Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimal design of multi‐arm multi‐stage trials

In drug development, there is often uncertainty about the most promising among a set of different treatments. Multi‐arm multi‐stage (MAMS) trials provide large gains in efficiency over separate randomised trials of each treatment. They allow a shared control group, dropping of ineffective treatments before the end of the trial and stopping the trial early if sufficient evidence of a treatment being superior to control is found. In this paper, we discuss optimal design of MAMS trials. An optimal design has the required type I error rate and power but minimises the expected sample size at some set of treatment effects. Finding an optimal design requires searching over stopping boundaries and sample size, potentially a large number of parameters. We propose a method that combines quick evaluation of specific designs and an efficient stochastic search to find the optimal design parameters. We compare various potential designs motivated by the design of a phase II MAMS trial. We also consider allocating more patients to the control group, as has been carried out in real MAMS studies. We show that the optimal allocation to the control group, although greater than a 1:1 ratio, is smaller than previously advocated and that the gain in efficiency is generally small. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of an Agrobacterium tumefaciensd-Psicose 3-Epimerase That Converts d-Fructose to d-Psicose

ABSTRACT The noncharacterized gene previously proposed as the d-tagatose 3-epimerase gene from Agrobacterium tumefaciens was cloned and expressed in Escherichia coli. The expressed enzyme was purified by three-step chromatography with a final specific activity of 8.89 U/mg. The molecular mass of the purified protein was estimated to be 132 kDa of four identical subunits. Mn2+ significantly increased the epimerization rate from d-fructose to d-psicose. The enzyme exhibited maximal activity at 50°C and pH 8.0 with Mn2+. The turnover number (kcat) and catalytic efficiency (kcat/Km) of the enzyme for d-psicose were markedly higher than those for d-tagatose, suggesting that the enzyme is not d-tagatose 3-epimerase but d-psicose 3-epimerase. The equilibrium ratio between d-psicose and d-fructose was 32:68 at 30°C. d-Psicose was produced at 230 g/liter from 700-g/liter d-fructose at 50°C after 100 min, corresponding to a conversion yield of 32.9%.
Insulin stimulates Na+, Cl-, Ca2+, and Mg2+ transports in TAL of mouse nephron: cross-potentiation with AVP.

Insulin (Ins) decreases Na+ delivery in the final urine. To determine whether the loop of Henle participates in this reduction, the effects of Ins were tested on cortical (CTAL) and medullary thick ascending limbs (MTAL) of the mouse nephron, microperfused in vitro. In the MTAL, Ins increased the transepithelial potential difference (Vt) and the Na+ and Cl- net reabsorption fluxes (JNa and JCl, respectively) in a dose-dependent manner, the threshold being below 10(-9) M. At 10(-7) M, Ins reversibly increased JNa and JCl, leaving Mg2+ and Ca2+ fluxes (JMg and JCa, respectively) close to zero. In the CTAL, 10(-7) M Ins reversibly increased Vt, JNa, JCl, JMg, and JCa. In CTAL segments perfused under asymmetrical conditions, with a bath-to-lumen-directed NaCl gradient (lumen 50 mM NaCl, bath 150 mM NaCl), addition of 10(-7) M Ins to the bath resulted in a large increase in JMg and JCa. Thus the responses of CTAL and MTAL to Ins are in all ways similar to those already reported for the adenosine 3',5'-cyclic monophosphate (cAMP)-generating hormones acting on these nephron segments. When 10(-10) M arginine vasopressin (AVP) and 10(-7) M Ins were used in combination, previous addition of one hormone to the bath potentiated the response to the second hormone. In cAMP accumulation experiments, performed in the presence of a phosphodiesterase inhibitor, the amounts of cAMP formed with 10(-7) M Ins and 10(-10) M AVP (which elicit maximal physiological responses in these segments) were in the same range. (ABSTRACT TRUNCATED AT 250 WORDS)
MoNoise: Modeling Noise Using a Modular Normalization System

We propose MoNoise: a normalization model focused on generalizability and efficiency, it aims at being easily reusable and adaptable. Normalization is the task of translating texts from a non- canonical domain to a more canonical domain, in our case: from social media data to standard language. Our proposed model is based on a modular candidate generation in which each module is responsible for a different type of normalization action. The most important generation modules are a spelling correction system and a word embeddings module. Depending on the definition of the normalization task, a static lookup list can be crucial for performance. We train a random forest classifier to rank the candidates, which generalizes well to all different types of normaliza- tion actions. Most features for the ranking originate from the generation modules; besides these features, N-gram features prove to be an important source of information. We show that MoNoise beats the state-of-the-art on different normalization benchmarks for English and Dutch, which all define the task of normalization slightly different.
Viscous Marangoni propulsion

Abstract Marangoni propulsion is a form of locomotion wherein an asymmetric release of surfactant by a body located at the surface of a liquid leads to its directed motion. We present in this paper a mathematical model for Marangoni propulsion in the viscous regime. We consider the case of a thin rigid circular disk placed at the surface of a viscous fluid and whose perimeter has a prescribed concentration of an insoluble surfactant, to which the rest of its surface is impenetrable. Assuming a linearized equation of state between surface tension and surfactant concentration, we derive analytically the surfactant, velocity and pressure fields in the asymptotic limit of low capillary, Péclet and Reynolds numbers. We then exploit these results to calculate the Marangoni propulsion speed of the disk. Neglecting the stress contribution from Marangoni flows is seen to over-predict the propulsion speed by 50 %.
CorrSieve: software for summarizing and evaluating Structure output

The clustering software Structure has been used extensively to infer population structure in natural populations from multilocus genotype data. Determining meaningful values of K, the assumed number of subpopulations is one of the primary challenges of making biological inferences from Structure data. The package CorrSieve summarizes Structure output and performs a number of tests, including both previously reported methods and novel ones, to help determine meaningful values of K.
Impact of botulinum toxin a on the quality of life of subjects following treatment of facial lines.

OBJECTIVE To investigate quality of life and its correlation to patient satisfaction before and after treatment with botulinum toxin A. METHODS Quality of life was assessed using the Schedule for the Evaluation of Individual Quality of Life Direct-Weighting tool. Patients identified the five areas of their life of the greatest importance to them, weighted the areas as to their relative importance, and rated their status in each area on a visual scale before treatment (old cues) and 28 days later (using both old cues and newly defined and weighted cues). At both visits, patients also rated their overall quality of life using a visual analogue scale. Patient satisfaction with their appearance was measured using a 10-point scale in conjunction with standardized photographs taken at each visit. RESULTS Fifty-three patients (median age 39.5 years; 87% women) with moderate-to-severe wrinkles of the glabella, forehead, or crow's feet were enrolled. Treatment with incobotulinumtoxinA consistently resulted in a significant improvement in quality of life according to Schedule for the Evaluation of Individual Quality of Life Direct-Weighting tool index scores (old cues, P=0.0006; new cues P=0.0235) and patient assessment of their overall quality of life (P<0.0001 for both old and new cues). Family, work, finance, relationships, and health were the five most frequently identified cues at each assessment. No correlation between quality of life and satisfaction scores was found, although both were significantly increased after treatment. CONCLUSION These results support the contention that quality of life is significantly improved following botulinum toxin A treatment and that consideration should be given to incorporating the measurement of quality of life as an outcome measure following botulinum toxin A treatment, especially as satisfaction does not correlate to quality of life.
Cohort Size Effects and Migration

This article explores whether changes in the size of cohorts entering the labor force affect the propensity to migrate and the socioeconomic circumstances of migrants at destination. The flow of young in-migrants to large SMSAs declined during the 1965–76 period, but the relative socioeconomic standing of migrants at destination was unaffected by either cohort size or regional differentials in economic growth. It is suggested that a significant reduction in the volume of migration among members of the baby boom cohort was the primary adjustment mechanism, hence reducing the need for degrading the opportunities available to migrants.
Eco‐hydrological controls on summertime convective rainfall triggers

Triggers of summertime convective rainfall depend on numerous interactions and feedbacks, often compounded by spatial variability in soil moisture and its impacts on vegetation function, vegetation composition, terrain, and all the complex turbulent entrainment processes near the capping inversion. To progress even within the most restricted and idealized framework, many of the governing processes must be simplified and parameterized. In this work, a zeroth‐order representation of the dynamical processes that control convective rainfall triggers – namely land surface fluxes of heat and moisture – is proposed and used to develop a semianalytical model to explore how differential sensitivities of various ecosystems to soil moisture states modify convective rainfall triggers. The model is then applied to 4 years (2001–2004) of half‐hourly precipitation, soil moisture, environmental, and eddy‐covariance surface heat flux data collected at a mixed hardwood forest (HW), a maturing planted loblolly pine forest (PP), and an abandoned old field (OF) experiencing the same climatic and edaphic conditions. We found that the sensitivity of PP to soil moisture deficit enhances the trigger of convective rainfall relative to HW and OF, with enhancements of about 25% and 30% for dry moisture states, and 5% and 15% for moist soil moisture states, respectively. We discuss the broader implications of these findings on potential modulations of convective rainfall triggers induced by projected large‐scale changes in timberland composition within the Southeastern United States.
Microarray analysis of the differential transformation mediated by Kirsten and Harvey Ras oncogenes in a human colorectal adenocarcinoma cell line

Colorectal cancer arises after a series of mutational events in the colon epithelia and is often used as a model of the multistep progression of tumorigenesis. Mutations in Ki‐Ras have been detected in some 50% of cases and are thought to occur at an early stage. Almost never do mutations arise in the loci of other Ras isoforms (Ha‐ and N‐), leading to the assumption that Ki‐Ras plays a unique role in tumorigenesis. In order to examine the distinctive function that Ki‐Ras plays in cancer development in the colon, we introduced constitutively active mutant Ki‐ and Ha‐Ras genes into an intermediate‐stage colon adenoma cell line (Caco‐2). We found that mutant active Ha‐RasV12 was more efficient at transforming these colon epithelial cells as assessed by anchorage‐independent growth, tumor formation in SCID mice and the development of mesenchymal morphology compared to transformation by Ki‐RasV12. We conducted microarray analysis in an attempt to reveal the genes whose aberrant expression is a direct result of overexpression of either Ki‐RasV12 or Ha‐RasV12. We used Clontech's Atlas cancer cDNA (588 genes) and RZPD's Onco Set 1 (1,544 genes) arrays. We identified fewer genes that were commonly regulated than were differentially expressed between Ki‐ and Ha‐RasV12 isoforms. Specifically, we found that Ki‐RasV12 regulated genes involved in cytokine signaling, cell adhesion and colon development, whereas Ha‐RasV12 mainly regulated genes involved in controlling cell morphology, correlating to an epithelial‐mesenchymal transition only observed in these cells. Our results demonstrate how 2 Ras isoforms regulate disparate biologic processes, revealing a number of genes whose deregulated expression may influence colon carcinogenesis (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html). © 2005 Wiley‐Liss, Inc.
Rat uterine progesterone receptor analyzed by [3H]R5020 photoaffinity labeling: evidence that the A and B subunits are not equimolar.

The hormone-binding components of the rat uterine progesterone receptor were investigated by the methods of [3H]R5020 photoaffinity labeling and sodium dodecyl sulfatepolyacrylamide gel electrophoresis analysis. Two specifically labeled peaks were observed at mol wt of 85,600 +/- 1,200 and 109,600 +/- 1,200 (n = 31), resembling the A and B progesterone receptor components previously described in other systems. However, in contrast to the equimolar ratio reported in other systems, the level of subunit A observed was consistently greater than that of B (A/B ratio = 3.2 +/- 0.3; n = 31). The unusual A/B ratio prompted a complete validation of the photolabeling procedure in this system. Although the levels of specific binding increased, there was no change in the A/B ratio with varying [3H]R5020 concentrations (5-80 nM) or with time of UV exposure (0.5 min to 3 h). Although adsorption to hydroxylapatite indicated that specific [3H]R5020 binding was reduced by 72.0 +/- 6.4% within 5 min of UV exposure, relabeling the irradiated preparations with [3H]R5020 resulted in little change in specific [3H]R5020 binding. TLC analysis of [3H]R5020 (Rf = 0.48 +/- 0.01; n = 4) after irradiation demonstrated rapid photolysis resulting in a 94.3 +/- 2.5% (n = 3) loss of authentic [3H]R5020 within 5 min. After photolysis, at least two new tritiated products were recovered with Rf values of 0.20 +/- 0.03 and 0.72 +/- 0.02. Analysis by adsorption to hydroxylapatite indicated that the photolysis products competed for specific [3H]R5020-binding sites in cytosol with only 10-fold lower relative binding activity than authentic R5020. Thus, these compounds probably account for the increase in specific photolabeling of the A and B peaks achieved when UV exposure is prolonged from 5 to 30 min. Further study indicated that the A/B subunit ratio in this system was not changed under a variety of in vitro conditions, including the absence or presence of molybdate, sulfhydryl protective reagents (dithiothreitol and thioglycerol), protease inhibitors (phenylmethylsulfonylfluoride and leupeptin), glycerol (0%, 10%, and 30%, vol/vol), or 1.5 mM EGTA, or after precipitation with 40% ammonium sulfate. This consistency of the A/B ratio under a wide variety of adverse in vitro conditions suggests that in vitro artefacts may not account for the ratio's deviation from unity. Estrogen withdrawal (48 h) enhanced by progesterone treatment (0.5 mg for 24 h) resulted in only a modest reduction in the A/B ratio to 1.9 +/- 0.1. (ABSTRACT TRUNCATED AT 400 WORDS)
Risk factors associated with postoperative persistent hypertension in patients with primary aldosteronism.

BACKGROUND Unilateral adrenalectomy was performed in 63 patients with primary aldosteronism. During a mean follow-up time of 4.1 years, none of the patients showed recurrence of hyperaldosteronism. However, 24 patients (38%) had persistent hypertension. The purpose of this study was to determine factors responsible for postoperative persistent hypertension. METHODS A stepwise multivariate logistic regression analysis was performed to assess the combined predictive effects of the clinicopathologic variables. RESULTS Age, sex, and pathologic findings were the best predictive factors of postoperative persistent hypertension. For a patient aged 50 years or more, the odds of persisting hypertension are 10.6:1, compared with those of a patient under 40 years of age. A male patient appears to have a greater chance of hypertension than a female patient; the odds ratio is 5.9:1. Persistent hypertension develops in patients with multiple adenomas or with an adenoma associated with macronodules more frequently than in those patients with a solitary adenoma; the odds ratio is 8.1. CONCLUSIONS This study suggests that early surgical intervention at a younger age results in a more favorable outcome for patients with primary aldosteronism. The presence of macronodules in association with an adenoma is a cautious predictor of persistent hypertension after adrenalectomy.
The Effect of Sleep Deprivation on Signal Detection Parameters

Twelve subjects performed a high signal rate vigilance task, once after a night's sleep, and once after a night without sleep. Raw scores were transformed into the signal detection parameters, d′ and β. After sleep deprivation, detection performance was significantly impaired. This was reflected in a fall of d′, whereas β was not significantly altered. Analysing the control data alone for comparison with other vigilance studies revealed a decrement in % signals detected and d′, and an increase in β from the first to the second half of the test.
Loss of PTEN promotes podocyte cytoskeletal rearrangement, aggravating diabetic nephropathy

In diabetic nephropathy (DN), podocyte cytoskeletal rearrangement occurs followed by podocyte effacement and the development of proteinuria. PTEN (phosphatase and tensin homologue) is a ubiquitously expressed phosphatase that plays a critical role in cell proliferation, cytoskeletal rearrangement, and motility. In mouse models of diabetes mellitus, PTEN expression is reportedly decreased in mesangial cells, contributing to expansion of the mesangial matrix, but how PTEN in the podocyte influences the development of DN is unknown. We observed that PTEN expression is down‐regulated in the podocytes of diabetic db/db mice and patients with DN. In cultured podocytes, PTEN inhibition caused actin cytoskeletal rearrangement and this response was associated with unbalanced activation of the small GTPases Rac1/Cdc42 and RhoA. In mice treated with PTEN inhibitor, actin cytoskeletal rearrangement occurred in podocytes and was accompanied by increased albumin excretion. We also created mice with an inducible deletion of PTEN selectively in podocytes. These mice exhibited increased albumin excretion and moderate foot process effacement. When the mice were challenged with a high fat diet, podocyte‐specific knockout of PTEN resulted in substantially increased proteinuria and glomeruloclerosis compared to control mice fed a high fat diet or mice with PTEN deletion fed a normal diet. These results indicate that PTEN is involved in the regulation of cytoskeletal rearrangement in podocytes and that loss of PTEN predisposes to the development of proteinuria and DN. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Effects of loading on chondrocyte hypoxia, HIF-1α and VEGF in the mandibular condylar cartilage of young rats.

OBJECTIVES To investigate hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expression under altered loading, and to explore the relationship between loading and hypoxia in the mandibular condylar cartilage of young rats. SETTING AND SAMPLE POPULATION Eighty Sprague-Dawley rats. MATERIAL AND METHODS The reduced loading group was fed soft food, and their incisors were cut to avoid occlusal contact. The increased loading group was fed hard food and had forced jaw-opening. Ten rats from each group (n = 10) were sacrificed at 12, 24, 48, and 96 hours after initiation of the experiment. Pimonidazole hydrochloride (Hypoxyprobe-1, HP-1) was used as a hypoxia marker to confirm the hypoxic state. Hypoxic chondrocytes as indicated by HP-1, HIF-1α and VEGF protein expressions were recognized by immunohistochemical detection. HIF-1α and VEGF mRNA expressions were detected by semi-quantitative RT-PCR. RESULTS Hypoxyprobe-1 was confined in the upper layers of cartilage, and was most strongly expressed in the weight-bearing area of TMJ at 12 and 96 hours. Staining of HIF-1α and VEGF was most strongly expressed in the chondrocytes of the fibrous and proliferative layer at all time points. Furthermore, expressions were also displayed in the hypertrophic and calcified layers at 48 and 96 hours. The expressions of HIF-1α and VEGF mRNA were higher in the increased loading group than in the reduced loading group at 48 and 96 hours (P < . 05). CONCLUSION Mechanical loading seems to directly induce weight-bearing area hypoxia followed by new vessel formation, which indicates that these factors are related and important for the development of cartilage.
Effect of poverty and other socioeconomic variables on renal allograft survival.

BACKGROUND Socioeconomic variables including low income and noncompliance impact negatively upon long-term renal allograft survival, especially in African Americans. We sought to determine whether other socioeconomic variables contributed to noncompliance and allograft survival. METHODS A detailed history of socioeconomic variables was made at the time of renal transplant evaluation in 450 consecutive candidates, 128 of whom (89 African American, 39 Caucasian) have thus far undergone transplantation. Variables evaluated included household income, zip code income, insurance coverage, years of education, literacy, marital status, pretransplantation compliance, and history of substance abuse as well as the usual pre- and posttransplantation demographics. RESULTS Immunologic graft loss occurred primarily in young African Americans with income below the federal poverty level, whereas nonimmunologic graft loss was distributed across racial, income, and other socioeconomic variables. Immunologic graft loss was also associated with a greater number of HLA mismatches, lower levels of education, and noncompliance with transplant medications and follow-up visits. Recipients with gross illiteracy, however, had excellent graft survival. Pretransplantation substance abuse, but not pretransplantation compliance, was predictive of posttransplantation noncompliance. By multivariate analysis, posttransplantation compliance emerged as the single most important factor predictive of graft survival. CONCLUSIONS Immunologic graft loss in our population is related to noncompliance with transplant medications, which occurred primarily in recipients with a pretransplantation history of substance abuse and is not related to an inability to pay for medications at the time of graft loss. A change in criteria for acceptance of transplant candidates with a prior history of substance abuse might significantly improve graft survival in this patient population.