gebhart/patrepeval huggingface dataset:
Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 1. Identification of the 4-Quinolinecarboxamide Framework (1997)

A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and clear structure-activity relationships (SARs) have been established. From SARs, (R)-N-[alpha-(methoxycarbonyl)benzyl]-2-phenylquinoline-4-carboxamide (65, SB 218795, hNK-3-CHO binding Ki = 13 nM) emerged as one of the most potent compounds of this novel class. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 65 is about 90-fold selective for hNK-3 versus hNK-2 receptors (hNK-2-CHO binding Ki = 1221 nM) and over 7000-fold selective versus hNK-1 receptors (hNK-1-CHO binding Ki = > 100 microM). In vitro functional studies in rabbit isolated iris sphincter muscle preparation demonstrated that 65 is a competitive antagonist of the contractile response induced by the potent and selective NK-3 receptor agonist senktide with a Kb = 43 nM. Overall, the data indicate that 65 is a potent and selective hNK-3 receptor antagonist and a useful lead for further chemical optimization.
Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial (2013)

We could not prove the efficacy of oral Pex administration in the prevention of heterotopic ossifications in FOP. Serum levels of ALP and BAP appear to be promising biomarkers for monitoring the development of ectopic ossifications and efficacy of the therapy. Quantification of change in the total bone volume by whole body CT scanning could be a reliable evaluation tool for disease progression in forthcoming clinical trials of FOP.
Synthesis, Characterization, and Biological Properties of Cyanine-Labeled Somatostatin Analogues as Receptor-Targeted Fluorescent Probes (2001)

We present the synthesis and characterization of the somatostatin receptor-specific peptide H(2)N-(D-Phe)-cyclo[Cys-Phe-(D-Trp)-Lys-Thr-Cys]-Thr-OH, which is labeled with a carboxylated indodicarbo- and an indotricarbocyanine dye at the N-terminal amino group. The preparation was performed by automated solid-phase synthesis, with subsequent attachment of the cyanine dye and cleavage of the entire conjugate from the resin. The compounds display high molar absorbance and fluorescence quantum yields typical for cyanine dyes and are thus suitable receptor-targeted contrast agents for molecular optical imaging. The ability of these agents to target the somatostatin receptor was demonstrated by flow cytometry in vitro, in which the indotricarbocyanine conjugate led to elevated cell-associated fluorescence on somatostatin receptor-expressing tumor cells. In contrast, the corresponding linearized derivative of the sequence H(2)N-(D-Phe)-Met-Phe-(D-Trp)-Lys-Thr-Met-Thr-OH produced only minimal cell fluorescence, hence confirming the specificity of the cyclic somatostatin analogue. Intracellular localization could be visualized by near-infrared (NIR) fluorescence microscopy. In conclusion, receptor-specific peptides are promising tools for designing site-directed optical contrast agents for use in molecular optical imaging.
Universal MOSFET hole mobility degradation models for circuit simulation (1993)

Universal, semi-empirical MOSFET hole inversion layer mobility degradation models for use in circuit simulation programs such as SPICE are presented. By accurately predicting the mobility degradation due to acoustic phonon scattering and surface roughness scattering for p-channel MOSFETs at room temperature, these models eliminate the need for fitting parameters for each technology, which is required in the current SPICE level 3 model. The expressions reported accurately predict the mobility over a very wide range of channel doping concentrations, gate oxide thicknesses, gate voltage, and substrate bias, and they agree very well with recently published experimental mobility degradation data. When implemented in a circuit simulation code, these models will accurately determine the channel mobility in surface p-channel MOSFETs using only the channel doping concentration, gate oxide thickness, substate bias, and applied gate drive voltage as input parameters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Rabring7, a Novel Rab7 Target Protein with a RING Finger Motif (2003)

Rab7, a member of the Rab family small G proteins, has been shown to regulate intracellular vesicle traffic to late endosome/lysosome and lysosome biogenesis, but the exact roles of Rab7 are still undetermined. Accumulating evidence suggests that each Rab protein has multiple target proteins that function in the exocytic/endocytic pathway. We have isolated a new Rab7 target protein, Rabring7 (Rab7-interacting RING finger protein), using a CytoTrap system. It contains an H2 type RING finger motif at the C termini. Rabring7 shows no homology with RILP, which has been reported as another Rab7 target protein. GST pull-down and coimmunoprecipitation assays demonstrate that Rabring7 specifically binds the GTP-bound form of Rab7 at the N-terminal portion. Rabring7 is found mainly in the cytosol and is recruited efficiently to late endosomes/lysosomes by the GTP-bound form of Rab7 in BHK cells. Overexpression of Rabring7 not only affects epidermal growth factor degradation but also causes the perinuclear aggregation of lysosomes, in which the accumulation of the acidotropic probe LysoTracker is remarkably enhanced. These results suggest that Rabring7 plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis.
Physiological Versatility of the Extremely Thermoacidophilic Archaeon Metallosphaera sedula Supported by Transcriptomic Analysis of Heterotrophic, Autotrophic, and Mixotrophic Growth (2009)

Comparative transcriptomic analysis of autotrophic, heterotrophic, and mixotrophic growth of the archaeon Metallosphaera sedula (70 degrees C, pH 2.0) revealed candidates for yet-to-be-confirmed components of the 3-hydroxypropionate/4-hydroxybutyrate pathway and implicated a membrane-bound hydrogenase (Msed_0944-Msed_0946) for growth on H(2). Routes for generation of ATP and reducing equivalents were also identified.
Prospective molecular profiling of melanoma metastases suggests classifiers of immune responsiveness. (2002)

We amplified RNAs from 63 fine needle aspiration (FNA) samples from 37 s.c. melanoma metastases from 25 patients undergoing immunotherapy for hybridization to a 6108-gene human cDNA chip. By prospectively following the history of the lesions, we could correlate transcript patterns with clinical outcome. Cluster analysis revealed a tight relationship among autologous synchronously sampled tumors compared with unrelated lesions (average Pearson's r = 0.83 and 0.7, respectively, P < 0.0003). As reported previously, two subgroups of metastatic melanoma lesions were identified that, however, had no predictive correlation with clinical outcome. Ranking of gene expression data from pretreatment samples identified approximately 30 genes predictive of clinical response (P < 0.001). Analysis of their annotations denoted that approximately half of them were related to T-cell regulation, suggesting that immune responsiveness might be predetermined by a tumor microenvironment conducive to immune recognition.
A Belt‐Shaped, Blue Luminescent, and Semiconducting Covalent Organic Framework (2008)

Blue belt: Condensation polymerization of pyrene (blue) and triphenylene (green) monomers leads to the formation of a hexagonal mesoporous covalent organic framework (see picture). This material exists in a belt shape, absorbs photons over a wide wavelength range to emit them as blue luminescence, and is semiconducting, as well as being capable of repetitive on–off switching. 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.
Non-negative tensor factorization with applications to statistics and computer vision (2005)

We derive algorithms for finding a non-negative n-dimensional tensor factorization (n-NTF) which includes the non-negative matrix factorization (NMF) as a particular case when n = 2. We motivate the use of n-NTF in three areas of data analysis: (i) connection to latent class models in statistics, (ii) sparse image coding in computer vision, and (iii) model selection problems. We derive a "direct" positive-preserving gradient descent algorithm and an alternating scheme based on repeated multiple rank-1 problems.
Improving calibration accuracy in gel dosimetry (1998)

A new method of calibrating gel dosimeters (applicable to both Fricke and polyacrylamide gels) is presented which has intrinsically higher accuracy than current methods, and requires less gel. Two test-tubes of gel (inner diameter 2.5 cm, length 20 cm) are irradiated separately with a 10 x 10 cm2 field end-on in a water bath, such that the characteristic depth-dose curve is recorded in the gel. The calibration is then determined by fitting the depth-dose measured in water, against the measured change in relaxivity with depth in the gel. Increased accuracy is achieved in this simple depth-dose geometry by averaging the relaxivity at each depth. A large number of calibration data points, each with relatively high accuracy, are obtained. Calibration data over the full range of dose (1.6-10 Gy) is obtained by irradiating one test-tube to 10 Gy at dose maximum (Dmax), and the other to 4.5 Gy at Dmax. The new calibration method is compared with a 'standard method' where five identical test-tubes of gel were irradiated to different known doses between 2 and 10 Gy. The percentage uncertainties in the slope and intercept of the calibration fit are found to be lower with the new method by a factor of about 4 and 10 respectively, when compared with the standard method and with published values. The gel was found to respond linearly within the error bars up to doses of 7 Gy, with a slope of 0.233 +/- 0.001 s(-1) Gy(-1) and an intercept of 1.106 +/- 0.005 Gy. For higher doses, nonlinear behaviour was observed.
Fourier-plane Characteristics of a Liquid-crystal Light Valve (1987)

Abstract A lack of symmetry in the intensities of the plus and minus diffraction orders in the output Fourier plane of a liquid-crystal light valve has been observed. Measurement results and an intuitive discussion of this effect are presented.
Uterine endocrinology and paracrinology: insulin-like growth factor binding protein-1 and placental protein 14 revisited* (1994)

A large number of proteins and peptides have been identified in the endometrium where they are likely to exert local biological effects. These substances may be enzymes, their inhibitors, proteinases, proteinase inhibitors, hormones, or bioactive peptides with diverse functions. Endometrial function and embryo-endometrial interactions require synchronized actions between endocrine and local factors. As examples of local factors recent studies on the insulin-like growth factor (IGF) system and placental protein 14 (PP14) are reviewed. IGF binding protein-1 (IGFBP-1) and PP14 are products of the secretory phase endometrium: IGFBP-1 is produced by decidualized stromal cells and PP14 by glandular epithelial cells. IGFBP-1 may inhibit the action of IGFs at the endometrial-trophoblastic interphase, and it may also have a role in stromal-epithelial interaction. PP14 has immunosuppressive properties, and recent findings indicate that it may play a part in the fertilization process by inhibiting binding of spermatozoa to the zona.
Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study (2012)

Full funding sources listed at end of paper (see Acknowledgments).
DNA Vaccination against Tuberculosis: Expression of a Ubiquitin-Conjugated Tuberculosis Protein Enhances Antimycobacterial Immunity (2000)

Genetic immunization is a promising new technology for developing vaccines against tuberculosis that are more effective. In the present study, we evaluated the effects of intracellular turnover of antigens expressed by DNA vaccines on the immune response induced by these vaccines in a mouse model of pulmonary tuberculosis. The mycobacterial culture filtrate protein MPT64 was expressed as a chimeric protein fused to one of three variants of the ubiquitin protein (UbG, UbA, and UbGR) known to differentially affect the intracellular processing of the coexpressed antigens. Immunoblot analysis of cell lysates of in vitro-transfected cells showed substantial differences in the degradation rate of ubiquinated MPT64 (i.e., UbG64 < UbA64 < UbGR64). The specific immune response generated in mice correlated with the stability of the ubiquitin-conjugated antigen. The UbA64 DNA vaccine induced a weak humoral response compared to UbG64, and a mixed population of interleukin-4 (IL-4)- and gamma interferon (IFN-gamma)-secreting cells. Vaccination with the UbGR64 plasmid generated a strong Th1 cell response (high IFN-gamma, low IL-4) in the absence of a detectable humoral response. Aerogenic challenge of vaccinated mice with Mycobacterium tuberculosis indicated that immunization with both the UbA64- and UbGR64-expressing plasmids evoked an enhanced protective response compared to the vector control. The expression of mycobacterial antigens from DNA vaccines as fusion proteins with a destabilizing ubiquitin molecule (UbA or UbGR) shifted the host response toward a stronger Th1-type immunity which was characterized by low specific antibody levels, high numbers of IFN-gamma-secreting cells, and significant resistance to a tuberculous challenge.
Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in postmenopausal women (2010)

The 7.9-fold difference between low and high serum DHEA levels provides an explanation for the lack of signs of hormone deficiency in some women, whereas most of them have symptoms or signs. The approximately 20% contribution of the ovary to the total pool of DHEA with no direct secretion of estrogens or androgens in the circulation could possibly explain the reported negative effect of oophorectomy on longevity, especially from coronary heart disease events.
Detailed analysis of the DNA recognition motifs of the Xanthomonas type III effectors AvrBs3 and AvrBs3Δrep16 (2009)

The Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) employs a type III secretion system to translocate effector proteins into plant cells where they modulate host signaling pathways to the pathogen's benefit. The effector protein AvrBs3 acts as a eukaryotic transcription factor and induces the expression of plant genes termed UPA (up-regulated by AvrBs3). Here, we describe 11 new UPA genes from bell pepper that are induced by AvrBs3 early after infection with Xcv. Sequence comparisons revealed the presence of a conserved AvrBs3-responsive element, the UPA box, in all UPA gene promoters analyzed. Analyses of UPA box mutant derivatives confirmed its importance for gene induction by AvrBs3. We show that DNA binding and gene activation were strictly correlated. DNase I footprint studies demonstrated that the UPA box corresponds to the center of the AvrBs3-protected DNA region. Type III delivery of AvrBs3 and mutant derivatives showed that some UPA genes are induced by the AvrBs3 deletion derivative AvrBs3Deltarep16, which lacks four repeats. We show that AvrBs3Deltarep16 recognizes a mutated UPA box with two nucleotide exchanges in positions that are not essential for binding and activation by AvrBs3.
Universal one-way hash functions and their cryptographic applications (1989)

We define a Universal One-Way Hash Function family, a new primitive which enables the compression of elements in the function domain. The main property of this primitive is that given an element x. We prove constructively that universal one-way hash functions exist if any 1-1 one-way functions exist.
Optimal binary differencing filters: design, logic complexity, precision analysis, and application to digital document processing (1996)

For given binary image and degradation processes, an optimal mean-absolute-error translation-invariant filter can be designed via the representation of such filters as a union of morphological hit-or-miss transforms. The present paper investigates a different optimization methodology by representing translationinvariant filters as differencing filters. Rather than employing structuring templates to build the entire output image, as is done with direct hit-or-miss representation, differencing filters only employ templates that locate value flips (black-to-white or white-to-black). Differencing filters play a central role in several digital document processing tasks and the paper considers their optimal design. The paper compares the logic designs of differencing and direct hit-ormiss representations, the combinational logic costs of the two representations, and the estimation precision of optimization approaches based on each. Both combinational logic cost and precision are relative to image models. It is also shown how differencing filters are statistically designed and applied in the digital document setting for image restoration and resolution conversion.
Expression of transforming growth factor‐β superfamily receptors in rat eyes (1999)

The cornea, ciliary body, iris, lens, retinal cells, RPE and vascular cells expressed the receptors for TGF-beta superfamily at protein level.
Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function (2015)

Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing.
Catalytic Hydroaminoalkylation (2009)

Excellent couplings: Recent developments in the metal-catalyzed C-H activation of sp(3) centers in an alpha position relative to an amine nitrogen atom are presented. Their reaction with alkenes to give alkylamines (hydroaminoalkylation) is also summarized (see general scheme).
Increased prevalence of autoantibodies to Ku antigen in African American versus white patients with systemic lupus erythematosus (2001)

Anti-Ku antibodies are common in African American patients with SLE but rare in whites, probably explaining the different estimates of their prevalence. In African Americans, the frequency is comparable with that of anti-La/SSB. Along with anti-Ku, anti-nRNP and anti-Sm autoantibodies are also overrepresented in African Americans, suggesting that a group of specificities is characteristically associated with SLE in African Americans.
Intrahepatic cholestasis of pregnancy (2007)

Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by (i) pruritus with onset in the second or third trimester of pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii) spontaneous relief of signs and symptoms within two to three weeks after delivery. ICP is observed in 0.4-1% of pregnancies in most areas of Central and Western Europe and North America, while in Chile and Bolivia as well as Scandinavia and the Baltic states roughly 5-15% and 1-2%, respectively, of pregnancies are associated with ICP. Genetic and hormonal factors, but also environmental factors may contribute to the pathogenesis of ICP. Intrahepatic cholestasis of pregnancy increases the risk of preterm delivery (19-60%), meconium staining of amniotic fluid (27%), fetal bradycardia (14%), fetal distress (22-41%), and fetal loss (0.4-4.1%), particularly when associated with fasting serum bile acid levels > 40 micromol/L. The hydrophilic bile acid ursodeoxycholic acid (10-20 mg/kg/d) is today regarded as the first line treatment for intrahepatic cholestasis of pregnancy. Delivery has been recommended in the 38th week when lung maturity has been established.
Cytokine profile and induction of T helper type 17 and regulatory T cells by human peripheral mononuclear cells after microbial exposure (2011)

The immunomodulatory effects of probiotics were assessed following exposure of normal peripheral blood mononuclear cells (PBMC), cord blood cells and the spleen-derived monocyte/macrophage cell line CRL-9850 to Lactobacillus acidophilus LAVRI-A1, Lb. rhamnosus GG, exopolysaccharides (EPS)-producing Streptococcus thermophilus St1275, Bifidobacteriun longum BL536, B. lactis B94 and Escherichia coli TG1 strains. The production of a panel of pro- and anti-inflammatory cytokines by PBMC following bacterial stimulation was measured, using live, heat-killed or mock gastrointestinal tract (GIT)-exposed bacteria, and results show that (i) all bacterial strains investigated induced significant secretion of pro- and anti-inflammatory cytokines from PBMC-derived monocytes/macrophages; and (ii) cytokine levels increased relative to the expansion of bacterial cell numbers over time for cells exposed to live cultures. Bifidobacteria and S. thermophilus stimulated significant concentrations of transforming growth factor (TGF)-β, an interleukin necessary for the differentiation of regulatory T cells (T(reg) )/T helper type 17 (Th17) cells and, as such, the study further examined the induction of Th17 and T(reg) cells after PBMC exposure to selected bacteria for 96 h. Data show a significant increase in the numbers of both cell types in the exposed populations, measured by cell surface marker expression and by cytokine production. Probiotics have been shown to induce cytokines from a range of immune cells following ingestion of these organisms. These studies suggest that probiotics' interaction with immune-competent cells produces a cytokine milieu, exerting immunomodulatory effects on local effector cells, as well as potently inducing differentiation of Th17 and T(reg) cells.