gebhart/patrepeval huggingface dataset:
Comparative effects of exopolysaccharides from lactic acid bacteria and fructo-oligosaccharides on infant gut microbiota tested in an in vitro colonic model with immobilized cells (2006)

The aim of this study was to compare the effects of purified exopolysaccharides from Lactobacillus rhamnosus RW-9595M with those of a well-known prebiotic (short-chain fructo-oligosaccharides) on infant colonic microbiota using a new three-stage chemostat model with immobilized infant faecal microbiota. Two continuous cultures with different faecal inocula were tested with different compositions of carbohydrate media. During the first fermentation (F1), fructo-oligosaccharides tested at a concentration of 9.8 g L(-1) increased the number of lactobacilli and decreased coliforms both in gel beads and in effluent from all three reactors, in agreement with data from the literature. During the second fermentation (F2), the effect of fructo-oligosaccharides tested at a lower concentration (7.5 g L(-1)) was reduced compared with F1. Fructo-oligosaccharides also increased total organic acid concentration and decreased ammonia production. Results obtained for exopolysaccharide tested at 1.5 g L(-1) indicate that exopolysaccharides from L. rhamnosus RW-9595M was not metabolized by infant microbiota and lacked any prebiotic effect.
Development of an automation technique for the establishment of functional lipid bilayer arrays (2009)

In the present work, a technique for establishing multiple black lipid membranes (BLMs) in arrays of micro structured ethylene tetrafluoroethylene (ETFE) films, and supported by a micro porous material was developed. Rectangular 8 × 8 arrays with apertures having diameters of 301 ± 5 µm were fabricated in ETFE Teflon film by laser ablation using a carbon dioxide laser. Multiple lipid membranes could be formed across the micro structured 8 × 8 array ETFE partitions. Success rates for the establishment of cellulose-supported BLMs across the multiple aperture arrays were above 95%. However, the time course of the membrane thinning process was found to vary considerably between multiple aperture bilayer experiments. An airbrush partition pretreatment technique was developed to increase the reproducibility of the multiple lipid bilayers formation during the time course from the establishment of the lipid membranes to the formation of bilayers. The results showed that multiple lipid bilayers could be reproducible formed across the airbrush-pretreated 8 × 8 rectangular arrays. The ionophoric peptide valinomycin was incorporated into established membrane arrays, resulting in ionic currents that could be effectively blocked by tetraethylammonium. This shows that functional bimolecular lipid membranes were established, and furthermore outlines that the established lipid membrane arrays could host functional membrane-spanning molecules.
Dual stimulatory and inhibitory effect of NK cell stimulatory factor/IL-12 on human hematopoiesis. (1994)

NK cell stimulatory factor, or IL-12 (NKSF/IL-12), is a heterodimeric cytokine produced by monocyte-macrophages, B cells, and possibly other accessory cell types. Although the major biologic effects of NKSF/IL-12 have been demonstrated on mature T and NK cells, in which it induces cytokine secretion, increased cytotoxicity, and proliferation, recent evidence in the murine system has suggested that NKSF/IL-12 may play a role in the differentiation of early lymphohematopoietic progenitor cells and thymocytes. In this paper, we have analyzed the effect of human rNKSF/IL-12 on the formation of colonies by highly enriched hematopoietic progenitor cells from human peripheral blood and bone marrow. At concentrations between 1 and 10 ng/ml, NKSF/IL-12 synergizes with a combination of steel factor and IL-3 to induce formation of mixed, erythroid, and myeloid colonies. Therefore, human NKSF/IL-12, like murine NKSF/IL-12, seems to belong to a small group of early acting cytokines, including IL-6, granulocyte-CSF, leukemia-inhibitory factor, and IL-11, which are able to synergize with steel factor and IL-3 to induce proliferation and differentiation of very early hematopoietic progenitor cells. However, in the presence of enriched preparations of NK cells cultured together with the progenitor cells, NKSF/IL-12 inhibits formation of hematopoietic colonies supported by IL-3 and granulocyte-macrophage CSF, by inducing production of IFN-gamma and TNF-alpha, two cytokines with synergistic inhibitory effects on hematopoietic colony formation. Because cell types that are able to produce NKSF/IL-12 are present in normal bone marrow and NKSF/IL-12 production in vivo and can be stimulated during bacterial or parasitic infection, it is possible that the direct stimulatory effect of NKSF/IL-12 on hematopoietic progenitor cells and the indirect inhibitory effect mediated by secondary cytokine production by lymphoid cells may play a role in the regulation of physiologic hematopoiesis and in its alterations during infection.
An automated method for finding molecular complexes in large protein interaction networks (2003)

Dense regions of protein interaction networks can be found, based solely on connectivity data, many of which correspond to known protein complexes. The algorithm is not affected by a known high rate of false positives in data from high-throughput interaction techniques. The program is available from ftp://ftp.mshri.on.ca/pub/BIND/Tools/MCODE.
The metabolic syndrome in overweight epileptic patients treated with valproic acid (2009)

Patients who gain weight during VPA therapy can develop MS with a possible risk of cardiovascular disease.
A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. (1996)

The propeptide sequences of the vitamin K-dependent clotting factors serve as a recognition site for the enzyme gamma-glutamylcarboxylase, which catalyzes the carboxylation of glutamic acid residues at the NH2 terminus of the mature protein. We describe a mutation in the propeptide of Factor IX that results in warfarin sensitivity because of reduced affinity of the carboxylase for the Factor IX precursor. The proband has a Factor IX activity level of > 100% off warfarin and < 1% on warfarin, at a point where other vitamin K-dependent factors were at 30-40% activity levels. Direct sequence analysis of amplified genomic DNA from all eight exons and exon-intron junctions showed a single guanosine-->adenosine transition at nucleotide 6346 resulting in an alanine to threonine change at residue -10 in the propeptide. To define the mechanism by which the mutation resulted in warfarin sensitivity, we analyzed wild-type and mutant recombinant peptides in an in vitro carboxylation reaction. The peptides that were analyzed included the wild-type sequence, the Ala-10-->Thr sequence, and Ala-10-->Gly, a substitution based on the sequence in bone gamma-carboxyglutamic acid protein. Measurement of C02 incorporation at a range of peptide concentrations yielded a Vmax of 343 cpm/min/reaction for the wild-type peptide, and Vmax values of 638 and 726 for A-10T and A-10G respectively, a difference of only twofold. The Km values, on the other hand, showed a 33-fold difference between wild-type and the variants, with a value of 0.29 microM for wild-type, and 10.9 and 9.50 microM, respectively, for A-10T and A-10G. Similar kinetic experiments showed no substantial differences between wild-type and mutant peptides in kinetic parameters of the carboxylase-peptide complexes for reduced vitamin K. We conclude that the major defect resulting from the Factor IX Ala-l0-->Thr mutation is a reduction in affinity of the carboxylase for the mutant propeptide. These studies delineate a novel mechanism for warfarin sensitivity. In addition, the data may also explain the observation that bone Gla protein is more sensitive to warfarin than the coagulation proteins.
Rationale for Development of a Synthetic Vaccine Against Plasmodium falciparum Malaria (1985)

Protective immunity against malaria can be obtained by vaccination with irradiated sporozoites. The protective antigens known as circumsporozoite (CS) proteins, are polypeptides that cover the surface membrane of the parasite. The CS proteins contain species-specific immunodominant epitopes formed by tandem repeated sequences of amino acids. Here it is shown that the dominant epitope of Plasmodium falciparum is contained in the synthetic dodecapeptide Asn-Ala-Asn-Pro-Asn-Ala-Asn-Pro-Asn-Ala-Pro or (NANP)3. Monoclonal antibodies and most or all polyclonal human antibodies to the sporozoites react with (NANP)3, and polyclonal antibodies raised against the synthetic peptide (NANP)3 react with the surface of the parasite and neutralize its infectivity. Since (NANP)3 repeats are present in CS proteins of P. falciparum from many parts of the world, this epitope is a logical target for vaccine development.
Deducing molecular similarity using Voronoi binding sites (1993)

We have devised a new measure of molecular similarity with respect to given simple partitions of space into regions. The similarity is determined by numerical integration of the difference in the optimal interaction between the two molecules and the regions over a large range of interaction parameter values. Compounds differing in empirical formula are differentiated by a single infinite region; cis/trans or ortho/meta/para isomers are distinguishable by two adjacent regions that are half-spaces; and stereoisomers require five regions. This can be viewed as a natural classification of isomers. The concept can also be applied to drug binding studies to determine which molecules may bind alike in a given biological receptor and to elucidate a necessary starting geometry when a binding site is modeled for inhibitors whose experimental binding energies are different.
Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown. (1984)

Previous studies suggest that the conjugation of ubiquitin to NH2 groups of proteins is required for protein breakdown. We now show that the selective modification of NH2-terminal alpha-NH2 groups of globin and lysozyme prevents their degradation by the ubiquitin proteolytic system from reticulocytes. The conjugation by ubiquitin of epsilon-NH2 groups of lysine residues, usually seen in multiples, was also inhibited in alpha-NH2-blocked proteins. Naturally occurring N alpha-acetylated proteins are not degraded by the ubiquitin system at a significant rate, while their nonacetylated counterparts from other species are good substrates. This suggests that one function of N alpha-acetylation of cellular proteins is to prevent their degradation by the ubiquitin system. alpha-NH2-blocked proteins can have their activity as substrates for degradation increased by incorporation of alpha-NH2 groups through the introduction of polyalanine side chains. Proteins in which most epsilon-NH2 groups are blocked but the alpha-NH2 group is free are degraded by the ubiquitin system, but at a reduced rate. It is therefore suggested that the exposure of a free NH2 terminus of proteins is required for degradation and probably initiates the formation of ubiquitin conjugates committed for degradation.
Nemos: a framework for axiomatic and executable specifications of memory consistency models (2004)

Summary form only given. Conforming to the underlying memory consistency rules is a fundamental requirement for implementing shared memory systems and developing multiprocessor programs. In order to promote understanding and enable automated verification, it is highly desirable that a memory model specification be both declarative and executable. We present a specification framework called Nemos (Nonoperational yet Executable Memory Ordering Specifications), which supports precise specification and automatic execution in the same framework. We employ a uniform notation based on predicate logic to define shared memory semantics in an axiomatic as well as compositional style. We also apply constraint logic programming and SAT solving to make the axiomatic specifications executable for memory model analysis. To illustrate our approach, we formalize a collection of classical memory models, including sequential consistency, coherence, PRAM, causal consistency, and processor consistency.
Immunotherapy with CAR-Modified T Cells: Toxicities and Overcoming Strategies (2018)

T cells modified via chimeric antigen receptors (CARs) have emerged as a promising treatment modality. Unparalleled clinical efficacy recently demonstrated in refractory B-cell malignancy has brought this new form of adoptive immunotherapy to the center stage. Nonetheless, its current success has also highlighted its potential treatment-related toxicities. The adverse events observed in the clinical trials are described in this review, after which, some innovative strategies developed to overcome these unwanted toxicities are outlined, including suicide genes, targeted activation, and other novel strategies.
Turning Blood into Brain: Cells Bearing Neuronal Antigens Generated in Vivo from Bone Marrow (2000)

Bone marrow stem cells give rise to a variety of hematopoietic lineages and repopulate the blood throughout adult life. We show that, in a strain of mice incapable of developing cells of the myeloid and lymphoid lineages, transplanted adult bone marrow cells migrated into the brain and differentiated into cells that expressed neuron-specific antigens. These findings raise the possibility that bone marrow-derived cells may provide an alternative source of neurons in patients with neurodegenerative diseases or central nervous system injury.
Invariant Amino Acids in the Mur Peptide Synthetases of Bacterial Peptidoglycan Synthesis and Their Modification by Site-Directed Mutagenesis in the UDP-MurNAc:l-Alanine Ligase from Escherichia coli (1997)

The comparison of the amino acid sequences of 20 cytoplasmic peptidoglycan synthetases (MurC, MurD, MurE, MurF, and Mpl) from various bacterial organisms has allowed us to detect common invariants: seven amino acids and the ATP-binding consensus sequence GXXGKT/S all at the same position in the alignment. The Mur synthetases thus appeared as a well-defined class of closely functionally related proteins. The conservation of a constant backbone length between certain invariants suggested common structural motifs. Among the other enzymes catalyzing a peptide bond formation driven by ATP hydrolysis to ADP and Pi, only folylpoly-gamma-l-glutamate synthetases presented the same common conserved amino acid residues, except for the most N-terminal invariant D50. Site-directed mutageneses were carried out to replace the K130, E174, H199, N293, N296, R327, and D351 residues by alanine in the MurC protein from Escherichia coli taken as model. For this purpose, plasmid pAM1005 was used as template, MurC being highly overproduced in this genetic setting. Analysis of the Vmax values of the mutated proteins suggested that residues K130, E174, and D351 are essential for the catalytic process whereas residues H199, N293, N296, and R327 were not. Mutations K130A, H199A, N293A, N296A, and R327A led to important variations of the Km values for one or more substrates, thereby indicating that these residues are involved in the structure of the active site and suggesting that the binding order of the substrates could be ATP, UDP-MurNAc, and alanine. The various mutated murC plasmids were tested for their effects on the growth, cell morphology, and peptidoglycan cell content of a murC thermosensitive strain at 42 degrees C. The observed effects (complementation, altered morphology, and reduced peptidoglycan content) paralleled more or less the decreased values of the MurC activity of each mutant.
Rapid Diagnosis of Bacterial Meningitis by a Seminested PCR Strategy (1995)

A polymerase chain reaction (PCR) based diagnostic assay has been developed for the simultaneous detection in cerebrospinal fluid (CSF) of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Listeria monocytogenes and bacteria in general. In the present communication we describe the design of primers for S. pneumoniae, S. agalactiae, and L. monocytogenes, and a general PCR protocol for the assay. The diagnostic outcome is presented for a small collection of CSF specimens including 2 samples from patients with culture-negative purulent meningitis.
The Use of Silylation in Organic Syntheses (1965)

Abstract The term silylation is used to denote the introduction of a triorganosilyl moiety, especially the trimethylsilyl species, into organic compounds. ‐ Silylated amino acids and sugars are particularly suitable for the syntheses of peptides and saccharides, respectively, since the silyl group can be cleaved off readily under mild conditions. Many diamines undergo ring closure, e.g. with phosgene, only after silylation. ‐ O‐silylated lactim ethers (i.e. cyclic imino ethers) are converted into N‐alkyl derivatives by alkyl halides. Compounds with a strongly polarized SiC bond may be used for chain extension. Silyl esters of halogeno fatty acids yield lactones with silver cyanate. ‐ Trimethylsilyl azide is thermally very stable and behaves like organic azides. It reacts with acetylenic compounds, trialkylphosphines, and triarylphosphines to yield silylated triazole derivatives, trialkylphosphines N‐silylimines, and triarylphosphines to yield silylated triazole dervatives, trialkylphosphine N‐silylimines, and triarylphosphine N‐silylimines, respectively, from which the silyl groups can be removed under mild conditions.
Lithium in the Prevention of Suicidal Behavior and All-Cause Mortality in Patients With Mood Disorders: A Systematic Review of Randomized Trials (2005)

Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.
The Design and Exogenous Delivery of siRNA for Post-transcriptional Gene Silencing (2004)

RNA interference (RNAi) is a natural cellular process that effects post-transcriptional gene silencing in eukaryotic systems. Small interfering RNA (siRNA) molecules are the key intermediaries in this process which when exogenously administered can inhibit or "silence" the expression of any given target gene. Thus, siRNA molecules hold great promise as biological tools and as potential therapeutic agents for targeted inhibition of disease-causing genes. However, key challenges to the effective and widespread use of these polyanionic, macromolecular duplexes of RNA are their appropriate design and efficient delivery to cells in vitro and in vivo. This review highlights the current strategies used in the design of effective siRNA molecules and also summarises the main strategies being considered for the exogenous delivery of siRNA for both in vitro and in vivo applications.
Immunotherapy advances for glioblastoma (2014)

Survival for patients with glioblastoma, the most common high-grade primary CNS tumor, remains poor despite multiple therapeutic interventions including intensifying cytotoxic therapy, targeting dysregulated cell signaling pathways, and blocking angiogenesis. Exciting, durable clinical benefits have recently been demonstrated for a number of other challenging cancers using a variety of immunotherapeutic approaches. Much modern research confirms that the CNS is immunoactive rather than immunoprivileged. Preliminary results of clinical studies demonstrate that varied vaccine strategies have achieved encouraging evidence of clinical benefit for glioblastoma patients, although multiple variables will likely require systematic investigation before optimal outcomes are realized. Initial preclinical studies have also revealed promising results with other immunotherapies including cell-based approaches and immune checkpoint blockade. Clinical studies to evaluate a wide array of immune therapies for malignant glioma patients are being rapidly developed. Important considerations going forward include optimizing response assessment and identifiying correlative biomarkers for predict therapeutic benefit. Finally, the potential of complementary combinatorial immunotherapeutic regimens is highly exciting and warrants expedited investigation.
Highly specific and highly sensitive enzyme immunoassays for antibodies to human interleukin 3 (IL-3) and human erythropoietin (EPO) in serum. (1991)

Two versatile, rapid, easy-to-perform and highly sensitive enzyme immunoassays (ELISAs) were developed for the detection and quantification of antibodies to human IL-3 and human EPO in serum samples from both man and laboratory animals. These one-step assays are based on the "inverse sandwich" principle, where antibodies present in the sample linked both the solid phase antigen bound to a microtiter plate and the free antigen, which had been covalently coupled to horseradish peroxidase. The limits of detection are lower than those of the neutralization bioassays; antibodies to IL-3 and to EPO were detected at concentrations as low as 2 ng/ml and 5 ng/ml, respectively. No cross-reactivity with related proteins and no interfering matrix effects were observed when used for the estimation of antibodies against rhu IL-3 and rhu EPO in serum samples of various species. Thus both assays were used without modification for the screening of antibodies in serum samples from both man and animal during treatment with these hematopoietic hormones.
Evidence of Fibroblast Heterogeneity and the Role of Fibroblast Subpopulations in Fibrosis (1994)

This review article highlights the evidence supporting the concept that, like lymphocytes, fibroblasts also consist of subpopulations with unique phenotypes and functions. A new view of the fibroblast is that they are dynamic and consist of subsets which produce cytokines and interact with the immune system. For example, murine lung fibroblasts separated by fluorescence-activated cell sorting on the basis of the thymocyte-1 antigen are heterogeneous in their morphology, expression of surface markers, antigen presentation to T lymphocytes, ability to synthesize collagen, and cytokine production. Human lung fibroblasts have also been found to be heterogeneous in surface marker expression, proliferation, and collagen production. Investigation of pulmonary fibroblast heterogeneity is important since the lung is particularly susceptible to fibrosis induced by chemotherapy and radiation, inhaled particles, systemic autoimmune disease, etc. The inflammatory responses which typically precede fibrotic induction may be controlled by a subset of resident fibroblasts. Another subset may be important for the fibroblast hyperplasia and extensive extracellular matrix production which are hallmarks of fibrosis. In another model system, periodontal fibroblasts, namely those from periodontal ligament (PDL) and gingiva, also reveal heterogeneity. For example, PDL fibroblasts are composed of subpopulations based on collagen production, morphology, and glycogen pools. Subsets of gingival fibroblasts have also been obtained based on receptors for cyclosporin A and C1q. Specific fibroblast subsets may be involved in gingival repair and hyperplasia. Studies comparing fibroblasts from normal skin vs skin involved with scleroderma have found that scleroderma fibroblasts are activated and able to participate in an inflammatory response. How these fibroblasts become activated is unclear, but it is believed that a subset of fibroblasts is selectively recruited by cytokines at the inflammation site. Finally, investigation and identification of fibroblast subsets from various tissues and their interaction with the immune system could lead to strategies to prevent or reverse debilitating and potentially fatal fibrotic development.
A Short-Term Trial of Tacrolimus Ointment for Atopic Dermatitis (1997)

The short-term application of tacrolimus ointment is effective in the treatment of atopic dermatitis, with the sensation of burning being the main side effect.