Miracle-dz/UniFAR-FTUs huggingface dataset:
CDK INHIBITORY NUCLEOSIDE ANALOGS PREVENT TRANSCRIPTION FROM VIRAL GENOMES

Targeting viral proteins has lead to many successful antivirals. Yet, such antivirals rapidly select for resistance, tend to be active against only a few related viruses, and require previous characterization of the target proteins. Alternatively, antivirals may be targeted to cellular proteins. Replication of many viruses requires cellular CDKs and pharmacological CDK inhibitors (PCIs), such as the purine-based roscovitine (Rosco), are proving safe in clinical trials against cancer. Rosco inhibits replication of wild-type or (multi-)drug resistant HIV, HCMV, EBV, VZV, and HSV-1 and 2. However, the antiviral mechanisms of purine PCIs remain unknown. Our objective is to characterize these mechanisms using HSV as a model. We have shown that Rosco prevents initiation of transcription from viral, but not cellular, genomes. This inhibition is promoter independent, but genome dependent, and requires no viral proteins. This is a novel antiviral mechanism and a previously unknown activity for purine PCIs.
Hypoxia suppresses the production of matrix metalloproteinases and the migration of humanmonocyte‐derived dendritic cells

As most solid tumors are hypoxic, dendritic cells (DC) in solid tumors are also exposed to hypoxia. While many adaptation responses of tumor cells to hypoxia are known, it is yet to be determined how hypoxia affects the functions of DC. To explore the effects of hypoxia on the functions of DC, we compared the expression of surface markers, cytokines, chemokine receptors and matrix metalloproteinases (MMP) of human monocyte‐derived DC (hmDC) differentiated under hypoxia to those differentiated under normoxia. Both groups of hmDC expressed similar levels of surface markers and cytokines. However, expression of MMP‐9 and membrane type‐1‐MMP, as well as migrating activity, was significantly suppressed in hmDC differentiated under hypoxia compared with their normoxia counterparts. We also demonstrated that trichostatin A restored the production of MMP‐9 in hmDC, under hypoxia. Collectively, our findings show that a hypoxic microenvironment suppresses the production of MMP in hmDC, most probably through the deacetylation of promoter regions of MMP, thus suppressing the migrating activity of hmDC. Our results suggest that the hypoxic microenvironment in solid tumor tissues may suppress the function of DC.
In Vivo Blood-Brain Barrier Transport of Oxycodone in the Rat: Indications for Active Influx and Implications for Pharmacokinetics/Pharmacodynamics

The blood-brain barrier (BBB) transport of oxycodone was studied in rats. Microdialysis probes were inserted into the striatum and vena jugularis. Ten animals were given a bolus dose followed by a 120-min constant rate infusion to study the steady-state concepts of oxycodone BBB equilibration. Another 10 animals were given a 60-min constant rate infusion to study the rate of equilibration across the BBB. Oxycodone-D3 was used as a calibrator for the microdialysis experiments. The samples were analyzed with a liquid chromatography-tandem mass spectrometry method and a population pharmacokinetic model was used to simultaneously fit all the data using NONMEM. A two-compartment model which allowed for a delay between the venous and arterial compartments best described the pharmacokinetics for oxycodone in blood and plasma, whereas a one-compartment model was sufficient to describe the pharmacokinetics in the brain. The BBB transport of oxycodone was parameterized as CLin and Kp,uu. CLin describes the clearance of oxycodone across the BBB into the brain, whereas Kp,uu describes the extent of drug equilibration across the BBB. CLin across the BBB was estimated to 1910 μl/min · g brain. Kp,uu was estimated to 3.0, meaning that the unbound concentration of oxycodone in brain was 3 times higher than in blood, which is an indication of active influx of oxycodone at the BBB. This is the first evidence of an opioid having an unbound steady-state concentration in brain that is higher than unity, which can explain potency discrepancies between oxycodone and other opioids.
Tuning Parameter Selection in Penalized Frailty Models

The penalized likelihood approach of Fan and Li (2001, 2002) differs from the traditional variable selection procedures in that it deletes the non-significant variables by estimating their coefficients as zero. Nevertheless, the desirable performance of this shrinkage methodology relies heavily on an appropriate selection of the tuning parameter which is involved in the penalty functions. In this work, new estimates of the norm of the error are firstly proposed through the use of Kantorovich inequalities and, subsequently, applied to the frailty models framework. These estimates are used in order to derive a tuning parameter selection procedure for penalized frailty models and clustered data. In contrast with the standard methods, the proposed approach does not depend on resampling and therefore results in a considerable gain in computational time. Moreover, it produces improved results. Simulation studies are presented to support theoretical findings and two real medical data sets are analyzed.
Characterizing Botnets from Email Spam Records

We develop new techniques to map botnet membership using traces of spam email. To group bots into botnets we look for multiple bots participating in the same spam email campaign. We have applied our technique against a trace of spam email from Hotmail Web mail services. In this trace, we have successfully identified hundreds of botnets. We present new findings about botnet sizes and behavior while also confirming other researcher's observations derived by different methods [1, 15].
Dual control of caveolar membrane traffic by microtubules and the actin cytoskeleton

Live cell, time-lapse microscopy was used to study trafficking of caveolin-1-GFP in stably expressing CHO cells. Multiple cytological and biochemical tests verified that caveolin-1-GFP was a reliable marker for endogenous caveolin-1. At steady state, most caveolin-1-GFP was either at the cell surface associated with invaginated caveolae or near the centrosome in caveosomes. Live cell fluorescence imaging indicated that while much of the caveolin-1-GFP in caveolae at the cell surface was relatively sessile, numerous, highly motile caveolin-1-GFP-positive vesicles were present within the cell interior. These vesicles moved at speeds ranging from 0.3-2 μm/second and movement was abolished when microtubules were depolymerized with nocodazole. In the absence of microtubules, cell surface invaginated caveolae increased more than twofold and they became organized into linear arrays. Complete depolymerization of the actin cytoskeleton with latrunculin A, by contrast, triggered rapid and massive movements of caveolin-positive structures towards the centrosomal region of the cell. The caveolar membrane system of CHO cells therefore appears to be comprised of three caveolin-1-containing compartments. These include caveolae that are confined to the cell surface by cortical actin filaments, the peri-centrosomal caveosomes and caveolar vesicles, which we call `cavicles', that move constitutively and bi-directionally along microtubules between the cell surface and caveosomes. The behavior of cavicles suggests that they function as transport intermediates between caveolae and caveosomes.
FEDERAL RESERVE BANK o f ATLANTA WORKING PAPER SERIES Inference Based on SVARs Identified with Sign and Zero Restrictions : Theory and Applications

with them and for helpful comments. They also thank Grátula Bedátula for her support and help. Without her, this paper would have been impossible. This paper has circulated under the title “Algorithm for Inference with Sign and Zero Restrictions. ” Juan F. Rubio-Ramírez also thanks the National Science Foundation for support. The views expressed here are the authors’ and not necessarily those of the Federal Reserve Bank of Atlanta or the Federal Reserve System. Any remaining errors are the authors’ responsibility.
Trimethoprim-rifampin, a new combination agent: efficacy in localized urinary infection and influence on microflora

Twenty women with recurrent or persistent urinary tract infections were treated with a fixed combination of trimethoprim-rifampin (TMP-RAM). The site of infection was established by the antibody-coated bacteria test. Sixteen women had upper tract infections (antibody-coated bacteria tests positive); eight were cured, three failed, and five relapsed. All four women with lower tract infections (antibody-coated bacteria tests negative) were cured. Three of five patients with structural abnormalities failed. The 12 cures and 5 relapses were associated with organisms susceptible to either TMP (minimal inhibitory concentration, less than or = to 7 micrograms/ml) or RAM (minimal inhibitory concentration, less than or = to 32 micrograms/ml). In contrast, two of the three failures were associated with organisms resistant to both TMP and RAM. In one patient, RAM resistance emerged during treatment. During therapy, urinary strains were eradicated from the periurethral and anal-canal areas in all but 3 fo 16 patients. Adverse reactions, noted in 16 women, included nausea (10), dizziness (6), headaches (2), rash (1), an blurred vision (1). Antimicrobial susceptibility data on 246 isolated from urinary, periurethral, and anal-canal specimens are included. Our findings suggest that TMP-RAM is effective in urinary infections and may prevent the emergence of RAM-resistant strains.
The A-Type Cyclin CYCA2;3 Is a Key Regulator of Ploidy Levels in Arabidopsis Endoreduplication[W][OA]

Plant cells frequently undergo endoreduplication, a process in which chromosomal DNA is successively duplicated in the absence of mitosis. It has been proposed that endoreduplication is regulated at its entry by mitotic cyclin-dependent kinase activity. However, the regulatory mechanisms for its termination remain unclear, although plants tightly control the ploidy level in each cell type. In the process of searching for regulatory factors of endoreduplication, the promoter of an Arabidopsis thaliana cyclin A gene, CYCA2;3, was revealed to be active in developing trichomes during the termination period of endoreduplication as well as in proliferating tissues. Taking advantage of the situation that plants encode highly redundant cyclin A genes, we were able to perform functional dissection of CYCA2;3 using null mutant alleles. Null mutations of CYCA2;3 semidominantly promoted endocycles and increased the ploidy levels achieved in mature organs, but they did not significantly affect the proportion of cells that underwent endoreduplication. Consistent with this result, expression of the CYCA2;3–green fluorescent protein fusion protein restrained endocycles in a dose-dependent manner. Moreover, a mutation in the destruction box of CYCA2;3 stabilized the fusion protein in the nuclei and enhanced the restraint. We conclude that CYCA2;3 negatively regulates endocycles and acts as a key regulator of ploidy levels in Arabidopsis endoreduplication.
The Golgi S-acylation machinery comprises zDHHC enzymes with major differences in substrate affinity and S-acylation activity

The molecular machinery that catalyzes S-acylation reactions at the Golgi comprises zDHHC enzymes with major differences in substrate affinity and S-acylation activity. It is proposed that the coexistence of these two groups of enzymes in cells is important to allow the Golgi S-acylation machinery to modify a wide and diverse set of substrates.
Evidence of Rural and Suburban Sources of Urban Haze Formation in China: A Case Study From the Pearl River Delta Region

Although particulate matter (PM)‐driven haze is a common phenomenon in many Chinese cities, studies on the sources of its key components, such as organic carbon (OC) and elemental carbon (EC), are poorly constrained. In this study, PM with aerodynamic diameters less than 10 (PM10), 2.5 (PM2.5), and 1 μm (PM1) were collected at an urban site in the core city of the Pearl River Delta region in summer 2013. The average PM10, PM2.5, and PM1 mass concentrations were 109 ± 28.4, 57.7 ± 15.0, and 50.9 ± 13.2 μg/m3, respectively. A PM‐driven haze bloom‐decay process was observed from 9 to 14 July and studied based on radiocarbon (14C) and stable nitrogen isotope (15N). The 14C results revealed that 87% of EC and 53% of OC in PM2.5 were derived from fossil sources on a typical summer day (9 July), while these values fell to 79% and 40% on 12 July and 76% and 29% on 13 July, respectively, due to the invasion of nonfossil‐enriched air masses from rural/suburban areas. In addition, a 15N‐derived model showed that nonfossil sources contributed 5% of NH3 on 9 July, which increased to about 80% on 12 and 13 July. However, the 15N‐NO3− values were relatively stable, probably because of the large area of overlap in 15N‐NOx from biomass burning and traffic exhaust. To our knowledge, this work is the first study to report both daily 14C and 15N signals in China and identify nonfossil sources from rural/suburban areas as triggers of summer haze.
Effects of different vineyard altitudes and grapevine directions on some leaf characteristics of CV. Gamay vitis vinifera L

KOK, D. and E. BAHAR, 2015. Effects of different vineyard altitudes and grapevine directions on some leaf characteristics of cv. Gamay Vitis vinifera L. Bulg. J. Agric. Sci., 21: 320–324 This study was carried out in Ucmakdere Village of Sarkoy County in Tekirdag province of Turkey using cv. Gamay in the course of 2009 growing season. In this research, three levels of vineyard altitude (i.e., low, mid and high) and four different directions of grapevine (i.e., north, south, east and west) were assessed in terms of their effects on some leaf characteristics of cv. Gamay. Based on responses of cv. Gamay to different vineyard altitudes and grapevine directions, strong altitudinal relationships were found out in examined characteristics, including leaf area, stomatal density, stomata length and stomata width. The research results revealed that leaf area and stomatal characteristics were variously affected by vineyard altitudes and also collecting directions of leaves from grapevines. It was observed in research results that leaf stomatal density and stomata length increased with rising vineyard altitude, but leaf area and stomata width reduced with elevating vineyard altitude, regardless of grapevine directions.
Analysis of a mobile cellular systems with hand-off priority and hysteresis control

In this paper, we introduce and analyze a new cut-off priority scheme which provides a better grade-of-service to hand-off traffic while maintaining high throughput for the originating calls. A hysteresis control is used for additional robustness. The system model is found to have a general level-dependent quasi-birth-and-death (QBD) structure. An efficient solution methodology is used taking full advantage of the problem structure. Our model extends, generalizes and unifies the existing models for cut-off priority schemes in wireless cellular networks.
Hepatitis B Virus Gene Mutations in Liver Diseases: A Report from New Delhi

Objectives The study was designed to characterize the surface, core promoter, precore/core region sequences for the presence of mutations in hepatitis B virus (HBV) associated with different liver diseases. Methods 567 HBV associated patients with different liver diseases were enrolled in this study. All samples were analyzed for HBV surface, core promoter, precore/core region mutations and genotypes using PCR and direct sequencing. Results HBV genotype D (72.8%) was the predominant type followed by genotype A (27.2%). The serum viral load of HBV was highest in HBsAg carriers group and lowest in patients with hepatocellular carcinoma. 17.9% patients with cirrhosis and 24.6% hepatocellular carcinoma cases were ADV-resistant with rtA181T/V mutations in the S-gene. A1896T was found more frequently in fulminant hepatic failure compared to acute viral hepatitis patients (p = 0.038). T1753V mutation was significantly higher in patients with cirrhosis of liver (34.6%) than in chronic hepatitis (18.9%) and hepatocellular carcinoma patients (21.2%; p = 0.001). T1762/A1764 mutation was observed in all the groups. C1914G core gene mutation was associated with the hepatocellular carcinoma (32.2%) compared to other groups. HBV genotype D predominated in comparison to genotype A. An increased frequency of precore mutation and BCP double mutations amongst the population studied was also observed. Conclusion Mutations such as T1762/A1764, T1753V and C1914G were usually associated with advanced forms of liver disease and had an increased risk of HCC. The nucleotide variability in the basal core promoter and precore regions possibly plays a role in the progression of HBV disease. Prospective studies on the sequence variations of the preC/C region of the HBV genome and the molecular mechanisms in relation to progression of liver disease would aid in better understanding of the biological significance of HBV strains in India.
Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease

We investigated the magnetization transfer ratio (MTR) of normal-appearing white (NAWM) and grey matter (NAGM) in a relatively large group of multiple sclerosis (MS) patients, and the relations of MTR changes with clinical disability. MTR was measured in 66 MS patients (12 PP, 35 RR, 19 SP) and 23 healthy controls, using a whole-brain 3D-FLASH technique corrected post-hoc for B1-induced variation. Histogram parameters of conservatively selected NAWM and cortical NAGM were analysed using Bonferroni-corrected ANOVA with age as covariate. Additionally, manually outlined regions of interest were analysed using a multilevel method. Lesions had low MTR (mean 22.7±6.9%), but NAWM exhibited limited changes: MTR histogram peak position was 32.8±1.0% in controls and 32.4±0.9% in MS patients, with a significant decrease compared to controls only in SPMS patients (31.9±1.1%, p=0.045). Cortical NAGM histograms did not differ significantly between patients and controls. In SPMS, regional mean MTR was significantly decreased in corpus callosum and hippocampus. MTR histogram parameters of NAGM and NAWM were correlated with EDSS and MSFC scores, with lesion volume and with normalized brain volume. We conclude that disease-induced MTR changes were small in MS NAWM and NAGM, but did correlate with clinical decline, lesion volume and overall cerebral atrophy. Multiple Sclerosis 2007; 13: 708-716. http://msj.sagepub. com
Eye fixations when viewing faces.

BACKGROUND There is disagreement in the literature about the relative importance of the mouth and the teeth to facial attractiveness. Few investigators use objective measures for quantifying which facial features are important and their order of importance. Objective measures of the relative importance of a facial feature are in what order, for how long and how often viewers look at it. The authors conducted a study to determine the hierarchy and length of time study participants spent viewing features in facial images. METHODS The participants were 50 young adults. The authors used a pupillary-corneal reflection technique to measure viewers' eye movements when they were viewing images of faces after orthodontic treatment was completed. The authors took the measurements again after a two-week interval. They quantified eye fixations for six areas of interest: eyes, ears, nose, mouth, chin and other. The variables measured were the location of the first fixation, the location of the area of maximum fixation duration and the location of the area receiving the maximum number of fixations. RESULTS Intraobserver variability among the participants was high for most of the variables assessed (kappa < 0.30). For the smile image, first fixation, the most frequent and the longest fixations were other, eye, nose, mouth, ear and chin, in that order. The mouth, even the smiling mouth, received less than 10 percent of the viewers' visual attention. CONCLUSION Viewers' visual fixations on images of well-balanced faces do not preferentially go to any single facial feature. The mouth attracts only a small part of visual attention in well-balanced faces.
Integrated Electrokinetics-Adsorption Remediation of Saline-Sodic Soils: Effects of Voltage Gradient and Contaminant Concentration on Soil Electrical Conductivity

In this study, an integrated in situ remediation technique which couples electrokinetics with adsorption, using locally produced granular activated carbon from date palm pits in the treatment zones that are installed directly to bracket the contaminated soils at bench-scale, is investigated. Natural saline-sodic clay soil, spiked with contaminant mixture (kerosene, phenol, Cr, Cd, Cu, Zn, Pb, and Hg), was used in this study to investigate the effects of voltage gradient, initial contaminant concentration, and polarity reversal rate on the soil electrical conductivity. Box-Behnken Design (BBD) was used for the experimental design and response surface methodology (RSM) was employed to model, optimize, and interpret the results obtained using Design-Expert version 8 platform. The total number of experiments conducted was 15 with voltage gradient, polarity reversal rate, and initial contaminant concentration as variables. The main target response discussed in this paper is the soil electrical conductivity due to its importance in electrokinetic remediation process. Responses obtained were fitted to quadratic models whose R 2 ranges from 84.66% to 99.19% with insignificant lack of fit in each case. Among the investigated factors, voltage gradient and initial contaminant concentration were found to be the most significant influential factors.
Nontarget Biomolecules Alter Macromolecular Changes Induced by Bactericidal Low–Temperature Plasma

Low-temperature plasmas (LTPs) have a proven bactericidal activity governed by the generated reactive oxygen and nitrogen species (RONS) that target microbial cell components. However, RONS also interact with biomolecules in the environment. Here we assess the impact of these interactions upon exposure of liquid suspensions with variable organic content to an atmospheric-pressure dielectric barrier discharge plasma jet. <italic>Salmonella enterica</italic> serovar Typhimurium viability in the suspension was reduced in the absence [e.g., phosphate buffered saline (PBS)], but not in the presence of (high) organic content [Dulbecco's Modified Eagle's Medium (DMEM), DMEM supplemented with foetal calf serum, and Lysogeny Broth]. The reduced viability of LTP-treated bacteria in PBS correlated to a loss of membrane integrity, whereas double-strand DNA breaks could not be detected in treated single cells. The lack of bactericidal activity in solutions with high organic content correlated with a relative decrease of <sup>•</sup>OH and O<sub>3</sub>/O<sub>2</sub>(a<sup>1</sup><inline-formula> <tex-math notation="LaTeX">${\Delta }\text{g}$ </tex-math></inline-formula>)/O, and an increase of H<sub>2</sub>O<sub>2</sub> and <inline-formula> <tex-math notation="LaTeX">$\mathrm{NO}_{2}^{-}$ </tex-math></inline-formula> in the plasma-treated solutions. These results indicate that the redox reactions of LTP-generated RONS with nontarget biomolecules resulted in a RONS composition with reduced bactericidal activity. Therefore, the chemical composition of the bacterial environment should be considered in the development of LTP for antimicrobial treatment, and may affect other biomedical applications as well.
Seasonal Implication of Heavy Metal Contamination of Surface Water around Dhaka Export Processing Zone (DEPZ), Savar, Bangladesh

Wastewater discharged from unplanned and rapidly growing industrial units into surrounding aquatic ecosystems either directly or inadequate treatment can increase the concentrations of toxic heavy metals, and subsequently lower water quality, environmental sustainability and community health in the close vicinity of the Dhaka Export Processing Zone (DEPZ), the largest industrial belt in Bangladesh. Present work