gebhart/patrepeval huggingface dataset:
Hydrogen Elimination from a Hydroxycyclopentadienyl Ruthenium(II) Hydride:  Study of Hydrogen Activation in a Ligand−Metal Bifunctional Hydrogenation Catalyst (2005)

At high temperatures in toluene, [2,5-Ph(2)-3,4-Tol(2)(eta(5)-C(4)COH)]Ru(CO)(2)H (3) undergoes hydrogen elimination in the presence of PPh(3) to produce the ruthenium phosphine complex [2,5-Ph(2)-3,4-Tol(2)-(eta(4)-C(4)CO)]Ru(PPh(3))(CO)(2) (6). In the absence of alcohols, the lack of RuH/OD exchange, a rate law first order in Ru and zero order in phosphine, and kinetic deuterium isotope effects all point to a mechanism involving irreversible formation of a transient dihydrogen ruthenium complex B, loss of H(2) to give unsaturated ruthenium complex A, and trapping by PPh(3) to give 6. DFT calculations showed that a mechanism involving direct transfer of a hydrogen from the CpOH group to form B had too high a barrier to be considered. DFT calculations also indicated that an alcohol or the CpOH group of 3 could provide a low energy pathway for formation of B. PGSE NMR measurements established that 3 is a hydrogen-bonded dimer in toluene, and the first-order kinetics indicate that two molecules of 3 are also involved in the transition state for hydrogen transfer to form B, which is the rate-limiting step. In the presence of ethanol, hydrogen loss from 3 is accelerated and RuD/OH exchange occurs 250 times faster than in its absence. Calculations indicate that the transition state for dihydrogen complex formation involves an ethanol bridge between the acidic CpOH and hydridic RuH of 3; the alcohol facilitates proton transfer and accelerates the reversible formation of dihydrogen complex B. In the presence of EtOH, the rate-limiting step shifts to the loss of hydrogen from B.
A recombinant bispecific single‐chain Fv antibody against HLA class II and FcγRIII (CD16) triggers effective lysis of lymphoma cells (2004)

Bispecific antibodies offer the possibility of improving effector-cell recruitment for antibody therapy. For this purpose, a recombinant bispecific single-chain Fv antibody (bsscFv), directed against FcgammaRIII (CD16) and human leucocyte antigen (HLA) class II, was constructed and tested in functional assays. RNA from the hybridomas 3G8 and F3.3, reacting with CD16 and HLA class II, respectively, was used to generate phage display libraries. From these libraries, reactive phages were isolated and the bsscFv was constructed by connecting both single-chain Fv components through a 20 amino acid flexible linker. After expression in SF21 insect cells and chromatographic purification, the bsscFv bound specifically and simultaneously to both antigens. The affinities of the anti-CD16 and the anti-HLA class II scFv components of the bsscFv were 8.6 x 10(-8) mol/l and 13.7 x 10(-8) mol/l, respectively, which was approximately sevenfold lower than the F(ab) fragments of the parental antibodies. In antibody-dependent cellular cytotoxicity experiments with human mononuclear cells as effectors, the bsscFv-mediated specific lysis of both HLA class II-positive, malignant human B-lymphoid cell lines and primary cells from patients with chronic B-cell lymphocytic leukaemia. Optimal lysis was obtained at bsscFv concentrations of approximately 400 ng/ml, similar to the concentration required for maximum lysis by the corresponding chemically linked bispecific antibody. Thus, this recombinant bsscFv-antibody is an efficient molecule for effector-cell mediated lysis of malignant human B-lymphoid cells.
Aspergillus aculeatus β-1,4-Galactanase:  Substrate Recognition and Relations to Other Glycoside Hydrolases in Clan GH-A (2002)

The three-dimensional structure of Aspergillus aculeatus beta-1,4-galactanase (AAGAL), an enzyme involved in pectin degradation, has been determined by multiple isomorphous replacement to 2.3 and 1.8 A resolution at 293 and 100 K, respectively. It represents the first known structure for a polysaccharidase with this specificity and for a member of glycoside hydrolase family 53 (GH-53). The enzyme folds into a (beta/alpha)(8) barrel with the active site cleft located at the C-terminal side of the barrel consistent with the classification of GH-53 in clan GH-A, a superfamily of enzymes with common fold and catalytic machinery but diverse specificities. Putative substrate-enzyme interactions were elucidated by modeling of beta-1,4-linked galactobioses into the possible substrate binding subsites. The structure and modeling studies identified five potential subsites for the binding of galactans, of which one is a pocket suited for accommodating the arabinan side chain in arabinogalactan, one of the natural substrates. A comparison with the substrate binding grooves of other Clan GH-A enzymes suggests that shape complementarity is crucial in determining the specificity of polysaccharidases.
Helminths as governors of inflammatory bowel disease (2008)

The incidence of the inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn′s disease (CD) markedly increased in industrialised countries during the past decades. In contrast to these countries where helminthosis are rare, IBD is still uncommon in global areas where most people carry worms. Thus lack of exposure to parasites may critically contribute to the risk of IBD. In a recent article in Gut, Summers et al. demonstrated efficacy of treatment with Trichuris suis in active CD (Gut 2005;54:87-90). Trichuris suis was additionally shown to be effective in UC in a randomized trial carried out by the same group. Both studies did not address mechanisms of action. Here we present a real life scenario, which supports the impact of helminths in the prevention of IBD, and provide a rationale for the mechanisms of action.
Microbial Biotransformation Products of Cyclosporin A. (1996)

In order to mimic the human metabolic pathway of cyclosporin A (CyA) a total of 28 bacterial and 72 fungal strains was screened for their ability to transform CyA. Among 3 bacteria and 11 fungi, which produced the main human metabolite OL-17 [eta HyMeBmt1]CyA, Actinoplanes sp. (ATCC 53771) achieved the best transformation rate (5.4%). Furthermore, the two N-demethylated minor products [Leu4]CyA (3.2%) and [Leu9]CyA (4.7%) were isolated, both known as minor natural metabolites and the first one also as a human biotransformation product. Microbial conversion of CyA using the actinomycete Sebekia benihana (NRRL 11111) yielded [gamma HyMeLeu4]CyA (35%), [gamma HyLeu4]CyA (4.5%) and [gamma HyMeLeu4, gamma HyMeLeu6]CyA (8.6%). The structures of these derivatives correspond with those of the human metabolic pathway. The related compounds [Nva2]CyA (CyG) and [D-MeSer3]CyA were similarly converted to the corresponding 4-gamma-hydroxylated analogues. None of the biotransformation products showed a better immunosuppressive effect than CyA, although in various cases the cyclophilin binding affinity was comparable to that of CyA.
VACUTAINER CPT and Ficoll density gradient separation perform equivalently in maintaining the quality and function of PBMC from HIV seropositive blood samples. (2006)

These data suggest that CPT is an efficient system for the collection and cryopreservation of functionally active HIV+ PBMC, as well as a viable alternative to Ficoll gradient separation.
Varroa destructor is an effective vector of Israeli acute paralysis virus in the honeybee, Apis mellifera (2010)

The Israeli acute paralysis virus (IAPV) is a significant marker of honeybee colony collapse disorder (CCD). In the present work, we provide the first evidence that Varroa destructor is IAPV replication-competent and capable of vectoring IAPV in honeybees. The honeybees became infected with IAPV after exposure to Varroa mites that carried the virus. The copy number of IAPV in bees was positively correlated with the density of Varroa mites and time period of exposure to Varroa mites. Further, we showed that the mite-virus association could possibly reduce host immunity and therefore promote elevated levels of virus replication. This study defines an active role of Varroa mites in IAPV transmission and sheds light on the epidemiology of IAPV infection in honeybees.
Serotonergic and dopaminergic systems in anorexia nervosa: a role for atypical antipsychotics? (2005)

Objective: To review serotonergic and dopaminergic system function in anorexia nervosa in terms of potential modulation by atypical antipsychotic medications. Method: A systematic review of clinical, neurobiological and functional neuroimaging findings of serotonergic and dopaminergic system activity in anorexia nervosa was conducted via MEDLINE, PsycINFO and EMBASE psychiatry databases, with a critical review of dysregulation of these systems as therapeutic targets for atypical antipsychotics, in context of evidence regarding the utility and efficacy of these medications in this syndrome. Results: There is evidence of persistently altered serotonergic and dopaminergic function in anorexia nervosa independent to weight-recovery. Case reports, open-label and singleblinded studies, albeit sparse, suggest that atypical antipsychotics may be beneficial in the management of anorexia nervosa psychopathology beyond weight gain. Conclusions: Double-blind placebo controlled studies of atypical antipsychotics in anorexia nervosa with well defined outcome measures are required.
Pharmacokinetics of Intranasally Administered Dexmedetomidine in Chinese Children (2019)

<b>Background:</b> Intranasal application is a comfortable, effective, nearly non-invasive, and easy route of administration in children. To date, there is, however, only one pharmacokinetic study on intranasal dexmedetomidine in pediatric populations and none in Chinese children available. Therefore, this study aimed to characterize the pharmacokinetics of intranasally administered dexmedetomidine in Chinese children. <b>Methods:</b> Thirteen children aged 4 to 10 years undergoing surgery received 1 µg/kg dexmedetomidine intranasally. Arterial blood samples were drawn at various time points until 180 min after dose. Dexmedetomidine plasma concentrations were measured with high performance liquid chromatography (HPLC) and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models with first-order absorption. <b>Results:</b> An average peak plasma concentration of 748 ± 30 pg/ml was achieved after 49.6 ± 7.2 min. The pharmacokinetics of dexmedetomidine was best described by a two-compartment model with first-order absorption and an allometric scaling with estimates standardized to 70-kg body weight. The population estimates (SE) per 70 kg bodyweight of the apparent pharmacokinetic parameters were clearance CL/F = 0.32 (0.02) L/min, central volume of distribution V1/F = 34.2 (4.9) L, intercompartmental clearance Q2/F = 10.0 (2.2) L/min, and peripheral volume of distribution V2/F = 34.9 (2.3) L. The estimated absorption rate constant was Ka = 0.038 (0.004) min<sup>-1</sup>. <b>Conclusions:</b> When compared with studies in Caucasians, Chinese children showed a similar time to peak plasma concentration after intranasal administration, but the achieved plasma concentrations were about three times higher. Possible reasons are differences in age, ethnicity, and mode of administration.
Probabilistic method for virtual colonoscopy cleansing (2003)

Currently, virtual colonoscopy examinations require extensive bowel preparation because residual materials can occlude lesions or can be misinterpreted as polyps. Our goal is to investigate a probabilistic method to segment contrast enhanced residual materials and remove them from the rendering. The region around a sample position is modeled to contain mixtures of air, tissue and tagged intraluminal remains. For each image sample a probability vector is calculated expressing the probability that the materials of interest are present. A probability space is defined using the probabilities for pure materials as base vectors. Mixture vectors are constructed at 45-degree angles between the pure material vectors. The probability vectors are compared to the base vectors and the mixture vectors to classify them into material mixtures. Consider the layer between air and tagged fluid. Image intensities are similar to tissue. The scale at which the Gaussian averaged probability is calculated is increased until convergence: two successive scales result in the same classification. The Bayesian classification method shows good results with relatively large objects. However, edges of small or thin objects are likely to be misclassified: a too large environment is needed for convergence.
Targeting the Microtubules in Breast Cancer Beyond Taxanes: The Epothilones (2007)

Microtubule-targeting agents such as the taxanes are highly active against breast cancer and have become a cornerstone in the treatment of patients with early and advanced breast cancer. The natural epothilones and their analogs are a novel class of microtubule-stabilizing agents that bind tubulin and result in apoptotic cell death. Among this family of compounds, patupilone, ixabepilone, BMS-310705, ZK-EPO, and KOS-862 are in clinical development. Extensive preclinical studies have shown that epothilones are working through partially nonoverlapping mechanisms of action with taxanes. In the clinic, epothilones have been found in a series of phase I and phase II studies to be active even in patients who had recently progressed to taxanes. The toxicity profile of these agents consists mostly of sensory neuropathy, sometimes reversible. Neoadjuvant studies with epothilones have been conducted and a number of phase III studies in advanced breast cancer are either under way or have been recently completed. The results of these studies are eagerly awaited and it is anticipated that epothilones may become an important treatment option in patients with breast cancer.
Oral Administration of an Apo A-I Mimetic Peptide Synthesized From D-Amino Acids Dramatically Reduces Atherosclerosis in Mice Independent of Plasma Cholesterol (2002)

When apolipoprotein A-I mimetic peptides synthesized from either D- or L-amino acids were given orally to LDL receptor-null mice, only the peptide synthesized from D-amino acids was stable in the circulation and enhanced the ability of HDL to protect LDL against oxidation. The peptide synthesized from L-amino acids was rapidly degraded and excreted in the urine. When a peptide synthesized from D-amino acids (D-4F) was administered orally to LDL receptor-null mice on a Western diet, lesions decreased by 79%. When added to the drinking water of apoE-null mice, D-4F decreased lesions by approximately 75% at the lowest dose tested (0.05 mg/mL). The marked reduction in lesions occurred independent of changes in total plasma or HDL-cholesterol.
Efficacy of sphenopalatine ganglion blockade in 66 patients suffering from cluster headache: a 12- to 70-month follow-up evaluation (1997)

This study was conducted to evaluate the efficacy, based on 12- to 70-month follow-up data, of radiofrequency (RF) lesions of the sphenopalatine ganglion made in patients suffering from cluster headache. Sixty-six patients suffering from either episodic (Group A, 56 patients) or chronic (Group B, 10 patients) cluster headache who were not responsive to pharmacological management were treated by RF lesioning in the sphenopalatine ganglion. Complete relief of pain was achieved in 34 (60.7%) of 56 patients in Group A and in three (30%) of 10 patients in Group B. No relief was found in eight patients (14.3%) in Group A and in four (40%) in Group B. The mean time of follow up was 29.1 +/- 10.6 months in Group A and 24 +/- 9.7 months in Group B, ranging from 12 to 70 months. With regard to side effects and complications, temporary postoperative epistaxis was observed in eight patients and a cheek hematoma in 11 patients; a partial RF lesion of the maxillary nerve was inadvertently made in four patients. Nine patients complained of hypesthesia of the palate, which disappeared in all cases within 3 months. The authors conclude that RF lesioning in the sphenopalatine ganglion via the infrazygomatic approach may be performed in patients suffering from cluster headache that does not respond to pharmacological therapy.
Increased Vaccine-Specific T Cell Frequency After Peptide-Based Vaccination Correlates with Increased Susceptibility to In Vitro Stimulation But Does Not Lead to Tumor Regression (1999)

Although in vitro sensitization assays have shown increased melanoma Ag (MA)-specific CTL reactivity after vaccination with MA peptides, clinical responses have been uncommon. This paradox questions whether data obtained from the in vitro stimulation and expansion of T cells lead to an overestimation of the immune response to vaccines. Using HLA/peptide tetramer (tHLA), we enumerated MA-specific T cell precursor frequency (TCPF) directly in PBMC from 23 melanoma patients vaccinated with gp100:209-217(210M) (g209-2M) peptide. Vaccine-specific TCPF was higher in postvaccination PBMC from seven of seven patients treated with peptide alone and four of five patients treated with peptide plus IL-12 (range of postvaccination TCPF, 0.2-2.4% and 0.2-2.5%, respectively). The increased TCPF correlated with enhanced susceptibility to in vitro stimulation with the relevant epitope. Paradoxically, no increase in postvaccination TCPF was observed in most patients who had been concomitantly treated with IL-2 (1 of 11 patients; range of postvaccination TCPF, 0.02-1.0%), a combination associated with enhanced rates of tumor regression. The lack of increase in TCPF seen in these patients corresponded to inability to elicit expansion of vaccine-specific T cells in culture. This study shows that a peptide-based vaccine can effectively generate a quantifiable T cell-specific immune response in the PBMC of cancer patients, though such a response does not associate with a clinically evident regression of metastatic melanoma.
Transforms for the motion compensation residual (2009)

The Discrete-Cosine-Transform (DCT) is the most widely used transform in image and video compression. Its use in image compression is often justified by the notion that it is the statistically optimal transform for first-order Markov signals, which have been used to model images. In standard video codecs, the motion-compensation residual (MC-residual) is also compressed with the DCT. The MC-residual may, however, possess different characteristics from an image. Hence, the question that arises is if other transforms can be developed that can perform better on the MC-residual than the DCT. Inspired by recent research on direction-adaptive image transforms, we provide an adaptive auto-covariance characterization for the MC-residual that shows some statistical differences between the MC-residual and the image. Based on this characterization, we propose a set of block transforms. Experimental results indicate that these transforms can improve the compression efficiency of the MC-residual.
Vascular Endothelial Growth Factor Receptor Localization and Activation in Human Trophoblast and Choriocarcinoma Cells1 (1994)

Vascular endothelial growth factor (VEGF; also known as vascular permeability factor) is a secreted angiogenic growth factor. It is highly specific for endothelial cells, and its receptor, the fms-like tyrosine kinase (flt), has been localized only to endothelial cells in vivo. Here we describe the expression of mRNA encoding flt in human trophoblast as revealed by in situ hybridization. This mRNA is highly expressed in the cytotrophoblast shell and columns and also highly expressed by the extravillous trophoblast (EVT) in the maternal decidua both in the first trimester and at term. The trophoblast-like choriocarcinoma cell line BeWo also expresses this receptor and the related receptor, kinase domain-containing receptor (KDR), which is also a receptor for VEGF. Treatment of the cell line BeWo with VEGF165 stimulated 3H-thymidine incorporation and tyrosine phosphorylation of MAP (mitogen-activated protein) kinase in a time- and dose-dependent fashion. This study is the first demonstration of the presence of flt on non-endothelial cells in vivo and suggests a role for VEGF in the growth and differentiation of cytotrophoblast at implantation.
Hyperhomocysteinemia Alters Cardiac Substrate Metabolism by Impairing Nitric Oxide Bioavailability Through Oxidative Stress (2007)

HHcy directly modulates substrate use by the heart independent of changes in hemodynamics or ventricular function by reducing NO bioavailability through the generation of superoxide. The progression of cardiac or coronary heart disease associated with HHcy should be evaluated in light of the impact of alterations in the regulation of cardiac metabolism and substrate use.
Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins (1996)

Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of interleukin-1alpha (IL-1alpha). To analyze the mechanisms that lead to the expression of IL-1alpha in HTLV-I-infected cell lines, we studied regulatory regions of the human IL-1alpha promoter involved in activation of the IL-1alpha gene. IL-1alpha promoter constructs drive transcription of the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells, which constitutively produce IL-1alpha. In a cotransfection assay, the Tax protein of both HTLV-I and HTLV-II specifically activated transcription from the IL-1alpha promoter in an uninfected Jurkat cell line. A mutant Tax protein deficient in transactivation of genes by the nuclear factor (NF)-kappaB pathway was unable to induce transcriptional activity of IL-1alpha promoter-CAT constructs, but was rescued by exogenous provision of p65/p50 NF-kappaB. We found that two IL-1alpha kappaB-like sites (positions -1,065 to -1,056 and +646 to +655) specifically formed a complex with NF-kappaB-containing nuclear extract from MT-2 cells and that NF-kappaB bound with higher affinity to the 3' NF-kappaB binding site than to the 5' NF-kappaB site. Moreover, deletion of either 5' or 3' NF-kappaB sites reduced IL-1alpha promoter activity in MT-2 cells and transactivation of the IL-1alpha promoter by exogenous NF-kappaB and Tax in Jurkat cells. These data suggest a general role for Tax induction of IL-1alpha gene transcription by the NF-kappaB pathway. Expression of IL-1alpha by HTLV-I productively infected cells may be important in the hypercalcemia, osteolytic bone lesions, neutrophilia, elevation of C-reactive protein, and fever frequently seen in patients with HTLV-I-induced adult T-cell leukemia/lymphoma.
Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG. (1977)

Subpopulations of thymus-derived T lymphocytes bearing receptors for either IgM or IgG molecules were isolated from human peripheral blood. Those with receptors for IgM (T.M) provided help in a cell dose-dependent fashion for the pokeweed mitogen-induced differentiation of B lymphocytes in vitro, whereas cells with receptors for IgG (T.G) did not. T.G cells, on the hand, efficiently suppressed the differentiation and proliferation of B cells in the pokeweed system in the presence of helper T.M cells. This suppressive activity of T.G cells required prior interaction of the T.G cells with immune complexes. The helper activity of T.M cells was relatively radioresistant while the suppressor activity of T.G cells was radiosensitive. The results indicate that helper and suppressor functions of human T lymphocytes in this model system are mediated by different subpopulations of T cells which can be distinguished by their ability to bind IgM or IgG immune complexes, respectively.