Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of Orally Administered Camptothecins

Abstract: Phase I trials of oral camptothecins, including camptothecin (CPT) and irinotecan (CPT‐11), have reported substantial interpatient variability in systemic exposure, which could result in suboptimal antitumor activity in some patients or enhanced risk for toxicity in others. This investigation evaluates the contribution of intestinal absorption and first‐pass metabolism in the disposition of oral CPT and CPT‐11, respectively. The transport of CPT in Caco‐2 cell lines (validated model of intestinal drug transport) was concentration dependent and saturable (Vmax: 34×10−5 cm/sec and Km: 20 μM), and was temperature dependent with an activation energy (Ea) of 11.7 kcal/mole. Cumulatively, this data was indicative of carrier‐mediated intestinal transport. In addition, a reduction of transport in the presence of sodium azide plus deoxyglucose suggested ATP dependence. Thus, variable expression and availability of intestinal transporters could contribute to the observed wide variability in the exposure to oral CPT. CPT‐11 is hydrolyzed by the ubiquitous enzyme carboxyl esterase to active SN‐38, and first‐pass metabolism of oral CPT‐11 would include both intestinal and hepatic hydrolysis. Incubation of CPT‐11 with S9 fractions of human liver and intestinal tissues resulted in variable rates of formation of SN‐38. The mean (±SD) specific activities (pmoles/min/mg) were: liver (8.57 ± 10.4, n=8), duodenum (5.06 ± 3.7, n=4), jejunum (6.44 ± 2.8, n=5), ileum (4.81 ± 2.4, n=5), colon (1.93 ± 1.5, n=6), and rectum (0.82, n=1). Interestingly, there was a decrease in SN‐38 formation by tumor tissue compared to matched normal liver and colon tissues. Therefore variable first‐pass metabolism could contribute to the substantial differences in the systemic exposures to CPT‐11 and SN‐38 in patients receiving oral CPT‐11.
ENHANCEMENT OF BENTAZONE EFFICACY WITH NEWLY DEVELOPED ECOFRIENDLY ADJUVANTS

Adjuvants have been developed to enhance the activity of pesticide and possibly could allow reduction of pesticide rates. This is a very important fact as there are many concerns associated with pesticides use, because of their potential to cause adverse effects to operators, crops and environment. Because of that there is continued government regulatory pressure for safer pesticide products and for reduction of pesticides application rate. Trend towards minimum use of pesticides lead to development of new, more effective adjuvants to enhance biological activity of pesticide formulations, either built-in formulation or added in tank mix just before application. Among others, crop oil concentrates (COC) and soluble concentrates (SL) are bioenhancing adjuvants which enhance the effectiveness of pesticides. In our study we investigated how adjuvants with different compositions influenced bentazone efficacy. The first step was development of ecofriendly crop oil concentrates based on vegetable oils (sunflower oil, soybean oil and esterified rape seed oil) in combination with different surfactants. Then we compared the effects of the crop oil concentrates and the commercial adjuvant (Trend ® 90, soluble concentrate) during the application with bentazone on two different locations. The results after two year trials confirmed that all investigated adjuvants have beneficial effects on bentazone efficacy, but the effects of the developed crop oil concentrate with esterified rape seed oil was the most pronounced.
Predictive fuzzy PID control for temperature model of a heating furnace

In conventional PID scheme, the ensemble control performance may be unsatisfactory due to limited degrees of freedom. Based on such backgrounds, a novel PID control that inherits the advantages of fuzzy PID control and predictive functional control (PFC) is proposed and tested on the temperature model in a heating furnace in this paper. On the basis of the framework of PFC, the fuzzy PID control is introduced to acquire the optimal control law, then an improved PID control strategy is obtained. Finally, the case study on a temperature model of a heating furnace demonstrates the effectiveness of the proposed PID control scheme in comparison with the conventional PID control and the fuzzy self-adaptive PID control.
The Discontinuous Galerkin Material Point Method for the simulation of hyperbolic problems in finite deforming solids

A wide variety of dynamic physical problems, such as impact on structures or high-speed forming techniques, involves waves propagating in finite strained solids. The numerical simulation of this class of problems has been and is still mainly performed with the Finite Element Method despite well-known short-comings. Indeed, Lagrangian formulations of FEM may suffer from mesh entanglement and classical time integrators introduce high frequency noise in the vicinity of discontinuous solutions. Two families of numerical methods developed in parallel address each of these limitations. First, among ParticleIn-Cell methods, the Material Point Method [1] can be viewed as the classical FEM with moving quadrature points and is an effective tool for dealing with finite deformations due to the use of particles that can move in an arbitrary Eulerian grid. However, this method inherits the FEM spurious oscillations issues. Second, the Discontinuous Galerkin approximation [2], based on discontinuous shape functions across element boundaries, allows to accurately track waves fronts within a finite element formulation. Nevertheless, the DGFEM is also subjected to mesh tangling effects.
Population based randomised study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by faecal occult blood testing

Abstract Objectives: To compare the feasibility of mass screening by flexible sigmoidoscopy with screening by faecal occult blood testing (Haemoccult) and both tests combined. Design: Patients were randomised to screening by flexible sigmoidoscopy, faecal blood testing, or both tests. The flexible sigmoidoscopy examinations were performed by a general practitioner. Setting: General practice. Subjects: 3744 patients aged 50-75 years. Main outcome measures: Uptake, positive results, detection of neoplasia, complications, and recall for diagnostic colonoscopy. Results: Uptake was significantly higher in the flexible sigmoidoscopy group (46.6%) than in the faecal blood test group (31.6%; P<0.001) or than in the group having both tests (30.1%; P<0.001). Telephone reminders increased uptake of sigmoidoscopy to 61.8%. In total, 1116 sigmoidoscopy examinations were performed without major complication. Polyps were found in 19.3% (95% confidence interval 17.0% to 21.6%) but only 6.8% (5.3% to 8.3%) had adenomas and 2.4% (1.5% to 3.3%) “high risk” adenomas. Cancer was detected in four subjects. The faecal blood test yielded positive results in 0.8% (0.2% to 1.4%) but missed at least one cancer and 30 cases of adenoma which were found by sigmoidoscopy in the combined group. Use of histological criteria—shown elsewhere to correlate with future risk of colorectal cancer —to select “positive” patients could reduce recall for diagnostic colonoscopy from about 20% to less than 5%. Conclusions: Some of the predicted obstacles to screening with flexible sigmoidoscopy are surmountable. Clear evidence relating to efficacy will be obtained only from a randomised controlled trial.
A 3 GHz Wideband $\Sigma \Delta$ Fractional-N Synthesizer With Switched-RC Sample-and-Hold PFD

Designing high linearity phase-frequency-detectors (PFDs) in low-voltage, deep submicrometer processes is a challenging problem. Nonlinear PFDs can fold out of band phase noise, and increase in-band phase noise of fractional-N PLLs in deep submicron processes. A 3-GHz Type-I ΣΔ fractional-N PLL with an exponentially settling voltage-mode switched-RC phase frequency detector (PFD) is presented. A voltage-mode, fully settled switched-RC (SRC)-based sample-and-hold PFD, providing benefits of both an RC loop-filter and a zero-order hold sinc( ) suppressing reference clock leakage is presented. The exponentially settled SRC PFD is shown to reduce the in-band leakage of quantization noise by 13 dB in comparison to a similar current-mode charge pump PFD, enabling a measured loop-bandwidth of 890-kHz. The fractional-N PLL is fabricated in a 180-nm CMOS technology with 6 metal layers and consumes 18-mA from a 1.8-V power supply. The worst-case near-integer in-band spur is measured at -62 dBc. The measured in-band phase noise at 100-kHz offset from the 3-GHz carrier is -107 dBc/Hz and out-of-band phase noise at 3-MHz offset is -130 dBc/Hz. The phase-locked loop settling time for a frequency step of 45-MHz and 0.1-ppm accuracy is less than 10-μs.
New Constraints on Quantum Theories

Hierarchical relationships between physical theories are discussed. It is explained how a lower rank theory imposes constraints on an acceptable structure of its higher rank theory. This principle is applied to the case of quantum mechanics and quantum field theory of massive particles. It is proved that the Dirac equation is consistent with these constraints whereas the Klein-Gordon equation, as well as all other second order quantum equations are inconsistent with the Schrödinger equation. This series of arguments undermines the theoretical structure of the Standard Model.
The effect of garlic on cyclosporine-A-induced hyperlipidemia in male rats.

INTRODUCTION Cyclosporin A (CsA) is a potent immunosuppressive drug. However, it has adverse effects that include elevation of plasma low-density lipoprotein (LDL). This study was designed to determine the effect of garlic on CsA-induced hyperlipidemia in male rats. MATERIALS AND METHODS Baseline serum blood samples from forty 10-month-old, male Wistar rats were obtained. They received intraperitoneal (IP) injection of CsA (25 mg/kg) for 28 days. Blood samples were again obtained after the 28-day treatment. Sixteen of 40 rats showed increased serum LDL levels. These 16 were divided into 2 groups of 8 rats each. In the first (experimental) group, 8 rats received garlic (tablets, 400 mg/d), CsA (25 mg/kg IP), and regular diet for 28 days. In the second (control) group, 8 rats received the same regimen without the garlic tablets. At the end of the experiment, blood samples were taken from animals in both groups, and LDL levels were assessed. RESULTS The mean baseline LDL level in animals in the control group was 17.75 +/- 4.1 mg/dL. This increased to 21.5 +/- 1.6 mg/dL after 28 days of CsA administration. After 28 more days, the mean LDL level increased to 25.4 +/- 4.9 mg/dL (P = .004). In animals in the experimental group, the baseline LDL level was 23.8 +/- 3.7 mg/dL, which increased to 31.3 +/- 1.6 mg/dL after the first 28 days (P < .001). After the second 28 days, it decreased to 26.0 +/- 4.8 mg/dL (P = .06), and among 4 animals, the LDL level decreased more than 49%. CONCLUSION In a Wistar rat model, animals given cyclosporin A subsequently treated with garlic demonstrated reduced LDL levels compared with controls. This treatment may be useful in patients receiving organ transplantations.
Three-Phase Induction Motor ’ s Torque under Voltage Unbalance

Considering widely use of three-phase induction motors in industry, commercial and residential applications and the probability that they may exposed to the unbalanced voltages, it is very important to clarify the effects of voltage unbalance on the performance of them. In this paper, authors simulated a three phase squirrel cage induction motor under six types of unbalanced voltages with same VUF combined with under voltage or over voltage in one or more phases using two-dimensional finite element method. Electromagnetic torque of the mentioned motor analyzed and effects of voltage unbalance on its average torque and torque ripple investigated and also, emphasized to detect unbalance condition, torque frequency analysis can be used.
Occult Breast Cancer : A Diagnostic Dilemma . Case Report and Literature Review

Background: Occult breast cancer, or histologically-proven breast cancers without an identifiable primary breast cancer, is a rare disease. It remains challenging for clinicians to diagnose and treat it as there are currently no standardized diagnostic or treatment approach to patients with occult breast cancers. Patient Description: We report a case of a 59-year-old female with dyspnea and increased oxygen requirements, who on further investigation was found to have pulmonary lymphangitic carcinomatosis, axillary and supraclavicular lymphadenopathy, which was ultimately diagnosed as hormone positive occult breast cancer. She responded well to palliative hormone therapy and returned to baseline functional status and to breathing on room air. Conclusion: This case is a unique and unusual presentation of breast cancer that highlights the importance of recognizing that primary malignancies of unknown origin do exist. In this case, the patient was fortunate enough both to have her malignancy discovered early based on symptoms of metastasis and to have hormone positive disease that is more responsive to palliative endocrine therapies. However, there needs to be a clearer approach to diagnosing and treating occult breast cancers. Sanaz Ghafouri* and Alexandra Drakaki UCLA Medicial Center, USA Sanaz Ghafouri, et al., Annals of Clinical Case Reports Internal Medicine Remedy Publications LLC. , | http://anncaserep.com/ 2018 | Volume 3 | Article 1536 2 the patient was considering palliative care approach and eventually hospice. She was ultimately discharged from the hospital with home oxygen and oncology follow up. Given that no primary mass was identified in the initial staging imaging, patient had an MRI of the breasts as well as a mammogram that interestingly enough were both normal. She was started on an Aromatase Inhibitor (AI) as she was postmenopausal and within the first few weeks she had significant response on imaging, as well as clinically, with discontinuation of oxygen use and decreasing of her CA-125. After discussing different treatment options, mastectomy was deferred based on the fact that she had spread to the lungs and no obvious primary on presentation. She completed the course of antibiotics for her mycobacterial infection and continued to show improvement with hormone therapy for years after diagnosis. She had to transition from the non-steroidal AI anastrozole to exemestane due to arthralgias. After three years being on treatment with antiestrogen therapy, a staging CT chest showed some evidence of progression along with rising CA 125, and thus, she was transitioned to the novel combination of the antiestrogen Fulvestrant and the CDK4/6 inhibitor Palbociclib. She has been on this combination for one year, and is doing well, except the expected side effects of neutropenia. Her ECOG performance status has returned from a 3 to a 0, she is off home oxygen and her initially suspected poor prognosis was surprisingly invalidated.
Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction.

A prospective study was conducted on 34 stable septic patients to determine whether mild hyperlactatemia is a marker of lactate overproduction or an indicator of lactate underutilization during sepsis. Plasma lactate clearance and lactate production were evaluated by modeling the lactate kinetic induced by an infusion of 1 mmol/kg L-lactate over 15 min. The patients were divided in two groups depending on their blood lactate: < or = 1.5 mmol/L (n = 20, lactate = 1.2+/-0.2 mmol/L) or > or = 2 mmol/L (n = 10, lactate = 2.6+/-0.6 mmol/L). The hyperlactatemic patients had a lower lactate clearance (473+/-102 ml/kg/h) than those with normal blood lactate (1,002+/-284 ml/kg/h, p < 0.001), whereas lactate production in the two groups was similar (1,194+/-230 and 1,181+/-325 micromol/kg/h, p = 0.90). A second analysis including all the patients confirmed that the blood lactate concentration was closely linked to the reciprocal of lactate clearance (r2 = 0.73, p < 0.001) but not to lactate production (r2 = 0.03, p = 0.29). We conclude that a mild hyperlactatemia occurring in a stable septic patient is mainly due to a defect in lactate utilization.
Modeling Energy and Climate Policy in the Finnish Forest Sector

The development and structural changes that the forest sector in Finland is going through emphasizes the need to modify the forest policies in Finland. A shift from a focus on timber production and traditional forestry products toward new products as well as new services is called for. New services include the climate and bioenergy potential services, landscape, travelling and recreation, and ecological services. This report describes the structural context and principles of an ongoing modeling work in Metla. This work is part of the research project The Future Development of the Finnish Forest Sector, which is sponsored by Metla and Metsämiesten Säätiö Foundation. The purpose of the modeling work is to build a policy simulation model to be able to analyze policies relevant for the Finnish forest sector.
Does Corporate Governance Affect Earnings Management?: Evidence from Vietnam?

This study investigates how corporate governance characteristics affect earnings management of firms in Vietnam. In particular, we examine whether firm’s use of discretionary accruals is influenced by board size, state ownership and foreign ownership. Our empirical analysis is based on a relatively large sample of 570 non-financial Vietnamese listed firms from 2010 to 2014. We find that larger board size is effective to mitigate earnings management. In addition, shareholdings by state and foreign investors discourage the opportunistic behavior of management. We also observe that board size literally weakens the constructive effect of foreign ownership on earnings management. Our results are robust to alternative estimation methods and variable specifications.
The Performance Evaluation of the Listed Security Companies in China Based on the DEA Model

With the continuous development of domestic stock market, the listed security companies have stepped into a stable growth period, the study of their performance becomes also deeper. This paper firstly introduces the methods of evaluating the performance of the listed security companies, and discusses the DEA method in detail. Then we evaluate the corporate performance of 16 domestic security companies by the DEA method. Finally we analyses the empirical results from three aspects, which are technical efficiency, pure technical efficiency and scale efficiency. This paper evaluates the performance of the listed security companies with a more scientific method.
Does allergy begin in utero?

It has been recognized for centuries that allergic disease runs in families, implying a role for genetic factors in determining individual susceptibility. More recently, a range of evidence shows that many of these genetic factors, together with in utero environmental exposures, lead to the development of allergic disease through altered immune and organ development. Environmental exposures during pregnancy including diet, nutrient intake and toxin exposures can alter the epigenome and interact with inherited genetic and epigenetic risk factors to directly and indirectly influence organ development and immune programming. Understanding of these factors will be essential in identifying at‐risk individuals and possible development of therapeutic interventions for the primary prevention of allergic disease. In this review, we summarize the evidence that suggests allergic disease begins in utero, together with possible mechanisms for the effect of environmental exposures during pregnancy on allergic disease risk, including epigenetics.
Review on wrapper feature selection approaches

The main objective of feature selection process consists of investigating the optimal feature subset leading to better classification quality while spending less computational cost compared to maintaining the whole initial feature set. The problem of feature selection has been extensively researched since the early beginnings of machine learning. Even though several methods were proposed to handle the issue of feature selection using a variety of techniques, it is difficult to identify a specific method as the most fitted one regarding the feature subset selection issue. In this study, we provide an overview of existing wrapper methods pointing out their weaknesses and their strengths.
Using SIMEX for Smoothing-Parameter Choice in Errors-in-Variables Problems

SIMEX methods are attractive for solving curve estimation problems in errors-in-variables regression, using parametric or semiparametric techniques. However, nonparametric approaches are generally of quite a different type, being based on, for example, kernels, local-linear modeling, ridging, orthogonal series, or splines. All of these techniques involve the challenging (and not well studied) issue of empirical smoothing parameter choice. We show that SIMEX can be used effectively for selecting smoothing parameters when applying nonparametric methods to errors-in-variable regression. In particular, we suggest an approach based on multiple error-inflated (or remeasured) data sets and extrapolation.
Cross-Disciplinary Temporary Teams in Health Care Organizations: The Role of Partner Variety and Shared Experience

Health care organizations depend on temporary teams of professionals coming together and collaborating, only to quickly disband and reassemble in different configurations for each patient or shift. Yet, little is known about whether professionals learn from working with so many different partners in these temporary teams. This paper examines whether the way temporary teams are composed—either in ways that maximize team members’ partner variety or allow members to accumulate more shared experience together—impacts performance. We use data on physicians’ and nurses’ exogenous team assignments in a hospital emergency department (ED) to cleanly identify the performance effects of partner variety and shared experience, respectively, as they are accumulated either within a shift or over longer periods of time (e.g., a month). Our results demonstrate that shared experience accumulated within a shift and over time both improve performance. In contrast, partner variety accumulated within a shift positively affects performance, but it lowers performance when accumulated over time. This positive within-shift effect of partner variety is role-contingent, such that it is more beneficial for nurses than physicians. Using simulation, we show that staffing ED teams based on recommendations using our findings would allow our study ED to treat 6,000 or 5.3% more patients per year. Ultimately, this paper identifies staffing practices that can improve outcomes without increasing staffing levels.
DC and AC AIM-Spice Models for a-Si and Poly-Si TFTs

We review long and short-channel models for both a-Si and poly-Si TFTs [1,2,3], which we validated by comparison with experimental data for devices with gate lengths down to 2 μm (for poly-Si) and 4 μm (for a-Si) in a temperature range of 25-150 C and for frequencies up to 10 MHz. The most important features of our model are the use of continuous expressions valid through all operating regimes, the gate-bias dependent field-effect mobility, a new expression of the leakage current in deep subthreshold, the temperature and channel length dependence of model parameters and accounting for floating-body effects. We also model some effects that are unique to a-Si TFTs and to polySi TFTs.