gebhart/patrepeval huggingface dataset:
The potential role of prebiotic fibre for treatment and management of non‐alcoholic fatty liver disease and associated obesity and insulin resistance (2011)

Non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy for NAFLD and NASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non-digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impacts NAFLD by modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo-controlled, human, clinical trials using histological endpoints to address the effects of prebiotics on NAFLD and NASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target for NAFLD.
Analysis and Optimization of Copper‐Catalyzed Azide–Alkyne Cycloaddition for Bioconjugation (2009)

How to click with biomolecules: Copper-catalyzed azide–alkyne cycloaddition has been optimized for use with biological molecules. The key development is the addition of two reagents that allow ascorbate to be used as reducing agent whilst eliminating problems caused by copper ascorbate side reactions. The result is a robust, rapid, and convenient procedure for the modification of proteins, DNA, RNA, and other biomolecules (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Purification of Two Dipeptidyl Aminopeptidases II from Rat Brain and Their Action on Proline‐Containing Neuropeptides (1989)

From the soluble and membrane fractions of rat brain homogenate, two enzymes that liberate dipeptides of the type Xaa-Pro from chromogenic substrates were purified to homogeneity. The two isolated dipeptidyl peptidases had similar molecular and catalytic properties: For the native proteins, molecular weights of 110,000 were estimated; for the denatured proteins, the estimate was 52,500. Whereas the soluble peptidase yielded one band of pI 4.2 after analytical isoelectric focusing, two additional enzymatic active bands were detected between pI 4.2 and 4.3 for the membrane-associated form. As judged from identical patterns after neuraminidase treatment, both peptidases contained no sialic acid. A pH optimum of 5.5 was estimated for the hydrolysis of Gly-Pro- and Arg-Pro-nitroanilide. Substrates with alanine instead of proline in the penultimate position were hydrolyzed at comparable rates. Acidic amino acids in the ultimate N-terminal position of the substrates reduced the activities of the peptidases 100-fold as compared with corresponding substrates with unblocked neutral or, especially, basic termini. The action of the dipeptidyl peptidase on several peptides with N-terminal Xaa-Pro sequences was investigated. Tripeptides were rapidly hydrolyzed, but the activities considerably decreased with increasing chain length of the peptides. Although the tetrapeptide substance P 1-4 was still a good substrate, the activities detected for the sequential liberation of Xaa-Pro dipeptides from substance P itself or casomorphin were considerably lower. Longer peptides were not cleaved. The peptidases hydrolyzed Pro-Pro bonds, e.g., in bradykinin 1-3 or 1-5 fragments, but bradykinin itself was resistant. The enzymes were inhibited by serine protease inhibitors, like diisopropyl fluorophosphate or phenylmethylsulfonyl fluoride, and by high salt concentrations but not by the aminopeptidase inhibitors bacitracin and bestatin. Based on the molecular and catalytic properties, both enzymes can be classified as species of dipeptidyl peptidase II (EC 3.4.14.2) rather than IV (EC 3.4.14.5). However, some catalytic properties differentiate the brain enzyme from forms of dipeptidyl peptidase II of other sources.
Histopathological changes in tendinopathy--potential roles of BMPs? (2013)

The pathogenesis of tendinopathy remains unclear. Chondro-osteogenic BMPs such as BMP-2, BMP-4 and BMP-7 have been reported in clinical samples and animal models of tendinopathy. As chondrocyte-like cells and ossified deposits have been observed in both clinical samples and animal models of failed tendon healing tendinopathy, chondro-osteogenic BMPs might contribute to tissue metaplasia and other histopathological changes in tendinopathy. In this review I have summarized the current evidence supporting the roles of chondro-osteogenic BMPs in the histopathological changes of tendinopathy. The potential targets, effects and sources of these BMPs are discussed. I have also provided directions for future studies about the potential roles of BMPs in the pathogenesis of tendinopathy. Better understanding of the roles of these BMPs in the histopathological changes of tendinopathy could provide new options for the prevention and treatment of this disabling tendon disorder.
Treatment of Iron Deficiency With Intravenous Ferric Carboxymaltose in General Practice: A Retrospective Database Study (2014)

We conclude that treatment with intravenous ferric carboxymaltose is an efficient alternative for patients with iron deficiency in general practice, when oral products are not well tolarated or effective. As treatment with iron carboxymaltose is more expensive and potentially dangerous due to side effects, the indication should be placed with (more) care.
Transgenic and Mutation-Based Suppression of a Berberine Bridge Enzyme-Like (BBL) Gene Family Reduces Alkaloid Content in Field-Grown Tobacco (2015)

Motivation exists to develop tobacco cultivars with reduced nicotine content for the purpose of facilitating compliance with expected tobacco product regulations that could mandate the lowering of nicotine levels per se, or the reduction of carcinogenic alkaloid-derived tobacco specific nitrosamines (TSNAs). A berberine bridge enzyme-like (BBL) gene family was recently characterized for N. tabacum and found to catalyze one of the final steps in pyridine alkaloid synthesis for this species. Because this gene family acts downstream in the nicotine biosynthetic pathway, it may represent an attractive target for genetic strategies with the objective of reducing alkaloid content in field-grown tobacco. In this research, we produced transgenic doubled haploid lines of tobacco cultivar K326 carrying an RNAi construct designed to reduce expression of the BBL gene family. Field-grown transgenic lines carrying functional RNAi constructs exhibited average cured leaf nicotine levels of 0.684%, in comparison to 2.454% for the untransformed control. Since numerous barriers would need to be overcome to commercialize transgenic tobacco cultivars, we subsequently pursued a mutation breeding approach to identify EMS-induced mutations in the three most highly expressed isoforms of the BBL gene family. Field evaluation of individuals possessing different homozygous combinations of truncation mutations in BBLa, BBLb, and BBLc indicated that a range of alkaloid phenotypes could be produced, with the triple homozygous knockout genotype exhibiting greater than a 13-fold reduction in percent total alkaloids. The novel source of genetic variability described here may be useful in future tobacco breeding for varied alkaloid levels.
c-Jun N-Terminal Protein Kinase (JNK) 2/3 Is Specifically Activated by Stress, Mediating c-Jun Activation, in the Presence of Constitutive JNK1 Activity in Cerebellar Neurons (2002)

c-Jun is considered a major regulator of both neuronal death and regeneration. Stress in primary cultured CNS neurons induces phosphorylation of c-Jun serines 63 and 73 and increased c-Jun protein. However, total c-Jun N-terminal protein kinase (JNK) activity does not increase, and no satisfactory explanation for this paradox has been available. Here we demonstrate that neuronal stress induces strong activation of JNK2/3 in the presence of constitutively and highly active JNK1. Correspondingly, neurons from JNK1(-/-) mice show lower constitutive activity and considerably higher responsiveness to stress. p38 activity can be completely inhibited without effect on c-Jun phosphorylation, whereas 10 micrometer SB203580 strongly inhibits neuronal JNK2/3, stress-induced c-Jun phosphorylation, induced c-Jun activity, and neuronal death in response to trophic withdrawal stress. Neither constitutive JNK1 activity nor total neuronal JNK activity were significantly affected by this concentration of drug. Thus, neuronal stress selectively activates JNK2/3 in the presence of mechanisms maintaining constitutive JNK1 activity, and this JNK2/3 activity selectively targets c-Jun, which is isolated from constitutive JNK1 activity.
Gemcitabine in Combination With Oxaliplatin Compared With Gemcitabine Alone in Locally Advanced or Metastatic Pancreatic Cancer: Results of a GERCOR and GISCAD Phase III Trial (2005)

These results confirm the efficacy and safety of GemOx, but this study failed to demonstrate a statistically significant advantage in terms of OS compared with Gem. Because GemOx is the first combined treatment to be superior to Gem alone in terms of clinical benefit, this promising regimen deserves further development.
Low-power high-efficiency wavelength conversion based on modulational instability in high-nonlinearity fiber (1998)

Bandwidth and peak efficiency are enhanced for wavelength conversion based on induced modulation instability by use of dispersion-shifted fiber in which the nonlinearity (n(2)/A(eff)) is enhanced by a factor of ~4.5 over that of conventional dispersion-shifted fiber. We experimentally obtain a peak conversion efficiency as high as 28 dB over a 40-nm bandwidth with 600 mW of peak pump power. Considerations for further enhancement of fiber-based wavelength conversion are also discussed.
A Fully Integrated Wireless SoC for Motor Function Recovery After Spinal Cord Injury (2017)

This paper presents a wirelessly powered, fully integrated system-on-a-chip (SoC) supporting 160-channel stimulation, 16-channel recording, and 48-channel bio-impedance characterization to enable partial motor function recovery through epidural spinal cord electrical stimulation. A wireless transceiver is designed to support quasi full-duplex data telemetry at a data rate of 2 Mb/s. Furthermore, a unique in situ bio-impedance characterization scheme based on time-domain analysis is implemented to derive the Randles cell electrode model of the electrode-electrolyte interface. The SoC supports concurrent stimulation and recording while the high-density stimulator array meets an output compliance voltage of up to ±10 V with versatile stimulus programmability. The SoC consumes 18 mW and occupies a chip area of 5.7 mm × 4.4 mm using 0.18 μm high-voltage CMOS process. In our in vivo rodent experiment, the SoC is used to perform wireless recording of EMG responses while stimulation is applied to enable the standing and stepping of a paralyzed rat. To facilitate the system integration, a novel thin film polymer packaging technique is developed to provide a heterogeneous integration of the SoC, coils, discrete components, and high-density flexible electrode array, resulting in a miniaturized prototype implant with a weight and form factor of 0.7 g and 0.5 cm<sup>3</sup>, respectively.
Effect of CO2 Concentration on Carbonic Anhydrase and Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Expression in Pea (1996)

The effect of external CO2 concentration on the expression of carbonic anhydrase (CA) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) was examined in pea (Pisum sativum cv Little Marvel) leaves. Enzyme activities and their transcript levels were reduced in plants grown at 1000 [mu]L/L CO2 compared with plants grown in ambient air. Growth at 160 [mu]L/L CO2 also appeared to reduce steady-state transcript levels for rbcS, the gene encoding the small subunit of Rubisco, and for ca, the gene encoding CA; however, rbcS transcripts were reduced to a greater extent at this concentration. Rubisco activity was slightly lower in plants grown at 160 [mu]L/L CO2, and CA activity was significantly higher than that observed in air-grown plants. Transfer of plants from 1000 [mu]L/L to air levels of CO2 resulted in a rapid increase in both ca and rbcS transcript abundance in fully expanded leaves, followed by an increase in enzyme activity. Plants transferred from air to high-CO2 concentrations appeared to modulate transcript abundance and enzyme activity less quickly. Foliar carbohydrate levels were also examined in plants grown continuously at high and ambient CO2, and following changes in growth conditions that rapidly altered ca and rbcS transcript abundance and enzyme activities.
The development of an experimental discrete dictation recognizer (1985)

This paper describes an experimental real-time recognizer of isolated word dictation implemented at the IBM Thomas J. Watson Research Center, on a system of commercially available computers and array processors. The recognizer's intended use is creation of office memoranda. It is based on a 5000-word vocabulary. A specially designed workstation enables the user to correct and edit the transcribed speech. The paper outlines the self-organized, statistical approach underlying the basic algorithms of the recognizer. Results of several recognition experiments are then presented. The rest of the paper considers important issues in the future development of dictation recognizers, such as vocabulary selection, language model creation, and human factors.
Perovskite Crystals for Tunable White Light Emission (2015)

A significant fraction of global electricity demand is for lighting. Enabled by the realization and development of efficient GaN blue light-emitting diodes (LEDs), phosphor-based solid-state white LEDs provide a much higher efficiency alternative to incandescent and fluorescent lighting, which are being broadly implemented. However, a key challenge for this industry is to achieve the right photometric ranges and application-specific emission spectra via cost-effective means. Here, we synthesize organic–inorganic lead halide-based perovskite crystals with broad spectral tuneability. By tailoring the composition of methyl and octlyammonium cations in the colloidal synthesis, meso- to nanoscale 3D crystals (5–50 nm) can be formed with enhanced photoluminescence efficiency. By increasing the octlyammonium cations content, we observe platelet formation of 2D layered perovskite sheets; however, these platelets appear to be less emissive than the 3D crystals. We further manipulate the halide composition of the perovskite crystals to achieve emission covering the entire visible spectrum. By blending perovskite crystals with different emission wavelengths in a polymer host, we demonstrate the potential to replace conventional phosphors and provide the means to replicate natural white light when excited by a blue GaN LED.
Dimension Reduction for Multivariate Response Data (2003)

This article concerns the analysis of multivariate response data with multivariate regressors. Methods for reducing the dimensionality of response variables are developed, with the goal of preserving as much regression information as possible. We note parallels between this goal and the goal of sliced inverse regression, which intends to reduce the regressor dimension in a univariate regression while preserving as much regression information as possible. A detailed discussion is given for the case where the response is a curve measured at fixed points. The problem in this setting is to select basis functions for fitting an aggregate of curves. We propose that instead of focusing on goodness of fit, attention should be shifted to the problem of explaining the variation of the curves in terms of the regressor variables. A data-adaptive basis searching method based on dimension reduction theory is proposed. Simulation results and an application to a climatology problem are given.
Breast and Other Cancers in Families with Ataxia-Telangiectasia (1987)

Patients who are homozygous for ataxia-telangiectasia have an exceptionally high incidence of cancer. In a group of families expected to have a high proportion of heterozygotes for ataxia-telangiectasia, we tested the hypothesis that such heterozygotes, estimated to make up 0.68 to 7.7 percent of the U.S. white population, also have an excess cancer risk. Retrospective cancer incidence rates in adult blood relatives of patients with ataxia-telangiectasia in 110 white non-Amish families were significantly elevated over the incidence rates in spouse controls (rate ratios, 1.6 for men [P = 0.032]; 2.0 for women [P = 0.013]). For persons who are heterozygous for ataxia-telangiectasia, the relative risk of cancer was estimated to be 2.3 for men (P = 0.014) and 3.1 for women (P = 0.004). Breast cancer in women was the cancer most clearly associated with heterozygosity for ataxia-telangiectasia (rate ratio, 3.0 [P = 0.028]; heterozygote relative risk, 6.8 [P = 0.006]). On the basis of this estimated relative risk of 6.8 and an estimated heterozygote frequency in the general population of 1.4 percent, 8.8 percent of patients with breast cancer in the U.S. white population would be heterozygous for ataxia-telangiectasia. We conclude that heterozygous carriers of the gene for ataxia-telangiectasia have an excess risk of cancer, particularly breast cancer in women.
Regulation of nerve growth factor and its low-affinity receptor (p75NTR) during myogenic differentiation (1998)

In our preceding report, we have shown that nerve growth factor (NGF) and its low-affinity receptor (p75NTR) are expressed in C2C12 myoblasts and downregulated during myogenic differentiation. Furthermore, NGF affects myogenic differentiation and cell growth via p75NTR and downregulation of p75NTR is essential for myogenic differentiation (Seidl et al., 1998). Here we show that NGF and p75NTR are regulated by mechanisms preceding terminal differentiation in myogenic cells. These mechanisms include cell-density phenomena such as cell-cell contact as well as signaling of basic fibroblast growth factor (FGF-2) and its receptor (FGFR1). Downregulation of NGF and p75NTR occurred as a consequence of increasing cell density, an important trigger for the onset of myogenic differentiation. FGF-2 and FGFR1 were shown to be present in C2C12 cells and exogenous FGF-2 induced NGF and p75NTR expression, implying that FGF/FGFR signaling is an upstream regulator of the NGF/p75NTR system. The fact that FGF-2 could suspend yet not abolish density-induced downregulation indicates that cell-cell contact counteracts the FGF effect and ultimately terminates NGF/p75NTR signaling. This evidence, together with the observation that p75NTR expression is suppressed in muscle progenitors, which constitutively express adenovirus E1A proteins and thus lack the competence of myogenic differentiation, underline the important role for the NGF/p75NTR system in the interplay of multiple factors and biological systems that balance myogenic differentiation at the appropriate spatial and temporal level.
The STK2 Gene, Which Encodes a Putative Ser/Thr Protein Kinase, Is Required for High-Affinity Spermidine Transport in Saccharomyces cerevisiae (1997)

Eukaryotic polyamine transport systems have not yet been characterized at the molecular level. We have used transposon mutagenesis to identify genes controlling polyamine transport in Saccharomyces cerevisiae. A haploid yeast strain was transformed with a genomic minitransposon- and lacZ-tagged library, and positive clones were selected for growth resistance to methylglyoxal bis(guanylhydrazone) (MGBG), a toxic polyamine analog. A 747-bp DNA fragment adjacent to the lacZ fusion gene rescued from one MGBG-resistant clone mapped to chromosome X within the coding region of a putative Ser/Thr protein kinase gene of previously unknown function (YJR059w, or STK2). A 304-amino-acid stretch comprising 11 of the 12 catalytic subdomains of Stk2p is approximately 83% homologous to the putative Pot1p/Kkt8p (Stk1p) protein kinase, a recently described activator of low-affinity spermine uptake in yeast. Saturable spermidine transport in stk2::lacZ mutants had an approximately fivefold-lower affinity and twofold-lower Vmax than in the parental strain. Transformation of stk2::lacZ cells with the STK2 gene cloned into a single-copy expression vector restored spermidine transport to wild-type levels. Single mutants lacking the catalytic kinase subdomains of STK1 exhibited normal parameters for the initial rate of spermidine transport but showed a time-dependent decrease in total polyamine accumulation and a low-level resistance to toxic polyamine analogs. Spermidine transport was repressed by prior incubation with exogenous spermidine. Exogenous polyamine deprivation also derepressed residual spermidine transport in stk2::lacZ mutants, but simultaneous disruption of STK1 and STK2 virtually abolished high-affinity spermidine transport under both repressed and derepressed conditions. On the other hand, putrescine uptake was also deficient in stk2::lacZ mutants but was not repressed by exogenous spermidine. Interestingly, stk2::lacZ mutants showed increased growth resistance to Li+ and Na+, suggesting a regulatory relationship between polyamine and monovalent inorganic cation transport. These results indicate that the putative STK2 Ser/Thr kinase gene is an essential determinant of high-affinity polyamine transport in yeast whereas its close homolog STK1 mostly affects a lower-affinity, low-capacity polyamine transport activity.