 6 h increased linearly (P less than .01) from d 7 to 28 for early sows. Early sows had a higher LH mean and more LH peaks per 6 h on d 14, 21, and 28 than did late sows (P less than .05). Early sows had higher serum insulin on d 7 (P less than .05) and d 21 (P less than .01) than did late sows. Concentrations of other metabolites did not differ (P less than .10) between early and late sows. (ABSTRACT TRUNCATED AT 250 WORDS)
Influence of the endothelium and alpha‐adrenoreceptor antagonists on responses to noradrenaline in the rabbit basilar artery.

1. Noradrenaline (10(‐6)‐10(‐2) M) produced slow, concentration‐dependent depolarization of smooth muscle cells in the rabbit basilar artery, which preceded the onset of contraction by around 8 s (n = 18). 2. With concentrations greater than 10(‐4) M, noradrenaline produced action potentials and fast rhythmic depolarizations superimposed on the slow depolarization. Each fast event was followed by a clear increase in the rate of smooth muscle contraction. The selective alpha 1‐adrenoreceptor agonist phenylephrine produced very similar membrane and contractile responses. 3. Action potentials were not produced in artery segments where the endothelium had been removed. In these segments, the amplitude of both contraction and slow depolarization to noradrenaline was similar to that observed in segments with an intact endothelium, but the tension increased more slowly; 84 s compared to the 52 s required to produce 50% of total contraction when the endothelium was functional. 4. The selective alpha 1‐antagonist prazosin (10(‐6) M) either abolished or significantly reduced both the slow depolarization (with concentrations less than 10(‐3) M‐noradrenaline) and smooth muscle contraction to noradrenaline. When prazosin was present, action potentials with 10(‐3) M‐noradrenaline were only produced in 50% of the cells studied. 5. Irreversible blockade of alpha‐adrenoreceptors with benextramine (10(‐5) M for 20 min) abolished action potentials and both the depolarization and contraction produced with all but the highest concentrations of noradrenaline. With 10(‐3) M‐noradrenaline, depolarization was produced but it was significantly reduced and usually not associated with smooth muscle contraction. 6. The results show that smooth muscle depolarization, contraction and possibly endothelium‐dependent action potentials are produced by alpha‐adrenoreceptor stimulation. They also show that noradrenaline‐induced action potentials produce smooth muscle contraction, and that slow depolarization is an important, but not absolute requirement for contraction. The fact that action potentials were produced in response to high concentrations of noradrenaline in the presence of prazosin, but not after benextramine, suggests that these concentrations of noradrenaline can surmount competitive antagonism with prazosin.
Screening Older Latinos for Dementia in the Primary Care Setting

Abstract The purpose was to compare the Spanish language picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR) and the Mini Mental State Exam (MMSE) in identifying very mild dementia among Spanish speaking Latino patients. The tests and an independent diagnostic assessment were administered to 112 Latino patients free of medically diagnosed dementia from an urban primary care clinic. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to examine differences in the operating characteristics of the pFCSRT+IR and the MMSE. Cut scores were manipulated to equate sensitivities (specificities) at clinically relevant values to compare differences in specificities (sensitivities) using the Pearson Chi Square test. Youden’s index was used to select the optimal cut scores. Twenty-four of the 112 primary care patients (21%) received a research dementia diagnosis, indicating a substantial burden of unrecognized dementia. MMSE scores but not free recall scores were associated with years of education in patients free of dementia. AUC was significantly higher for free recall than for MMSE. Free recall performed significantly better than the MMSE in sensitivity and in specificity. Using optimal cut scores, patients with impaired free recall were 10 times more likely to have dementia than patients with intact recall, and patients with impaired MMSE scores were 4.5 times more likely to have dementia than patients with intact scores. These results suggest that the Spanish language pFCSRT+IR may be an effective tool for dementia screening in educationally diverse Latino primary care populations. (JINS, 2014, 20, 1–8)
Protocol dependency of VO2max during arm cycle ergometry in males with quadriplegia.

The purpose of this study was to determine whether maximal oxygen uptake (VO2max) is protocol dependent during arm cycle ergometry (ACE) for quadriplegic males with spinal cord injuries (SCI). Twenty-four non-ambulatory subjects (aged 20-38 yr) with cervical SCI were divided into two groups based on wheelchair sports classification (IA group = 14; IB/IC group = 10). They underwent three different, continuous graded exercise tests spaced at least 1 wk apart on an electronically braked arm cycle ergometer. Following a 3-min, unloaded warm-up at 60 rpm, the work rate was increased 2, 4, or 6 W.min-1 for the IA group and 4, 6, or 8 W.min-1 for the IB/IC group. Ventilation and gas exchange were measured breath-by-breath with a SensorMedics 4400 computerized system. Repeated-measures ANOVA showed no significant difference among the three protocols for VO2max in the IA group (P greater than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 10.8 (+/- 3.4), 11.0 (+/- 2.7), and 10.2 (+/- 2.9) for the 2, 4, and 6 W.min-1 protocols, respectively. In contrast, the IB/IC group showed a significant difference among the protocols for VO2max (P less than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 16.8 (+/- 4.5), 15.3 (+/- 4.3), and 14.6 (+/- 4.3) for 4, 6, and 8 W.min-1, respectively. Post hoc analysis revealed a difference between the 4 and 8 W.min-1 protocols. Our results suggest that graded exercise testing of SCI persons with quadriplegia, using ACE, should employ work rate increments between 2-6 W.min-1 and that work rate increments of 8 W.min-1 or greater will underestimate VO2max.
The JMJD2A demethylase regulates apoptosis and proliferation in colon cancer cells

JMJD2A is a transcriptional cofactor and enzyme that catalyzes demethylation of histone H3 lysines 9 and 36 and is overexpressed in human tumors, but its role in oncogenesis remains unclear. Here, we show that JMJD2A interacts with the tumor suppressor p53 both in vitro and in HCT116 colon cancer cells. Chromatin immunoprecipitation assays demonstrated that JMJD2A was recruited together with p53 to the promoter of the p21 cell cycle inhibitor upon stimulation with the DNA damaging agent, adriamycin. Downregulation of JMJD2A resulted in increased expression of p21 and of the pro‐apoptotic Puma protein, whereas levels of the anti‐apoptotic Bcl‐2 protein were decreased. Furthermore, JMJD2A knock‐down led to reduced HCT116, DLD‐1 and HT‐29 colon cancer cell proliferation, while overexpression of JMJD2A enhanced HCT116 proliferation in low serum media. Finally, JMJD2A depletion induced apoptosis in HCT116 cells and this effect was less pronounced in the absence of p53. Collectively, these data indicate that JMJD2A is a novel promoter of colon cancer cell proliferation and survival, which mediates its effects in p53‐dependent and ‐independent ways. JMJD2A may therefore be a valid target to sensitize tumor cells to chemotherapy‐induced cell death and growth suppression. J. Cell. Biochem. 113: 1368–1376, 2012. © 2011 Wiley Periodicals, Inc.