gebhart/patrepeval huggingface dataset:
Diminished platelet binding in vitro by Staphylococcus aureus is associated with reduced virulence in a rabbit model of infective endocarditis (1996)

The direct binding of platelets by bacteria is a postulated central mechanism in the pathogenesis of endocarditis. To address the role of binding more definitively, we employed Tn551 insertional mutagenesis of Staphylococcus aureus parental strain ISP479 to generate an isogenic variant (strain PS12) that bound platelets minimally. As compared with the binding of ISP479, the binding of PS12 to platelet monolayers was reduced by 67.2%. Similarly, the binding of PS12 to platelets in suspension was reduced by 71.3%, as measured by flow cytometry. The low-binding phenotype was transducible into both ISP479 and S. aureus Newman. Southern blotting indicated that a single copy of Tn551 was inserted within the chromosomes of PS12 and the transductants. When tested in a rabbit model, animals inoculated with PS12 were significantly less likely to develop endocarditis and had lower densities of organisms (CFU per gram) within vegetations and a decreased incidence of renal abscess formation, as compared with animals inoculated with the parental strain. The diminished virulence of PS12 was not attributable to a reduction in the initial attachment of organisms to the damaged endocardium, since 30 min after inoculation, PS12-infected animals had microbial densities on the valve surface comparable to those seen with the parental strain. These results indicate that the direct binding of Staphylococcus aureus to platelets is a major determinant of virulence in the pathogenesis of endocarditis. Staphylococcus-platelet binding appears to be critical for pathogenetic events occurring after the initial colonization of the valve surface, such as vegetation formation and septic embolization.
Muscle-derived hematopoietic stem cells are hematopoietic in origin (2002)

It has recently been shown that mononuclear cells from murine skeletal muscle contain the potential to repopulate all major peripheral blood lineages in lethally irradiated mice, but the origin of this activity is unknown. We have fractionated muscle cells on the basis of hematopoietic markers to show that the active population exclusively expresses the hematopoietic stem cell antigens Sca-1 and CD45. Muscle cells obtained from 6- to 8-week-old C57BL/6-CD45.1 mice and enriched for cells expressing Sca-1 and CD45 were able to generate hematopoietic but not myogenic colonies in vitro and repopulated multiple hematopoietic lineages of lethally irradiated C57BL/6-CD45.2 mice. These data show that muscle-derived hematopoietic stem cells are likely derived from the hematopoietic system and are a result not of transdifferentiation of myogenic stem cells but instead of the presence of substantial numbers of hematopoietic stem cells in the muscle. Although CD45-negative cells were highly myogenic in vitro and in vivo, CD45-positive muscle-derived cells displayed only very limited myogenic activity and only in vivo.
Experimental visceral leishmaniasis: role of endogenous IFN-gamma in host defense and tissue granulomatous response. (1989)

The capacity of BALB/c mice to acquire resistance to and eliminate intracellular visceral Leishmania donovani is T cell dependent, associated with a granulomatous tissue reaction, and correlates with the ability to secrete the macrophage-activating lymphokine, IFN-gamma. These responses appear by 4 wk after infection and are fully established by 8 wk. To examine the role of endogenous IFN-gamma, BALB/c mice were injected with anti-IFN-gamma mAb before and for 8 wk after infection. At 4 wk, mAb treatment inhibited the acquisition of resistance to L. donovani and abolished mature granuloma formation. Although liver parasite burdens in mAb-treated mice were fivefold higher than in controls at 8 wk, continually treated mice nevertheless began for form tissue granulomas and decreased their parasite loads by 50% from peak values. The levels of anti-IFN-gamma antibody in the serum of mice injected for 8 wk were appreciably reduced, thus raising the possibilities of either insufficient neutralization of endogenous IFN-gamma at this time point or a pathway independent of IFN-gamma. Although the role of IFN-gamma and the potential effect of an IFN-gamma-independent mechanism in the resolution of visceral infection remain to be defined, these results indicate that IFN-gamma plays a critical role in the early immune response that both optimally controls L. donovani infection and induces the tissue granuloma.
The power of stem cells reconsidered? (1999)

The consumption of opportunistic foods is part of the behavioral repertoire used by hominins for subsistence. The acquisition of opportunistic animal resources is sometimes associated with stressful conditions. But, there are other conditions ...The acquisition of opportunistic animal resources by hunter-gatherers—such as scavenged carcasses—is a well-known subsistence strategy. It is frequently mentioned in the context of the history of early human evolution, but not regularly considered among ...
Dipeptidyl peptidase IV inhibitors for the treatment of impaired glucose tolerance and type 2 diabetes. (2003)

Glucagon-like peptide-1 (GLP-1 (7-36) amide) is a gut hormone released from L-cells in the small intestine in response to the ingestion of nutrients and enhances the glucose-dependent secretion of insulin from pancreatic beta-cells. In type 2 diabetic patients, the continuous infusion of GLP-1 (7-36) amide decreases plasma glucose and hemoglobin A1c concentrations and improves beta-cell function. Hormone action is rapidly terminated by the N-terminal cleavage of GLP-1 at Ala2 by the aminopeptidase, dipeptidyl peptidase IV (DPPIV). The short in vivo half-life of GLP-1 (< 3 min) poses challenges to the development of exogenous GLP-1-based therapy. The inhibition of endogenous GLP-1 degradation by reducing DPPIV activity is an alternative strategy for improving the incretin action of GLP-1 in vivo. This review summarizes recent advances in the design of potent and selective small molecule inhibitors of DPPIV and the potential challenges to the development of DPPIV inhibitors for the treatment of impaired glucose tolerance and type 2 diabetes.
Molecular evidence that the asexual industrial fungus Trichoderma reesei is a clonal derivative of the ascomycete Hypocrea jecorina. (1996)

The relationship of the important cellulase producing asexual fungus Trichoderma reesei to its putative teleomorphic (sexual) ancestor Hypocrea jecorina and other species of the Trichoderma sect. Longibrachiatum was studied by PCR-fingerprinting and sequence analyses of the nuclear ribosomal DNA region containing the internal transcribed spacers (ITS-1 and ITS-2) and the 5.8S rRNA gene. The differences in the corresponding ITS sequences allowed a grouping of anamorphic (asexual) species of Trichoderma sect. Longibrachiatum into Trichoderma longibrachiatum, Trichoderma pseudokoningii, and Trichoderma reesei. The sexual species Hypocrea schweinitzii and H. jecorina were also clearly separated from each other. H. jecorina and T. reesei exhibited identical sequences, suggesting close relatedness or even species identity. Intraspecific and interspecific variation in the PCR-fingerprinting patterns supported the differentiation of species based on ITS sequences, the grouping of the strains, and the assignment of these strains to individual species. The variations between T. reesei and H. jecorina were at the same order of magnitude as found between all strains of H. jecorina, but much lower than the observed interspecific variations. Identical ITS sequences and the high similarity of PCR-fingerprinting patterns indicate a very close relationship between T. reesei and H. jecorina, whereas differences of the ITS sequences and the PCR-fingerprinting patterns show a clear phylogenetic distance between T. reesei/H. jecorina and T. longibrachiatum. T. reesei is considered to be an asexual, clonal line derived from a population of the tropical ascomycete H. jecorina.
Ultratrace Determination of Selected Lanthanides by Luminescence Enhancement (1996)

The luminescence intensity of trivalent lanthanides, especially terbium(III) and europium(III), is shown to be enhanced by coordination with the ligand 2,6-pyridinedicarboxylic acid (DPA). Further enhancement can be obtained by forming a columinescent complex aggregate with ions such as gadolinium(III), terbium(III), lanthanum(III), or yttrium(III), where the Y(III) complex shows the greatest enhancement. A surfactant, sodium dodecyl sulfate (SDS), can be added to the solution to enhance the luminescence intensity of many lanthanide-ligand complexes by segregating the complex from quenchers. In this study, SDS has little effect on the limit of detection, but it does act to extend the linear dynamic range to include higher concentrations. The combination of columinescent complex with surfactant resulted in decreased luminescence intensity coupled with an increase in the background due to the light scattered by the surfactant micelles. A mechanism for the enhancement of the lanthanide luminescent intensity by energy transfer has been described by Xu et al. This study differs in that a lanthanide ion excitation band represents the most efficient excitation path and not a ligand excitation band. The complexes examined in this study have advantages over those used in prior studies since they do not require surfactants to achieve low limits of detection (100 parts per quadrillion, ppq, for Eu(DPA)(3)(3)(-) and 60 ppq for Tb(DPA)(3)(3)(-)), and they exhibit longer linear dynamic ranges (from 4 to 6 decades) than other columinescent systems.
The Radioprotective Effect of Vitamins C, E and Vitamin E + Glutathione on the Small Intestine and the Thyroid Gland in Rats Irradiated with X- Rays (2000)

This investigation was carried out in order to determine the protective effects of long term administration at supraphysiologi- cal doses of vitamin E, vitamin C and a compound of vitamin E + glutathione against damage induced by free radicals produced by ionizing radiation. Five groups of 8-10-week-old Wistar albino rats were used in the study. Group I was the sham group and Group II was the radiation group (i.e. radiation alone). The rats in Group III were given a daily dose of 400 mg/kg of vit. C for one month. The rats in Group IV were given a daily dose of vit. E for one month. The rats in Group V received a mix- ture of 400 mg/kg vit. E plus 1000 mg/kg of glutathione per day for 15 days. All the com- pounds were administered via a nasogastric tube. At the end of the drug administration period, the rats in all but the sham group were exposed to X-ray with an radiation ener- gy dose of 8.90 Gy. All the rats were sacri- ficed 1 day after irradiation. Thyroid and intestinal tissues were examined for histopathological changes and T3 , T4 , TSH hormone levels were determined by radioim- munoassay (RIA). The radiation damage observed in the thy- roidal and intestinal cross-sections of the Group II rats was also seen to a lesser extent in the Group III (vit. C group) and Group IV (vit. E) rats. Toxic effects were observed in the Group V (vit. E + glutathione) rats. Sig- nificant T3 and TSH level changes (p
A Framework for Dynamic Car and Taxi Pools with the Use of Positioning Systems (2009)

Carpooling is the concept of people sharing a vehicle for a ride when their departure and destination locations are similar. Dynamic car pool [1] is the dynamic coordination of ride offerings and ride requests based on the, in real time created, transportation and offering needs. Taxi pool [2] is a mode of transport that falls between private transport and conventional bus transport. The routes are fixed or semi-fixed, but with the added convenience of stopping anywhere to pick or drop passengers and not having fixed time schedules. Positioning Systems are systems for finding the location of a mobile device using several different positioning technologies. This paper describes how Positioning Systems can be utilized in order to support a dynamic network of car and taxi pool services that will maximize the exploitation of empty seats traveling with tenable advantages.
Inhibition of endotoxin-induced interleukin-6 production by synthetic lipid A partial structures in human peripheral blood mononuclear cells (1991)

The effect of two synthetic lipid A partial structures, compound 406 (or LA-14-PP, identical in structure to the lipid A precursor, known as Ia or IVa) and compound 401 (lipid X), on the in vitro modulation of endotoxin (lipopolysaccharide)-induced interleukin-6 production by human blood mononuclear cells was investigated. Lipopolysaccharide of Salmonella abortus equi and synthetic Escherichia coli-type lipid A (compound 506, or LA-15-PP) had potent interleukin-6-inducing capacities. The maximum release of interleukin-6 was found after stimulation with 1 to 10 ng of lipopolysaccharide or 10 to 100 ng of synthetic E. coli-type lipid A per ml. Both synthetic lipid A partial structures (compounds 406 and 401) failed to induce interleukin-6 release. However, they inhibited lipopolysaccharide- or lipid A-induced interleukin-6 production in a dose-dependent manner. Inhibition was found not only in mononuclear cells but also in purified monocytes and was not due to a shift in the kinetics of cytokine production. Suppression was manifested in the early stage of interleukin-6 production. Inhibition was also found in the presence of recombinant gamma interferon, indicating that compound 406 and recombinant gamma interferon act in different, independent pathways. Our data, therefore, indicate that the inhibition of interleukin-6 production by lipid A partial structures may help elucidate the mechanism of interaction of the lipid A component of lipopolysaccharide with immune cells in the inflammatory reaction during gram-negative infection.
38.1: Invited Paper : Photo‐Aligned Anisotropic Optical Thin Films (2003)

Abstract Photo‐alignment of anisotropic optical thin films enables realization of novel optical elements, which were not feasible so far. Photo‐aligned anisotropic thin films can be applied to rigid or flexible substrates, which may be flat or curved. The optical performance of such films can be tailored to application specific requirements by introducing tilt profiles of the optical axis and/or generate patterned retarders with continuous or periodical in‐plane variation of the optical axis.
Embedding an intelligent tutoring system in a business gaming-simulation environment (1994)

Gaming-Simulation environments have recently become valuable tools for education and training. To enhance their pedagogical effectiveness as a teaching environment they have to be equipped with intelligent tutoring support. The integration of an Intelligent Tutoring System into a Man-Machine Gaming-Simulation Environment provides such an intelligent teaching tool. This paper presents INTUITION, the implementation of the Metal Box Business Simulation Game, that illustrate show an Intelligent Tutoring System may be embedded within a Gaming-Simulation Environment.
The cystine knot of a squash-type protease inhibitor as a structural scaffold for Escherichia coli cell surface display of conformationally constrained peptides (1999)

The Ecballium elaterium trypsin inhibitor II (EETI-II), a member of the squash family of protease inhibitors, is composed of 28 amino acid residues and is a potent inhibitor of trypsin. Its compact structure is defined by a triple-stranded antiparallel beta-sheet, which is held together by three intramolecular disulfide bonds forming a cystine knot. In order to explore the potential of the EETI-II peptide to serve as a structural scaffold for the presentation of randomized oligopeptides, we constructed two EETI-II derivatives, where the six-residue inhibitor loop was replaced by a 13-residue epitope of Sendai virus L-protein and by a 17-residue epitope from human bone Gla-protein. EETI-II and derived variants were produced via fusion to maltose binding protein MalE. By secretion of the fusion into the periplasmic space, fully oxidized and correctly folded EETI-II was obtained in high yield. EETI-II and derived variants could be presented on the Escherichia coli outer membrane by fusion to truncated Lpp'-OmpA', which comprises the first nine residues of mature lipoprotein plus the membrane spanning beta-strand from residues 46-66 of OmpA protein. Gene expression was under control of the strong and tightly regulated tetA promoter/operator. Cell viability was found to be drastically reduced by high level expression of Lpp'-OmpA'-EETI-II fusion protein. To restore cell viability, net accumulation of fusion protein in the outer membrane was reduced to a tolerable level by introduction of an amber codon at position 9 of the lpp' sequence and utilizing an amber suppressor strain as expression host. Cells expressing EETI-II variants containing an epitope were shown to be surface labeled with the respective monoclonal antibody by indirect immunofluorescence corroborating the cell surface exposure of the epitope sequences embedded in the EETI-II cystine knot scaffold. Cells displaying a particular epitope sequence could be enriched 10(7)-fold by combining magnetic cell sorting with fluorescence-activated cell sorting. These results demonstrate that E.coli cell surface display of conformationally constrained peptides tethered to the EETI-II cystine knot scaffold has the potential to become an effective technique for the rapid isolation of small peptide molecules from combinatorial libraries that bind with high affinity to acceptor molecules.
Backup and storage management in distributed heterogeneous environments (2002)

Powerful but nevertheless easy-to-operate systems for backing up and reconstructing data from clients are necessary in a distributed heterogeneous environment. The concept of the Siemens Nixdorf Informationssysteme (SNI) AG is based on a client/server model. It runs under the control of a SINIX server and includes backup clients for various Unix systems, PCs such as those with MS-DOS/Windows, and PCs in the Novell NetWare network. Logical data backup and restore actions for any file or disk partition in a Unix system and for any file in a PC system can be performed automatically and at defined times during an operation. The backup media are tapes, DAT cartridges, magneto-optical disks, and associated autochangers and jukeboxes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In vivo generation of human CD 19‐ CAR T cells results in B‐cell depletion and signs of cytokine release syndrome (2018)

Chimeric antigen receptor (CAR) T cells brought substantial benefit to patients with B-cell malignancies. Notwithstanding, CAR T-cell manufacturing requires complex procedures impeding the broad supply chain. Here, we provide evidence that human CD19-CAR T cells can be generated directly <i>in vivo</i> using the lentiviral vector CD8-LV specifically targeting human CD8<sup>+</sup> cells. Administration into mice xenografted with Raji lymphoma cells and human peripheral blood mononuclear cells led to CAR expression solely in CD8<sup>+</sup> T cells and efficacious elimination of CD19<sup>+</sup> B cells. Further, upon injection of CD8-LV into mice transplanted with human CD34<sup>+</sup> cells, induction of CAR T cells and CD19<sup>+</sup> B-cell depletion was observed in 7 out of 10 treated animals. Notably, three mice showed elevated levels of human cytokines in plasma. Tissue-invading CAR T cells and complete elimination of the B-lymphocyte-rich zones in spleen were indicative of a cytokine release syndrome. Our data demonstrate the feasibility of <i>in vivo</i> reprogramming of human CD8<sup>+</sup> CAR T cells active against CD19<sup>+</sup> cells, yet with similar adverse effects currently notorious in the clinical practice.
Development of psoriasis after B cell depletion with rituximab (2007)

The B cell-depleting monoclonal antibody rituximab is a novel therapy for the rheumatic diseases, with an increasing body of evidence regarding its safety and efficacy in an expanding range of indications. However, there is uncertainty over its potential use in, and impact on, autoantibody-negative diseases. We describe 3 patients, with no known risk factor for psoriasis, who developed psoriasis (and 1 who also developed features of psoriatic arthritis) after receiving rituximab for a variety of indications, namely, seropositive and seronegative rheumatoid arthritis and systemic lupus erythematosus. In all cases, the underlying disease responded well to rituximab. The interpretation of this possible side effect of rituximab remains unclear, but a B cell-depleted environment may induce abnormal T cell responses, possibly provoked either by subclinical infection or by the removal of mechanisms whereby B cells regulate T cells. These cases suggest that the pathogenesis of psoriasis may not require normal numbers of B cells and that proposed treatment of psoriasis and psoriatic arthritis with rituximab may result in unpredictable responses.
An endoscopic capsule robot: a meso-scale engineering case study (2009)

A number of unique challenges arise in fabricating and assembling complex mechanisms at the meso-scale (hundreds of microns to centimetres). In general, for a complex multi-part mechanism at this length scale, no single machining technique can produce all the necessary parts—or often even a single individual part. Towards developing a comprehensive set of 'best practices' for combining multiple precision micromachining operations at the meso-scale, we present a case study on fabricating and assembling an endoscopic capsule robot. Existing passive imaging capsules have proven exceptionally useful in the diagnosis of the gastrointestinal tract, and robotic capsules promise to enhance their diagnostic capabilities and enable non-invasive treatment delivery. In this case study, we describe the fabrication of a robotic capsule (2.6 cm3 in volume) containing a complex mechanism consisting of 72 components, each of which requires a variety of meso- or even micro-scale features. We describe the manufacturing processes used to produce these components and features (combinations of high precision, multiply refixtured computer numerical control processes, sink and wire electro discharge machining, laser cutting, etc). These results contribute to the emerging framework of best practices in meso-scale design and manufacture, illustrating ways to effectively combine several processes to produce a complex meso-scale device.