Miracle-dz/UniFAR-FTUs huggingface dataset:
The Structure of Human Microsomal Cytochrome P450 3A4 Determined by X-ray Crystallography to 2.05-Å Resolution*

The structure of P450 3A4 was determined by x-ray crystallography to 2.05-Å resolution. P450 3A4 catalyzes the metabolic clearance of a large number of clinically used drugs, and a number of adverse drug-drug interactions reflect the inhibition or induction of the enzyme. P450 3A4 exhibits a relatively large substrate-binding cavity that is consistent with its capacity to oxidize bulky substrates such as cyclosporin, statins, taxanes, and macrolide antibiotics. Family 3A P450s also exhibit unusual kinetic characteristics that suggest simultaneous occupancy by smaller substrates. Although the active site volume is similar to that of P450 2C8 (PDB code: 1PQ2), the shape of the active site cavity differs considerably due to differences in the folding and packing of portions of the protein that form the cavity. Compared with P450 2C8, the active site cavity of 3A4 is much larger near the heme iron. The lower constraints on the motions of small substrates near the site of oxygen activation may diminish the efficiency of substrate oxidation, which may, in turn, be improved by space restrictions imposed by the presence of a second substrate molecule. The structure of P450 3A4 should facilitate a better understanding of the substrate selectivity of the enzyme.
Clawback Enforcement, Executive Pay, and Accounting Manipulation

Clawback provisions entitle shareholders to recover previously-awarded incentive compensation from managers involved in accounting manipulation or misconduct. I study theoretically and empirically the impact of clawback provisions on the horizon of executive pay when shareholders face clawback enforcement frictions. In a principal-agent model, I show that strong clawback enforcement reduces the need for long-term compensation to avoid the manager's manipulation incentives. However, clawback adoption may be attached to an increase in long-term compensation if clawback enforcement is weak. The model shows that weak enforcement hinders the effectiveness of clawbacks, but firms may voluntarily complement these provisions with a lengthening of the pay horizon. Empirical tests using samples of propensity-score matched firms provide support to the model's mechanisms.
PENGARUH INTELLECTUAL CAPITAL TERHADAP PRICE BOOK VALUE MELALUI LABA PERUSAHAAN PADA PERUSAHAAN PERBANKAN YANG TERDAFTAR DI BEI TAHUN 2011-2013

The purpose of this study is to examine the Intellectual Capital to Price Book Value through the Company's Profit calculated by measuring Return On Equity (ROE) and Return On Asset (ROA), so it can be described for the following problem formulation: (1) test the partial intellectual (3) testing the effect of intellectual capital on PBV through ROE, (4) testing the effect of intellectual capital on PBV through ROA. While the population of this study are all banking companies listed on the BEI 2011-2013. Determination of the sample is done by using purposive sampling method to obtain 18 banking companies listing in BEI period 2011-2013. The type of data used is quantitative and is secondary data obtained from Indonesian Capital Market Directory (ICMD) in 2011-2013. Data analysis using path analysis technique (path analysis). The results of this study explain that (1) intellectual capital has a significant positive effect on PBV, ROE and ROA, (2) ROE and ROA have a significant positive effect on PBV, (3) intellectual capital influence on PBV through ROE, (4) intellectual capital PBV through ROA. So the result of path analysis showed that Intellectual Capital influences PBV through ROE and ROA. ROE and ROA status as intervening variable that acts as a booster for the direct relationship of intellectual capital to PBV in banking companies listing on BEI 2011-2013. keywords : Intellectual Capital (IC), Price Book Value (PBV), Return On Equity (ROE) dan Return On Asset (ROA).
Positron emission tomography in the early diagnosis of Huntington's disease

We studied 10 patients with early Huntington's disease and 7 normal age-matched controls with positron emission tomography (PET) using fluorodeoxyglucose. Subjects had little or no caudate nucleus atrophy and had not received any medications. The results demonstrated that hypometabolism of glucose preceded tissue loss. Furthermore, patients with minimal neurologic or psychiatric symptoms and no obvious CT changes may be differentiated from normal persons with high accuracy by PET. PET is helpful in the early diagnosis of Huntington's disease irrespective of the mode of presentation. PET may also be useful for preclinical detection and may supplement information from DNA studies.
Removal Characteristics of Wipe Devices under Various Conditions

Understanding the removal factor for specific conditions is essential to estimate removable surface contamination levels by wiping. The removal characteristics of dry foamed polystyrene pads and filter paper applied to polyvinyl chloride flooring are investigated using 14C-thymidine under various conditions (i.e., weight of contaminants, wax coating, temperature and humidity). Eight wipes were performed per flooring piece with a uniformly deposited contaminant to estimate the total removable surface contamination. The wipe devices were pressed against the surface by 2 kg-force with fingertips. The first wipe ratio (the ratio of the activity removed by the first wipe to the activity removed by eight wipes) from flooring on which was deposited 500 &mgr;g mL−1 of 14C-thymidine solution varies between 24% and 71% for polystyrene pads and between 33% and 83% for filter papers, depending on the atmospheric humidity and temperature. For deposition concentrations of 1 &mgr;g mL−1, the mean first wipe ratio using polystyrene pads, which are almost constant vs. humidity and temperature, are 68% and 24% for waxed and unwaxed surfaces, respectively. Under the same conditions, the mean first wipe ratio for filter paper varied with both the surface and the environmental conditions. The total recovery (the ratio of the total activity removed by eight wipes to the total deposited activity) for deposition concentrations of 500 &mgr;g mL−1 tended to increase with humidity for both wiping devices. The total recovery for deposition concentrations of 1 &mgr;g mL−1 is generally low. The first wipe ratio in the lowest case with foamed polystyrene pads in this study was 19%. In that case, the total removable activity is speculated to increase from the sum of eight wipes, if additional wipes are performed. Therefore, the theoretical value of 0.1 recommended by ISO for the removal factor is appropriate when wiping polyvinyl chloride flooring using foamed polystyrene pads.
Are altered states of consciousness detrimental, neutral or helpful for the origins of symbolic cognition? A response to Hodgson and Lewis-Williams

We respond to the commentaries by Hodgson and Lewis-Williams by clarifying the novelty of our theory. We argue that whenever Turing instabilities of neural activity play a role in generating visual hallucinations, they do more than shape the geometric patterns. Their relatively autonomous self-organization is a source of intrinsic value related to their self-maintenance as a pattern of activity, and they would also thereby decouple “higher-level” stages of neural processing from external stimulation, thus facilitating a more abstract mode of cognition. These additional features of our proposal support Hodgson and Lewis-Williams in their respective theories about the very first origins of human artistic activity. We also evaluate the critical literature regarding the possibility of ritualized enaction of altered states of consciousness (ASC) in early prehistory. We conclude that ASC were indeed possible, and suggest that they were likely involved in facilitating the social development of more symbolic forms of life and mind.
Glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPARγ in breast cancer pathophysiology

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor and plays important roles in breast cancer cell proliferation. The complexity of the underlying biochemical and molecular mechanisms of breast cancer and the involvement of PPARγ in breast cancer pathophysiology are unclear. In this study, we carried out prediction of the peroxisome proliferator response element (PPRE) motifs in 2332 genes reported to be involved in breast cancer in literature. A total of 178 genes were found to have PPRE (DR1/DR2) and/or PPAR-associated conserved motif (PACM) motifs. We further constructed protein-protein interaction network, disease gene network and gene ontology (GO) analyses to identify novel key genes for experimental validation. We identified two genes in the glycolytic pathway (phosphoglycerate kinase 1 (PGK1) and pyruvate kinase M2 (PKM2)) at the ATP production steps and experimentally validated their repression by PPARγ in two breast cancer cell lines MDA-MB-231 and MCF-7. Further analysis suggested that this repression leads to decrease in ATP levels and apoptosis. These investigations will help us in understanding the molecular mechanisms by which PPARγ regulates the cellular energy pathway and the use of its ligands in human breast cancer therapeutics.
La décomposition orthogonale aux valeurs propres et l'analyse de l'organisation tridimensionnelle des écoulements turbulents cisaillés libres

On presente une etude des possibilites de la decomposition orthogonale aux valeurs propres, basee sur l'analyse du tenseur des correlations de la vitesse en deux points, pour qualifier l'organisation a grande echelle des ecoulements cisailles libres turbulents. Cette etude est menee principalement a partir de l'etude experimentale de l'ecoulement d'une couche de melange plane turbulente incompressible. On utilise egalement des donnees experimentales issues de couches de melange planes compressibles et de sillages de plaque ou de barreau. Les mesures sont realisees par l'intermediaire de peignes de sondes a fil chaud simple ou a fils croises, fournissant une description spatio-temporelle fine d'une ou deux composantes de la vitesse dans des tranches de l'ecoulement. Plusieurs decompositions sont realisees, prenant progressivement en compte la complexite de l'organisation de l'ecoulement: des decompositions scalaires ou vectorielles basees uniquement sur une tranche de l'ecoulement puis des decompositions vectorielles prenant en compte la direction transversale de l'ecoulement. Les performances de ces decompositions sont quantifiees en termes de l'energie turbulente qu'elles peuvent representer. On montre que grace a l'utilisation de peignes de sondes, il est possible d'acceder a la contribution instantanee des modes de cette decomposition et ainsi a l'organisation de l'ecoulement. L'analyse des differentes decompositions utilisees met en evidence le fait que la prise en compte de plus en plus complete des degres de liberte de l'ecoulement permet une representation de plus en plus fine de l'organisation de l'ecoulement. Finalement, on utilise une theorie complementaire: la theorie du shot-noise pour acceder a une representation physique du mode dominant l'ecoulement
Prevalence and Intensity of Infection of Gastro-Intestinal Parasites in Babadjou, West Region of Cameroon

Helminth infections, such as Ascaris lumbricoides, Trichuris trichiura and Hookworms are major public health concerns. The aim of this study was to evaluate the prevalence and intensity of infection of gastro-intestinal helminthiasis in Babadjou. Qualitative and quantitative analyses were carried out on eight hundred and twenty five (825) stool samples collected from residents using the simple centrifugal flotation and McMaster count technique respectively. Out of the 825 samples examined, 70(8.5%) were infected with at least one helminth parasite with prevalence and intensities of infection of 4.4% and 2594.44 ± 3897.17 for A. lumbricoides, 4.2% and 72.86 ± 110.04 for T. trichiura, 1.9% and 83.33 ± 72.37 for Hookworms and 0.2% and 50 ± 00 for Capillaria hepatica respectively. Males (13.8%) were more infected than females (8.6%). The prevalence of A. lumbricoides and T. trichiura vary significantly with age groups with those of 1-10 years taking the lead (17.9%). The prevalence between the three educational levels differed significantly (P < 0.05) for A. lumbricoides, T. trichiura and Hookworm where those from the primary level were most infected (28.6%). The locality of Bamedji showed very high prevalences of A. lumbricoides (35.7%) and T. trichiura (17.9%) with significant differences as well. From the different occupations involved in the current study, students harboured all the four nematodes encountered. Cases of double and triple infections were recorded with A. lumbricoides+ T. trichiura (2.4%) being the highest and A. lumbricoides+ T. trichiura+ Hookworms (0.2%) the only triple infection registered. According to fecal concentration of eggs, 77.01% of infections were light infections, 3.44% moderate and 19.54% heavy infections. Only A. lumbricoides had heavy infections while all Hookworm infections were light. The results found on this study show that, it is important to control and prevent gastrointestinal helminths in and around Babadjou.
Adenylate cyclase and guanylate cyclase of normal and denervated skeletal muscle

Cyclic nucleotides mediate the intracellular effects of various extracellular influences. To explore the possibility that nerve-muscle influences are mediated by cyclic nucleotides, we studied the effect of denervation on the cyclase enzymes of rabbit gastrocnemius using the contralateral, unoperated limb as the control. Adenylate cyclase activity decreased dramatically after denervation, while guanylate cyclase activity increased several times in all tissue fractions studied. Neither enzyme demonstrated cholinergic responsiveness. The dramatic changes in cyclase activities following denervation could result from a role of these enzymes in the mediation of nerve-muscle influences.
Neutralization of Membrane TNF, but Not Soluble TNF, Is Crucial for the Treatment of Experimental Colitis

Background:Agents neutralizing membrane tumor necrosis factor (mTNF) and soluble TNF (sTNF) are widely used for the treatment of inflammatory bowel disease (IBD). Neutralization of mTNF, however, is associated with increased susceptibility to infectious diseases. The aim of this study was to determine whether neutralization of sTNF exclusively, by the use of a dominant negative mutant of TNF (XENP1595), could reduce the severity of colitis in mice. Methods:Colitis was induced in immunodeficient mice by transfer of CD45RBhi CD25− T-cells. Once the disease had developed, mice were treated twice a week with XENP1595, phosphate-buffered saline (PBS), anti-TNF monoclonal antibody (mAb), or isotype control. The anti-TNF mAb blocks both mTNF and sTNF. Weights, disease activity index, macroscopic inflammation of the colon, and histological sections were evaluated. T-cell populations from the colon were analyzed by flow cytometry. Results:Treatment of mice with XENP1595 did not change the course of the disease, whereas mice treated with anti-TNF mAb recovered weight soon after the first treatment dose. Inflammation in the colon was reduced in mice treated with anti-TNF mAb compared to isotype control-treated animals. Mice treated with XENP1595 had a similar degree of inflammation in the colon as PBS-treated animals. The number of effector and regulatory T-cells in the colon remained unaffected by all treatments. Conclusions:Neutralization of sTNF exclusively was unable to induce remission in T-cell-mediated colitis, suggesting that neutralization of mTNF is crucial for the treatment of IBD.
Testing Horizontal and Vertical Alignment of HR Practices Designed To Achieve Strategic Organizational Goals

The purpose of this paper is to measure the effect of aligning HR practices horizontally and vertically to support organizational strategic goals. ,Hypotheses were tested using 85,840 employees’ responses collected from a single, large public organization’s annual employee survey. Factor analysis with principal axis factoring and varimax rotation was used to confirm the variables being studied. The relationships were analyzed using ordered logistic regression. ,Results suggest that compensation practices, workforce planning, and work/life balance-focused HR practices can be used to predict job satisfaction and turnover intentions. Additionally, when the combined effects of the three HR practice types are considered together, an increased reduction in turnover intention is indicated. ,To achieve optimal performance organizations should be diligent in their efforts to align their functional area HRM strategies and practices with each other and with the overall strategic goals and objectives guiding the organization. ,While the positive effect of alignment has been proposed by many scholars, empirical examinations of the binary approach are rare. This paper contributes to the field by providing a unique empirical examination of an organization’s implementation of HR practices designed to achieve stated strategic objectives through a large scale study.
Suitable Dialytic Indicators for Pediatric Peritoneal Dialysis Patients: The Alternative to Creatinine Clearance

← Objective Owing to the discord between body weight and body surface area (BSA), creatinine clearance (CCr) is predisposed to be small in pediatric patients on peritoneal dialysis (PD). Alternatively, Kt/V creatinine (Kt/V creat), which is normalized to total body water (TBW) rather than BSA, could be a better dialytic indicator. In this study, the efficiency of dialysis and the nutritional status of pediatric patients on chronic PD were examined, and the utility of dialytic indicators was evaluated. ← Patients and Methods 49 patients under 20 years old, in stable condition, and on PD were analyzed. Weekly total Kt/V of urea (Kt/V urea), CCr, Kt/V creat, and normalized protein equivalent of nitrogen appearance (nPNA) were measured for all patients and for patients under 6 years old. The target value was 2.0/week for Kt/V urea and 60 L/week/1.73 m2 for CCr, as recommended by the Kidney Disease Outcomes Quality Initiative guidelines. The target value for Kt/V creat was set as 1.52/week, using a male model with a height of 170 cm and a body weight of 65 kg. ← Results The mean values of delivered Kt/V urea, CCr, Kt/V creat, and nPNA (and proportion of patients that achieved each target value) for all patients were 2.25 ± 0.57/week (67.4%), 53.8 ± 19.3 L/week/1.73 2m (26.5%), 1.83 ± 0.73/week (65.3%), and 1.11 ± 0.42 g/day, respectively. The values for patients under 6 years old were 2.38± 0.26/week (90.0%), 45.9 ± 12.8 L/week/1.73 2m (10.0%), 1.94 ± 0.51/week (90.0%), and 1.52 ± 0.67 g/day, respectively. Stepwise multiple regression analyses revealed that the relationship between CCr and Kt/V urea was affected by the patient's age. ← Conclusions Our pediatric patients achieved the recommended target value of Kt/V urea. At the same time, the nPNA results reflected the patient's status well. However, CCr appeared to be inappropriate as an indicator for patients under 6 years old. Kt/V creat is suggested to be a better dialytic indicator for these patients.
The effect of eye position on the orientation of sound lateralization

Conclusions. The data suggest that sound lateralization sensitivity during interaural time difference (ITD) discrimination is altered by eccentric gaze and that sound lateralization shifts toward the direction of the gaze. Objective. Using dichotic sounds, the effect of eye position on the orientation of sound lateralization was investigated in humans. Subjects and methods. The subjects were studied by testing ITD discrimination under different conditions of visual fixation. Results: The amplitudes obtained during the ITD discrimination tests during eccentric fixation were significantly greater than those obtained while gazing straight ahead (p<0.05). The median line of amplitude obtained during the ITD discrimination test shifted toward the direction of the gaze.
Clinical heterogeneity and tumor control probability

Abstract Heterogeneity in tumor sensitivity to therapy within patient populations is a major factor affecting tumor control probability (TCP) models, typically flattening dose-response curves. Knowledge of the major clinical factors affecting TCP would allow incorporation of these factors into TCP models, or stratification of patients and tumors, yielding steeper and more specific and predictive TCP curves. Methods. Literature review of the results of therapy for oropharyngeal cancer. Results. In recent years an improvement in control rates of cancers such as oropharyngeal cancer has been reported as potentially gained due to the dosimetric superiority of intensity modulated radiotherapy (IMRT). However, the emergence of Human Papilloma Virus (HPV)-related oropharyngeal cancer in recent years is an example of a major clinical factor which likely supersedes the dosimetric gains of IMRT. Conclusions. Clinical factors such as the example discussed in this paper: HPV-related oropharyngeal cancer, must be taken into account in TCP models in order for such models to be relevant.
Prevalence and nature of connexin 26 mutations in children with non-syndromic deafness.

OBJECTIVE To determine (1) the prevalence and nature of connexin 26 mutations in a cohort of Australian children with non-syndromic hearing loss, and (2) the carrier frequency of the common connexin 26 mutation (35delG) in the general population. DESIGN A cohort, case-finding study. Mutation analysis was performed on DNA extracted from white blood cells, buccal cells, or Guthrie blood spots. SETTING A hearing loss investigation clinic and a deafness centre in two Australian capital cities, 1 January 1998 to 31 October 2000. PARTICIPANTS (1) 243 children (age range, 4 weeks to 16 years; median, 4 years), attending hearing loss clinics in Sydney and Melbourne; (2) 1000 blood samples obtained from anonymous Guthrie card blood spots collected in 1984 [corrected] by the Victorian Clinical Genetics Service as part of the newborn screening program. MAIN OUTCOME MEASURES (1) The prevalence and types of connexin 26 mutations in a cohort of children with prelingual deafness; (2) the carrier frequency of the common connexin 26 mutation, 35delG, in the general population. RESULTS Connexin 26 mutations were identified and characterised in 52 (21%) of the 243 children; 14 different mutations, including four previously unreported mutations (135S, C53R, T123N and R127C), were identified. The common 35delG mutation was found in 56 of the 104 alleles (ie, 86 of the connexin 26 alleles in which a mutation was positively identified). The mutations V371 and M34T were also relatively common. The carrier frequency of connexin 26 mutations and of the common 35delG connexin 26 mutation in the Victorian population was estimated to be 1 in 54 and 1 in 100, respectively. CONCLUSIONS Mutations in the connexin 26 gene (especially the 35delG mutation) are a common cause of prelingual hearing loss in Australia.
Impact of Gaucher disease on COVID‐19

cal variation on classification of diabetes in a large non-pregnant population cohort in Singapore. Using numerical simulations, accounting for CVi for FBG (5.7%) and OGTT (16.7%) and analytical variations, they found a potential 14.4% increase in diabetes diagnosis if glucose measurements were repeated for the group with original classification of impaired fasting glucose (World Health Organization criteria). Furthermore, a potential 26.6% increase in diabetes diagnosis was estimated if glucose measurements were repeated for the group with impaired glucose tolerance. The use of the average of results of the repeat laboratory tests appears to improve the consistency of disease classification. The COVID-19 pandemic has led to a revisit of laboratory testing. We should never waste a good crisis.