gebhart/patrepeval huggingface dataset:
Unusual β-D-Xylosides That Prime Glycosaminoglycans in Animal Cells (1996)

The biosynthesis of glycosaminoglycans (GAG) takes place while the polysaccharide chains are usually attached to a proteoglycan core protein. Cells also will assemble GAG chains on beta-D-xylosides containing hydrophobic aglycones. In order to evaluate the relationship of the structure of the sugar to priming activity of the glycoside, we synthesized beta-D-xyloside analogs in which the hydroxyls were substituted with hydrogen, fluorine, -O-methyl, amino, -O-isopropyl, and -O-benzyl groups. Epimers at the 2-, 3-, and 4-position of xylose also were made. Their ability to prime GAGs was tested in Chinese hamster ovary cells by measuring 35SO4 incorporation into polysaccharide chains and by assaying the transfer of galactose to the xylosides by galactosyltransferase I (UDP-D-galactose:xylose beta1-4-galactosyltransferase) in vitro. All of the analogs failed to act as primers of GAGs in vivo and as substrates in vitro with the following exceptions. Substitution of 2-OH and 3-OH with -OCH3 were active at high concentration (1 mM), but the deoxygenated derivatives were inactive. Efficient priming also occurred on a derivative with fluorine instead of the 3-OH group, suggesting that the oxygen atoms at C-2 and C-3 were involved as hydrogen bond acceptors. Methylated and deoxy analogs at C-4 were inactive, due to the loss of the acceptor hydroxyl group. Interestingly, benzyl-beta-D-threo-pentopyranos-4-uloside (4-keto derivative) and benzyl-4-methyl-beta-D-xyloside, with a methyl group in place of an axial hydrogen at C-4, primed GAG chains. Priming by these unusual xylosides suggests the possibility of designing inhibitors of GAG synthesis based on xyloside analogs with reactive groups in key positions.
Enzyme-linked immunosorbent assay (ELISA) for direct quantification of surface-bound platelet immunoglobulins (1983)

Surface-bound platelet IgG and IgM were measured by an enzyme-linked immunosorbent assay (ELISA) using washed platelets and commercially available alkaline phosphatase anti-human immunoglobulins (Fc-specific). With this technique platelets from normal donors had small amounts of platelet-bound IgG ranging from 0.00 to 0.16 A405 (absorbance at 405 nm wavelength) (10(7) platelets)-1 (0 to 124 ng) and of platelet-bound IgM ranging from 0.00 to 0.05 A405 (10(7) platelets)-1. Eight out of 10 (80%) thrombocytopenic patients with idiopathic autoimmune thrombocytopenic purpura (IATP) had values of both IgG and IgM exceeding the normal range. In addition, one patient (8%) had platelet-bound IgM only. An inverse relationship was demonstrated in patients with IATP between the blood platelet count and the amount of both IgG and IgM. Increased values were also demonstrated in patients with SLE and patients with monoclonal hypergammaglobulinaemia. The direct ELISA is a useful and reproducible technique for platelet-bound IgG and IgM, which requires standard laboratory equipment only.
Interaction of proteins with sorghum tannin: Mechanism, specificity and significance (1984)

Abstract The grain of some varieties of sorghum contains 2% or more condensed tannin; many other varieties contain no tannin at all. Agronomic advantages, e.g., resistance to bird depredation, are associated with high‐tannin sorghums, which have relatively low nutritional value for nonruminants. The biological effects of tannin are a result of its propensity for binding proteins; both hydrogen bonding and hydrophobic interactions are involved. Sorghum tannins can bind dietary proteins and reduce their digestibility. Purified digestive enzymes are inhibited by tannin, but significant inhibition in vivo is unlikely. Proteins differ greatly in their affinity for tannin. Those with highest affinity are large, have an open structure, contain no bound carbohydrate and are rich in proline. Sorghum proteins of the alcohol‐soluble prolamine fraction associate strongly with tannin, are difficult to remove during tannin purification and are found combined with tannin in the indigestible residue after in vitro digestion with pepsin. On germination, the seed may sacrifice a portion of these proteins to bind the tannin that might otherwise interfere with metabolism by inhibiting seed enzymes. During seed development, tannin molecules are relatively short and do not effectively precipitate proteins; as the seed dries, tannins undergo polymerization to an average of ca. 6 flavan‐3‐ol units/molecule. The antinutritional effects of sorghum tannins can be eliminated by soaking the grain in dilute aqueous alkali, but not by cooking. When rats are put on high‐tannin sorghum diets, their parotid glands undergo hypertrophy and produce a group of unique salivary proteins with extremely high affinity for tannin. These proteins contain over 40% proline and are devoid of sulfur‐containing and aromatic amino acids. This metabolic adaption may protect rats against tannin by binding and inactivating it immediately when it enters the digestive tract.
Conformational Flexibility, Internal Hydrogen Bonding, and Passive Membrane Permeability:  Successful in Silico Prediction of the Relative Permeabilities of Cyclic Peptides (2006)

We report an atomistic physical model for the passive membrane permeability of cyclic peptides. The computational modeling was performed in advance of the experiments and did not involve the use of "training data". The model explicitly treats the conformational flexibility of the peptides by extensive conformational sampling in low (membrane) and high (water) dielectric environments. The passive membrane permeabilities of 11 cyclic peptides were obtained experimentally using a parallel artificial membrane permeability assay (PAMPA) and showed a linear correlation with the computational results with R(2) = 0.96. In general, the results support the hypothesis, already well established in the literature, that the ability to form internal hydrogen bonds is critical for passive membrane permeability and can be the distinguishing factor among closely related compounds, such as those studied here. However, we have found that the number of internal hydrogen bonds that can form in the membrane and the solvent-exposed polar surface area correlate more poorly with PAMPA permeability than our model, which quantitatively estimates the solvation free energy losses upon moving from high-dielectric water to the low-dielectric interior of a membrane.
Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease (2001)

Autoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD(+) and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading > 3 s.d. higher than the mean value of control I, 10.4% of patients with thyroiditis and 7.7% of Graves' patients were anti-CD38 positive (P = 0.0009 versus 1.8% of control I). Similarly, 13.1% of patients with thyroiditis and 10.5% of Graves' patients had a standardized optical reading > 3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0.002 versus 1.2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0.03) and they were more frequent in Graves' patients with ophthalmopathy (P < 0.05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated.
Optical Network Synthesis Using Birefringent Crystals V Synthesis of Lossless Networks Containing Equal-Length Crystals and Compensators* (1966)

Part I of this series reported a procedure for synthesizing birefringent networks having a prescribed amplitude transmittance. The desired transmittance C(ω) was written as C(ω) = C0 + C1e−iαω + C2e−i2aω + ⋯ + Cne−inaω, where the Ci could be arbitrarily chosen as long as each was real. The synthesis procedure of this paper is a generalization of the procedure of Part I and allows for the realization of C(ω) having complex Ci. The resulting network consists of n stages between an input and output polarizer, with each stage containing a birefringent crystal and (achromatic) optical compensator. The form of this network is essentially the same as the practical form of the network obtained from Part I, and hence the additional versatility is obtained at no extra cost in network complexity.
The Pharmacokinetics and Pharmacodynamics of Iron Preparations (2011)

Standard approaches are not appropriate when assessing pharmacokinetics of iron supplements due to the ubiquity of endogenous iron, its compartmentalized sites of action, and the complexity of the iron metabolism. The primary site of action of iron is the erythrocyte, and, in contrast to conventional drugs, no drug-receptor interaction takes place. Notably, the process of erythropoiesis, i.e., formation of new erythrocytes, takes 3-4 weeks. Accordingly, serum iron concentration and area under the curve (AUC) are clinically irrelevant for assessing iron utilization. Iron can be administered intravenously in the form of polynuclear iron(III)-hydroxide complexes with carbohydrate ligands or orally as iron(II) (ferrous) salts or iron(III) (ferric) complexes. Several approaches have been employed to study the pharmacodynamics of iron after oral administration. Quantification of iron uptake from radiolabeled preparations by the whole body or the erythrocytes is optimal, but alternatively total iron transfer can be calculated based on known elimination rates and the intrinsic reactivity of individual preparations. Degradation kinetics, and thus the safety, of parenteral iron preparations are directly related to the molecular weight and the stability of the complex. High oral iron doses or rapid release of iron from intravenous iron preparations can saturate the iron transport system, resulting in oxidative stress with adverse clinical and subclinical consequences. Appropriate pharmacokinetics and pharmacodynamics analyses will greatly assist our understanding of the likely contribution of novel preparations to the management of anemia.
Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts (2015)

High affinity antisense oligonucleotides (ASOs) containing bicylic modifications (BNA) such as locked nucleic acid (LNA) designed to induce target RNA cleavage have been shown to have enhanced potency along with a higher propensity to cause hepatotoxicity. In order to understand the mechanism of this hepatotoxicity, transcriptional profiles were collected from the livers of mice treated with a panel of highly efficacious hepatotoxic or non-hepatotoxic LNA ASOs. We observed highly selective transcript knockdown in mice treated with non-hepatotoxic LNA ASOs, while the levels of many unintended transcripts were reduced in mice treated with hepatotoxic LNA ASOs. This transcriptional signature was concurrent with on-target RNA reduction and preceded transaminitis. Remarkably, the mRNA transcripts commonly reduced by toxic LNA ASOs were generally not strongly associated with any particular biological process, cellular component or functional group. However, they tended to have much longer pre-mRNA transcripts. We also demonstrate that the off-target RNA knockdown and hepatotoxicity is attenuated by RNase H1 knockdown, and that this effect can be generalized to high affinity modifications beyond LNA. This suggests that for a certain set of ASOs containing high affinity modifications such as LNA, hepatotoxicity can occur as a result of unintended off-target RNase H1 dependent RNA degradation.
Processing and Secretion of Envelope Glycoproteins of Human Immunodeficiency Virus Type 1 in the Presence of Trimming Glucosidase Inhibitor Deoxynojirimycin (1989)

The processing and secretion of the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) were studied in chronically infected cells treated with the trimming glucosidase inhibitor deoxynojirimycin (DNM). In Molt3 cells infected with human T-lymphotropic virus type III (HTLV-IIIB), DNM inhibited the intracellular proteolytic processing of gp160 to gp120 and gp41. A clone of the HUT78 cell line called 6D5, when chronically infected with the HIV-1 isolate HTLV-III451 was shown to release both gp160 and gp120 into the culture medium. The secretion of envelope glycoproteins from these infected cells was not inhibited by DNM treatment. The secreted proteins had higher molecular weights than gp160 and gp120 from cultures not treated with DNM, presumably due to the presence of unprocessed carbohydrate residues on the polypeptide chain. These secreted glycoproteins from DNM-treated cells exhibited specific interaction with the CD4 molecule on the surface of target cells. However, the syncytium formation induced by HIV-1-infected cells on CD4+ cells was significantly inhibited in the presence of the glucosidase inhibitor. The minimal cytotoxicity of the DNM coupled with its strong inhibitory effect on the cell-to-cell spread of the virus suggest that it may be potentially useful in antiviral drug therapy of HIV-1 infection.
Anforderungsprofil einer innovativen Behörde (1997)

Bei der Analyse und Diagnose des Verwaltungs- bzw. Behördenkörpers wurden bereits punktuell Therapieansätze erkennbar. Dies war im Sinne einer Verdeutlichung der strukturellen Schwächen unvermeidlich. Eine ganzheitliche Diagnose aber erfordert eine ebenso ganzheitlich angelegte Therapie, da alle Körperfunktionen — hier die des Behördenkörpers — in engem Verbund stehen (vgl. Abbildung 16).
Synthesis of Substituted Quinoline-4-carboxylic Acids (1993)

A high yielding synthesis of a variety of quinoline-4-carboxylic acids has been accomplished using a modified Pfitzinger approach involving the condensation of a ketone with an isatin derivative employing aqueous acid conditions. A convenient synthesis of the substituted isatin precursor is also described.
TRANSCRIPTION FACTORS: Structural Families and Principles of DNA Recognition (1992)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Biobased Polyols Using Thiol-Ene Chemistry for Rigid Polyurethane Foams with Enhanced Flame-Retardant Properties (2017)

Biobased polyol was synthesized using 1-thioglycerol and limonene, an extract of orange peel, via thiol-ene chemistry as an alternative to petrochemical-based polyol for preparation of rigid polyurethane foams (RPFs). Fire-re... | Find, read and cite all the research you need on Tech Science Press
Studies on the capacity of B cells to serve as antigen-presenting cells. (1981)

Abstract In this paper we have tested the hypothesis that B cells, via their Ig receptors, can take up, process, and present antigen to T cells in an analogous manner to macrophages. Rabbit IgG (NRGG) was used to immunize mice for an antigen-specific proliferative response. Rabbit anti-mouse Ig (RAMIG), a test antigen that could bind to all B cells via their membrane Ig, and NRGG, an antigen that would bind to only a very few antigen-specific B cells, were compared for their capacity to stimulate a T cell proliferative response when macrophages or B cells, in the form of macrophage-depleted spleen cells (MDSC), were used as the source of antigen-presenting cells. When macrophages were used as antigen-presenting cells, NRGG and RAMIG were indistinguishable in their capacity to stimulate a proliferative response in NRGG-primed T cells. In contrast, when MDSC were used as a source of antigen-presenting B cells, only RAMIG, and not NRGG, stimulated T cell proliferation. That the T cells, also present in the MDSC, were not involved in the antigen presentation was demonstrated by the fact that treatment of MDSC with anti-Thy 1 and complement did not decrease the capacity of RAMIG-pulsed MDSC to stimulate a proliferative response. A variety of experiments were carried out in an attempt to rule out the possibility that contaminating macrophages might have been responsible for these results. The fact that NRGG-pulsed MDSC did not induce proliferation indicated that insufficient macrophages were present in the MDSC to account for the proliferative response by a mechanism involving the direct uptake of antigen by such contaminating cells. The inability of MDSC to present another antigen, ovalbumin, in a similar T cell proliferative response strengthens that conclusion. The possibility that the immune complexes formed between RAMIG and B cell Ig created a “super antigen” that could be taken up very efficiently by a small number of contaminating macrophages was also investigated. The evidence against this possibility was: 1) Heat-aggregated NRGG did not stimulate a proliferative response when MDSC were used as presenting cells. 2) If after being pulsed with RAMIG the MDSC were inactivated by freeze-thawing or ultraviolet irradiation, no proliferative response was induced. Furthermore, the presentation of RAMIG by MDSC was shown to be genetically restricted in that T cells incorporated 10- to 30-fold more 3H-thymidine when presented antigen by syngeneic compared with allogeneic RAMIG-pulsed MDSC. We concluded from these experiments that under the experimental conditions employed, B cells were capable of directly presenting antigen to T ceils in a genetically restricted fashion. If correct, this could represent a mechanism by which antigen-specific T-B interaction takes place.
Gene therapy for phenylketonuria: phenotypic correction in a genetically deficient mouse model by adenovirus-mediated hepatic gene transfer. (1994)

Classical phenylketonuria (PKU), which predisposes affected individuals to severe mental retardation, is caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). A recombinant adenoviral vector containing the human PAH cDNA was constructed and administered to PAH-deficient mice (strain PAHenu2). The hyperphenylalaninemic phenotype of these animals was completely normalized within 1 week of treatment. Although this therapeutic effect did not persist, analysis of the relationship between hepatic PAH activity and serum phenylalanine levels indicated that only 10-20% of normal enzymatic activity in the mouse liver is sufficient to restore normal serum phenylalanine levels. These results demonstrate that PKU and other metabolic disorders secondary to hepatic deficiencies can be completely corrected by gene therapy when more persistent vector systems are developed.
A Synthesis of 9-Methoxy-1-Methyl-1H,6H-Pyrazolo[4,3-c]Carbazole (1996)

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Physiological Monitoring for Critically Ill Patients: Testing a Predictive Model for the Early Detection of Sepsis (2007)

The results support the use of some of the guidelines of the Surviving Sepsis Campaign. However, the lowest mean temperature was significantly less for patients without sepsis than for patients with sepsis, a finding that calls into question the clinical usefulness of using hypothermia as an early predictor of sepsis. Alone the group of variables used is not sufficient for discriminating between critically ill patients with and without sepsis.
The Lysine Decarboxylase CadA Protects Escherichia coli Starved of Phosphate against Fermentation Acids (2007)

Conflicting results have been reported for the rate and extent of cell death during a prolonged stationary phase. It is shown here that the viability of wild-type cells (MG1655) could decrease >or=10(8)-fold between days 1 and 14 and between days 1 and 6 of incubation under aerobic and anaerobic phosphate (P(i)) starvation conditions, respectively, whereas the cell viability decreased moderately under ammonium and glucose starvation conditions. Several lines of evidence indicated that the loss of viability of P(i)-starved cells resulted primarily from the catabolism of glucose into organic acids through pyruvate oxidase (PoxB) and pyruvate-formate lyase (PflB) under aerobic and anaerobic conditions, respectively. Weak organic acids that are excreted into the medium can reenter the cell and dissociate into protons and anions, thereby triggering cell death. However, P(i)-starved cells were efficiently protected by the activity of the inducible GadABC glutamate-dependent acid resistance system. Glutamate decarboxylation consumes one proton, which contributes to the internal pH homeostasis, and removes one intracellular negative charge, which might compensate for the accumulated weak acid anions. Unexpectedly, the tolerance of P(i)-starved cells to fermentation acids was markedly increased as a result of the activity of the inducible CadBA lysine-dependent acid resistance system that consumes one proton and produces the diamine cadaverine. CadA plays a key role in the defense of Salmonella at pH 3 but was thought to be ineffective in Escherichia coli since the protection of E. coli challenged at pH 2.5 by lysine is much weaker than the protection by glutamate. CadA activity was favored in P(i)-starved cells probably because weak organic acids slowly reenter cells fermenting glucose. Since the environmental conditions that trigger the death of P(i)-starved cells are strikingly similar to the conditions that are thought to prevail in the human colon (i.e., a combination of low levels of P(i) and oxygen and high levels of carbohydrates, inducing the microbiota to excrete high levels of organic acids), it is tempting to speculate that E. coli can survive in the gut because of the activity of the GadABC and CadBA glutamate- and lysine-dependent acid resistance systems.
Human monoclonal antibodies to a genus-specific chlamydial antigen, produced by EBV-transformed B cells. (1983)

Stable B cell lines producing human monoclonal antibodies to Chlamydia were established from salpingitis patients in the early convalescence phase. The antibody-producing cells were immortalized by Epstein Barr virus (EBV) transformation. Specific antibody-secreting clones were enriched by a stepwise microtiter plate cloning procedure. The selected B cell clones showed stable antibody production for more than 1 yr in continuous culture. Serologic specificity was demonstrated by micro-immunofluorescence (micro-IF) tests against a panel of Chlamydia reference strains. The antibodies were of the IgG1 subclass, and complement fixation could be demonstrated for one clone. There was no cross-reactivity against a large number of other bacteria. The monoclonal antibodies are directed against a common genus-specific surface antigen of the Chlamydia organism. Infected McCoy cells showed a brilliant, punctuated fluorescence surrounded by an inclusion membrane. Compared with conventional antisera, the monoclonal antibodies showed a clearer fluorescence pattern with very low background.