Miracle-dz/UniFAR-FTUs huggingface dataset:
DMD055947 407..414

Hepatocytes provide an integrated model to study drug metabolism and disposition. As a result of a loss of polarity or a significant decrease in the expression of enzymes and transporters, suspended and sandwich-cultured hepatocytes have limitations in determining hepatocellular drug concentrations. Underprediction of the extent of glucuronidation is also a concern for these hepatocyte models. Faldaprevir is a hepatitis C virus protease inhibitor in late-stage development that has demonstrated significant liver enrichment in in vivo rat models based on quantitative whole-body autoradiography (QWBA) and liver-to-plasma area under-the-curve ratio. In bile duct cannulated rats, the primary biliary metabolite was a glucuronide. Owing to ethical concerns, it is difficult to assess liver enrichment in humans, and a lack of in vitro and in vivo correlation of glucuronidation has been reported. The current study was conducted to verify whether a hepatocyte model, rat HepatoPac, could overcome some of these limitations and provide validity for follow-up studies with human HepatoPac. With rat HepatoPac, liver enrichment values averaged 34-fold and were consistent with rat QWBA (26.8-fold) and in vivo data (42-fold). In contrast, liver enrichment in suspended hepatocytes was only 2.8-fold. Furthermore, the extent of faldaprevir glucuronidation in HepatoPac studies was in agreement with in vivo results, with glucuronidation as the major pathway (96%). Suspended rat hepatocytes did not generate the glucuronide or two key hydroxylated metabolites that were observed in vivo. Overall, our studies suggest that HepatoPac is a promising in vitro model to predict in vivo liver enrichment and metabolism, especially for glucuronidation, and has demonstrated superiority over suspended hepatocytes.
Experimental Approach Alters N and P Addition Effects onLeaf Traits and Growth Rate of Subtropical Schima superba(Reinw. ex Blume) Seedlings

Nitrogen (N) and/or phosphorus (P) addition has controversial effects on tree functional traits and growth; however, this experimental approach may clarify these controversial results. In this study, field and pot experiments were designed with +N (100 kg N ha−1 yr−1), +P (50 kg P ha−1 yr−1), +NP (100 kg N plus 50 kg P ha−1 yr−1), and a control (no N or P addition) to comparatively investigate the effects of N and P addition on 24 leaf traits and the growth rate of Schima superba (Reinw. ex Blume ) seedlings in subtropical China. We found that the experimental approach alters N and P addition effects on leaf traits and tree growth. Nitrogen addition strongly altered leaf biochemical and physiological traits and limited tree growth compared to P addition in the pot experiment, while the effects of N and P addition on leaf traits and tree growth were weaker in the field, since the seedlings might be mainly limited by light availability rather than nutrient supplies. The inference from the pot experiment might amplify the impact of N deposition on forest plants in complicated natural systems. These findings will help guide refining pot fertilization experiments to simulate trees in the field under environmental change. Future directions should consider reducing the confounding effects of biotic and abiotic factors on fertilization in the field, and refinement of the control seedlings’ genetic diversity, mycorrhizal symbiont, and root competition for long-term fertilization experiments
Major icesheet change in the Weddell Sector of West Antarctica over the last 5000 years

19 Until recently, little was known about the Weddell Sea sector of the West Antarctic Ice Sheet. 20 In the last 10 years, a variety of expeditions and numerical modelling experiments have 21 improved knowledge of its glaciology, glacial geology, and tectonic setting. Two of the 22 sector’s largest ice streams rest on a steep reverse-sloping bed yet, despite being 23 vulnerable to change, satellite observations show contemporary stability. There is clear 24 evidence for major ice-sheet reconfiguration in the last few thousand years, however. 25 Knowing precisely how the ice sheet has changed in the past, and when, would allow us to 26 better understand whether it is now at risk. Two competing hypotheses have been 27 established for this glacial history. In one, the ice sheet retreated and thinned progressively 28 from its Last Glacial Maximum position. Retreat stopped at, or very near, the present 29 position in the Late Holocene. Alternatively, in the Late Holocene the ice sheet retreated 30 significantly upstream of the present grounding line, and then advanced to the present 31 location due to glacial isostatic adjustment, and ice-shelf and ice rise buttressing. Both 32 hypotheses point to data and theory in their support, yet neither has been unequivocally 33 tested or falsified. Here, we review geophysical evidence to determine how each hypothesis 34 has been formed, where there are inconsistencies in the respective glacial histories, how 35 they may be tested or reconciled, and what new evidence is required to reach a common 36 model for the Late Holocene ice sheet history of the Weddell Sea sector of West Antarctica. 37 Plain Language Summary 38 The West Antarctic Ice Sheet is vulnerable to climate and ocean warming because it rests 39 on a bed more than 2 km below sea level in some places. Understanding how this ice sheet 40 has changed in the recent past guides our appreciation of how it will change in the near 41 future. Getting such information requires measurement of: (1) structures in the ice that are 42 influenced by former ice-sheet change; (2) the age of sediment on surfaces exposed above 43 the ice now but that were previously covered; and (3) numerical modelling of ice-sheet 44 processes to understand what change is realistic. The ice sheet was certainly a lot bigger at 45 the ice age, 20,000 years ago, but two alternative histories exist on how it shrank to today’s 46 size. In one, the ice sheet gets smaller gradually over time and, in the other, the ice sheet 47 becomes smaller than today before it expands and comes to rest. Arriving at a single history 48 for the ice sheet may allow us to better understand whether to expect change to occur here 49 in future and how it may happen. 50
Robust active fault-tolerant control for internal combustion gas engine for air–fuel ratio control with statistical regression-based observer model

Fault-tolerant control systems are utilized in safety and critical applications to achieve greater reliability and availability for continued operation despite faults in the system components. These systems can be utilized in the process plants to avoid costly production loss due to abnormal and unscheduled tripping of the machines. In this paper, advanced fault-tolerant control systems of active type are proposed for air–fuel ratio control of internal combustion gas engine in a process plant to achieve greater reliability and availability to avoid a shutdown of the gas engine. Gas engines are extensively used equipment in the process industry and proper air–fuel ratio control in the fuel system of these engines is quite important to achieve greater engine efficiency, fuel energy savings and environmental protection. Active fault-tolerant control system is proposed in this paper in which linear regression–based observer model is used in the fault detection and isolation unit for fault detection, isolation and reconfiguration. Fuel actuator is introduced in the fuel supply line and proportional feedback controller is implemented to maintain the air–fuel ratio in faulty conditions. Redundancy in the sensors and fuel actuator is proposed to avoid engine shutdown in case of simultaneous faults in more than one sensor and to avoid a single point of failure due to fault in the single actuator. Noise is introduced in the sensor measurements to determine the robustness of proposed active fault-tolerant control system in noisy and faulty conditions. Results show that the proposed system remains stable, maintaining air–fuel ratio well in faulty conditions and is robust to noise.
Implications for nurse managers arising from immigrant women’s experience of midwifery care in a hospital

tebid r. , du plessis d. , beukes s. , van niekerk v. & jooste k. (2011) Journal of Nursing Management19, 967–975 Implications for nurse managers arising from immigrant women’s experience of midwifery care in a hospital Aim This paper focuses on implications for nurse managers to support midwives in delivering nursing care to immigrant mothers in some government hospitals in Gauteng, South Africa. Background Immigration and poverty in Africa has led to midwives providing nursing care to immigrant mothers in a culturally sensitive environment. This necessitates an environment in which nurse managers should support midwives in caring for these mothers as unique individuals. Method An exploratory, descriptive phenomenological design was followed. The target population included nine immigrant mothers living in the inner centre of Johannesburg who, for the first time, attended, had antenatal clinics, laboured and gave birth at a Government Hospital in the Gauteng province of South Africa. After purposive sampling, phenomenological interviews were conducted until data saturation occurred. Results The findings indicate that nurse managers should ensure that midwifery care of immigrant mothers comply with the ethical–legal context of the South African constitution. Actions should be taken in combating issues related to impaired maternal–midwife relationship, lack of cultural sensitivity and psychological distress. Conclusion The delivery of maternity care to immigrant mothers is below the standard expected in the South African context. Implications for nursing management The nurse manager should support midwives to ensure an environment to care for immigrant mothers in maternity wards.
Fixed point free action with regular orbits.

Let A be a finite group of operators on the fmite group G and assume (\A\, \G\) = l and CG(A) = 1. Let l (A) denote the length of the longest chain of subgroups of A and let h(G) denote the Fitting height of G. It is known [14], that given A up to isomorphism, we can find infmitely many G's such that h(G) = l(A). We still don't know whether h(G)^l(A) holds in general. In [14] it is proved that if the action of A on G is "generic", then h(G)^l(A). In this context "generic" means that the action of every proper subgroup of A on G produces enough regulär orbits and modules. It is the purpose of this paper to prove that in order for h(G)^l(A) to hold, it is enough to assume that the action of every proper subgroup of A produces enough regulär orbits. More precisely we prove:
First Test Results on ITER CS Model Coil and CS Insert

The Inner and Outer modules of the Central Solenoid Model Coil (CSMC) were built by US and Japanese home teams in collaboration with European and Russian teams to demonstrate the feasibility of a superconducting Central Solenoid for ITER and other large tokamak reactors. The CSMC mass is about 120 t, OD is about 3.6 m and the stored energy is 640 MJ at 46 kA and peak field of 13 T. Testing of the CSMC and the CS Insert took place at the Japan Atomic Energy Research Institute (JAERI) from mid March until mid August 2000. This paper presents the main results of the tests performed.
IDENTIFING THE ENDURANCE OF PATIENTS WITH P53 JOINTS IN GASTRIC DISEASES

Aim: Gastric disease is the most powerful type of malignant growth. The immunohistochemical articulation of the proteins of the p53 has been proposed as a potential device to evaluate the natural conduct of gastric malignant growth. The research aim was of p53 for endurance is questionable; henceforth this examination has been detailed to know the endurance of patients with p53 joints in gastric diseases. Methods: Our current research was led at Jinnah Hospital, Lahore from May 2018 to April 2019, including 64 patients back-to-back gastric malignant growth. Examples of biopsies were treated in immunohistochemistry and the articulation of p53 quality was decomposed by immunoreactive score (IRS). These findings were then contrasted and clinically obsessive parameters such as age, sexual orientation, tumor area, tumor size, Laurens characterization and TNM organization as indicated by the joint U.S. Board of Directors for the rules of disease, using CT belly exit, and histopathological evaluation and types as indicated by WHO arrangement. RESULTS: Mp53 joint was observed in 95% of patients with gastric malignancy, with 39 (64.9%) having a high joint and 22 (38.3%) having a low p53 joint. The joint level p53 was found to be essentially related to age, tumor site, tumor size, histological evaluation, T organization, M arrangement and clinical stage. A multivariate study shows that a high p53 joint is a free indicator of endurance. At the Kaplan-Meier endurance examination, patients with a high p53 joint had a significantly shorter overall endurance than patients with a low p53 joint. Conclusion: The expression of p53 is associated with endurance and is a basic, binding and reproducible methodology for deciding on prediction and endurance in the different assessments and phases of gastric disease.
Detection of Meridional Currents in the Equatorial Ionosphere

Theoretical investigations predict meridional currents in the dynamo region of the ionosphere a few degrees north and south of the magnetic equator as a consequence of the equatorial electrojet. The magnetic fields of these currents are perpendicular to the permanent magnetic field of the earth and cause a height variation of the magnetic declination. It was the aim of six rocket launches performed in 1970 near noon at Natal, Brazil, to detect these currents. To reach this objective, identical payloads each consisting of two flux-gate magnetometers, a solar aspect sensor, an experiment to measure the angle between the magnetic field and the direction to the sun, and an impedance probe to determine the electron density were launched under different magnetic conditions. The predicted variation of the declination has been observed but with considerably higher amplitude than was expected. On the other hand, the measured height integrated current density in the west-east direction was smaller than deduced from ground based magnetic H-variations. These discrepancies can be explained by currents flowing at 5 degrees off the magnetic equator, on both sides, with intensities of about 0.3 of the electrojet intensity at the same height but in reversed direction. Such reversed currents have recently been observed from ground based magnetic observations by others and have also been interpreted theoretically by ionospheric wind effects.
Volatile Organic Compounds in Primary Schools in Ho Chi Minh City, Vietnam: Characterization and HealthRisk Assessment

Limited information about exposure to volatile organic compounds (VOCs) in primary schools in Vietnam is available. In this study, we aimed to characterize indoor VOCs in four primary schools situated in Ho Chi Minh City, a metropolis in the south of Vietnam and assess health risks linked to the students’ exposure to VOCs. Indoor and outdoor air samples were collected in the schools and analyzed for volatile composition using gas chromatography coupled with mass spectrometry. Different classes of VOCs, including aromatic hydrocarbons, alkanes, aldehydes, esters, cyclic terpenes, and chlorinated hydrocarbons, were identified and quantified in classrooms of the schools. The results showed that the concentrations of the VOCs differed significantly among the schools and between ground-floor and first floor classrooms. In addition, VOC profiles differed considerably between air-conditioned and non-air-conditioned classrooms. Limonene, a compound associated with fragrance products, was the most abundant VOC, with the median (range) concentration of 26.12 (10.29, 50.08) μg/m3. The concentrations of the compounds examined in the study were in general found to be higher indoors compared with outdoors, signifying indoor emission sources. Potential harmful effects are expected as a result of exposure to benzene, ethylbenzene, naphthalene, 1,4-dichlorobenzene and tetrachloroethylene in the investigated schools. Further research is needed to fully assess the health risks to students, teachers, and staff in these educational environments.
Antibacterial Efficacy

Strains of Escherichia coli, Enterobacter aerogenes, and Enterobacter cloacae that were resistant to ceftazidime (MIC > 16 ,ug/ml) but susceptible to BMY 28142 (MIC < 4 ,ug/ml) were found to contain higher levels of j-lactamase activity (50to 3,340-fold) than control strains of the corresponding species. Ceftazidime was at least as resistant as BMY 28142 to hydrolysis by these enzymes. However, the apparent K, ofBMY 28142 for each enzyme was larger (8to >20-fold) than that of ceftazidime; i.e., the affinity of these enzymes for BMY 28142 appeared to be lower than that for ceftazidime. Thus, BMY 28142 was affected less than ceftazidime by a mechanism of resistance that depends, at least in part, on the relative affinities of cephalosporins for the j3-lactamases of these species. These results indicate that the affinity between a jI-lactamase and a cephalosporin may be a distinguishing factor in the evaluation of ,-lactamase-resistant cephalosporins and suggest that affinity can play a major role in susceptibility to highly ,(-lactamase-resistant cephalosporins.
NEW DEBATE

The variability in the numbers of treatment cycles couples may undertake with assisted reproductive technology (ART) and the length of time they may have to wait between successive cycles of treatment make the evaluation of treatment efficacy and prognosis complicated. The cumulative pregnancy rate using the life table method of analysis is being used more frequently to estimate the effectiveness of treatment. Although this approach is valid in some areas of infertility research, its use in ART is not appropriate, because the factors necessary for the analysis (particularly the scale for measuring the passage of time and lack of informative censoring) are not satisfied. Consequently, an overestimation of the effect of treatment is produced that may lead to biased decision making. Although there is no easy solution to this problem, several options for summarizing the outcome data are offered: pregnancy rate per cycle, time-limited analysis using proportions, conservative cycle-based cumulative pregnancy rate and real-time-based cumulative pregnancy rate. In this manner, more realistic information can be generated to counsel patients, evaluate the efficacy of treatments, compare rates among centres and guide the formulation of policies for infertility management and resource allocation.
DENTO-SKELETAL EFFECTS OF TWIN BLOCK-HEADGEAR IN TREATMENT OF CLASS II MALOCCLUSION CASES

Objective: To evaluate dental and skeletal effects of Twin Block-Headgear combination in treatment of Class II malocclusion cases. Material and Methods: Twenty five female growing patients with skeletal Class II due to both mandibular retrognathism and maxillary prognathism were selected. Fifteen patients were treated using Twin Block with high pull headgear (TB-HG group) for nine months, while the other ten patients had no treatments (control group). For each patient, lateral cephalometric x-ray film was taken at the start and the end of active functional treatment period and then traced and analyzed. The collected data were subjected to t test to assess the significant differences in the changes in measurements between the two groups. Results: The TB-HG group showed a significant maxillary growth restriction and enhancement of the mandibular growth. The upper and lower incisors were significantly retroclined and proclined respectively. The maxillary molars moved distally while the mandibular molars moved mesialy. The mandibular plane and palatal plane angles showed no significant changes. Conclusions: Twin Block-Headgear appliance could be used successfully in treatment of skeletal Class II malocclussion due to maxillary protrusion and mandibular retrusion without adverse changes in the mandibular plane angle.
Modelling Turbulence Using Vortex with Varying Strain Rate

In the last three decades, the study of turbulence, one of the great unsolved problems of classical physics, based on the dynamics of vortices and vortex motions has received continuing attention by physicists, engineers, and mathematicians. Here the solutions of Navier-Stokes (N-S) equations are used to show the dynamical behaviour of Lagrangian particles on the invariant plane of Velocity Gradient Tensors (VGT) for vortex with unsteady rate of strain. The results show that, for particles not too far from the vortex centre, the VGT invariant follows trajectories spiralling in towards the origin of the invariant plane, and follow a shape closely resembling to the conditional average from Direct Numerical Simulation of isotropic turbulence. These vortices of unsteady strain rates offer an explanation on forward and backward energy transfer
RMHP_A_263579 1335..1341

College of Pharmacy, Pusan National University, Busan, South Korea Background: The Korean Ministry of Food and Drug Safety (MFDS) issued a safety letter regarding metoclopramide use and its adverse drug event of extrapyramidal disorder in October 2013. However, this safety letter had controversial effects on pharmacovigilance and management policies. The objective of this study was to estimate the impact of this government safety letter on the use of metoclopramide. Patients and Methods: We conducted an interrupted time-series analysis using national claims data from January 2011 to December 2015 to assess the difference in metoclopramide utilization (ie, the total number of prescriptions per month, the average administration period per prescription per month, and the average dose per prescription per month) before and after the publication of the safety letter in October 2013. Results: The number of prescriptions, the average administration period per prescription, and the average dose per prescription of metoclopramide decreased after the publication of the safety letter. Notably, the decrease in the average administration period per prescription after the safety letter was statistically significant. Conclusion: Our results indicate that the changes in the number of prescriptions, dose, and the duration of prescription may have occurred as a result of the restrictions and recommendations in the safety letter. Further research is needed to optimize the use of metoclopramide and to identify the risk of adverse drug events since the safety letter was issued.