Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Purine Nucleoside Phosphorylase in Interactions between 2′,3′-Dideoxyinosine and Allopurinol, Ganciclovir, or Tenofovir

ABSTRACT The level of systemic exposure to 2′,3′-dideoxyinosine (ddI) is increased 40 to 300% when it is coadministered with allopurinol (Allo), ganciclovir (GCV), or tenofovir. However, the mechanism for these drug interactions remains undefined. A metabolic route for ddI clearance is its breakdown by purine nucleoside phosphorylase (PNP). Consistent with previous reports, enzymatic inhibition assays showed that acyclic nucleotide analogs can inhibit the phosphorolysis of inosine. It was further established that the mono- and diphosphate forms of tenofovir were inhibitors of PNP-dependent degradation of ddI (Kis, 38 nM and 1.3 μM, respectively). Allo and its metabolites were found to be relatively weak inhibitors of PNP (Kis, >100 μM). Coadministration of tenofovir, GCV, or Allo decreased the amounts of intracellular ddI breakdown products in CEM cells, while they increased the ddI concentrations (twofold increase with each drug at approximately 20 μM). While inhibition of the physiological function of PNP is unlikely due to the ubiquitous presence of high levels of enzymatic activity, phosphorylated metabolites of GCV and tenofovir may cause the increased level of exposure to ddI by direct inhibition of its phosphorolysis by PNP. The discrepancy between the cellular activity of Allo and the weak enzyme inhibition by Allo and its metabolites may be explained by an indirect mechanism of PNP inhibition. This mechanism may be facilitated by the unfavorable equilibrium of PNP and the buildup of one of its products (hypoxanthine) through the inhibition of xanthine oxidase by Allo. These findings support the inhibition of PNP-dependent ddI degradation as the molecular mechanism of these drug interactions.
Ultrastructural localization of lectin-binding sites on the zonae pellucidae and plasma membranes of mammalian eggs

Receptors for Ricinus communis agglutinin I (RCAI), concanavalin A (Con A), and wheat germ agglutinin (WGA) were localized on the zonae pellucidae and plasma membranes of hamster, mouse, and rat eggs with ferritin-lectin conjugates. Intact eggs labeled with the ferritin conjugates showed dense concentrations of RCAI and WGA receptors in the outermost regions of their zonae pellucidae and sparse distributions of Con A receptors throughout the zonae. Ferritin-lectin labeling was specific, since inhibitory saccharides effectively blocked labeling. The asymmetric density of RCAI receptors across the zona was confirmed by ferritin-RCAI and fluorescein-RCAI labeling of mechanically isolated zonae pellucidae, indicating that the RCAI-binding sites are more densely distributed in the exterior zona regions. Plasma membranes of rodent eggs contained RCAI, WGA, and Con A receptors. These receptors were found to be more or less randomly distributed on surfaces of aldehyde-fixed eggs or on eggs labeled near 0 degrees C. However, eggs incubated at 25 degrees C showed aggregated WGA- and Con A-binding site distributions on their plasma membranes. This indicates that lectin- induced receptor redistribution occurs at this temperature. The possibility that plasma membrane receptor mobility is a requirement for sperm-egg fusion is discussed.
A photometric study of chemically peculiar stars with the STEREO satellites - I. Magnetic chemically peculiar stars

About 10 per cent of upper main-sequence stars are characterized by the presence of chemical peculiarities, often found together with a structured magnetic field. The atmospheres of most of those chemically peculiar stars present surface spots, leading to photometric variability caused by rotational modulation. The study of the light curves of those stars therefore permits a precise measurement of their rotational period, which is important to study stellar evolution and to plan further detailed observations. We analysed the light curves of 1028 chemically peculiar stars obtained with the STEREO spacecraft. We present here the results obtained for the 337 magnetic chemically peculiar stars in our sample. Thanks to the cadence and stability of the photometry, STEREO data are perfectly suitable to study variability signals with a periodicity typical of magnetic chemically peculiar stars. Using a matched filter algorithm and then two different period searching algorithms, we compiled a list of 82 magnetic chemically peculiar stars for which we measured a reliable rotational period; for 48 of them, this is the first measurement of their rotational period. The remaining 255 stars are likely to be constant, although we cannot exclude the presence of long-period variability. In some cases, the presence of blending or systematic effects prevented us from detecting any reliable variability and in those cases we classified the star as constant. For each star we classified as variable, we determined temperature, luminosity, mass and fractional age, but the limited statistics, biased towards the shorter periods, prevented us from finding any evolutionary trend of the rotational period. For a few stars, the comparison between their projected rotational velocity and equatorial velocity let us believe that their real rotational period might be longer than that found here and previously obtained. For the 82 stars identified as variable, we give all necessary information needed to plan further phase-dependent observations.
Long QTc predicts future cardiac death in stroke survivors

Objectives: To test the hypothesis that the QTc of any lead of the ECG predicts death after stroke, and to determine which lead of the ECG carries the greatest risk of cardiac death when its QTc is measured. Design: Standard 12 lead ECGs were analysed by one observer who was blind to patient outcome. Setting: A major teaching hospital in Scotland. Patients: 404 stroke survivors were studied at approximately one year after the cerebrovascular event and followed for up to 6.3 years. Outcome measures: Death from any cause and cardiac mortality. Results: The QTc measured from any lead of the ECG (except aVR) was associated with death from any cause. A prolonged QTc in limb lead III and chest lead V6 carried the highest relative risk of cardiac death (a 3.1-fold incease). After adjusting for overt ischaemic heart disease, pulse pressure, glucose, and cholesterol, a prolonged QTc in lead V6 was associated with a relative risk of cardiac death of 2.8 (95% confidence interval (CI) 1.1 to 7.3) (p = 0.028) and of death from all causes of 2.9 (95% CI 1.6 to 5.3) (p < 0.001). If the QTc in V6 exceeded 480 ms, then the specificity of predicting cardiac death within five years after the stroke was 94%. Conclusions: Although treatment of the conventional modifiable risk factors is important, stroke survivors with a prolonged QTc in lead V6 are still at a high risk of cardiac death and may need more intensive investigations and treatments than are currently routine practice.
Structural insights into how GTP-dependent conformational changes in a metallochaperone UreG facilitate urease maturation

Significance Our work provides insights into how cells solve the problem of delivering nickel, a toxic metal, to the active site of a metalloenzyme such as urease. Urease, a nickel-containing enzyme, is a virulence factor for Helicobacter pylori, which infects half of the human population and causes peptic ulcers. Supported by structural and biochemical evidence, we present a paradigm on how a metallochaperone UreG couples GTP hydrolysis/binding to allosterically control the binding/release of nickel ions and to switch protein-binding partners along the metal-delivery pathway so that the nickel ions are passing from one metallochaperone to another, without releasing the “free” toxic metal to the cytoplasm. The ability of metallochaperones to allosterically regulate the binding/release of metal ions and to switch protein-binding partners along the metal delivery pathway is essential to the metallation of the metalloenzymes. Urease, catalyzing the hydrolysis of urea into ammonia and carbon dioxide, contains two nickel ions bound by a carbamylated lysine in its active site. Delivery of nickel ions for urease maturation is dependent on GTP hydrolysis and is assisted by four urease accessory proteins UreE, UreF, UreG, and UreH(UreD). Here, we determined the crystal structure of the UreG dimer from Klebsiella pneumoniae in complex with nickel and GMPPNP, a nonhydrolyzable analog of GTP. Comparison with the structure of the GDP-bound Helicobacter pylori UreG (HpUreG) in the UreG2F2H2 complex reveals large conformational changes in the G2 region and residues near the 66CPH68 metal-binding motif. Upon GTP binding, the side chains of Cys66 and His68 from each of the UreG protomers rotate toward each other to coordinate a nickel ion in a square-planar geometry. Mutagenesis studies on HpUreG support the conformational changes induced by GTP binding as essential to dimerization of UreG, GTPase activity, in vitro urease activation, and the switching of UreG from the UreG2F2H2 complex to form the UreE2G2 complex with the UreE dimer. The nickel-charged UreE dimer, providing the sole source of nickel, and the UreG2F2H2 complex could activate urease in vitro in the presence of GTP. Based on our results, we propose a mechanism of how conformational changes of UreG during the GTP hydrolysis/binding cycle facilitate urease maturation.
Desmoplasia Influenced Recurrence of Disease and Mortality in Stage III Colorectal Cancer within Five Years after Surgery and Adjuvant Therapy

Background/Aims: In patients with colon cancer who undergo resection for potential cure, 40–60% have advanced locoregional disease (stage III). Those who are suitable for adjuvant treatment had a definite disease-free-survival benefit. The aim of the present study was to demonstrate whether the presence of desmoplasia influenced the mortality rate of stage III colorectal cancer (CRC) within 5 years from the surgery and adjuvant therapy. Patients and Methods: Sixty-five patients with stage III CRC underwent resection and adjuvant therapy. Qualitative categorization of desmoplasia was obtained using Ueno's stromal CRC classification. Desmoplasia was related to mortality using Spearman correlation and stratified with other histological variables (inflammation, grading) that concurred to the major determinant of malignancy (venous invasion and lymph nodes) using the Chi-square test. Result: The 5-year survival rate was 65% and the relapse rate was 37%. The mortality rate in patients with immature desmoplasia was 86%, 27% in intermediate desmoplasia, and 0% in mature desmoplasia (Spearman correlation coefficient: −0.572,P= 0.05). Conclusion: Immature desmoplasia appears to be associated with disease recurrence and mortality in stage III CRC patients.
BANDWIDTH CONSIDERATIONS FOR A MICROSTRIP REFLECTARRAY

The paper describes a theoretical investigation into a limited bandwidth operation of a microstrip reflectarray. Two main factors limiting the bandwidth are considered. One is related to the requirement of phase compensation to convert a spherical wavefront launched by a feed into a planar wavefront. The other one is linked to the limited phasing range of microstrip antenna elements. The two factors contribute to the reflectarray phasing errors that in turn reduce its gain as a function of frequency. Simple formulas for an upper bound of gain bandwidth are derived, assuming the phase compensation by the elements is independent of frequency changes and verified against the results produced by other researchers. It is shown that the phase errors incurred in the path equalization to obtain conversion from spherical to planar wavefronts have a more profound effect on the reduction of operational bandwidth of the reflectarray than the phase truncation implemented on the required phase from each element.
Polymerase chain reaction-based discrimination of viable from non-viable Mycoplasma gallisepticum.

The present study was based on the reverse transcription polymerase chain reaction (RT-PCR) of the 16S ribosomal nucleic acid (rRNA) of Mycoplasma for detection of viable Mycoplasma gallisepticum. To determine the stability of M. gallisepticum 16S rRNA in vitro, three inactivation methods were used and the suspensions were stored at different temperatures. The 16S rRNA of M. gallisepticum was detected up to approximately 20-25 h at 37 °C, 22-25 h at 16 °C, and 23-27 h at 4 °C. The test, therefore, could detect viable or recently dead M. gallisepticum (< 20 h). The RT-PCR method was applied during an in vivo study of drug efficacy under experimental conditions, where commercial broiler-breeder eggs were inoculated with M. gallisepticum into the yolk. Hatched chicks that had been inoculated in ovo were treated with Macrolide 1. The method was then applied in a flock of day 0 chicks with naturally acquired vertical transmission of M. gallisepticum, treated with Macrolide 2. Swabs of the respiratory tract were obtained for PCR and RT-PCR evaluations to determine the viability of M. gallisepticum. This study proved that the combination of both PCR and RT-PCR enables detection and differentiation of viable from non-viable M. gallisepticum.
Statistical methods in genetics

In recent years, a very large variety of statistical methodologies, at various levels of complexity, have been put forward to analyse genotype data and detect genetic variations that may be responsible for increasing the susceptibility to disease. This review provides a concise account of a number of selected statistical methods for population-based association mapping, from single-marker tests of association to multi-marker data mining techniques for gene-gene interaction detection.
Managing Addiction as a Chronic Condition

This article reviews progress in adapting addiction treatment to respond more fully to the chronic nature of most patients’ problems. After reviewing evidence that the natural history of addiction involves recurrent cycles of relapse and recovery, we discuss emerging approaches to recovery management, including techniques for improving the continuity of care, monitoring during periods of abstinence, and early reintervention; recent developments in the field related to self-management, mutual aid, and other recovery supports; and system-level interventions. We also address the importance of adjusting treatment funding and organizational structures to better meet the needs of individuals with a chronic disease.
Cancer stem cells and epithelial-to-mesenchymal transition in lung cancer

+ sorted cells showed enhanced SOX2 expression and increased spheroid forming potential compared to CD44-sorted cells in all three cell lines upon growth in serum-free neurobasal media (NBM). To conclude, we could not demonstrate differences in EMT marker expression in this cell line panel reflecting disease progression, however observed an increase in several CSC properties. Taken together, our results suggest that SCLC cells acquire enhanced CSC properties during disease progression and that more distant lesions differ in invasive capacity compared to the primary tumor.
Writer Identification for Handwritten Telugu Documents Using Directional Morphological Features

Linking a person based on handwritten documents is one of the oldest techniques that is used by crime investigators and forensic scientists. The importance of writer recognition in anthrax letter cases has made this examination popular in recent years. In this paper we propose four feature set namely directional opening, directional closing, direction erosion and k-curvature features for writer recognition on Telugu handwritten documents. Each of the features is extracted from the words after dividing them into a number of cells and then subjected to a nearest neighbor classifier for writer recognition. Although the results of each of the feature set is quite encouraging, the directional opening feature outperforms other feature sets.
Leaderless and Leader-Following Consensus With Communication and Input Delays Under a Directed Network Topology

In this paper, time-domain (Lyapunov theorems) and frequency-domain (the Nyquist stability criterion) approaches are used to study leaderless and leader-following consensus algorithms with communication and input delays under a directed network topology. We consider both the first-order and second-order cases and present stability or boundedness conditions. Several interesting phenomena are analyzed and explained. Simulation results are presented to support the theoretical results.
Generation as Dependency Parsing

Natural-Language Generation from flat semantics is an NP-complete problem. This makes it necessary to develop algorithms that run with reasonable efficiency in practice despite the high worst-case complexity. We show how to convert TAG generation problems into dependency parsing problems, which is useful because optimizations in recent dependency parsers based on constraint programming tackle exactly the combinatorics that make generation hard. Indeed, initial experiments display promising runtimes.
Currently, children with congenital heart disease are not limited in their submaximal exercise performance.

OBJECTIVES In several former studies, adolescents and adults with congenital heart disease (CHD) had a reduced exercise capacity even with defects considered to be simple. Currently, children might get better medical management and less restrictions concerning an active lifestyle or sports activities. The exercise performance of this new generation of children with CHD has to be evaluated. METHODS In the year 2010, 88 children (12.7 years, 52 males), 11-14 years old, with various CHD performed a cardiopulmonary exercise test in our institution. These children were matched for age and gender with healthy subjects who underwent the same procedure at a school survey. RESULTS In comparison with healthy controls, children with CHD had a diminished peak oxygen uptake (CHD: 35.5 ml/min/kg vs controls: 42.4 ml/min/kg; P < 0.001) corresponding to 87.1% (CHD) and 99.5% (Controls) of the reference value, respectively. Peak oxygen uptake decreased with the severity of the heart defect (r = -0.410; P < 0.001). However, there was no difference in oxygen uptake at the ventilatory threshold (CHD: 20.6 ml/min/kg vs controls: 21.5 ml/min/kg; P = 0.68). CONCLUSIONS Currently, children with CHD are not limited in their submaximal exercise performance. However, there is still a reduction in peak oxygen uptake.
Ecological Momentary Interventions Delivered by Smartphone Apps: Applications in Substance Use Treatment in Indian Scenario

© 2017 Indian Psychiatric Society | Published by Wolters Kluwer Medknow Sir, Ecological momentary interventions (EMIs) are defined as treatments which are provided to patients between sessions during their everyday lives (i.e., in real time) and in natural settings (i.e., natural settings). [1] Clinicians have tried to extend some aspects of psychotherapy into patients’ everyday lives to encourage activities and skill building in a variety of conditions including mental illnesses. EMI can be delivered in a variety of ways which includes unstructured recommendations to structured interventions. Such kind of interventions has been delivered using mobile and palmtop computers in previous decades. Mobile technology is ideal for delivering EMI because of its widespread usage and acceptability among the general population. [1] To date, EMIs have been delivered to patients with illnesses such as diabetes, obesity, and mental illnesses among many others. [1]
Kinematics Comparison between Dominant and Non-Dominant Kinematics Comparison between Dominant and Non-Dominant Lower Limbs in Thai Boxing Lower Limbs in Thai Boxing

Muay Thai, also known as Thai Boxing, is Thailand's national sport, and it involves athletes using different stand-up striking and clinching techniques. There are a limited number of research studies that have examined Thai Boxing skills and specifically none have examined the kinematics of the dominant and non-dominant legs while in a double collar or double underhook clinching position. The purpose of the study was to investigate the kinematics of the dominant (right) and non-dominant leg (left) between the double collar and double underhook Thai Boxing clinching positions. Participants executed six continuous knee strikes with the dominant leg and non-dominant leg in each of the two clinching positions for twelve knee strikes. A standard two-dimensional video motion analysis was conducted. The results revealed statistical significant difference at the hip joint angle between both clinching positions ( p = .013) but not at the knee and ankle joints. There were no statistical significant differences in the joint angular velocity and acceleration for the hip, knee, and ankle joint between both clinching positions . However, there was a statistical significant difference found in the joint angular velocity for the knee joint ( p = 0.00) between the dominant and non-dominant leg. Lastly, there was a significant correlation of the joint angle ( r = 0.65 and 0.63; double collar and double underhook) and the angular velocity ( r = 0.76 and 0.67; double collar and double underhook) for the left and right knee between both clinching positions. In addition, there was a significant correlation of the joint angle between the left and right hip ( r = 0.66) for the double collar position but not for the double underhook position. This study demonstrates the importance of hip joint flexibility and the angular velocity of the knee between the dominant and non-dominant leg. Future
Hydraulic Performance of Concrete Block Pavement under High Rainfall Intensities

High rainfall intensity will generate different response on the concrete block pavement (CBP) performance. A study found that larger openings of CBP did not lead more water penetrated. In other study, larger openings can lead greater decrease in runoff velocity. The correlation between the openings, water penetration and runoff velocity has remained unclear. In this study, we investigated hydraulic performance of CBP as an impact of surface roughness condition, under high rainfall intensities, saturated sub-base layer, and various slope surfaces. We conducted experiment using a 2 m by 6 m of rectangular CBP layer with herringbone 90 and basket-weave pattern. We used a modified dye tracing method in view to monitor the surface flow velocity under various high rainfall intensities. The results showed that hydraulic performance of surface runoff in the CBP layer was more influenced by the surface roughness condition. The roughness condition was very sensitive to the change in surface configuration of the CBP. The relationship between rainfall intensity, surface slope and roughness number followed polynomial functions. A further study is required to investigate the appropriate quality of CBPs, which have high durability applied over a steep slope surface and under high rainfall intensities.
Discrimination of Solid from Liquid Precipitation over Northern Eurasia Using Surface Atmospheric Conditions

AbstractDaily synoptic observations were examined to determine the critical air temperatures and dewpoints that separate solid versus liquid precipitation for the fall and spring seasons at 547 stations over northern Eurasia. The authors found that critical air temperatures are highly geographically dependent, ranging from −1.0° to 2.5°C, with the majority of stations over European Russia ranging from 0.5° to 1.0°C and those over south-central Siberia ranging from 1.5° to 2.5°C. The fall season has a 0.5°–1.0°C lower value than the spring season at 42% stations. Relative humidity, elevation, the station's air pressure, and climate regime were found to have varying degrees of influences on the distribution of critical air temperature, although the relationships are very complex and cannot be formulated into a simple rule that can be applied universally. Although the critical dewpoint temperatures have a spread of −1.5° to 1.5°C, 92% of stations have critical values of 0.5°–1.0°C. The critical dewpoint is l.