gebhart/patrepeval huggingface dataset:
In Vitro and In Vivo Activities of a Triterpenoid Saponin Extract (PX-6518) from the Plant Maesa balansae against Visceral Leishmania Species (2003)

The in vitro and in vivo activities of a mixture of six oleane triterpene saponins, recovered from the methanolic extract of the leaves of the Vietnamese plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral Leishmania strains. The in vitro 50% inhibitory concentration (IC(50)) against intracellular Leishmania infantum amastigotes was 0.04 micro g/ml. The cytotoxic concentrations causing 50% cell death (CC(50)s) were about 1 micro g/ml in murine macrophage host cells and >32 micro g/ml in human fibroblasts (MRC-5 cell line). Evaluation in the Leishmania donovani BALB/c mouse model indicated that a single subcutaneous administration of 0.4 mg/kg at 1 day after infection reduced liver amastigote burdens by about 95% in all treated animals. If treatment was delayed until 14 days after infection, a dose of 1.6 mg/kg of body weight was required to maintain the same level of activity. Single 250-mg/kg doses of sodium stibogluconate (Pentostam) 1 and 14 days after infection produced comparable efficacies. A single dose of PX-6518 at 2.5 mg/kg administered 5 days before infection was still 100% effective in preventing liver infection, suggesting a particularly long residual action. Spleen and bone marrow could not be cleared by PX-6518 nor sodium stibogluconate. PX-6518 did not show activity after oral dosing at up to 200 mg/kg for 5 days. This study concludes that triterpenoid saponins from M. balansae show promising in vitro and in vivo antileishmanial potential and can be considered as new lead structures in the search for novel antileishmanial drugs.
Aqueous Sulfate Separation by Crystallization of Sulfate–Water Clusters (2015)

An effective approach to sulfate separation from aqueous solutions is based on the crystallization of extended [SO4(H2O)5(2-)]n sulfate-water clusters with a bis(guanidinium) ligand. The ligand was generated in situ by hydrazone condensation in water, thereby bypassing the need for elaborate syntheses, tedious purifications, and organic solvents. Crystallization of sulfate-water clusters represents an alternative approach to the now established sulfate separation strategies that involve encapsulation of the "naked" anion.
Measuring semantic relatedness using people and WordNet (2006)

In this paper, we (1) propose a new dataset for testing the degree of relatedness between pairs of words; (2) propose a new WordNet-based measure of relatedness, and evaluate it on the new dataset.
Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance (1998)

In the past decade, the frequency of diagnosed fungal infections has risen sharply due to several factors, including the increase in the number of immunosuppressed patients resulting from the AIDS epidemic and treatments during and after organ and bone marrow transplants. Linked with the increase in fungal infections is a recent increase in the frequency with which these infections are recalcitrant to standard antifungal therapy. This review summarizes the factors that contribute to antifungal drug resistance on three levels: (i) clinical factors that result in the inability to successfully treat refractory disease; (ii) cellular factors associated with a resistant fungal strain; and (iii) molecular factors that are ultimately responsible for the resistance phenotype in the cell. Many of the clinical factors that contribute to resistance are associated with the immune status of the patient, with the pharmacology of the drugs, or with the degree or type of fungal infection present. At a cellular level, antifungal drug resistance can be the result of replacement of a susceptible strain with a more resistant strain or species or the alteration of an endogenous strain (by mutation or gene expression) to a resistant phenotype. The molecular mechanisms of resistance that have been identified to date in Candida albicans include overexpression of two types of efflux pumps, overexpression or mutation of the target enzyme, and alteration of other enzymes in the same biosynthetic pathway as the target enzyme. Since the study of antifungal drug resistance is relatively new, other factors that may also contribute to resistance are discussed.
Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: Prominent role of Wnt‐induced signaling protein 1 (2009)

This study included a comprehensive characterization of Wnt and Frizzled gene expression in experimental and human OA articular joint tissue. The data demonstrate, for the first time, that WISP-1 expression is a feature of experimental and human OA and that WISP-1 regulates chondrocyte and macrophage MMP and aggrecanase expression and is capable of inducing articular cartilage damage in models of OA.
Determination of Redundancy and Systems Properties of the Metabolic Network of Helicobacter pylori Using Genome-Scale Extreme Pathway Analysis (2002)

The capabilities of genome-scale metabolic networks can be described through the determination of a set of systemically independent and unique flux maps called extreme pathways. The first study of genome-scale extreme pathways for the simultaneous formation of all nonessential amino acids or ribonucleotides in Helicobacter pylori is presented. Three key results were obtained. First, the extreme pathways for the production of individual amino acids in H. pylori showed far fewer internal states per external state than previously found in Haemophilus influenzae, indicating a more rigid metabolic network. Second, the degree of pathway redundancy in H. pylori was essentially the same for the production of individual amino acids and linked amino acid sets, but was approximately twice that of the production of the ribonucleotides. Third, the metabolic network of H. pylori was unable to achieve extensive conversion of amino acids consumed to the set of either nonessential amino acids or ribonucleotides and thus diverted a large portion of its nitrogen to ammonia production, a potentially important result for pH regulation in its acidic habitat. Genome-scale extreme pathways elucidate emergent system-wide properties. Extreme pathway analysis is emerging as a potentially important method to analyze the link between the metabolic genotype and its phenotypes.
Detection of a Novel ATP-Dependent Cross-Linked Protein at the 5′ Splice Site-U1 Small Nuclear RNA Duplex by Methylene Blue-Mediated Photo-Cross-Linking (1998)

Assembly of spliceosomes involves a number of sequential steps in which small nuclear ribonucleoprotein particles (snRNPs) and some non-snRNP proteins recognize the splice site sequences and undergo various conformational rearrangements. A number of important intermolecular RNA-RNA duplexes are formed transiently during the process of splice site recognition. Various steps in the assembly pathway are dependent upon ATP hydrolysis, either for protein phosphorylation or for the activity of helicases, which may modulate the RNA structures. Major efforts have been made to identify proteins that interact with specific regions of the pre-mRNA during the stages of spliceosome assembly and catalysis by site-specific UV cross-linking. However, UV cross-linking is often inefficient for the detection of proteins that interact with base-paired RNA. Here we have used the complementary approach of methylene blue-mediated photo-cross-linking to detect specifically proteins that interact with the duplexes formed between pre-mRNA and small nuclear RNA (snRNA). We have detected a novel cross-link between a 65-kDa protein (p65) and the 5' splice site. A range of data suggest that p65 cross-links to the transient duplex formed by U1 snRNA and the 5' splice site. Moreover, although p65 cross-linking requires only a 5' splice site within the pre-mRNA, it also requires ATP hydrolysis, suggesting that its detection reflects a very early ATP-dependent event during splicing.
Release of colony-stimulating activity from thymus-derived lymphocytes. (1975)

Colony-stimulating activity (CSA) is essential for in vitro differentiation of bone marrow cells into colonies of granulocytes and mononuclear cells. While blood monocytes and macrophages are a major source of CSA, recent studies have indicated that CSA may be produced by lymphocytes responding to immunologic stimulation. Lymphocytes, purified from spleens and thymuses of mice by glass wool columns, were incubated in CMRL-1066 medium with fetal calf serum in vitro. Lymphocytes from the thumus and spleen released CSA when cultured in vitro, with peak levels of CSA observed after 7 days of incubation. Stimulation of cultures with phytohemagglutinin, concanavalin A, or pokeweed mitogen resulted in a 2-5-fold increase in CSA release, with peak levels of CSA released after 4 days of incubation. Thymus-dependent lymphocytes were responsible for the release of CSA from unstimulated and mitogen-stimulated cultures, since the incubation of these cultures with rabbit anti-mouse T cell sera abolished their ability to release CSA. Anti-mouse B cell sera had no effect on the ability of lymphocyte cultures to release CSA. These studies suggest that thymocytes and thymus-derived lymphocytes can release CSA in vitro and may be responsible for the increase in CSA observed in certain immunologic reactions.
Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. (1989)

Chimeric mouse-human IgG was used to study the structural and functional roles of the carbohydrate present in the CH2 domain of human IgG molecules. To remove this N-linked carbohydrate, Asn-297, the oligosaccharide attachment residue, was changed to either Gln (a conservative replacement) or His for IgG1 or Lys for IgG3 (nonconservative replacements) by site-directed mutagenesis. Carbohydrate-deficient antibodies are properly assembled and secreted and bind Ag and protein A. However, aglycosylated IgG are more sensitive to most proteases than their corresponding wild-type IgG, indicating some conformational changes have occurred. Aglycosylated IgG do not bind to the human Fc gamma RI and do not activate C; depending on the isotype, C1q binding ability is either completely lost (IgG1) or dramatically decreased (IgG3). The serum half-life in mice of aglycosylated IgG1-Gln remains the same as wild-type IgG1, 6.5 +/- 0.5 days, whereas aglycosylated IgG3-Gln has a shorter half-life, 3.5 +/- 0.2 days, compared to that of wild-type IgG3, 5.1 +/- 0.4 days. These results indicate the carbohydrate interposed between CH2 domain of human IgG is necessary to maintain the appropriate structure for the maintenance of many of the effector functions dependent on the CH2 domain.
Secondary glaucoma in patients with juvenile rheumatoid arthritis‐associated iridocyclitis (2000)

Glaucoma is a common complication of JRA-associated iridocyclitis. It results from prolonged, inadequately treated intraocular inflammation and in some instances, from steroid use. Medical and surgical therapy for the glaucoma associated with JRA-uveitis is challenging and incompletely effective. We suspect that a more aggressive approach to the treatment of JRA-associated uveitis, earlier in the course of the disease may reduce this vision robbing contribution to the process.
Synthesis and Biological Properties of New Constrained CCK-B Antagonists:  Discrimination of Two Affinity States of the CCK-B Receptor on Transfected CHO Cells (1997)

To improve our knowledge of the bioactive conformation of CCK-B antagonists, we have developed a new series of constrained dipeptoids whose synthesis and biochemical properties are reported here. These compounds, of general structure N alpha-[(2-adamantyloxy)carbonyl]-alpha-methyltryptophanyl-(4 -X)-proline, were designed by introducing a cyclization in the structure of the previously described CCK-B/peptoid antagonist RB 210, N-[N-[(2-adamantyloxy)carbonyl]-DL-alpha-methyltryptophanyl] -N-(2-phenylethyl)glycine (Blommaert et al. J. Med. Chem. 1993, 36, 2868-2877), by means of a five-membered ring. Structure-affinity relationship studies showed that an R configuration of Trp-C alpha and a cis configuration of the pyrrolidine substituents were favorable for receptor recognition. The most potent compounds of this new series had similar affinities for the CCK-B receptor as RB 210 and proved to be far more efficient in inhibiting inositol phosphate production in CHO cells stably transfected with rat brain CCK-B receptor, with IC50 values approaching those of the commonly used antagonists L-365,260 and PD-134,308. Moreover, binding studies performed using transfected CHO cells showed that two affinity states of the CCK-B receptor can be discriminated by some of these compounds which also have different biological profiles and are therefore highly interesting tools for the biochemical and pharmacological characterization of CCK-B receptor heterogeneity.
Prevention of Hemodialysis Catheter-Related Bloodstream Infection Using an Antimicrobial Lock (2002)

Among currently available vascular access options for hemodialysis, central venous catheters show the poorest reliability, with frequent complications of thrombosis and stenosis impairing patency. The most serious problem, however, is catheter-related bloodstream infection (CRBI), which is typically a cause for removal of the catheter and protracted systemic antibiotic therapy. In our experience, a totally implanted device (Dialock, Biolink Corp.) seems to confer a better global protection against catheter-related infections than standard tunneled catheters, accounting for 0.97 vs. 4.75 infection episodes/1,000 catheter-days, respectively (p < 0.001). Bloodstream infection rates, however, are not statistically different in the two groups (0.85 vs. 0.81 per 1,000 catheter-days; p = n.s.), indicating that the improvement is mainly related to local cutaneous infections. On the other hand, in the Sodemann experience, a new taurolidine-based lock solution (Neutrolin, Biolink Corp.) greatly reduced CRBI rates with both subcutaneous ports and tunneled catheters to 0.29 and 0.20 episodes/1,000 catheter-days, respectively. These promising results await further confirmation from ongoing clinical trials.
A key for the identification of the more common planktonic copepoda of Indian coastal waters (1963)

This key has been prepared for the use mainly of non-specialists in the group Copepoda, to aid them in the ready identification of the commoner species occurring in marine plankton. In framing the key an attempt ha, been made to avoid excessive technicality on the one hand and too gre?t artificiality on the other. It \\vill be seen that the species are treated in a linear order that is not very different from the taxonoinic order. The ~l~orphological characters used for differentiation are, as far as possible, such as could he verified by non-specia!ists and offel less of difficulty in the actual working. The characters are those of the sexually mature individuals only, since the larval and copepodite stages are excluded from the purvlelv of the key.
Novel Direct Evidence That Adult Bone Marrow-Derived Very Small Embryonic Like (VSEL) Stem Cells Are Mobilized into Peripheral Blood - Leukopheresis as a Potential Tool To Isolate Pluripotent Stem Cells for Therapeutic Pruposes. (2007)

Abstract Recently, we identified in adult bone marrow (BM) a population of very small embryonic like (VSEL) stem cells (Leukemia2006:20;857) that are very small in size (∼3.5 μm), CXCR4+Oct-4+ SSEA-1+Sca-1+CD45−lin−, respond to SDF-1 gradient and contain large nuclei with open type of euchromatin. We asked if VSEL are mobilized into peripheral blood (PB) similarly as BM-derived hematopoietic stem cells. To address this question, we evaluated VSEL level in PB after pharmacological (G-CSF) and stress/organ damage-induced mobilization (toxic liver and skeletal muscle damage after exposure to CCl4 and cardiotoxin respectively). The number of circulating VSEL in PB was measured by FACS, direct histochemical staining of PB-cells for SSEA-1 and Oct-4 expression, and RQ-PCR analysis of pluripotent genes (Oct-4, Nanog). Finally, VSEL sorted from the PB were tested for their pluripotency in our established assay based on formation of embryoid-like spheres by VSEL in co-cultures with C2C12 cells. We report that in steady state conditions, VSEL circulate at very low levels in PB (∼100–200 cells/ml) and that the number of these cells/ml of PB is five times higher in two month old mice as compared to one year old animals. Furthermore, we found that VSEL are mobilized into PB both by G-CSF- and tissue injury and the number of circulating VSEL increases 5–6 and 2–3 times after G-CSF and after liver or skeletal muscle injury, respectively. Furthermore, the mobilization of VSEL could be additionally enhanced by blocking CXCR4 receptor by T140 antagonist. Based on this, we provide the evidence that VSEL is a mobile pool of primitive CXCR4+SSEA-1+Oct-4+ stem cells, is released into circulation during tissue/organ injury and their trafficking is regulated by SDF-1-CXCR4 axis. Further studies will asses if the level of mobilized VSEL correlates with overall regenerative potential of an organism and could become a helpful prognostic indicator for the clinical outcome from organ damage/injury (e.g., stroke, heart infarct). Finally, mobilized VSEL could also be employed in regenerative medicine and we are testing this possibility in appropriate animal models.
Metabolic Engineering of Propanediol Pathways (1998)

Microbial fermentation is an important technology for the conversion of renewable resources to chemicals. In this paper, we describe the application of metabolic engineering for the development of two new fermentation processes: the microbial conversion of sugars to 1,3-propanediol (1,3-PD) and 1,2-propanediol (1,2-PD). A variety of naturally occurring organisms ferment glycerol to 1,3-PD, but no natural organisms ferment sugars directly to 1,3-PD. We first describe the fed-batch fermentation of glycerol to 1,3-PD by Klebsiella pneumoniae. We then present various approaches for the conversion of sugars to 1,3-PD, including mixed-culture fermentation, cofermentation of glycerol and glucose, and metabolic engineering of a "sugars to 1,3-PD" pathway in a single organism. Initial results are reported for the expression of genes from the K. pneumoniae 1,3-PD pathway in Saccharomyces cerevisiae. The best naturally occurring organism for the fermentation of sugars to 1,2-PD is Thermoanaerobacterium thermosaccharolyticum. We describe the fermentation of several different sugars to 1,2-PD by this organism in batch and continuous culture. We report that Escherichia coli strains engineered to express either aldose reductase or glycerol dehydrogenase convert glucose to (R)-1,2-PD. We then analyze the ultimate potential of fermentation processes for the production of propanediols. Linear optimization studies indicate that, under aerobic conditions, propanediol yields that approach the theoretical maximum are possible and CO2 is the primary coproduct. Without the need to produce acetate, final product titers in the range of 100 g/L should be possible; the high titers and low coproduct levels should make product recovery and purification straightforward. The examples given in this paper illustrate the importance of metabolic engineering for fermentation process development in general.
Biotransformation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1-H-dibenz[2,3:6,7]oxepin o [4,5-c]pyrrolidine maleate in rats. (1990)

The metabolism of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1 H-dibenz[2,3:6,7]oxepinol [4,5-c]pyrrolidine maleate (Org 5222) labelled with [3H] or [14C] was investigated in Wistar rats. Metabolites were identified by mass spectrometry, 13C- and 1H-NMR analysis, IR spectroscopy and, wherever possible, by comparison with authentic reference compounds. The metabolites found in plasma, bile, faeces and urine revealed the processes of metabolism in which Org 5222 underwent oxidation to yield an N-oxide existing in two diastereoisomeric forms, or N-demethylation to yield a demethyl metabolite. A novel metabolite was found in bile, viz. a carbamate glucuronide, formed from an intermediate carbamic acid, derived from the addition of CO2 to the demethyl metabolite.
The Concept of Type-1 and Type-2 Helper T Cells and Their Cytokines in Humans (1998)

In both mice and humans, functionally distinct helper T (Th)-cell subsets, known as Th1 and Th2 cells, are characterized by the patterns of cytokines they produce. These two polarized forms of the specific cellular immune response provide a useful model for explaining not only the different types of protection, but also the pathogenic mechanisms of several immunopathological disorders. The development of polarized Th1 or Th2 responses depends on either environmental factors, including dose of antigen, nature of immunogen and cytokines (IL-12 and interferons or IL-4) at the time of antigen presentation, or other undefined factors in the individual genetic background, mainly at level of the so-called "natural immunity". Th1-dominated responses are potentially effective in eradicating infectious agents, including those hidden within the host cells. When the Th1 response is poorly effective or exhaustively prolonged, it may result in host damage. In contrast, Th2 responses are apparently insufficient to protect against the majority of infectious agents, but can provide some protection against parasites. Th2 cells are able to make unpleasant the life of parasites in the host and tend to limit potentially harmful Th1-mediated responses. Thus, Th2 cells may be regarded as a part of down regulatory (or suppressor) mechanism for exaggerated and/ or inappropriate Th1 responses. The Th1/Th2 paradigm applied to the study of chronic inflammatory disorders or autoimmune diseases allowed to understand that a number of diseases are mediated by Th1 cells, the two clearest examples being multiple sclerosis and thyroid autoimmunity. In other disorders, Th1/Th2 polarization is less prominent, or rather Th2 responses tend to predominate, such as in systemic lupus erythematosus, progressive systemic sclerosis or allergic diseases. It is of note that in experimental models in animals, a number of diseases can be prevented by switching immune responses from Th1 to Th2 or from Th2 to Th1. Moreover, the Th1/Th2 concept suggests that modulation of the relative contribution of Th1- or Th2-type cytokines makes possible to regulate the balance between protection and immunopathology, as well as the development and/or the severity of some immunologic disorders.
Dependence of transcriptional repression on CpG methylation density. (1994)

CpG methylation is known to suppress transcription. This repression is generally thought to be related to alterations of chromatin structure that are specified by the methylation. The nature of these chromatin alterations is unknown. Moreover, it has not been clear if the methylation repression occurs in an all-or-none fashion at some critical methylation density, or if intermediate densities of methylation can give intermediate levels of repression. Here I report a stable episomal system which recapitulates many dynamic features of methylation observed in the genome. I have determined the extent of transcriptional repression as a function of four densities of CpG methylation. I find that the repression is a graded but exponential function of the CpG methylation density such that low levels of methylation yield a 67 to 90% inhibition of gene expression. Higher levels of methylation extinguished gene expression completely. Transcription from methylated minichromosomes can be increased by butyrate treatment, suggesting that histone acetylation can reverse some of the repression specified by the methylated state. Sites of preferential demethylation occurred and may have resulted from transcription factor binding or DNA looping.