Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects after oral administration of dabigatran etexilate

Summary Ethnic differences in drug disposition may potentially influence therapeutic response to dabigatran, a reversible direct thrombin inhibitor used for the prevention and/or treatment of various thromboembolic disorders. This analysis of data from 18 clinical studies in healthy volunteers and patients with non-valvular atrial fibrillation (AF) or undergoing knee or hip arthroplasty investigated whether there were any clinically relevant differences in the pharmacokinetics and pharmacodynamics of dabigatran, the active form of dabigatran etexilate, between Japanese and Caucasian subjects. In pooled data from 14 phase I trials, total exposure (i.e. area under the plasma concentration-time curve [AUC]) after administration of dabigatran 150 mg once or twice-daily was on average 20% higher in Japanese than Caucasian subjects (median [10th to 90th percentile] 1,110 [644–1,824] vs. 924 [420–1,654] ng·h/ml) although the difference between the groups was not significant. Within-trial comparisons in subjects treated with dabigatran 150 mg twice-daily showed that AUC and maximum plasma concentration differed by less than 10% between the two groups. In patients with AF, trough concentrations after administration of 150 mg twice-daily were similar in Japanese and Caucasian subjects (80.1 [34.5–193.8] vs. 71.0 [34.0–190] ng/ml). Various factors, including body weight and renal clearance, may explain these observed pharmacokinetic differences. The relationship between plasma concentration and coagulation markers was similar and indicative of no difference in the exposure-pharmacodynamic response between these two groups. In conclusion, the results of this analysis show that the pharmacokinetics and pharmacodynamics of dabigatran are similar in Japanese and Caucasian subjects and suggest that there is no need for dose adjustment of dabigatran in Japanese subjects.
Gender, Excessive Body Weight, and Psychological Well-Being in Adulthood

We examined gender differences in the association between body mass index (BMI) and psychological well-being. Regression analysis involving 3,251 adults indicated that gender moderated the BMI–psychological well-being link. In follow-up analyses, higher BMI predicted lower psychological well-being only among women. When participants were categorized into 5 BMI groups, women reported lower psychological well-being than men in the overweight and obese I groups, but no gender differences were observed in the more seriously obese or normal-weight groups. Also, among women, all 4 groups with higher-than-normal BMI had lower psychological well-being than normal-weight women; for men, no significant differences were found across the 5 groups. These findings are discussed in relation to research on stigma theory and gender-differentiated cultural norms regarding weight.
Comparison of various refined nonlocal beam theories for bending, vibration and buckling analysis of nanobeams

In this paper, unified nonlocal shear deformation theory is proposed to study bending, buckling and free vibration of nanobeams. This theory is based on the assumption that the in-plane and transverse displacements consist of bending and shear components in which the bending components do not contribute toward shear forces and, likewise, the shear components do not contribute toward bending moments. In addition, this present model is capable of capturing both small scale effect and transverse shear deformation effects of nanobeams, and does not require shear correction factors. The equations of motion are derived from Hamilton\'s principle. Analytical solutions for the deflection, buckling load, and natural frequency are presented for a simply supported nanobeam, and the obtained results are compared with those predicted by the nonlocal Timoshenko beam theory and Reddy beam theories.
Term premia and interest rate forecasts in affine models

The standard class of affine models produces poor forecasts of future Treasury yields. Better forecasts are generated by assuming that yields follow random walks. The failure of these models is driven by one of their key features: Compensation for risk is a multiple of the variance of the risk. Thus risk compensation cannot vary independently of interest rate volatility. I also describe a broader class of models. These “essentially affine” models retain the tractability of standard models, but allow compensation for interest rate risk to vary independently of interest rate volatility. This additional f lexibility proves useful in forecasting future yields. CAN WE USE F INANCE THEORY to tell us something about the empirical behavior of Treasury yields that we do not already know? In particular, can we sharpen our ability to predict future yields? A long-established fact about Treasury yields is that the current term structure contains information about future term structures. For example, long-maturity bond yields tend to fall over time when the slope of the yield curve is steeper than usual. These predictive relations are based exclusively on the time-series behavior of yields. To rule out arbitrage, the cross-sectional and time-series characteristics of the term structure are linked in an internally consistent way. In principle, imposing these restrictions should allow us to exploit more of the information in the current term structure, and thus improve forecasts. But in practice, existing no-arbitrage models impose other restrictions for the sake of tractability; thus their value as forecasting tools is a priori unclear. I examine the forecasting ability of the affine class of term structure models. By “affine,” I refer to models where zero-coupon bond yields, their physical dynamics, and their equivalent martingale dynamics are all affine functions of an underlying state vector. A variety of nonaffine models have been developed, but the tractability and apparent richness of the affine class has led the finance profession to focus most of its attention on such models. Although forecasting future yields is important in its own right, a model that is consistent with finance theory and produces accurate forecasts can make a deeper contribution to finance. It should allow us to address a key
Administration of recombinant interleukin 2 in vivo induces a polyclonal IgM response

We studied the potential immunoenhancing effects of high doses of rIL-2 on murine T and B cell functions in vivo. Injection of rIL-2 caused a threefold or more increase in the frequencies of antigen-specific proliferative T cells, suggesting that rIL-2 initiated a polyclonal T cell response. In primary and secondary humoral immune responses, administration of rIL-2 in vivo selectively enhanced the production of IgM antibodies, whereas the IgG response was unaffected. Coadministration of rIL-2 with antigen failed to induce an isotype switch from IgM to IgG in genetically low-responding mice. Interestingly, in mice treated with rIL-2 alone (in the absence of exogenous antigen), polyclonal IgM production was induced. Polyclonal IgM production of lesser magnitude was found when mice were immunized with specific antigen in the absence of exogenous rIL-2, suggesting that local IL-2 concentrations in a primary immune response might be sufficient to elicit a polyclonal IgM response.
Jaagsiekte Sheep Retrovirus Env Protein Stabilizes Retrovirus Vectors against Inactivation by Lung Surfactant, Centrifugation, and Freeze-Thaw Cycling

ABSTRACT Jaagsiekte sheep retrovirus (JSRV) replicates in the lungs of sheep and causes the secretion of copious lung fluid containing the virus. Adaptation of JSRV to infection and replication in the lung and its apparent resistance to the denaturing activity of lung fluid suggest that vectors based on JSRV would be useful for gene therapy targeted to the lung. We show here that a retrovirus vector bearing the JSRV Env is stable during treatment with lung surfactant while an otherwise identical vector bearing an amphotropic Env is inactivated. Furthermore, the JSRV vector was stable during centrifugation, allowing facile vector concentration, and showed no loss of activity after six freeze-thaw cycles. However, the JSRV vector was inactivated by standard disinfectants, indicating that JSRV vectors pose no unusual safety risk related to their improved stability under other conditions.
Correlation of progression-free and post-progression survival with overall survival in advanced colorectal cancer.

BACKGROUND Polychemotherapy and biological drugs have increased therapeutic options and outcomes of advanced colorectal cancer (CRC). We examined the relation between progression-free survival (PFS), post-progression survival (PPS) and overall survival (OS) in trials of modern (oxaliplatin- and irinotecan-based) chemotherapy alone or with targeted therapies for advanced CRC. We also evaluated surrogacy of PFS and OS. PATIENTS AND METHODS A PubMed search identified 34 randomized trials. We split the OS, PFS and PPS and evaluated the correlation between OS and either PFS or PPS. RESULTS The median PPS and PFS were 10.75 and 8.4 months, respectively. For all trials, PPS was strongly associated with OS [regression coefficient (R2)=0.8; Spearman's rank correlation coefficient (r)=0.88], whereas PFS was moderately associated with OS (R2)=0.43; r=0.64). In trials with targeted therapies, the correlation of PPS with OS was 0.88. However, across all trials, correlation between differences in median PFS (ΔPFS) and median OS (ΔOS) is 0.59 (P=0.0007), confirming PFS/OS surrogacy. CONCLUSION Our findings indicate that in recent first-line, phase III, trials, OS becomes more associated with PPS than PFS. However, improvements in PFS are strongly associated with improvements in OS. In this setting so, PFS may be an appropriate surrogate for OS.
Immune, swarm, and evolutionary algorithms. Part I: basic models

These two papers have three main aims. First (Part I), to review the general algorithms of immune, swarm and evolutionary systems. Second (Part II), to present a philosophical discussion about the similarities and differences between these paradigms, in terms of components, architecture, adaptation, interactions, and metaphors. Finally (Part II), to highlight the main features embodied in each approach, such that avenues for the creation of hybrid models can be suggested.
Host Instar Susceptibility and Selection and Interspecific Competition of Three Introduced Parasitoids of the Mealybug Paracoccus marginatus (Hemiptera: Pseudococcidae)

ABSTRACT Three previously introduced parasitoids (Acerophagus papayae Noyes and Schauff, Anagyrus loecki Noyes and Menezes, and Pseudleptomastix mexicana Noyes and Schauff [Hymenoptera: Encyrtidae]) of the mealybug Paracoccus marginatus Williams and Granara de Willink (Hemiptera: Pseudococcidae) were studied for their host instar susceptibility and sex ratio, host instar selection, and interspecific competition in the laboratory. All three parasitoids were able to develop in the second instars, third-instar females, and adult females of P. marginatus. No progeny emerged from first-instar mealybugs. The proportion of female emergence was increased with increasing host size. Parasitoids selected their host instars for oviposition when they had a choice. Between secondand third-instar hosts, A. papayae and P. mexicana had significantly higher parasitism in second-instar mealybugs, whereas A. loecki had higher parasitism in the third-instar mealybugs. When competed with either one or two parasitoid species, A. papayae was significantly more successful in second-instar hosts and A. loecki was significantly more successful in third-instar mealybugs. P. mexicana was significantly less competitive when with A. papayae in both second and third instars, with A. loecki in third instars and with both A. papayae and A. loecki in second and third instars. Overall, A. papayae provided a better control of the host, when present singly or with the other two parasitoids. This information is important in evaluating the efficiency of A. papayae, A. loecki, and P. mexicana and understanding the outcome of their recovery and establishment in field studies conducted in Florida.
A neural network regression model for tropical cyclone forecast

In recent years a large amount of literature has evolved on the usage of artificial neural network (ANNs) for weather forecasting, particularly because of ANNs' ability to model an unspecified nonlinear relationship of various meteorological variables. In this paper we proposed a dynamic competitive neural network classifier to predict the maximum potential intensity (MPI) of a given tropical cyclone, based on a 10-year period of Western North Pacific tropical cyclones and monthly mean sea surface temperature (MSST). A procedure to select most significant-correlated attributes of tropical cyclones is designed to for fast and accurate neural network training. A binary trigger is adopted to adjust the structure of the network layers. To justify the performance, we carry out a set of experiments to prove that our proposed model is promising.
Structure Formation of Blend and Sheath/Core Conjugated Fibers in High-Speed Spinning of PET, Including a Small Amount of PMMA

The blend of poly(ethylene terephthalate) (PET) and a small amount of polymer that has higher T g than PET, such as polymethylmethacrylate (PMMA)—and is dispersed finely as immiscible particles in PET—exhibits lower molecular orientation than pure PET under high-speed fiber spinning. To obtain insight into the mechanism of the lower molecular orientation of the blend fiber, the sheath/core structure of PET (sheath)/PMMA (core) conjugated fiber (the same PET/PMMA weight ratio as in the blend fiber), was produced as a model. The thinning profile of the fiber diameter along the spinning line and the birefringence distribution of the cross-section were examined and compared among pure PET fiber, the conjugated fiber, and the blend fiber. The conjugated fiber had the lowest molecular orientation of PET in the sheath part, and its thinning process was accelerated similar to the blend fiber. As a result of the distribution of molecular orientation across the diameter of the conjugated fiber, it is considered that PMMA, having the high T g , tends to solidify at a higher temperature (upstream) than PET in the thinning process, making the flow of PET accelerate as if it was pushed by PMMA. This causes the maximum dv/dx just before the solidification point to be smaller; therefore, the lower spinning stress, resulting in smaller birefringence of PET, can be considerable. This acceleration was generated at the interface of PET and PMMA, and spread toward the fiber surface as both polymers were thinning in elongational flow (in melt). On the other hand, close to the interface, molecules of PET were stretched by PMMA, resulting in an increase of birefringence. Such discussion is also considered to apply to the blend fiber. However, because the blend fiber had a significantly larger interface area compared with the conjugated fiber, it is considered that the increase of birefringence of PET by the interface drag force cannot be neglected. The larger particles of PMMA dispersed in PET results in the lower birefringence of PET that is supported by the elongation effect (i.e., the interface drag force).
A Fast Time Stepping Method for Evaluating Fractional Integrals

We evaluate the fractional integral $I^\alpha[f](t)=\frac{1}{\Gamma(\alpha)}\int_0^t(t-\tau)^{\alpha-1}\,f(\tau)\,d\tau$, $0<\alpha<1$, at time steps $t=\Delta t,2\Delta t,\dots,N\Delta t$ by making use of the integral representation of the convolution kernel $t^{\alpha-1}=\frac{1}{\Gamma(1-\alpha)}\int_0^{\infty}e^{-\xi\,t}\,\xi^{-\alpha}\,d\xi$. We construct an efficient $Q$-point quadrature of this integral representation and use it as a part of a fast time stepping method. The new method has algorithmic complexity $O(NQ)$ and storage requirement $O(Q)$. The number of quadrature nodes $Q$ is independent of $N$ and grows like $O\bigl(\bigl(-\log\epsilon-\log\Delta t\bigr)^2\bigr)$, where $\epsilon$ is the quadrature error tolerance and $\Delta t$ is the size of the time step. The (possible) singularity of $f$ near $\tau=0$ is taken into account. This new method is particularly well-suited for long time simulations.
Interaction between Mitochondria and the Endoplasmic Reticulum: Implications for the Pathogenesis of Type 2 Diabetes Mellitus

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated with β-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ER stress causes apoptotic cell death by disturbing mitochondrial Ca2+ homeostasis. In addition, recent studies have shown that mitochondrial dysfunction causes ER stress. In this paper, we summarize the roles that mitochondrial dysfunction and ER stress play in the pathogenesis of type 2 DM. Structural and functional communications between mitochondria and the ER are also discussed. Finally, we focus on recent findings supporting the hypothesis that mitochondrial dysfunction and the subsequent induction of ER stress play important roles in the pathogenesis of type 2 DM.
Emergence of a Candida krusei Isolate with Reduced Susceptibility to Caspofungin during Therapy

ABSTRACT Clinical failure associated with reduced susceptibility to caspofungin has been described in Candida albicans and C. parapsilosis. We report a case of Candida krusei infection that progressed despite caspofungin therapy. Reduced microbial susceptibility to all three echinocandins (caspofungin, anidulafungin, and micafungin) was noted but was not associated with mutations in FKS1.
Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.
Post-packaging auto repair techniques for fast row cycle embedded DRAM

A test flow using a auto repair technique has also been proposed. It assumes a conventional wafer testing, but puts much weight on the post-package test by utilizing the proposed auto repair technique. This is implemented in a 36 Mb embedded DRAM macro of 6ns cycle time. It consists of internal compare circuit, redundancy analyzer, and anti-fuses. The internal auto programming of anti-fuse fixes post-packaging failures that might appear by final at-speed test and contributes to yield improvement.
Pathogenicity of Low and Highly Virulent Chlamydia psittaci Isolates for Specific-Pathogen-Free Chickens

SUMMARY In commercially raised poultry, chlamydiosis mostly seems to occur on turkey or duck farms, sometimes associated with zoonotic transmission and disease (psittacosis) in humans. However, Chlamydia infections are apparently emerging in chickens, and information on the virulence of Chlamydia in chickens is limited. Up-to-date Chlamydia psittaci genotypes B and D are most frequently found in broilers. We examined the pathogenicity of the well-characterized C. psittaci genotype B (CP3) and D (92/1293) strains in experimentally (aerosol) infected specific-pathogen-free chickens. Both strains caused conjunctivitis, rhinitis, and dyspnea. Pharyngeal and cloacal C. psittaci excretion was observed in all infected animals, indicative for systemic dissemination as proven by immunofluorescence staining of frozen tissue sections. Histopathologic lesions were present in all infected chickens. However, differences in pathology were observed. Genotype D led to mortality and more severe clinical signs and lesions as compared to genotype B, which showed lower virulence. RESUMEN Patogenicidad de aislamientos baja y alta virulencia de Chlamydia psittaci para aves libres de patógenos específicos. La clamidiosis puede presentarse en aves criadas comercialmente, principalmente en granjas de pavos y patos, a veces asociados con la transmisión zoonótica y la presentación de la enfermedad (psitacosis) en humanos. Sin embargo, las infecciones por Chlamydia aparentemente están surgiendo en los pollos y la información sobre la virulencia de Chlamydia en los pollos es limitada. Hasta la fecha, los genotipos B y D de Chlamydia psittaci son los más frecuentes en pollos de engorde. Se examinó la patogenicidad de las cepas bien caracterizadas de C. psittaci genotipo B (CP3) y genotipo D (92/1293) en aves libres de patógenos específicos infectados experimentalmente por aerosol. Ambas cepas causaron conjuntivitis, rinitis, y disnea. Se observó excreción faríngea y cloacal de C. psittaci en todos los animales infectados, indicativas de diseminación sistémica como fue demostrado por la tinción de inmunofluorescencia de cortes de tejido congelados. Las lesiones histopatológicas estaban presentes en todos los pollos infectados. Sin embargo, se observaron diferencias en la patología. El genotipo D ocasionó mortalidad además de signos clínicos y lesiones más graves en comparación con el genotipo B, que mostró una menor virulencia.
Correction: Constitutive scaffolding of multiple Wnt enhanceosome components by Legless/BCL9

Copyright van Tienen et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Abstract Wnt/b-catenin signaling elicits context-dependent transcription switches that determine normal development and oncogenesis. These are mediated by the Wnt enhanceosome, a multiprotein complex binding to the Pygo chromatin reader and acting through TCF/LEF-responsive enhancers. Pygo renders this complex Wnt-responsive, by capturing b-catenin via the Legless/BCL9 adaptor. We used CRISPR/Cas9 genome engineering of Drosophila legless (lgs) and human BCL9 and B9L to show that the C-terminus downstream of their adaptor elements is crucial for Wnt responses. BioID proximity labeling revealed that BCL9 and B9L, like PYGO2, are constitutive components of the Wnt enhanceosome. Wnt-dependent docking of b-catenin to the enhanceosome apparently causes a rearrangement that apposes the BCL9/B9L C-terminus to TCF. This C-terminus binds to the Groucho/TLE co-repressor, and also to the Chip/LDB1-SSDP enhanceosome core complex via an evolutionary conserved element. An unexpected link between BCL9/B9L, PYGO2 and nuclear co-receptor complexes suggests that these b-catenin co-factors may coordinate Wnt and nuclear hormone responses.