gebhart/patrepeval huggingface dataset:
Differentiation induction by a tumor-necrosis-factor mutant 471 in human myelogenous leukemic cellsvia tumor-necrosis-factor receptor-p55 (1998)

The present study examined differentiation-inducing activity by various tumor-necrosis-factor(TNF) mutants against the human leukemic cell lines HL-60 and U-937. Mutant TNF 471, from which 7 N-terminal amino acids of native TNF were deleted and Pro8, Ser9 and Asp10 were replaced by Arg, Lys and Arg, possessed the highest activity among the TNF mutants, and its activity was 120-fold that of native TNF. The various biological activities of TNF were signaled through 2 distinct receptors, p55 and p75. Although cytotoxicity was reported to involve mainly p55, this differentiation-inducing activity was not well understood. The fact that the affinity of TNF 471 was higher to p55 and lower to p75 than that of native TNF by a binding competition assay suggested that the differentiation-inducing activity was also signaled through p55. To verify this hypothesis, the human myelogenous leukemic cell line, KG-1, which scarcely expresses either receptor and does not differentiate with TNF, was transduced with the p55 or p75 gene. Subsequently p55 transfectants manifested a greater ability to differentiate; however, p75 transfectants did not differ from parental cells or from mock-transfectants. Further, the differentiation of p55 transfectants induced by TNF was reduced by the inhibitor of protein-kinase-C (PKC), staurosporine. These results indicate that the differentiation-inducing activity was signaled through the TNF receptor, p55, via PKC and that the excellent ability of TNF 471 to induce differentiation was related to its high affinity for p55.
Increased Infarct Wall Thickness by a Bio-Inert Material Is Insufficient to Prevent Negative Left Ventricular Remodeling after Myocardial Infarction (2011)

The results of this study demonstrate that passive structural reinforcement alone was insufficient to prevent post-MI remodeling, suggesting that bioactivity and/or cell infiltration due to degradation of injectable materials are likely playing a key role in the preservation of cardiac function, thus providing a deeper understanding of the influencing properties of biomaterials necessary to prevent post-MI negative remodeling.
Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzymegene (2011)

Based on our SNP and haplotype results, we delineate the model that IDE promoter and 3' untranslated region/downstream variation may have different effects on IDE expression, presumably a relevant endophenotype with disorder-specific effects on AD and T2DM susceptibility.
Detection of Organic Mercaptan Vapors Using Thin Films of Alkylamine-Passivated Gold Nanocrystals (2003)

Alkylamine-capped gold nanocrystals have been used as chemically sensitive resistors for the detection of volatile organic mercaptan vapors. Thin (<1 × 10-4 cm) films of dodecylamine-capped, 6−7 nm diameter Au nanocrystals produced dc electrical resistances of 10 kΩ to 10 MΩ when deposited onto interdigitated Au/Cr electrodes. These chemiresistive vapor detectors displayed a reversible increase in dc electrical resistance when exposed to non-thiol-containing vapors such as water, acetone, or toluene delivered at a constant fraction (0.05) of their vapor pressure, with relative differential resistance responses to these vapors of ≈5% under such conditions. In contrast, the amine-capped Au nanocrystal films exhibited a much larger, irreversible decrease in resistance upon exposure to vapors possessing the thiol (−SH) functionality, including H2S, CH3SH, and propanethiol. Optical spectroscopic and transmission electron microscopy data indicated that the thiols displaced the amine caps, allowing the gold cores to move closer together and in some cases enter into contact, thereby lowering the film resistance. Consistently, the resistance of such films did not decrease upon exposure to octanethiol. For CH3SH, the rate of resistance change under repeated experimental conditions allowed extraction of the concentration of analyte over the range 4 ppb to 1.5 ppm in air.
CHOLINERGIC NEUROMODULATION BY ATP, ADENOSINE AND ITS N6‐SUBSTITUTED ANALOGUES IN GUINEA‐PIG ILEUM (1985)

The effects of ATP, adenosine and N6-substituted adenosines, adenosine receptor agonists, on the twitch contraction of guinea-pig ileum evoked by transmural stimulation were evaluated. Adenosine and ATP produced an immediate and concentration dependent inhibition of the twitch, IC50 being 1.1 X 10(-5) mol/l and 1.2 X 10(-5) mol/l, respectively. N6-l-phenylisopropyl adenosine (L-PIA), N6-cyclohexyl adenosine (CHA) and N6-allyl adenosine also induced inhibitions which were gradual and persistent, IC50 being 2.6 X 10(-8), 2.7 X 10(-8) and 5.4 X 10(-7) mol/l, respectively. Dipyridamole (10(-7) mol/l), an adenosine uptake inhibitor, markedly augmented the inhibition evoked by adenosine and ATP, but not that by three N6-substituted adenosines, while theophylline (10(-4) mol/l) almost completely antagonized the inhibitory effects of all purine compounds. IC50 value of adenosine in the presence of dipyridamole (5 X 10(-7) mol/l) was shifted to the left about 50 times from the control, whereas that of L-PIA was virtually unchanged. Tissue-medium ratios indicating uptake of [3H]adenosine, [3H]ATP and [3H]CHA into the segment were 3.23 (s.e.m. = 0.59), 3.59 (s.e.m. = 0.78) and 0.41 (s.e.m. = 0.04), respectively. These results suggest that not only adenosine and ATP but also these N6-substituted adenosines are potent agonists for the P1 receptor, implying a similarity between P1 and A1 receptor in a functional role and these purine compounds may thereby modulate cholinergic neurotransmission by altering adenylate cyclase activity.
U.S. Economic Troubles May Affect U.S.-China Economic Relations (2008)

Originally published in: “U.S. Economic Troubles May Affect U.S.-China Economic Relations,” China Currents 7.1 (Winter 2008)<br />www.chinacurrents.com. Posted with permission from the publisher.
Genetically modified proteins: functional improvement and chimeragenesis (2015)

This review focuses on the emerging role of site-specific mutagenesis and chimeragenesis for the functional improvement of proteins in areas where traditional protein engineering methods have been extensively used and practically exhausted. The novel path for the creation of the novel proteins has been created on the farther development of the new structure and sequence optimization algorithms for generating and designing the accurate structure models in result of x-ray crystallography studies of a lot of proteins and their mutant forms. Artificial genetic modifications aim to expand nature's repertoire of biomolecules. One of the most exciting potential results of mutagenesis or chimeragenesis finding could be design of effective diagnostics, bio-therapeutics and biocatalysts. A sampling of recent examples is listed below for the in vivo and in vitro genetically improvement of various binding protein and enzyme functions, with references for more in-depth study provided for the reader's benefit.
Conjugate gradient minimization of the energy functional: A new method for electronic structure calculation (1989)

A new robust iterative method for electronic structure calculations based on a convenient adaptation of the conjugate gradient minimization of the energy functional is presented. The method is compared with some other techniques using the direct minimization of the density functional and with a more traditional Davidson approach. Numerical results for silicon and carbon are used to compare the different schemes. The new method is shown to be rapidly convergent, irrespective of the system under consideration, thus providing an efficient solution to a variety of large-scale electronic structure calculations.
Sacral window for the surgery of L5 neurofibroma: a technical note. (2007)

L5-S1 neurofibroma was totally resected through a surgical window in the base of the sacrum.
Synthesis and Rietveld Refinement of the Small-Pore Zeolite SSZ-16 (1996)

Rietveld refinement of synchrotron X-ray powder diffraction data of SSZ-16 shows that this zeolite is the aluminosilicate analogue of SAPO-56 (AFX). SSZ-16 contains a three-dimensional pore system with pores bounded by eight tetrahedral atoms, and is a member of the ABC... type of zeolites with an AABBCCBB... layer sequence. There is a very good fit between the size of the organic structure-directing agents used during the zeolite synthesis and the size of the large cages of SSZ-16.
CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia (2001)

CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL. Peripheral blood samples from 218 patients with B-CLL were analyzed by flow cytometry for CD38 expression on CD5/19(+) leukemic cells. Various patient characteristics were studied including age, sex, Rai and Binet stages, splenomegaly, hepatomegaly, hemoglobin (Hgb) level, beta-2 microglobulin (beta2M) level in the serum, number of nodal sites involved with disease, and length of survival. The Kaplan-Meier method was used to construct survival curves, and the log-rank statistic was used to compare these curves. CD38 was expressed in 20% or more of leukemic cells in 43% of the patients. Patients with high CD38 expression (20% or more) had significantly shorter survival times (P =.00005). Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P =.004), lower hemoglobin level (P =.001), hepatomegaly (P =.05), and high beta2M level (P =.00005). CD38 expression identified a group of patients with aggressive disease that was considered by Rai staging to be early-stage disease (Rai stages 0-II). Patients with CD38(+) samples have significantly aggressive disease regardless of their clinical stage. Measurement of CD38 expression by flow cytometry should become a routine test in the evaluation of patients with CLL.
N‐Glycans on the receptor for advanced glycation end products influence amphoterin binding and neurite outgrowth (2002)

In this study we show that embryonic neurite growth-promoting protein amphoterin binds to carboxylated N -glycans previously identified on mammalian endothelial cells. Since amphoterin is a ligand for the receptor for advanced glycation end products (RAGE), and the ligand-binding V-domain of the receptor contains two potential N -glycosylation sites, we hypothesized that N -glycans on RAGE may mediate its interactions with amphoterin. In support of this, anti-carboxylate antibody mAbGB3.1 immunoprecipitates bovine RAGE, and PNGase F treatment reduces its molecular mass by 4.5 kDa, suggesting that the native receptor is a glycoprotein. The binding potential of amphoterin to RAGE decreases significantly in presence of soluble carboxylated glycans or when the receptor is deglycosylated. Oligosaccharide analysis shows that RAGE contains complex type anionic N -glycans with non-sialic acid carboxylate groups, but not the HNK-1 (3-sulfoglucuronyl beta1-3 galactoside) epitope. Consistent with the functional localization of RAGE and amphoterin at the leading edges of developing neurons, mAbGB3.1 stains axons and growth cones of mouse embryonic cortical neurons, and inhibits neurite outgrowth on amphoterin matrix. The carboxylated glycans themselves promote neurite outgrowth in embryonic neurons and RAGE-transfected neuroblastoma cells. This outgrowth requires full-length, signalling-competent RAGE, as cells expressing cytoplasmic domain-deleted RAGE are unresponsive. These results indicate that carboxylated N -glycans on RAGE play an important functional role in amphoterin-RAGE-mediated signalling.
Tyrosine hydroxylase-immunoreactive neurons are decreased in number in the cerebral cortex of Parkinson's disease (1999)

Tyrosine hydroxylase (TH)-immunoreactive (IR) neurons and their relationship with Lewy bodies were investigated in Parkinson's disease. Using anti-TH and/or anti-ubiquitin antibodies, we evaluated the cerebral cortices included superior frontal gyrus, precentral gyrus, postcentral gyrus, inferior temporal gyrus, cuneus, cingulate gyrus, short and long gyri of insula, and parahippocampal gyrus from 18 autopsy cases of Parkinson's disease and 16 controls. The appearance of TH-IR neurons in cerebral cortices was suggestive of non-pyramidal interneurons. The mean number of TH-IR neurons and the density of TH-IR fibers in Parkinson's disease were decreased in comparison with the controls. The cognitive impairment in Parkinson's disease has been accounted for by the lesions of the basal nucleus of Meynert, the locus ceruleus, and the cortical Lewy bodies in the cerebral cortex. In addition to these lesions, the global loss of non-pyramidal TH-IR cortical neurons and TH-IR fibers would induce the dysfunction of higher-order control of the neocortex and the limbic system in Parkinson's disease. Double-immunostaining with anti-TH and anti-ubiquitin antibodies did not show the TH-IR neuron with cortical Lewy body in the cerebral cortices of Parkinson's disease. In the cerebral cortices of Parkinson's disease, TH-IR non-pyramidal neurons in which cortical Lewy body is not formed decreased in number.
Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells (2001)

A magnetic twisting stimulator was developed based on the previously published technique of magnetic twisting cytometry. Using ligand-coated ferromagnetic microbeads, this device can apply mechanical stresses with varying amplitudes, duration, frequencies, and waveforms to specific cell surface receptors. Biochemical and biological responses of the cells to the mechanical stimulation can be assayed. Twisting integrin receptors with RGD (Arg-Gly-Asp)-containing peptide-coated beads increased endothelin-1 (ET-1) gene expression by >100%. In contrast, twisting scavenger receptors with acetylated low-density lipoprotein-coated beads or twisting HLA antigen with anti-HLA antibody-coated beads did not lead to alterations in ET-1 gene expression. In situ hybridization showed that the increase in ET-1 mRNA was localized in the cells that were stressed with the RGD-coated beads. Blocking stretch-activated ion channels with gadolinium, chelating Ca2+ with EGTA, or inhibiting tyrosine phosphorylation with genistein abolished twist-induced ET-1 mRNA elevation. Abolishing cytoskeletal tension with an inhibitor of the myosin ATPase, with an inhibitor of myosin light chain kinase, or with an actin microfilament disrupter blocked twisted-induced increases in ET-1 expression. Our results are consistent with the hypothesis that the molecular structural linkage of integrin-cytoskeleton is an important pathway for stress-induced ET-1 gene expression.
Analysis of prediction performance of training-based models using real network traffic (2009)

Traffic prediction constitutes a hot research topic of network metrology. This work focuses on the design and the empirical evaluation of the behaviour of training-based models for predicting the input rate of a single link. Via experimentation on real network traffic, we study the effect of some parameters on the prediction performance such as the amount of data needed to identify the model, the inputs of the model, the data granularity, and packet size distribution. Experiments show that the models provide accurate prediction using one lag. We also show that count of large packets is sufficient to predict the throughput.
Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi (2001)

Microsporidia are obligate intracellular parasites infesting many animal groups. Lacking mitochondria and peroxysomes, these unicellular eukaryotes were first considered a deeply branching protist lineage that diverged before the endosymbiotic event that led to mitochondria. The discovery of a gene for a mitochondrial-type chaperone combined with molecular phylogenetic data later implied that microsporidia are atypical fungi that lost mitochondria during evolution. Here we report the DNA sequences of the 11 chromosomes of the approximately 2.9-megabase (Mb) genome of Encephalitozoon cuniculi (1,997 potential protein-coding genes). Genome compaction is reflected by reduced intergenic spacers and by the shortness of most putative proteins relative to their eukaryote orthologues. The strong host dependence is illustrated by the lack of genes for some biosynthetic pathways and for the tricarboxylic acid cycle. Phylogenetic analysis lends substantial credit to the fungal affiliation of microsporidia. Because the E. cuniculi genome contains genes related to some mitochondrial functions (for example, Fe-S cluster assembly), we hypothesize that microsporidia have retained a mitochondrion-derived organelle.
The stability, toxicity and effectiveness of unmodified and phosphorothioate antisense oligodeoxynucleotides in Xenopus oocytes and embryos (1990)

The properties of antisense phosphorothioate and unmodified oligodeoxynucleotides have been studied in Xenopus oocytes and embryos. We find that phosphorothioates, like unmodified oligodeoxynucleotides, can degrade Vg1 mRNA in oocytes via an endogenous RNase H-like activity. In oocytes, phosphorothioate oligodeoxynucleotides are more stable than unmodified oligodeoxynucleotides and are more effective in degrading Vg1 mRNA. In embryos, neither unmodified nor phosphorothioate deoxyoligonucleotides were effective in degrading Vg1 message at sub-toxic doses.
Ferritin Concentrations, Metabolic Syndrome, and Type 2 Diabetes in Middle-Aged and Elderly Chinese (2008)

Elevated circulating ferritin concentrations were associated with higher risk of type 2 diabetes and metabolic syndrome in middle-aged and elderly Chinese independent of obesity, inflammation, adipokines, and other risk factors. Our data support the crucial role of iron overload for metabolic diseases, even in a country with relatively high prevalence of iron deficiency.
Involvement of the carboxyl terminus of vertebrate poly(A) polymerase in U1A autoregulation and in the coupling of splicing and polyadenylation. (1997)

Interactions required for inhibition of poly(A) polymerase (PAP) by the U1 snRNP-specific U1A protein, a reaction whose function is to autoregulate U1A protein production, are examined. PAP inhibition requires a substrate RNA to which at least two molecules of U1A protein can bind tightly, but we demonstrate that the secondary structure of the RNA is not highly constrained. A mutational analysis reveals that the carboxy-terminal 20 amino acids of PAP are essential for its inhibition by the U1A-RNA complex. Remarkably, transfer of these amino acids to yeast PAP, which is otherwise not affected by U1A protein, is sufficient to confer U1A-mediated inhibition onto the yeast enzyme. A glutathione S-transferase fusion protein containing only these 20 PAP residues can interact in vitro with an RNA-U1A protein complex containing two U1A molecules, but not with one containing a single U1A protein, explaining the requirement for two U1A-binding sites on the autoregulatory RNA element. A mutational analysis of the U1A protein demonstrates that amino acids 103-119 are required for PAP inhibition. A monomeric synthetic peptide consisting of the conserved U1A amino acids from this region has no detectable effect on PAP activity. However, the same U1A peptide, when conjugated to BSA, inhibits vertebrate PAP. In addition to this activity, the U1A peptide-BSA conjugate specifically uncouples splicing and 3'-end formation in vitro without affecting uncoupled splicing or 3'-end cleavage efficiencies. This suggests that the carboxy-terminal region of PAP with which it interacts is involved not only in U1A autoregulation but also in the coupling of splicing and 3'-end formation.
A Role for the Protease-sensitive Loop Region of Shiga-like Toxin 1 in the Retrotranslocation of Its A1 Domain from the Endoplasmic Reticulum Lumen (2005)

Shiga-like toxin I (Slt-I) is a ribosome-inactivating protein that undergoes retrograde transport to the endoplasmic reticulum to exert its cytotoxic effect on eukaryotic cells. Its catalytically active A(1) domain subsequently migrates from the endoplasmic reticulum (ER) lumen to the cytoplasm. To study this final retrotranslocation event, a suicide assay was developed based on the cytoplasmic expression and ER-targeting of the cytotoxic Slt-I A(1) fragment in Saccharomyces cerevisiae. Expression of the Slt-I A(1) domain (residues 1-251) with and without an ER-targeting sequence was lethal to the host and demonstrated that this domain can efficiently migrate from the ER compartment to the cytosol. Deletion analyses revealed that residues 1-239 represent the minimal A(1) segment displaying full enzymatic activity. This fragment, however, accumulates in the ER lumen when directed to this compartment. The addition of residues 240-251 restores the translocation property of the A(1) chain in yeast. However, single mutations within this region do not significantly alter this function in the context of the 251-residue long A(1) domain or affect the toxicity of the resulting Slt-I variants toward Vero cells in the context of the holotoxin. Since this mechanism of retrotranslocation is common to other protein toxins lacking a peptide motif similar in sequence to residues 240-251, the present results suggest that the ER export mechanism may involve the recognition of a more universal structural element, such as a misfolded or altered peptide domain localized at the C terminus of the A(1) chain (residues 240-251) rather than a unique ER export signal sequence.
Isophthalate Ester-Terminated Dendrimers:  Versatile Nanoscopic Building Blocks with Readily Modifiable Surface Functionalities (1996)

The preparation and modification of highly functionalized polyether dendrimers containing a versatile diethyl isophthalate terminal group is presented. The convergent synthesis consists of the construction of diester-terminated dendrons containing benzylic bromide functions at the focal point and their subsequent attachment to 4,4‘-biphenol cores. Dendrons up to the third generation can be prepared using recrystallization alone as the primary means of purification, allowing the synthesis to be performed on the scale of tens to hundreds of grams. The third and fourth generation bidendron dendrimers (with 32 and 64 terminal ester functionalities, respectively) have been subjected to a variety of surface modification reactions including hydrolysis, ester interchange, and amide−ester interchange, many of which proceed with complete conversion of the functional groups and in high isolated yield. The addition of alcohols such as benzyl alcohol or a first generation 3,5-di(benzyloxy)benzyl alcohol dendron to the dendrimer surface serves to increase the generation number of the dendrimers by one or two in what amounts to a “double convergent growth” approach. The analysis of these structurally precise dendrimers by matrix-assisted laser desorption ionization time of flight is described.