gebhart/patrepeval huggingface dataset:
Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone Resorption (1999)

We demonstrated previously that a single injection of recombinant human macrophage colony-stimulating factor (rhM-CSF) is sufficient for osteoclast recruitment and survival in osteopetrotic (op/op) mice with a deficiency in osteoclasts resulting from a mutation in M-CSF gene. In this study, we show that a single injection of recombinant human vascular endothelial growth factor (rhVEGF) can similarly induce osteoclast recruitment in op/op mice. Osteoclasts predominantly expressed VEGF receptor 1 (VEGFR-1), and activity of recombinant human placenta growth factor 1 on osteoclast recruitment was comparable to that of rhVEGF, showing that the VEGF signal is mediated through VEGFR-1. The rhM-CSF-induced osteoclasts died after injections of VEGFR-1/Fc chimeric protein, and its effect was abrogated by concomitant injections of rhM-CSF. Osteoclasts supported by rhM-CSF or endogenous VEGF showed no significant difference in the bone-resorbing activity. op/op mice undergo an age-related resolution of osteopetrosis accompanied by an increase in osteoclast number. Most of the osteoclasts disappeared after injections of anti-VEGF antibody, demonstrating that endogenously produced VEGF is responsible for the appearance of osteoclasts in the mutant mice. In addition, rhVEGF replaced rhM-CSF in the support of in vitro osteoclast differentiation. These results demonstrate that M-CSF and VEGF have overlapping functions in the support of osteoclastic bone resorption.
Effect of Murine Gamma-Interferon on the Mouse Liver and Its Drug-Metabolizing Enzymes: Comparison with Human Hybrid Alpha-Interferon (1985)

Murine IFN(gamma) and human IFN(alpha)-AD:Bgl were compared over a limited dose range and after single and multiple dosing for their effect on male mouse liver oxidative and conjugative drug metabolizing enzymes. Both IFNs depressed the microsomal cytochrome P-450 concentration but did not alter cytosolic glutathione S-transferase nor microsomal UDP-glucuronosyltransferase activity. Both IFNs showed some slight hepatotoxicity (elevated serum ALT), alpha AD:Bgl more than gamma, especially after multiple dosing. While the IFNs did not produce significant increases in liver weight, they did increase the yield of microsomal protein. The increased endoplasmic reticulum may compensate for the decreased cytochrome P-450 concentration and so account for the lack of observed effect of the IFNs on hexobarbital sleep times in vivo. Overall, the minimal effects of murine gamma-IFN on the mouse liver were no different than those of human alpha AD:Bgl.
Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. (1991)

The neural cell adhesion molecule (NCAM) exists in various types of neuroendocrine cells and their tumors. A typical feature of NCAM is polysialic acid, of which the chain length is developmentally regulated. The authors have performed a comparative immunohistochemical study on small cell lung carcinomas and bronchial as well as gastrointestinal carcinoids with the monoclonal antibody (MAb) 735 reactive with the long-chain form of polysialic acid. The small cell lung carcinomas, irrespective of their histological type, were positive for polysialic acid. Metastatic tumor cell complexes also exhibited immunostaining. The tumor cell-surface-associated immunostaining for polysialic acid was sensitive to endoneuraminidase. The mature and atypical bronchial and gastrointestinal carcinoids were not immunoreactive for polysialic acid. Cytoplasmic staining in groups of cells of carcinoids (2 of 28 cases) was due to nonspecific antibody binding, which could be prevented by increased ion strength. These data indicate that neuroendocrine tumors of the lung can be distinguished by their content of highly sialylated NCAM.
High density molecular linkage maps of the tomato and potato genomes. (1992)

High density molecular linkage maps, comprised of more than 1000 markers with an average spacing between markers of approximately 1.2 cM (ca. 900 kb), have been constructed for the tomato and potato genomes. As the two maps are based on a common set of probes, it was possible to determine, with a high degree of precision, the breakpoints corresponding to 5 chromosomal inversions that differentiate the tomato and potato genomes. All of the inversions appear to have resulted from single breakpoints at or near the centromeres of the affected chromosomes, the result being the inversion of entire chromosome arms. While the crossing over rate among chromosomes appears to be uniformly distributed with respect to chromosome size, there is tremendous heterogeneity of crossing over within chromosomes. Regions of the map corresponding to centromeres and centromeric heterochromatin, and in some instances telomeres, experience up to 10-fold less recombination than other areas of the genome. Overall, 28% of the mapped loci reside in areas of putatively suppressed recombination. This includes loci corresponding to both random, single copy genomic clones and transcribed genes (detected with cDNA probes). The extreme heterogeneity of crossing over within chromosomes has both practical and evolutionary implications. Currently tomato and potato are among the most thoroughly mapped eukaryotic species and the availability of high density molecular linkage maps should facilitate chromosome walking, quantitative trait mapping, marker-assisted breeding and evolutionary studies in these two important and well studied crop species.
A Highly Functional Decision Paradigm Based on Nonlinear Adaptive Genetic Algorithm (1997)

Abstract : In the first year of this Phase 2 research program, POC refined the GA Optimizer by rewriting it in DLL format and optimizing the fuzzy logic-based GA control rules. We also evaluated existing neural network training methods using the GA, and examined areas in which our algorithm can improve their performance. POC has also initiated a new line of optimization development tools, the route optimizer. Initial development efforts demonstrate the proof of concept, and show that the algorithm can be applied to many optimization problems; these include making financial predictions, medical predictions, medical diagnoses, and market classifications, as well as modeling manufacturing processes and the anticipated resulting product quality, classifying biological organisms estimating job costs, detecting fraud, and many others. Finally, POC has begun developing the protocol of a development tool combining fuzzified genetic algorithm (GA) and a neural network (NN). This tool will find the optimal structure for the NN by training based on various combinations of the input data, and will optimize it by using NN performance as a fitness value.
A massively scalable persistent content distribution system (2007)

This paper proposes a novel form of peercasting system as an improved solution for IP-based mass media content delivery. Several approaches are discussed, some of which are already widely deployed, or undergoing such deployment, as homogeneous systems. In particular, IP multicast and Peer-to-Peer (P2P) overlay network techniques are described in isolation- as they form the bedrock of the new peercasting system proposal. This proposal aims to improve existing homogenous and heterogeneous systems for mass media distribution to very large user bases, with needs for timely and reliable delivery, and content persistence. Thus IP multicast has great advantages for delivery with controlled last-mile elements, both for mobile and fixed usage. However, persistence while the number of still-receiving users dwindle, and reliability at reasonable network cost, are better served by P2P techniques. The work primarily considers discrete media delivery, which is useful both alongside with streaming media and in standalone applications. The feasibility of such a combined multicast and P2P system is shown and the working prototype implementation of this proposal, Delco, is introduced.
Effects of Retroviral‐Mediated MDR1 Expression on Hematopoietic Stem Cell Self‐Renewal and Differentiation in Culturea (1999)

Ex vivo expansion of hematopoietic stem cells would be useful for bone marrow transplantation and gene therapy applications. Toward this goal, we have investigated whether retrovirally-transduced murine stem cells could be expanded in culture with hematopoietic cytokines. Bone marrow cells were transduced with retroviral vectors expressing either the human multidrug resistance 1 gene (HaMDR1), a variant of human dihydrofolate reductase (HaDHFR), or both MDR1 and DHFR in an internal ribosomal entry site (IRES)-containing bicistronic vector (HaMID). Cells were then expanded for 15 days in cultures stimulated with interleukin (IL)-3, IL-6, and stem cell factor. When very low marrow volumes were injected into lethally irradiated recipient mice, long-term reconstitution with 100% donor cells was seen in all mice injected with HaMDR1- or HaMID-transduced cells. By contrast, engraftment with HaDHFR- or mock-transduced cells ranged from partial to undetectable despite injection of significantly larger marrow volumes. In addition, mice transplanted with expanded HaMDR1- or HaMID-transduced stem cells developed a myeloproliferative disorder that was characterized by an increase in abnormal peripheral blood leukocytes. These results show that MDR1-transduced stem cells can be expanded in vitro with hematopoietic cytokines, but indicate that an increased stem cell division frequency can lead to stem cell damage.
50 million years of chordate evolution: Seeking the origins of adaptive immunity (2000)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Acute Myeloid Leukemia (2002)

In this chapter, Drs. Keating and Willman review recent advances in our understanding of the pathophysiology of acute myeloid leukemia (AML) and allied conditions, including the advanced myelodysplastic syndromes (MDS), while Drs. Goldstone, Avivi, Giles, and Kantarjian focus on therapeutic data with an emphasis on current patient care and future research studies. In Section I, Dr. Armand Keating reviews the role of the hematopoietic microenvironment in the initiation and progression of leukemia. He also discusses recent data on the stromal, or nonhematopoietic, marrow mesenchymal cell population and its possible role in AML. In Section II, Drs. Anthony Goldstone and Irit Avivi review the current role of stem cell transplantation as therapy for AML and MDS. They focus on data generated on recent Medical Research Council studies and promising investigation approaches. In Section III, Dr. Cheryl Willman reviews the current role of molecular genetics and gene expression analysis as tools to assist in AML disease classification systems, modeling of gene expression profiles associated with response or resistance to various interventions, and identifying novel therapeutic targets. In Section IV, Drs. Hagop Kantarjian and Francis Giles review some promising agents and strategies under investigation in the therapy of AML and MDS with an emphasis on novel delivery systems for cytotoxic therapy and on targeted biologic agents.
Topography of a binding site for small amnestic peptides deduced from structure-activity studies: relation to amnestic effect of amyloid beta protein. (1994)

Four peptides homologous to amyloid beta protein containing the Val-Phe-Phe (VFF) sequence administered intracerebroventricularly after training caused amnesia for footshock active avoidance training in mice. Results with VFF and other peptides containing VFF or portions thereof were used to generate a topographic map for a hypothetical binding surface for amnestic peptides, termed Z. Effects on retention of footshock active avoidance training were rationalized in terms of fit to Z, making possible design of potential memory-modulating peptidic and nonpeptidic substances. Three peptides that neither improved nor impaired retention blocked the amnestic effects of beta-(12-28), a peptide homologous to amyloid beta protein, opening the way to development of substances that can antagonize the neurotoxic effects of amyloid beta protein on neural structures and thus attenuate symptoms and progression of Alzheimer disease.
Molecular cloning of the pyrE gene from the extreme thermophile Thermus flavus (1995)

Mutants of the extreme thermophile Thermus flavus in the pyrimidine biosynthetic pathway (Pyr-) were isolated by resistance to 5-fluoroorotic acid. The pyrE gene, which codes for the orotate phosphoribosyltransferase, was cloned by recombination with one of the isolated Pyr- T. flavus mutant strains. It was subcloned by complementation of an Escherichia coli pyrE mutant strain and was sequenced. The deduced polypeptide sequence extends over 183 amino acids. Several independent Pyr- mutations were mapped within the pyrE locus by recombination with fragments of the cloned gene.
Bubble-Free Wafer Bonding of GaAs and InP on Silicon in a Microcleanroom (1989)

A technology is presented that will allow the fabrication of thin III-V compound semiconductor layers of low dislocation density on silicon substrates. GaAs and InP wafers were successfully bonded to bare and oxidized silicon substrates in an experimental setup that produces a microcleanroom for bubble-free bonding in any environment. The bonding strength was found to be comparable to that of Si on oxidized Si and sufficient to subsequent grinding and polishing of the bonded wafers.
Construction and characterization of ack knock‐out mutants of Propionibacterium acidipropionici for enhanced propionic acid fermentation (2006)

Propionibacterium acidipropionici produces propionic acid from glucose with acetic acid, succinic acid, and CO2 as byproducts. In this work, inactivation of ack gene, encoding acetate kinase (AK), by gene disruption and integrational mutagenesis was studied as a method to reduce acetate formation in propionic acid fermentation. The partial ack gene of approximately 750 bp in P. acidipropionici was cloned using a PCR-based method with degenerate primers and sequenced. The deduced amino acid sequence had 88% similarity and 76% identity with the amino acid sequence of AK from Bacillus subtilis. The partial ack gene was used to construct a linear DNA fragment with an inserted tetracycline resistance cassette and a nonreplicative integrational plasmid containing a tetracycline resistance gene cassette. These DNA constructs were then introduced into P. acidipropionici by electroporation, resulting in two mutants, ACK-Tet and TAT-ACK-Tet, respectively. Southern hybridization confirmed that the ack gene in the mutant ACK-Tet was disrupted by the inserted tetracycline resistance gene. As compared to the wild-type, the activities of AK were reduced by 26% and 43% in ACK-Tet and TAT-ACK-Tet mutants, respectively. The specific growth rate of these mutants was reduced by approximately 25% to 0.10/h (0.13/h for the wild-type), probably because of reduced acetate and ATP production. Both mutants produced approximately 14% less acetate from glucose. Although ack disruption alone did not completely eliminate acetate production, the propionate yield was increased by approximately 13%.
Exopolysaccharide Sugars Contribute to Biofilm Formation bySalmonella entericaSerovar Typhimurium on HEp-2 Cells and Chicken Intestinal Epithelium (2005)

Recently, we demonstrated that Salmonella enterica serovar Typhimurium can form biofilm on HEp-2 cells in a type 1 fimbria-dependent manner. Previous work on Salmonella exopolysaccharide (EPS) in biofilm indicated that the EPS composition can vary based upon the substratum on which the bacterial biofilm forms. We have investigated the role of genes important in the production of colanic acid and cellulose, common components of EPS. A mutation in the colanic acid biosynthetic gene, wcaM, was introduced into S. enterica serovar Typhimurium strain BJ2710 and was found to disrupt biofilm formation on HEp-2 cells and chicken intestinal tissue, although biofilm formation on a plastic surface was unaffected. Complementation of the wcaM mutant with the functional gene restored the biofilm phenotype observed in the parent strain. A mutation in the putative cellulose biosynthetic gene, yhjN, was found to disrupt biofilm formation on HEp-2 cells and chicken intestinal epithelium, as well as on a plastic surface. Our data indicate that Salmonella attachment to, and growth on, eukaryotic cells represent complex interactions that are facilitated by species of EPS.
[Treatment of eventrations with a special apparatus]. (1997)

A new method of treating eventrations has been designed. It is based on the use of a special device that enforces the abdominal wall by connecting the wound edges. Besides, a plastic sponge impregnated with an antiseptic substance should be used for local treatment of the wound and for prevention of the external damage of the intestines. The method was successfully used in 8 patients. The advantages of the method are the following: safe closure of the abdominal wall wound, opportunity of performing complete surgical treatment of the wound, step-by-step connection of the wound edges, improvement of lung function. The rate of mortality is 12.5%.
Reactivity of Human Natural Antibodies to Endothelial Cells From Gal??(1,3)Gal-Deficient Pigs (2007)

The generation of Gal-deficient pigs has overcome hyperacute anti-Gal-mediated xenograft rejection in nonhuman primates. Non-Gal anti-porcine NAb represent a potentially relevant immunological hurdle in a subgroup of individuals by inducing endothelial damage in xenografts.
Enzymic degradation of a beta-lactam antibiotic, ampicillin, in the gut: a novel treatment modality (2003)

Antibiotics can cause severe alterations in the gut microflora and promote diarrhoea and overgrowth of pathogenic bacteria. The present study investigated the potency of targeted recombinant beta-lactamase (TRBL) to degrade a beta-lactam antibiotic in the jejunum of fistula-operated beagles. We used different peroral doses of purified beta-lactamase (PenP) of Bacillus licheniformis in enteric-coated pellets together with intravenous ampicillin. Serum and jejunal samples were collected for ampicillin and beta-lactamase analysis. A dose-response effect of TRBL on ampicillin concentrations in the jejunal samples could be observed. The highest doses applied decreased the jejunal ampicillin concentrations to undetectable levels. In the serum samples, the ampicillin concentrations were not affected by the beta-lactamase dose used. Our results indicate that it may be possible to evolve a targeted treatment to degrade beta-lactam antibiotics intestinally and, thus, decrease antibiotic-induced adverse effects on the gut microflora.
Macromol. Rapid Commun. 8/2007 (2007)

Cover: The cover picture shows the self‐assembled wormlike nanostructures in bulk films of an azobenzene‐containing diblock liquid‐crystalline copolymer. Eliminating the scattering of visible light by confining mesogenic segments in nanoscale microphase‐separated domains, the copolymer films showed highly transparent and stable under room light. Further details can be found in the article by H. Yu, A. Shishido, T. Iyoda, and T. Ikeda * on page 927.
Combination antibody‐based cancer immunotherapy (2007)

It is now commonly recognized that tumor-targeting monoclonal antibodies (mAb) demonstrate significant therapeutic effects in cancer patients. Multiple effector mechanisms are involved in the primary response; however, the induction of tumor-specific immunity has sometimes been a desired outcome and in some cases has contributed to the success of mAb-based therapy. Initiating the antitumor immune response by creating a tumor antigen supply from dying (apoptotic) tumor cells is a goal of tumor-targeting mAb therapy, and ideally a sufficiently immunogenic tumor cell death might provide a platform on which combination immunotherapies can be based. In this review, the authors discuss the possible utility and pitfalls of using such a therapy, which combines tumor cell death with immune activation therapy. The ideas are largely based on the observation that three-mAb (anti-DR5 mAb, anti-CD40 mAb, and anti-CD137 mAb [trimAb]) therapy has been shown to be very effective in a number of mouse experimental tumor models. The authors believe that this rational activation and inhibition of key points in the immune response can be an effective strategy to apply in human cancer patients.
Lysophosphatidic Acid Inhibits C-Type Natriuretic Peptide Activation of Guanylyl Cyclase-B (2002)

C-type natriuretic peptide (CNP), found in endothelial cells, chondrocytes, and neurons, binds its cognate transmembrane receptor, natriuretic peptide receptor-B (NPR-B/GC-B), and stimulates the synthesis of the intracellular signaling molecule, cGMP. The known physiologic consequences of this binding event are vasorelaxation, inhibition of cell proliferation, and the stimulation of long bone growth. Here we report that 10% fetal bovine serum markedly reduced CNP-dependent cGMP elevations in NIH3T3 fibroblast. The purified serum components platelet-derived growth factor and lysophosphatidic acid (LPA) mimicked the effect of serum on CNP-dependent cGMP elevations, but the latter factor resulted in the most dramatic reductions. The LPA-dependent inhibition was rapid and dose dependent, having t(1/2) and IC(50) values of approximately 5 min and 3.0 micro M LPA, respectively. The decreased cGMP concentrations resulted from reduced CNP-dependent NPR-B guanylyl cyclase activity that did not require losses in receptor protein or activation of protein kinase C, indicating a previously undescribed desensitization pathway. These data suggest that NPR-B is repressed by LPA and that one mechanism by which LPA exerts its effects is through the heterologous desensitization of the CNP/NPR-B/cGMP pathway. We hypothesize that cross-talk between the LPA and CNP signaling pathway maximizes the response of fibroblasts in the wound-healing process.
Definition of a responder in clinical trials for functional gastrointestinal disorders: report on a symposium (1999)

On 10 and 11 September 1998, about 125 participants met at a symposium in Vienna, Austria, with the goal of determining whether a consensus could be developed on the definition of responders in clinical trials in the functional gastrointestinal disorders. Present at this meeting were representatives of the Food and Drug Administration (FDA) (Robert Prizont, MD, and John Senior, MD*), a representative of the Japanese International Motility Society (Kei Matsueda, MD, PhD), academic investigators from around the world, and representatives of several pharmaceutical companies currently engaged in the development of therapeutic compounds for the functional gastrointestinal disorders. The discussion centered primarily on the irritable bowel syndrome (IBS), the functional gastrointestinal disorder for which there is the largest development program underway. However, the discussion also addressed the measurement of outcomes in functional constipation.

This conference was sponsored by the Multinational Working Teams to Develop Diagnostic Criteria for Functional Gastrointestinal Disorders (MWT). Over a two year period, the executive committee of the MWT held a series of informal meetings with representatives of the FDA, and on one occasion, with a representative of the European Agency for the Evaluation of Medicinal Products. During these meetings, representatives of the regulatory groups indicated that there was a need for a more broad-based consensus on the best ways of defining responders in clinical trials. The MWT organized this conference …