gebhart/patrepeval huggingface dataset:
Synthesis, molecular conformation and biological activity of 6-amino-5-azacytidine (1989)

Reaction of N-ethoxycarbonylguanidine III with 2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate ( II ) afforded N-ethoxycarbonylamidinourea IV , which was cyclized by bis(trimethylsilyl)acetamide to the 6-ethoxy derivative VII . Ammono- and methanolysis of intermediate VII yielded 6-amino and 6-methoxy derivatives of 5-azacytidine I and VIII , respectively. Reaction of amidinourea IV with a mixture of chlorotrimethylsilane and triethylamine gave the blocked nucleoside V which was also formed by dealkylation of 6-ethoxy derivative VII with chlorotrimethylsilane or oxidation of tribenzoyl-5-azacytidine IX with hydrogen peroxide in acetic acid. Methanolysis of blocked nucleoside V gave ribosylammelide ( VI ). The measurement of 1 H NMR spectra of 6-amino-5-azacytidine ( I ) revealed a marked preference of g + (80%) rotamer around C(5')-C(4') bond, a predominance of S conformation of the ribose ring ( K eq 2.12) and a preference of anti conformation around the C-N glycosyl bond. These data indicate a conformational resemblance of 6-amino-5-azacytidine ( I ) to purine nucleosides. 6-Amino-5-azacytidine ( I ) inhibits the growth of bacteria E. coli while 6-methoxy and 6-oxo derivatives VIII and VI , respectively, are bacteriostatically inactive. 6-Amino-5-azacytidine ( I ) had an ID 50 of 33.9 μM against CCRF-CEM cells and inhibited the growth of WI-L2 cells by 39% at 100 μM but did not inhibit L1210 and LoVo/L cells at ⪬ 100μM concentration.
The Acute Phase Protein Haptoglobin Is a Mammalian Extracellular Chaperone with an Action Similar to Clusterin (2005)

Haptoglobin (Hp) is an acidic glycoprotein present in most body fluids of humans and other mammals. Although the functions of Hp are not yet fully understood, the available evidence indicates that it is likely to play an important role in suppressing inflammatory responses. Some earlier work suggested that Hp might be a newly identified member of a small group of extracellular chaperones found at significant levels in human body fluids. Previously, the only well-characterized member of this group was clusterin, which shares functional similarities with the small heat-shock proteins. We report here that Hp specifically inhibited the precipitation of a variety of proteins induced by either heat or oxidation, including proteins in unfractionated human serum. We also show that, like clusterin, Hp (i) inhibits the precipitation of stressed proteins by forming solubilized high molecular weight complexes with them, (ii) cannot protect enzymes from heat-induced loss of function, and (iii) lacks ATPase activity and the ability to independently refold proteins following stresses. Furthermore, we show that Hp has maximum chaperone activity at mildly alkaline pH and, unlike clusterin, does not undergo significant changes in oligomerization state coincident with pH-induced changes in chaperone activity. Our results raise the possibility that Hp may exert an anti-inflammatory action in vivo by inhibiting the inappropriate self-association of "damaged" (misfolded) extracellular proteins.
Inhibition of Hedgehog Signaling Decreases Proliferation and Clonogenicity of Human Mesenchymal Stem Cells (2011)

Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology.
Role of dietary sulphate in the regulation of methanogenesis in the human large intestine. (1992)

Hydrogen produced during colonic fermentation may be excreted, or removed by H2 consuming bacteria such as methanogenic and sulphate reducing bacteria. In vitro, sulphate reducing bacteria compete with methanogenic bacteria for hydrogen when sulphate is present. In this study the hypothesis that sulphate in the diet could alter CH4 production in vivo has been tested. Six methane excreting volunteers were fed a low sulphate diet (1.6 mmol/d) for 34 days with the addition of 15 mmol sodium sulphate from days 11-20. Breath methane was measured and viable counts and metabolic activities of methanogenic bacteria and sulphate reducing bacteria determined in faeces. Whole gut transit time and daily stool weight were also measured. When sulphate was added to the diet, breath methane excretion decreased in three of the subjects while faecal sulphate reduction rates rose from 7.5 (0.5) to 20.3 (4.3) nmol SO4 reduced/h/g faeces. Sulphate reducing bacteria, which were not detected during the control diet, were found and viable counts of methanogenic bacteria fell from 10(7)-10(9)/g faeces to 10(6)/g. Methanogenic counts and breath CH4 recovered after sulphate addition was stopped. No change was found in the other three subjects. Faecal weights and transit times were not different between study periods. It is concluded that methanogenesis is regulated by dietary sulphate if sulphate reducing bacteria are present. Dietary sulphate may allow growth of sulphate reducing bacteria which inhibit the growth of methanogenic bacteria. This may explain the absence of CH4 in the breath of many people in western populations.
A role for the Drosophila Bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells (1995)

Cell differentiation commonly dictates a change in the cell cycle of mitotic daughters. Previous investigations have suggested that the Drosophila bag of marbles (bam) gene is required for the differentiation of germline stem cell daughters (cystoblasts) from the mother stem cells, perhaps by altering the cell cycle. In this paper, we report the preparation of antibodies to the Bam protein and the use of those reagents to investigate how Bam is required for germ cell development. We find that Bam exists as both a fusome component and as cytoplasmic protein and that cytoplasmic and fusome Bam might have separable activities. We also show that bam mutant germ cells are blocked in differentiation and are trapped as mitotically active cells like stem cells. A model for how Bam might regulate cystocyte differentiation is presented.
Cost management system: an operational overview (1998)

Defines cost management as “a set of techniques and methods for controlling and improving a company’s activities and processes, its products and services” to achieve continuous improvement and deal with global competition; with commitment from top management and worker involvement. Offers a model of a “self‐perpetuating system of improvement” to continuously improve value added and decrease non‐value added activities, using activity‐based costing to develop the information needed for activity‐based management, just‐in‐time, total quality management and process improvement. Explains these techniques, referring to research, and discusses the necessary conditions for top management commitment and worker involvement. A useful summary of the interaction of many modern management accounting tools
Production of single-stranded DNA in mammalian cells by means of a bacterial retron. (1994)

msDNA-Ec67, a peculiar multicopy single-stranded DNA of a specific sequence was produced in NIH3T3 mouse cells. Retron-Ec67, a retroelement from Escherichia coli, was introduced under the T7 polymerase promoter and the non-translated 5'-region of the encephalomyocarditis virus. The construct was then transfected into the NIH3T3 cells constitutively producing T7 RNA polymerase. Forty-eight hours after transfection, msDNA-Ec67 was detected in the cells by means of Southern blot hybridization and reverse transcriptase extension assay. The potential use of bacterial retrons as a vector for single-stranded DNA production in mammalian cells is discussed.
Voiding Dysfunction Following Cystourethropexy: Its Evaluation and Management (1990)

We report on 15 women who underwent cystourethropexy for anatomical stress incontinence and who subsequently had dysfunctional voiding symptoms. All 15 women underwent retropubic takedown of the prior repair and substitution with an obturator shelf repair. All 13 women who had symptoms of bladder instability experienced resolution of these symptoms. Of 7 patients who were in urinary retention and required clean intermittent catheterization only 1 continued to require clean intermittent catheterization to facilitate bladder emptying after obturator shelf substitution. In this series a successful outcome was achieved in 14 of 15 patients (93%).
Position based skinning of skeleton-driven deformable characters (2014)

This paper presents a real-time skinning technique for character animation based on a two-layered deformation model. For each frame, the skin of a generic character is first deformed by using a classic linear blend skinning approach, then the vertex positions are adjusted according to a Position Based Dynamics schema. We define geometric constraints which mimic the flesh behavior and produce interesting effects like volume conservation and secondary animations, in particular passive jiggling behavior, without relying on a predefined training set of poses. Once the whole model is defined, the character animation is synthesized in real-time without suffering of the inherent artefacts of classic interactive skinning techniques, such as the "candy-wrapper" effect or undesired skin bulging.
Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus. (1995)

The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesity, diabetes, and increased susceptibility to tumors. To try to define important functional domains of the agouti protein, we have analyzed the molecular defects present in a series of recessive viable agouti mutations. In total, six alleles (amJ, au, ada, a16H, a18H, ae) were examined at both the RNA and DNA level. Two of the alleles, a16H and ae, result from mutations in the agouti coding region. Four alleles (amJ, au, a18H, and ada) appear to represent regulatory mutations that down-regulate agouti expression. Interestingly, one of these mutations, a18H, also appears to cause an immunological defect in the homozygous condition. This immunological defect is somewhat analogous to that observed in motheaten (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous a18H DNA are consistent with the hypothesis that a18H results from a paracentric inversion where one end of the inversion maps in the 5' regulatory region of agouti and the other end in or near a gene that is required for normal immunological function. Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder.
Functional expression of the human transferrin receptor cDNA in Chinese hamster ovary cells deficient in endogenous transferrin receptor. (1987)

Transferrin (Tf) receptor-variant Chinese hamster ovary cells have been isolated by selection for resistance to two Tf-toxin conjugates. The hybrid toxins contain Tf covalently linked to ricin A chain or a genetically engineered diphtheria toxin fragment. The Tf-receptor-variant (TRV) cells do not have detectable cell-surface Tf receptor; they do not bind fluorescein-Tf or 125I-Tf. TRV cells are at least 100-fold more resistant to the Tf-diphtheria toxin conjugate than are the parent cells. The TRV cells have retained sensitivity to native diphtheria toxin, indicating that the increased resistance to the conjugate is correlated with the loss of Tf binding. The endocytosis of fluorescein-labeled alpha 2-macroglobulin is normal in TRV cells, demonstrating that the defect does not pleiotropically affect endocytosis. Since these cells lack endogenous Tf receptor activity, they are ideally suited for studies of the functional expression of normal or altered Tf receptors introduced into the cells by cDNA transfection. One advantage of this system is that Tf binding and uptake can be used to monitor the behavior of the transfected receptor. A cDNA clone of the human Tf receptor has been transfected into TRV cells. In the stably expressing transfectants, the behavior of the human receptor is very similar to that of the endogenous Chinese hamster ovary cell Tf receptor. Tf binds to cell surface receptors, and is internalized into the para-Golgi region of the cell. Iron is released from Tf, and the apo-Tf and its receptor are recycled back to the cell surface. Thus, the TRV cells can be used to study the behavior of genetically altered Tf receptors in the absence of interfering effects from endogenous receptors.
Classification with Quantum Neural Networks on Near Term Processors (2020)

We introduce a quantum neural network, QNN, that can represent labeled data, classical or quantum, and be trained by supervised learning. The quantum circuit consists of a sequence of parameter dependent unitary transformations which acts on an input quantum state. For binary classification a single Pauli operator is measured on a designated readout qubit. The measured output is the quantum neural network’s predictor of the binary label of the input state. We show through classical simulation that parameters can be found that allow the QNN to learn to correctly distinguish the two data sets. We then discuss presenting the data as quantum superpositions of computational basis states corresponding to different label values. Here we show through simulation that learning is possible. We consider using our QNN to learn the label of a general quantum state. By example we show that this can be done. Our work is exploratory and relies on the classical simulation of small quantum systems. The QNN proposed here was designed with near-term quantum processors in mind. Therefore it will be possible to run this QNN on a near term gate model quantum computer where its power can be explored beyond what can be explored with simulation.
The Structure of a Human Type III Fcγ Receptor in Complex with Fc (2001)

Fcgamma receptors mediate antibody-dependent inflammatory responses and cytotoxicity as well as certain autoimmune dysfunctions. Here we report the crystal structure of a human Fc receptor (FcgammaRIIIB) in complex with an Fc fragment of human IgG1 determined from orthorhombic and hexagonal crystal forms at 3.0- and 3.5-A resolution, respectively. The refined structures from the two crystal forms are nearly identical with no significant discrepancies between the coordinates. Regions of the C-terminal domain of FcgammaRIII, including the BC, C'E, FG loops, and the C' beta-strand, bind asymmetrically to the lower hinge region, residues Leu(234)-Pro(238), of both Fc chains creating a 1:1 receptor-ligand stoichiometry. Minor conformational changes are observed in both the receptor and Fc upon complex formation. Hydrophobic residues, hydrogen bonds, and salt bridges are distributed throughout the receptor.Fc interface. Sequence comparisons of the receptor-ligand interface residues suggest a conserved binding mode common to all members of immunoglobulin-like Fc receptors. Structural comparison between FcgammaRIII.Fc and FcepsilonRI.Fc complexes highlights the differences in ligand recognition between the high and low affinity receptors. Although not in direct contact with the receptor, the carbohydrate attached to the conserved glycosylation residue Asn(297) on Fc may stabilize the conformation of the receptor-binding epitope on Fc. An antibody-FcgammaRIII model suggests two possible ligand-induced receptor aggregations.
Muromonab-Cd3 and Antithymocyte Globulin in Renal Transplantation (1997)

While important benefits are realized from using antibody therapies in renal transplantation, their use is often associated with excess immunosuppression and increased treatment costs. Despite encouraging results from published trials, questions regarding the extent of their prophylactic use and impact on long-term outcomes need to be answered. The current literature contains no prospective, controlled, randomized comparisons of OKT-3 and ATG with standardized regimens of conventional immunosuppressive agents and antirejection protocols. The majority of studies use OKT-3 as part of the treatment protocol. Well-designed studies using ATG are lacking. Further research is needed to refine treatment protocols for ATG and OKT-3 to determine the optimal timing and dosing for these agents.
The Use and Limitations of a Chemiluminescent Thyrotropin Assay as a Single Thyroid Function Test in an Out-Patient Endocrine Clinic* (1990)

A chemiluminescent TSH assay (detection limit, less than 0.01 mU/L) allows for accurate measurement of subnormal TSH concentrations. We retrospectively analyzed serum TSH and the free T4 (fT4) index of 460 consecutive endocrine clinic visits to determine the usefulness of TSH measurements alone in the assessment of thyroid function. Additionally, case histories were presented nonconsecutively to one of us (TSH alone or TSH with fT4) to determine if knowledge of the fT4 level would alter management. Of hypothyroid patients on replacement therapy (n = 127), 60% had concordant fT4 and TSH, 14% had subnormal TSH with normal fT4, 18% had high TSH with normal fT4, and 4% normal TSH with high fT4; only 4% were managed differently when the fT4 level was known in addition to TSH. Of the patients receiving suppressive therapy with TSH levels above 0.05 mU/L (n = 81), only 4% were managed differently when fT4 was known; 4% had high fT4. With TSH levels below 0.05 mU/L (n = 64), knowledge of fT4 was felt to be necessary for management in all cases; 53% had high fT4. Twenty-three of 46 (50%) patients being treated for hyperthyroidism had discordant TSH and fT4, including 7 patients with low TSH and low fT4. Two of 21 (10%) patients screened with pituitary/hypothalamic disease had discordant TSH and fT4, and 4 of 9 (44%) patients treated with L-T4 for secondary hypothyroidism had subnormal TSH. Knowledge of fT4 was felt to be necessary in all these cases. We conclude that TSH alone is sufficient for screening and monitoring L-T4 replacement or suppression therapy if TSH levels are above 0.05 mU/L. These patients account for the majority of visits to our endocrine clinic. TSH alone is misleading in pituitary disease and during the treatment of hyperthyroidism. fT4 is needed if TSH levels are less than 0.05 mU/L to assess the degree of hyperthyroidism.
A gridless multilayer router for standard cell circuits using CTM cells (1999)

We present a gridless multilayer router suitable for standard cell circuits using central terminal model (CTM) cells. A CTM cell has pins in the middle which split the over-the-cell (OTC) routing region into top and bottom parts. Nets are routed in both the channel (if needed) and OTC by using a channel router. Our router uses a combined constraint graph and tile expansion algorithm. We report the first maze router to take advantage of a graph based algorithm to solve the net ordering problem. Unlike a laggard pure maze router, it has the time efficiency of a fast graph based algorithm and the better results of a maze routing algorithm. This is also the first report of the use of a tile expansion maze router for the variable height routing problem. By variable height routing we mean that a single execution of the routing algorithm will result in a completely routed solution. The only thing that is not determined a priori is the height or number of tracks needed. Our router achieves channelless solutions for the Primary1 circuit by routing over the cell in three layers. It also generates equal or better results compared to the best of the previous channel routers for all the examples we have tried. In fact, Sockeye is the first router to achieve density solutions for the r1, r3, and r4 examples for two layers and for the r3 example for three layers.
The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor (1997)

Vertebrate limb formation has been known to be initiated by a factor(s) secreted from the lateral plate mesoderm. In this report, we provide evidence that a member of the fibroblast growth factor (FGF) family, FGF10, emanates from the prospective limb mesoderm to serve as an endogenous initiator for limb bud formation. Fgf10 expression in the prospective limb mesenchyme precedes Fgf8 expression in the nascent apical ectoderm. Ectopic application of FGF10 to the chick embryonic flank can induce Fgf8 expression in the adjacent ectoderm, resulting in the formation of an additional complete limb. Expression of Fgf10 persists in the mesenchyme of the established limb bud and appears to interact with Fgf8 in the apical ectoderm and Sonic hedgehog in the zone of polarizing activity. These results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs.
Generation of a co-crystal phase with novel coloristic properties via solid state grinding procedures (2002)

Co-grinding of crystals of racemic-bis-beta-naphthol (rac-BN) and benzoquinone (BQ) produces a novel crystal adduct through crystal sheering and molecular diffusion processes in the solid state, which is structurally distinct from adducts obtained from solution or melt.
PCR amplification from single DNA molecules on magnetic beads in emulsion: application for high-throughput screening of transcription factor targets (2005)

We have developed a novel method of genetic library construction on magnetic microbeads based on solid-phase single-molecule PCR in a fine and robust water-phase compartment formed in water-in-oil (w/o) emulsions. In this method, critically diluted DNA fragments were distributed over the emulsion as templates, where beads crosslinked with multiple primers and other PCR components were encapsulated to form multiple reaction compartments. The delivered DNA was then amplified and covalently immobilized on the beads in parallel, within individual compartments, to construct a genetic library on beads (GLOBE), which was readily applicable to a genomewide global scanning of genetic elements recognized by a defined DNA-binding protein. We constructed a GLOBE of Paracoccus denitrificans and selected gene beads that were bound to the His-tagged transcription factor PhaR by flow cytometry. As a result of flow cytometry screening with an anti-His fluorescent antibody, the PhaR target fragments were enriched 1200-fold from this library with this system. Therefore, this system is a powerful tool for analyzing the transcription network on a genomewide scale.