gebhart/patrepeval huggingface dataset:
Identification of C-2 Hydroxyethyl Imidazopyrrolopyridines as Potent JAK1 Inhibitors with Favorable Physicochemical Properties and High Selectivity over JAK2 (2013)

Herein we report on the structure-based discovery of a C-2 hydroxyethyl moiety which provided consistently high levels of selectivity for JAK1 over JAK2 to the imidazopyrrolopyridine series of JAK1 inhibitors. X-ray structures of a C-2 hydroxyethyl analogue in complex with both JAK1 and JAK2 revealed differential ligand/protein interactions between the two isoforms and offered an explanation for the observed selectivity. Analysis of historical data from related molecules was used to develop a set of physicochemical compound design parameters to impart desirable properties such as acceptable membrane permeability, potent whole blood activity, and a high degree of metabolic stability. This work culminated in the identification of a highly JAK1 selective compound (31) exhibiting favorable oral bioavailability across a range of preclinical species and robust efficacy in a rat CIA model.
Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs (2013)

In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals.
Aperture scanning Fourier ptychographic microscopy (2016)

Fourier ptychographic microscopy (FPM) is implemented through aperture scanning by an LCOS spatial light modulator at the back focal plane of the objective lens. This FPM configuration enables the capturing of the complex scattered field for a 3D sample both in the transmissive mode and the reflective mode. We further show that by combining with the compressive sensing theory, the reconstructed 2D complex scattered field can be used to recover the 3D sample scattering density. This implementation expands the scope of application for FPM and can be beneficial for areas such as tissue imaging and wafer inspection.
Endosomolytic Anionic Polymer for the Cytoplasmic Delivery of siRNAs in Localized In Vivo Applications (2012)

The use of small interfering RNAs (siRNAs) to down-regulate the expression of disease-associated proteins carries significant promise for the treatment of a variety of clinical disorders. One of the main barriers to the widespread clinical use of siRNAs, however, is their entrapment and degradation within the endolysosomal pathway of target cells. Here we report the trafficking and function of PP75, a non-toxic, biodegradable, lipid membrane disruptive anionic polymer composed of phenylalanine derivatized poly(L-lysine <i>iso</i>-phthalamide). PP75 is readily endocytosed by cells, safely permeabilizes endolysosomes in a pH dependent manner and facilitates the transfer of co-endocytosed materials directly into the cytoplasm. The covalent attachment of siRNAs to PP75 using disulfide linkages generates conjugates that effectively traffic siRNAs to the cytoplasm of target cells both <i>in vitro</i> and <i>in vivo</i>. In a subcutaneous malignant glioma tumor model, a locally delivered PP75-stathmin siRNA conjugate decreases stathmin expression in tumor cells and, in combination with the nitrosourea chemotherapy carmustine, is highly effective at inhibiting tumor growth. PP75 may be clinically useful for the local delivery of siRNAs, in particular for the treatment of solid tumors.
Developmental competence of human in vitro aged oocytes as host cells for nuclear transfer (2006)

Thus, aneuploidy and spindle defects may contribute to poor parthenogenetic development and developmental outcomes following NT.
Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells (2000)

Natural tumor surveillance capabilities of the host were investigated in six different mouse tumor models where endogenous interleukin (IL)-12 does or does not dictate the efficiency of the innate immune response. Gene-targeted and lymphocyte subset-depleted mice were used to establish the relative importance of natural killer (NK) and NK1.1(+) T (NKT) cells in protection from tumor initiation and metastasis. In the models examined, CD3(-) NK cells were responsible for tumor rejection and protection from metastasis in models where control of major histocompatibility complex class I-deficient tumors was independent of IL-12. A protective role for NKT cells was only observed when tumor rejection required endogenous IL-12 activity. In particular, T cell receptor Jalpha281 gene-targeted mice confirmed a critical function for NKT cells in protection from spontaneous tumors initiated by the chemical carcinogen, methylcholanthrene. This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide.
Repeat Domain Diversity of avrBs3 -Like Genes in Ralstonia solanacearum Strains and Association with Host Preferences in the Field (2007)

Genes homologous to avrBs3 of Xanthomonas were detected in 309 strains of Ralstonia solanacearum biovars 3, 4, and 5 but not biovar 1 or 2. A statistically significant association between the originating plant species and internal repeats of the gene was found. Sequences of repeats and variation between nearly clonal strains revealed evidence of frequent recombination.
Adaptive Bayesian multiuser detection for synchronous CDMA with Gaussian and impulsive noise (2000)

We consider the problem of simultaneous parameter estimation and data restoration in a synchronous CDMA system in the presence of either additive Gaussian or additive impulsive white noise with unknown parameters. The impulsive noise is modeled by a two-term Gaussian mixture distribution. Bayesian inference of all unknown quantities is made from the superimposed and noisy received signals. The Gibbs sampler (a Markov chain Monte Carlo procedure) is employed to calculate the Bayesian estimates. The basic idea is to generate ergodic random samples from the joint posterior distribution of all unknown and then to average the appropriate samples to obtain the estimates of the unknown quantities. Adaptive Bayesian multiuser detectors based on the Gibbs sampler are derived for both the Gaussian noise synchronous CDMA channel and the impulsive noise synchronous CDMA channel. A salient feature of the proposed adaptive Bayesian multiuser detectors is that they can incorporate the a priori symbol probabilities, and they produce as output the a posteriori symbol probabilities. (That is, they are "soft-input soft-output" algorithms.) Hence, these methods are well suited for iterative processing in a coded system, which allows the adaptive Bayesian multiuser detector to refine its processing based on the information from the decoding stage, and vice versa-a receiver structure termed the adaptive turbo multiuser detector.
Mobility of the Active Site Bound Paraoxon and Sarin in Zinc-Phosphotriesterase by Molecular Dynamics Simulation and Quantum Chemical Calculation (2001)

The kinetic data published on phosphotriesterase (PTE), with various complexed metals, clearly indicates that the P=O and P=S bonds of phosphotriester and thiophosphotriester substrates, respectively, are strongly polarized by one or both of the active site complexed metal ions. However, this observation is not consistent with the three-dimensional X-ray crystal structure of zinc-substituted PTE with active site bound substrate analogue diethyl 4-methylbenzylphosphonate. In this structure, the distance between the phosphoryl oxygen and the nearest zinc is 3.4 A, a distance too large to afford strong polarization. In the present paper, the geometry and mobility of various PTE active site-substrate complexes are examined by performing both molecular dynamics (MD) simulations and quantum mechanical calculations. Two known substrates are considered, paraoxon and sarin, although their turnover rates vary about 100-fold. The results indicate that PTE forms a complex with either substrate in which the phosphoryl oxygen becomes strongly coordinated with the less buried zinc atom. It is shown that the geometry of the active site is changed when the protein is immersed in a water bath and relaxed by MD. The most substantial conformational change is the opening of the gateway in a pocket where the location of the leaving group is expected. The opening is observed for the pure enzyme as well as for the enzyme/substrate complexes and it ranges from 11 to 18 A. It is also shown that the pockets, in which the substrate substituents are localized, exhibit different flexibility and interact with the substrate with coordinated conformational adjustments.
Password authentication with insecure communication (1981)

A method of user password authentication is described which is secure even if an intruder can read the system's data, and can tamper with or eavesdrop on the communication between the user and the system. The method assumes a secure one-way encryption function and can be implemented with a microcomputer in the user's terminal.
Chemoenzymatic Synthesis of (R)- and (S)-4-Amino-3-Methylbutanoic Acids (1990)

Abstract (R)- and (S)-4-Amino-3-methylbutanoic acids were synthesized in high yields via initial enantioselective hydrolysis of dimethyl 3-methylglutarate to methyl (R)-3-methylglutarate with pig liver esterase. The ester group was converted to an amine to give (R)-4-amino-3-methylbutanoic acid; the carboxylic acid was converted to an amine to give (S)-4-amino-3-methylbutanoic acid.
Cobalt carbonyl-catalyzed reactions of cyclic ethers with a hydrosilane and carbon monoxide. A new synthetic reaction equivalent to nucleophilic oxymethylation (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCobalt carbonyl-catalyzed reactions of cyclic ethers with a hydrosilane and carbon monoxide. A new synthetic reaction equivalent to nucleophilic oxymethylationToshiaki Murai, Eiji Yasui, Shinzi Kato, Yoshio Hatayama, Satoshi Suzuki, Yasuhiro Yamasaki, Noboru Sonoda, Hideo Kurosawa, Yoshikane Kawasaki, and Shinji MuraiCite this: J. Am. Chem. Soc. 1989, 111, 20, 7938–7946Publication Date (Print):September 1, 1989Publication History Published online1 May 2002Published inissue 1 September 1989https://pubs.acs.org/doi/10.1021/ja00202a040https://doi.org/10.1021/ja00202a040research-articleACS PublicationsRequest reuse permissionsArticle Views650Altmetric-Citations52LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Wet corn distillers byproducts compared with dried corn distillers grains with solubles as a source of protein and energy for ruminants (1994)

Five trials investigated the feeding value of wet and dried corn distillers byproducts as a source of protein and energy for growing and finishing cattle and investigated the effect of heat damage on the feeding value of dried distillers byproducts. In a calf growth trial, no differences in rate of gain or protein efficiency were observed among calves fed wet distillers byproducts (wet distillers grains + thin stillage; WDB) or one of three composites of dried distillers grain + solubles (DDGS) having a low, medium, or high concentration of ADIN. A finishing trial compared the energy value of dry-rolled corn (DRC) with WDB or the three DDGS composites, fed at 40% of the diet DM replacing DRC. Cattle consuming WDB or DDGS gained faster (P < .05) and more efficiently (P < .05) than cattle fed DRC. Although gains were similar, cattle fed WDB consumed less feed (P < .10) and were more efficient (P < .10) than cattle fed DDGS. Level of ADIN in DDGS did not affect efficiency of gain (P > .10). In a lamb finishing trial, the addition of 5 or 10% ethanol did not affect (P > .10) daily gain, DMI, or feed efficiency. In two metabolism trials with steers, grain byproducts (wet distillers grains, dry distillers grains plus solubles, wet corn gluten feed, dry corn gluten feed, hominy feed) and DRC had similar effects on ruminal pH and total VFA. Feeding thin stillage or condensed solubles reduced (P < .10) ruminal pH and tended to reduce acetate:propionate. Wet corn distillers byproducts, fed at 40% of the diet DM, contain more NEg than did DRC and drying WDB reduces its NEg content. Acid detergent insoluble N is a poor indicator of protein and energy value in distillers grains.
Design of optimal quantizers for distributed source coding (2003)

The problem of designing optimal quantizers for distributed source coding is addressed. The generality of this formulation includes both the symmetric and asymmetric scenarios, together with a number of coding schemes, such as ideal coding achieving a rate equal to the joint conditional entropy of the quantized sources given the side information. The paper shows the optimality conditions that quantizers must satisfy, and generalizes the Lloyd algorithm for their design. Experimental results are shown for the Gaussian scalar asymmetric case.
An Orientation‐Controlled Pentacene Film Aligned by Photoaligned Polyimide for Organic Thin‐Film Transistor Applications (2004)

Abstract We have demonstrated that the photoalignment method could be used to control the structural anisotropy of pentacene films, an active semiconducting layer, in thin‐film transistors (TFTs) with conspicuously anisotropic electrical characteristics. The photoaligned pentacene films were characterized with respect to structure and morphology using X‐ray diffraction and atomic force microscopy. Compared to the pentacene films that are not controlled, a maximal 25‐times increase in field‐effect mobility (up to 0.75 cm V –1 s –1 ) has been achieved in the photoaligned pentacene‐based TFTs by aligning pentacene orientation parallel to the direction of current flow with the help of a photoaligned polyimide layer. Mobility anisotropic ratio in the range of 2.7–8.3 for the current flow parallel and perpendicular to the alignment of the photoaligned pentacene films have been observed for photoaligned pentacene‐based TFTs.
Multiple Amino Acid Substitutions in Hemagglutinin Are Necessary for Wild-Type MeaslesVirus To Acquire the Ability To Use Receptor CD46 Efficiently (2006)

Measles virus (MV) possesses two envelope glycoproteins, namely, the receptor-binding hemagglutinin (H) and fusion proteins. Wild-type MV strains isolated in B-lymphoid cell lines use signaling lymphocyte activation molecule (SLAM), but not CD46, as a cellular receptor, whereas MV vaccine strains of the Edmonston lineage use both SLAM and CD46 as receptors. Studies have shown that the residue at position 481 of the H protein is critical in determining the use of CD46 as a receptor. However, the wild-type IC-B strain with a single N481Y substitution in the H protein utilizes CD46 rather inefficiently. In this study, a number of chimeric and mutant H proteins, and recombinant viruses harboring them, were generated to determine which residues of the Edmonston H protein are responsible for its efficient use of CD46. Our results show that three substitutions (N390I and E492G plus N416D or T446S), in addition to N481Y, are necessary for the IC-B H protein to use CD46 efficiently as a receptor. The N390I, N416D, and T446S substitutions are present in the H proteins of all strains of the Edmonston lineage, whereas the E492G substitution is found only in the H protein of the Edmonston tag strain generated from cDNAs. The T484N substitution, found in some of the Edmonston-lineage strains, resulted in a similar effect on the use of CD46 to that caused by the E492G substitution. Thus, multiple residues in the H protein that have not previously been implicated have important roles in the interaction with CD46.
Potential biochemical markers of uterine receptivity (1999)

Implantation in humans is a complex process that involves embryo apposition and attachment to the maternal endometrial epithelium, traversing adjacent cells of the epithelial lining, and invasion into the endometrial stroma. These processes involve a variety of molecules which are not unique in themselves, but play unique roles in the process of implantation. The molecular dialogue that occurs between the implanting conceptus and the endometrium involves cell-cell and cell-extracellular matrix interactions, mediated by lectins, integrins, matrix degrading enzymes and their inhibitors, prostaglandins, and a variety of growth factors, cytokines, and angiogenic peptides, their receptors and modulatory proteins. It is likely that each of these, when appropriately expressed or inhibited, contributes to endometrial receptivity or non-receptivity to an implanting conceptus. Currently, a working definition of a receptive versus a non-receptive endometrium is incomplete. While histological normality of the endometrium does not necessarily imply functional normality, temporal and spatial expression of particular biochemical principles in the endometrium are highly suggestive of functional roles of these principles in implantation and endometrial receptivity. These potential markers of endometrial receptivity are discussed herein. It is envisioned that as regulation of these markers is elucidated, their expression may be manipulated to improve implantation rates and fertility or to limit implantation for successful contraception.
[Serum testosterone: a possible marker for colorectal cancer]. (1993)

A reduction of circulating testosterone has been reported in lung, stomach and pancreatic carcinoma. In order to evaluate the concentration of this hormone in patients with colorectal cancer, we studied 58 men with histologically confirmed disease. Seric testosterone, estradiol and carcinoembryogenic antigen were simultaneously measured in 24 patients under pre-surgical evaluation (group I) and in 34 patients after surgical resection (group II). The results were compared with a control group carrying benign gastrointestinal pathologies. According to the Kruskal-Wallis test, the testosterone level in cancer groups was significantly lower than in the control group (p < 0.0001). We have also observed a statistical significance between subgroups I and II compared to the control group (p < 0.001), while no conspicuous differences were perceived in estradiol concentrations between benign and cancer groups. Decreased serum levels of testosterone were found in 69% of patients with colon or rectal carcinoma and 56.9% of them had raised levels of carcinoembryonic antigen. The combined determination of both biomarkers increase to 86.2% the sensitivity of tumor screening compared with a single detection. Our results suggest that the combination of testosterone and carcinoembryonic antigen enhances the efficiency of tumor screening. We conclude that the evaluation of circulating testosterone could be a new and more sensitive assay for diagnosis and follow-up of colorectal carcinoma in males, specially in patients with normal levels of carcinoembryonic antigen.
Correlation between the concentrations of melatonin and the prognosis of stroke (2004)

Objective To preliminarily estimate the prognosis of the patient with stroke through measurig the quantity of melatonin in the serum.Methods Fifty healthy controls and 62 patients with stroke were determined the concentrations of melatonin in the serum at 2:00 and 8:00.Results The concentrations of melatonin in the serum of the patient with stroke at 2:00 were significantly lower than those of normal controls(P0.01),but there was no difference at 8:00(P0.05).In patients with a good curative effect,they were higher than those with no curative effect at 2:00 before treatment and were significantly elevated after treatment(P0.01).Conclusion Melatonin will be a valuable guideline for judging the prognosis of stroke.
Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease (2013)

Previous studies using MCP-induced protein 1 (MCPIP1)/Zc3h12a-deficient mice suggest that MCPIP1 is an important regulator of inflammation and immune homeostasis. However, the characterization of the immunological phenotype of MCPIP1-deficient mice has not been detailed. In this study, we performed evaluation through histological, flow cytometric, enzyme-linked immunosorbent assay and real-time PCR analysis and found that targeted disruption of MCPIP1 gene leads to fatal, highly aggressive and widespread immune-related lesions. In addition to previously observed growth retardation, splenomegaly, lymphoadenopathy, severe anemia and premature death, MCPIP1-deficient mice showed disorganization of lymphoid organs, including spleen, lymph nodes and thymus, and massive infiltration of lymphocytes, macrophages and neutrophils into many other non-lymphoid organs, primarily in lungs and liver. Flow cytometric analysis found significant increase in activated and differentiated T cells in peripheral blood and spleen of MCPIP1-deficient mice. Moreover, heightened production of inflammatory cytokines from activated macrophages and T cells were observed in MCPIP1-deficient mice. Interestingly, treatment of MCPIP1-deficient mice with antibiotics resulted in significant improvement of life span and a decrease in inflammatory syndrome. Taken together, these results suggest a prominent role for MCPIP1 in the control of inflammation and immune homeostasis.