gebhart/patrepeval huggingface dataset:
CD8+minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells (1999)

Effective immunotherapy for human leukemia based on infusions of T lymphocytes requires the identification of effector T cells that target the leukemic stem cell. The transplantation of human acute myeloid leukemia into nonobese diabetic/severe combined immune deficient (SCID) mice has identified a rare leukemic progenitor termed the SCID leukemia-initiating cell, which is present in low frequency in the leukemic population and is essential for establishing leukemic hematopoiesis. Thus, this transplant model may be ideally suited to identify effector T cells with antileukemic activity. We report that CD8(+) cytotoxic T lymphocyte (CTL) clones specific for minor histocompatibility antigens inhibit the engraftment of human acute myeloid leukemia cells in nonobese diabetic/SCID mice and demonstrate that this inhibition is mediated by direct CTL recognition of SCID leukemia-initiating cells. These results indicate that CD8(+) minor histocompatibility antigen-specific CTL may be mediators of the graft-versus-leukemia effect associated with allogeneic hematopoietic cell transplantation and provide an experimental model to identify and select T cell clones for immunotherapy to prevent or treat relapse after allogeneic hematopoietic cell transplantation.
Human secretory immunoglobulin M. An immunochemical and immunohistochemical study. (1975)

IgM was purified from normal human colostrum and salivary secretions devoid of IgA. The isolated immunoglobulin was found to contain J chain, and showed a slight affinity for free secretory component (SC). In the secretions IgM was saturated with SC, but only 60--70 per cent of the molecules had retained the component after purification. Moreover, the I determinant of SC was much more exposed in secretory IgM than in secretory IgA, indicating a relatively 'loose' quaternary structure of the former immunoglobulin. Paired immunofluorescence staining demonstrated that secretory epithelial cells of colonic glands contained IgM in exactly the same distribution as IgA. IgM appearing in exocrine secretions is therefore a true secretory immunoglobulin in contrast to IgG. However, the quaternary structure of secretory IgM is less covalently stabilized than that of secretory IgA.
The Novel Synthetic Retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene Carboxylic Acid (CD437) Causes Apoptosis in Acute Promyelocytic Leukemia Cells Through Rapid Activation of Caspases (1999)

The synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437), which was originally developed as an retinoic acid receptor (RAR)-gamma agonist, induces rapid apoptosis in all-trans retinoic acid (ATRA)-sensitive and ATRA-resistant clones of the NB4 cell line, a widely used experimental model of acute promyelocytic leukemia (APL). In addition, the compound is apoptogenic in primary cultures of freshly isolated APL blasts obtained from a newly diagnosed case and an ATRA-resistant relapsed patient. NB4 cells in the S-phase of the cycle are most sensitive to CD437-triggered apoptosis. CD437-dependent apoptosis does not require de novo protein synthesis and activation of RAR-gamma or any of the other nuclear retinoic acid receptors. The process is preceded by rapid activation of a caspase-like enzymatic activity capable of cleaving the fluorogenic DEVD but not the fluorogenic YVAD tetrapeptide. Increased caspase activity correlates with caspase-3 and caspase-7 activation. Inhibition of caspases by z-VAD suppresses the nuclear DNA degradation observed in NB4 cells treated with CD437, as well as the degradation of pro-caspase-3 and pro-caspase-7. CD437-dependent activation of caspases is preceded by release of cytochrome c from the mitochondria into the cytosol of treated cells. Leakage of cytochrome c lays upstream of caspase activation, because the phenomenon is left unaffected by pretreatment of NB4 cells with z-VAD. Treatment of APL cells with CD437 is associated with a caspase-dependent degradation of promyelocytic leukemia-RAR-alpha, which can be completely inhibited by z-VAD.
A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-β1 in the development of myelofibrosis (2005)

Idiopathic myelofibrosis (IM) is a disease characterized by marrow fibrosis, abnormal stem/progenitor cell trafficking, and extramedullary hematopoiesis frequently associated with alterations in megakaryocytes (Mks). Mice harboring genetic alterations in either the extrinsic (ectopic thrombopoietin expression, TPO(high) mice) or intrinsic (hypomorphic GATA-1 mutation, GATA-1(low) mice) control of Mk differentiation develop myelofibrosis, a syndrome similar to IM. The relationship, if any, between the pathobiologic mechanism leading to the development of myelofibrosis in the 2 animal models is not understood. Here we show that plasma from GATA-1(low) mice contained normal levels of TPO. On the other hand, Mks from TPO-treated wild-type animals (TPO(high) mice), as those from GATA-1(low) animals, had similar morphologic abnormalities and contained low GATA-1. In both animal models, development of myelofibrosis was associated with high transforming growth factor beta1 (TGF-beta1) content in extracellular fluids of marrow and spleen. Surprisingly, TPO treatment of GATA-1(low) mice restored the GATA-1 content in Mks and halted both defective thrombocytopoiesis and fibrosis. These data indicate that the TPO(high) and GATA-1(low) alterations are linked in an upstream-downstream relationship along a pathobiologic pathway leading to development of myelofibrosis in mice and, possibly, of IM in humans.
Behavioral Effects of d-Opioid Receptor Agonists: Potential Antidepressants? (2002)

The development of selective delta-opioid receptor agonists has revealed some very intriguing behavioral properties. delta-Opioid agonists have antinociceptive, seizuregenic and convulsive properties. A number of studies have identified a novel behavioral effect of delta-opioid-receptor agonists, implicating a role for the delta-opioid receptor in depression. Early clinical experiments demonstrated that exogenously administered opioid peptides had antidepressant activity in human patients. Also, enkephalinase inhibitors, which prevent the degradation of endogenous enkephalins, produced antidepressant-like effects mediated through the delta-opioid receptor in animal models of depression. More recently, the selective non-peptidic delta-opioid agonists SNC80 and (+)BW373U86 demonstrated antidepressant-like activity in the forced swim assay in rats. These studies propose that the delta-opioid receptor may provide a new therapeutic target for treating human depression.
Determination of modulation of ligand properties of synthetic complex‐type biantennary N‐glycans by introduction of bisecting GlcNAc in silico, in vitro and in vivo (2003)

We have investigated the consequences of introducing a bisecting GlcNAc moiety into biantennary N-glycans. Computational analysis of glycan conformation with prolonged simulation periods in vacuo and in a solvent box revealed two main effects: backfolding of the alpha1-6 arm and stacking of the bisecting GlcNAc and the neighboring Man/GlcNAc residues of both antennae. Chemoenzymatic synthesis produced the bisecting biantennary decasaccharide N-glycan and its alpha2-3(6)-sialylated variants. They were conjugated to BSA to probe the ligand properties of N-glycans with bisecting GlcNAc. To assess affinity alterations in glycan binding to receptors, testing was performed with purified lectins, cultured cells, tissue sections and animals. The panel of lectins, including an adhesion/growth-regulatory galectin, revealed up to a sixfold difference in affinity constants for these neoglycoproteins relative to data on the unsubstituted glycans reported previously [André, S., Unverzagt, C., Kojima, S., Dong, X., Fink, C., Kayser, K. & Gabius, H.-J. (1997) Bioconjugate Chem. 8, 845-855]. The enhanced affinity for galectin-1 is in accord with the increased percentage of cell positivity in cytofluorimetric and histochemical analysis of carbohydrate-dependent binding of labeled neoglycoproteins to cultured tumor cells and routinely processed lung cancer sections. Intravenous injection of iodinated neoglycoproteins carrying galactose-terminated N-glycans into mice revealed the highest uptake in liver and spleen for the bisecting compound compared with the unsubstituted or core-fucosylated N-glycans. Thus, this substitution modulates ligand properties in interactions with lectins, a key finding of this report. Synthetic glycan tailoring provides a versatile approach to the preparation of newly substituted glycans with favorable ligand properties for medical applications.
Reproducibility in Natural Language Processing: A Case Study of Two R Libraries for Mining PubMed/MEDLINE. (2016)

There is currently a crisis in science related to highly publicized failures to reproduce large numbers of published studies. The current work proposes, by way of case studies, a methodology for moving the study of reproducibility in computational work to a full stage beyond that of earlier work. Specifically, it presents a case study in attempting to reproduce the reports of two R libraries for doing text mining of the PubMed/MEDLINE repository of scientific publications. The main findings are that a rational paradigm for reproduction of natural language processing papers can be established; the advertised functionality was difficult, but not impossible, to reproduce; and reproducibility studies can produce additional insights into the functioning of the published system. Additionally, the work on reproducibility lead to the production of novel user-centered documentation that has been accessed 260 times since its publication-an average of once a day per library.
Aspen HYSYS Simulation of CO2 Removal by Amine Absorption from a Gas Based Power Plant (2007)

A simplified combined cycle gas power plant and a MEA (monoethanol amine) based CO2 removal process have been simulated with the process simulation tool Aspen HYSYS. The thermodynamic properties are calculated with the Peng Robinson and Amines Property Package models which are available in Aspen HYSYS. The adiabatic efficiencies in compressors, gas turbines and steam turbines have been fitted to achieve a total thermal efficiency of 58 % in the natural gas based power plant without CO2 removal. The efficiency is reduced to about 50 % with CO2 removal. The CO2 removal in % and the energy consumption in the CO2 removal plant are calculated as a function of amine circulation rate, absorption column height, absorption temperature and steam temperature. With CO2 removal of 85 %, heat consumption is calculated to 3.7 MJ/kg CO2 removed, close to a literature value of 4.0 MJ/kg CO2.
Aluminium triisopropoxide: An inexpensive and easy-to-handle catalyst of the copolymerisation of cyclohexene oxide with CO2 (2005)

Aluminium triisopropoxide, a versatile and cheap oligomeric Lewis acid catalyst, easily reacts with carbon dioxide to build complex oligomeric aluminium alkoxo-alkylcarbonato compounds. A first series of experiments with cyclohexene oxide and CO2 showed that the catalyst is highly active in the copolymerisation with carbon dioxide and that a satisfactory carbon dioxide insertion takes place when the reaction is run at temperatures between 50 and 80 °C and pressures around 100 bar CO2. High yields of polyether-carbonates can be obtained (up to 1000 g of copolymer per g aluminium) with molecular weight up to 11 000 g mol−1 and a better selectivity of the CO2-insertion than other aluminium trialkoxides (carbonate to ether linkages ratio: 1 to 3). On the basis of 27Al-NMR spectra it can be seen that the high reactivity of the catalyst is due to a rearrangement of the stable tetrameric aluminium isopropoxide in a more reactive oligomer and, most likely, during the copolymerisation, to a further fragmentation into reactive monomeric species.
S/MAR Element Facilitates Episomal Long-Term Persistence of Adeno-Associated Virus Vector Genomes in Proliferating Cells (2017)

Adeno-associated virus (AAV) vectors are one of the most frequently applied gene transfer systems in research and human clinical trials. Since AAV vectors do not possess an integrase activity, application is restricted to terminally differentiated tissues if transgene expression is required long term. To overcome this limitation and to generate AAV vectors that persist episomally in dividing cells, AAV vector genomes were equipped with a scaffold/matrix attachment region (S/MAR). After a mild antibiotic selection, cells transduced with AAV-S/MAR established colonies that maintained long-term transgene expression (>50 population doublings) from replicating AAV vector episomes in the absence of further selection. Unexpectedly, with a lesser but still significant efficiency, the control vector (AAV-ΔS/MAR), a standard single-stranded AAV vector, also established stable transgene-expressing colonies, most of which were maintained as replicating episomes rather than integrated vector genomes. Thus, based on the result in HeLa cells, it is concluded that AAV vector genomes per se possess the ability to establish episomal maintenance in proliferating cells, a feature that can be enhanced by incorporation of a foreign genomic element such as an S/MAR element.
Partial Rescue of Ethanol‐Induced Neuronal Apoptosis by Growth Factor Activation of Phosphoinositol‐3‐Kinase (2000)

The findings suggest that ethanol-induced apoptosis of insulin-stimulated neuronal cells can be reduced by activating PI3 K and inhibiting pro-apoptosis gene expression and intracellular signaling through non-insulin-dependent pathways.
Property Modelling Small Scale Heterogeneity of Carbonate Facies (2007)

Abstract A heterogeneously complex carbonate reservoir has been characterized texturally and petrophysically at the plug- and core-scale. This rock typing has been used as input to a series of dynamic "mini-models" aimed at correctly deriving static and dynamic rock properties for input into a full field model. Simulation of these mini-models clearly demonstrates the importance of small-scale heterogeneities on hydrocarbon displacement. These small-scale heterogeneities are commonly omitted from standard reservoir modeling workflows.
Genetic Determinants of Coxsackievirus B3 Pathogenesis (2002)

The development of high throughput genomic and bioinformatic analysis tools, coupled with established molecular techniques, has allowed new insights into the pathogenesis of infectious diseases. In humans, coxasackievirus B3 (CVB3) is the primary etiological agent of viral myocarditis, an inflammatory disease process involving the heart muscle. Early host cellular survival and apoptotic mechanisms during viral infections, as well as immune events, affect myocarditis progression and outcome. Therefore, our laboratory has been keenly interested in infectomics, defined here as the transcriptional events of both virus and host. We first elucidated up- or downregulated transcriptional activities in CVB3-infected hearts by mRNA differential display. Further characterization of these regulated genes including Nip21, IP10, and IGTPase, and study of their role in CVB3-infection are underway. In further dissection of the stages of myocarditis-peak viremia, inflammatory infiltration and tissue repair-we used cDNA microarrays to probe differential gene expression in the myocardium following virus infection. Following virus infection, there are global decreases in metabolic and mitochondrial genes, increases in signaling genes and distinctive patterns in other functional groups. To establish early gene expression profiles in infected cells by themselves, we also used oligonucleotide arrays in an in vitro model of CVB3 infection. Notably, we have found increased expression of transcription factors c-fos and c-jun down-stream of extracellular signal-related kinase, a pathway which is crucial for virus replication and pathogenesis. Our investigations based on gene profiling following CVB3 infection have thus far been fruitful in providing new experimental leads. High throughput genetic analysis has allowed us to simultaneously try on greater than 12,000 potential genetic "glass slippers." Our in vitro experimental plan has enabled us to chart prominent patterns of gene expression, analyzed by novel bioinformatic approaches, and to separate varied and potentially significant gene expression events.
Autologous Chondrocyte Transplantation (1999)

The intrinsic capacity of cartilage to repair chondral injuries is poor. Different techniques to induce cartilage repair with the use of extrinsic chondrogeneic cell sources have been explored in experimental models. Cells can be harvested autologously or as allografts from a healthy part of the donor tissue, isolated, expanded in vitro, and finally implanted into the defect in high densities. Pure chondrocytes, epiphyseal or mature, allogeneic or autologous, and other types of mesenchymal cells have been used. The composition and structure of the extracellular cartilage matrix are maintained through a balance of anabolic and catabolic activities controlled by the unique chondrocytes. They keep the cartilage alive; they alone maintain it and regulate it. It therefore seems important to use true committed chondrocytes to repair a local cartilaginous defect. The rational basis for the use of committed autologous chondrocytes in combination with a covering periosteal membrane in the treatment of deep cartilage defects is presented.
Synthesis and Crystal Structures of Substituted Benzenes and Benzoquinones as Tissue Factor VIIa Inhibitors (2003)

Several multistep syntheses of substituted benzenes are reported. The benzene analogues were designed such that their substitution pattern would occupy and interact with the S(1), S(2), and S(3) pockets of the tissue Factor VIIa enzyme. A variety of chemical transformations including nucleophilic additions, reductive aminations, Stille couplings, and polymer-assisted solution-phase (PASP) techniques were used to prepare key intermediates and final products. The initial analogues identified some weakly active compounds which ultimately led to a 340 nM (IC(50)) tissue Factor VIIa inhibitor with selectivity over other related enzymes. The structure-activity relationship of these inhibitors and the synthetic progression from the discovery of the lead compound to the development of potent analogues will be discussed. The X-ray crystal structures of fluorobenzene 50c and benzoquinone 54 inhibitors complexed with the TF/VIIa enzyme will also be described.
The expression of the Wilms' tumor gene in acute myelocytic leukemias as a possible marker for leukemic blast cells. (1994)

The Wilms' tumor gene (wt-1) is expressed in the developing fetal kidney, gonads and in Wilms' tumors. Recently, the expression of wt-1 in leukemia-derived cell lines and cases of acute leukemias (AL) was reported. The present study was designed to investigate the potential of wt-1 as genetic marker for acute myelocytic leukemias (AML). Blast cells from 52 patients with AML, 14 patients in complete remission (CR) and four leukemic cell lines were examined for expression of wt-1 mRNA. Peripheral blood mononuclear cells (PBMNC) and bone marrow (BM) from 13 healthy persons were used as negative controls. RNA of the wt-1 gene was expressed in 41/52 (79%) patients with previously untreated AML. The majority of the 14 patients studied in CR lost wt-1 expression. In three out of the four patients in CR reappearance of wt-1 expression preceded relapse of the disease. In three of the four tested cell lines wt-1 specific transcription was demonstrated. No correlation to FAB classification, immunophenotype or response to treatment was found. Our experiments indicate wt-1 expression in the majority of AML, but not in bone marrow or PBMNC of healthy controls. Therefore, wt-1 expression may be associated with the presence of malignant blast cells and the analysis of wt-1 gene expression via PCR may be a sensitive method for the detection of leukemic blast cells.
Essentials of Infectious Diseases (1985)

General principles : Microbiology for the clinician Disease mechanisms and host defenses Methods of rapid diagnosis of infectious diseases Serology and skin testing Antibiotics and antifungal drugs Antiviral chemotherapy Chemoprophylaxis of infections Immunization. Organ system infections : Infections of the central nervous system Infections involving the cardiovascular system Infections of the ear, nose, and throat Infections of the lower respiratory tract Intraabdominal infections Gastroenterocolitis and enteric fever syndromes Hepatitis Urinary tract infection Sexually transmitted diseases Osteomyelitis and septic arthritis Infections of the skin and soft tissue Ocular infections. Specific clinical syndromes : Fever of uncertain origin Infections in the immunocompromised host Postoperative infection Infections in burn patients Septic shock Nosocomial infections Parasitic infections.
Treatment of Moderately Severe Erythema Nodosum Leprosum with Thalidomide - A Double-blind Controlled Trial (1969)

This carefully planned, controlled, double-blind trial of the value of thalidomide in the treatment of long-standing, moderately severe erythema nodosmn leprosum showed that thalidomide was superior to a placebo, allowed for the concomitant reduction of other anti-ENL drugs, and was clearly prefeh-ed by the patients themselves.
Identity of nuclear high-mobility-group protein, HMG-1, and sulfoglucuronyl carbohydrate-binding protein, SBP-1, in brain (2001)

High-mobility-group (HMG) proteins are a family of non-histone chromosomal proteins which bind to DNA. They have been implicated in multiple aspects of gene regulation and cellular differentiation. Sulfoglucuronyl carbohydrate binding protein, SBP-1, which is also localized in the neuronal nuclei, was shown to be required for neurite outgrowth and neuronal migration during development of the nervous system. In order to establish relationship between SBP-1 and HMG family proteins, two HMG proteins were isolated and purified from developing rat cerebellum by heparin-sepharose and sulfatide-octyl-sepharose affinity column chromatography and their biochemical and biological properties were compared with those of SBP-1. Characterization by high performance liquid chromatography--mass spectrometry (HPLC-MS), partial peptide sequencing and western blot analysis showed the isolated HMG proteins to be HMG-1 and HMG-2. Isoelectric focusing, HPLC-MS and peptide sequencing data also suggested that HMG-1 and SBP-1 were identical. Similar to SBP-1, both HMG proteins bound specifically to sulfated glycolipids, sulfoglucuronylglycolipids (SGGLs), sulfatide and seminolipid in HPTLC-immuno-overlay and solid-phase binding assays. The HMG proteins promoted neurite outgrowth in dissociated cerebellar cells, which was inhibited by SGGLs, anti-Leu7 hybridoma (HNK-1) and anti-SBP-1 peptide antibodies, similar to SBP-1. The proteins also promoted neurite outgrowth in explant cultures of cerebellum. The results showed that the cerebellar HMG-1 and -2 proteins have similar biochemical and biological properties and HMG-1 is most likely identical to SBP-1.