gebhart/patrepeval huggingface dataset:
Myelosuppressive effects in vivo of purified recombinant murine macrophage inflammatory protein-1 alpha (1992)

Purified recombinant murine macrophage inflammatory protein-1 alpha (rmuMIP-1 alpha), a cytokine with myelopoietic activity in vitro, was assessed in vivo by injection into C3H/HeJ mice for effects on proliferation (percentage of cells in S phase DNA synthesis of the cell cycle) and absolute numbers of granulocyte-macrophage, erythroid, and multipotential progenitor cells in the femur and spleen, and on nucleated cellularity in the bone marrow, spleen, and blood. rmuMIP-1 alpha rapidly decreased cycling rates (at 2 to 10 micrograms/mouse i.v.) and absolute numbers (at 5 to 10 micrograms/mouse i.v.) of myeloid progenitor cells in the marrow and spleen. These effects were dose- and time-dependent and reversible. Suppressive effects were noted within 3 to 24 h for cell cycling and absolute numbers of progenitor cells in the marrow and spleen, and by 48 h for circulating neutrophils. A study comparing the effects of i.v. injection of rmuMIP-1 alpha versus rmuMIP-1 beta, a biochemically similar molecule but with no myelosuppressive effects in vitro, demonstrated myelosuppression in vivo by rmuMIP-1 alpha, but not by rmuMIP-1 beta. The results suggest that rmuMIP-1 alpha has myelosuppressive activity in vivo and offers the possibility that it may be a useful adjunct to treatments involving cytotoxic drugs because of its reversible suppressive effects on normal progenitor cell cycling.
[Diagnosis of bacterial contamination of the small intestine using the 1 g [14C] xylose breath test in various gastrointestinal diseases]. (1992)

The prevalence of the small intestine bacterial overgrowth syndrome has been assessed in 109 in-patients affected by various gastrointestinal disorders using the 1 g [14C]-xylose breath test; 18 healthy subjects acted as a control group: none of them showed abnormal results (100% specificity). None of 14 patients with colonic disease had abnormal results, whereas in 44 patients with ileal diseases the test was positive in 12% to 39% of the cases. Abnormal results were found in 46% of patients who underwent partial gastric resection greater than 20 years before, 29% of patients with irritable bowel syndrome without diarrhoea (faecal wet weight less than or equal to 600 g/72 h), 56% of those with diarrhoea of obscure origin, and 25% of celiac patients. Eight out of 8 patients with altered results showed normalization of the test after antibiotic therapy. Despite its high diagnostic value in the setting of clinical research, the 1 g [14C]-xylose breath test cannot as yet be proposed as a routine investigation.
1,3-Disubstituted Benzazepines as Novel, Potent, Selective Neuropeptide Y Y1 Receptor Antagonists (1999)

A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R(1) and R(3) substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K(i) values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R(1) and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R(3) in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido++ +))benzyl )-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [(125)I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K(i) = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca(2+) concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.
Synthesis, Antifolate and Anticancer Activities of N5‐Substituted 8,10‐Dideazatetrahydrofolate Analogues (2015)

Based on our previous work, seven N(5) -substituted 8,10-dideazatetrahydrofolate analogues and one 8-deazatetrahydrofolate analogue were designed and synthesized as human dihydrofolate reductase (hDHFR) inhibitors. All compounds were assayed versus DHFR and five different cancer cell lines. The biological assay indicated that replacing N(10) with carbon would significantly increase inhibitory activities against DHFR and cytotoxicities against cancer cell lines. Compound 19a with 4-amino and N(5) -formyl showed great antitumour activities against HL-60, Bel-7402 and BGC823 which were much better than MTX.
R-Cadherin Expression Inhibits Myogenesis and Induces Myoblast Transformation via Rac1 GTPase (2008)

Cadherins are transmembrane glycoproteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion and play a crucial role in proliferation, differentiation, and cell transformation. The goal of this study was to understand why R-cadherin is found in rhabdomyosarcomas (RMS), tumors of skeletal muscle origin, whereas it is absent in normal myoblasts. We show that R-cadherin expression in C2C12 myoblasts causes inhibition of myogenesis induction and impairment of cell cycle exit when cells are cultured in differentiation medium. Furthermore, R-cadherin expression elicits myoblast transformation, as shown by anchorage-independent growth in soft agar in vivo tumor formation assays and increased cell motility. In contrast, inhibition of R-cadherin expression using RNA interference hinders growth of RD cell line in soft agar and its tumorigenicity in mice. The analysis of the nature of R-cadherin-mediated signals shows that R-cadherin-dependent adhesion increases Rac1 activity. Dominant-negative forms of Rac1 inhibit R-cadherin-mediated signaling and transformation. In addition, expression of R-cadherin results in perturbed function of endogenous N-cadherin and M-cadherin. Together, these data suggest that R-cadherin expression inhibits myogenesis and induces myoblast transformation through Rac1 activation. Therefore, the properties of R-cadherin make it an attractive target for therapeutic intervention in RMS.
The myeloma-associated oncogene fibroblast growth factor receptor 3 is transforming in hematopoietic cells (2001)

Translocations involving fibroblast growth factor receptor 3 (fgfr3) have been identified in about 25% of patients with myeloma. To directly examine the oncogenic potential of fgfr3, murine bone marrow (BM) cells were transduced with retroviral vectors containing either wild-type fgfr3 or an activated mutant form of the receptor, fgfr3-TD. Mice transplanted with FGFR3-TD-expressing BM developed a marked leukocytosis and lethal hematopoietic cell infiltration of multiple tissues within 6 weeks of transplantation. Secondary and tertiary recipients of spleen or BM from primary fgfr3-TD mice also developed tumors within 6 to 8 weeks. Analysis of the circulating tumor cells revealed a pre-B-cell phenotype in most mice, although immature T-lymphoid or mature myeloid populations also predominated in some animals. Enhanced lymphoid but not myeloid colony formation was observed in the early posttransplantation period and only interleukin 7 and FGF-responsive pre-B-cell lines could be established from tumors. Cell expansions in primary recipients appeared polyclonal, whereas tumors in later passages exhibited either clonal B- or T-cell receptor gene rearrangements. Mice transplanted with wild-type FGFR3-expressing BM developed delayed pro-B-cell lymphoma/leukemias approximately 1 year after transplantation. These studies confirm that FGFR3 is transforming and can produce lymphoid malignancies in mice.
Cloning of Giardia lamblia heat shock protein HSP70 homologs: implications regarding origin of eukaryotic cells and of endoplasmic reticulum. (1994)

The genes for two different 70-kDa heat shock protein (HSP70) homologs have been cloned and sequenced from the protozoan Giardia lamblia. On the basis of their sequence features, one of these genes corresponds to the cytoplasmic form of HSP70. The second gene, on the basis of its characteristic N-terminal hydrophobic signal sequence and C-terminal endoplasmic reticulum (ER) retention sequence (Lys-Asp-Glu-Leu), is the equivalent of ER-resident GRP78 or the Bip family of proteins. Phylogenetic trees based on HSP70 sequences show that G. lamblia homologs show the deepest divergence among eukaryotic species. The identification of a GRP78 or Bip homolog in G. lamblia strongly suggests the existence of ER in this ancient eukaryote. Detailed phylogenetic analyses of HSP70 sequences by boot-strap neighbor-joining and maximum-parsimony methods show that the cytoplasmic and ER homologs form distinct subfamilies that evolved from a common eukaryotic ancestor by gene duplication that occurred very early in the evolution of eukaryotic cells. It is postulated that because of the essential "molecular chaperone" function of these proteins in translocation of other proteins across membranes, duplication of their genes accompanied the evolution of ER or nucleus in the eukaryotic cell ancestor. The presence in all eukaryotic cytoplasmic HSP70 homologs (including the cognate, heat-induced, and ER forms) of a number of autapomorphic sequence signatures that are not present in any prokaryotic or organellar homologs provides strong evidence regarding the monophyletic nature of eukaryotic lineage. Further, all eukaryotic HSP70 homologs share in common with the Gram-negative group of eubacteria a number of sequence features that are not present in any archaebacterium or Gram-positive bacterium, indicating their evolution from this group of organisms. Some implications of these findings regarding the evolution of eukaryotic cells and ER are discussed.
Biotechnology of Microbial Exopolysaccharides (1990)

This volume provides a thorough account of the structure and synthesis of microbial exopolysaccharides and of their widespread application across a broad range of industries, including food, oil and medicine. The successful exploitation of these polysaccharides requires a sound scientific understanding of their chemical and physical properties and also their biochemistry and biosynthesis; this volume covers all these aspects in a concise and coherent way. Interest in these polysaccharides has been fuelled by their increasing use in food, in the oil industry and in medicine. The author provides an account of all these areas as well as looking further ahead to speculate how their unique properties might be harnessed for future products and processes.
Properties of erythromycin-inducible transposon Tn917 in Streptococcus faecalis (1980)

Streptococcus faecalis strain DS16 harbors two plasmids, a conjugative plasmid, pAD1, which encodes hemolysin and bacteriocin activities, and a nonconjugative plasmid, pAD2, encoding resistance to streptomycin, kanamycin, and erythromycin, the latter of which is inducible. The erythromycin resistance determinant is located on a 3.3-megadalton transposable element designated Tn917, which could be transposed to pAD1 as well as to two other plasmids, pAm gamma 1 and pAM alpha 1. When strain DS16 was exposed to low (inducing) concentrations of erythromycin for a few hours, the frequency of Tn917 transposition from pAD2 to pAD1 increased by an order of magnitude. This induction paralleled induction of erythromycin resistance and was prevented by exposing the cells to inhibitors of deoxyribonucleic acid, ribonucleic acid or protein synthesis. The exposure of strain DS16 to inducing concentrations of erythromycin also enhanced the frequency of erythromycin-resistant transconjugants appearing during mating. Initially, cointegrate molecules, whose molecular weights were approximately the sum of pAD1 and pAD2, accounted for these transconjugants; however, as the induction time increased, pAD1::Tn917 became increasingly prominent.
A Likelihood Ratio Test of Speciation with Gene Flow Using Genomic Sequence Data (2010)

Genomic sequence data may be used to test hypotheses about the process of species formation. In this paper, I implement a likelihood ratio test of variable species divergence times over the genome, which may be considered a test of the null model of allopatric speciation without gene flow against the alternative model of parapatric speciation with gene flow. Two models are implemented in the likelihood framework, which accommodate coalescent events in the ancestral populations in a phylogeny of three species. One model assumes a constant species divergence time over the genome, whereas another allows it to vary. Computer simulation shows that the test has acceptable false positive rate but to achieve reasonable power, hundreds or even thousands of genomic loci may be necessary. The test is applied to genomic data from the human, chimpanzee, and gorilla.
Abstract 3836: Novel conditionally active biologic anti-Axl antibody-drug conjugate demonstrates anti-tumor efficacy and improved safety profile (2016)

Abstract Axl is a TAM family receptor tyrosine kinase that has been implicated in the pathogenesis of many cancer types. The high level of expression on the cancer cell surface has made it an attractive target for antibody therapeutics. However, Axl is expressed on many normal tissues and has been implicated in wide ranging requisite biological processes including response of endothelial cells to vascular injury, hematopoiesis, and regulation of immune responses. This normal tissue expression may limit Axl as a target for antibody-drug-conjugates (ADC). Conditionally Active Biologics (CAB) technology is a proprietary platform that selects antibodies that bind to target antigen in the context of diseased tissues, but not normal tissues, by taking advantage of the unique cancer microenvironment that is produced largely as a result of the Warburg effect. Using our CAB technology, we have identified anti-Axl Abs that reversibly bind to recombinant Axl and Axl expressing cells under conditions that are present in the tumor microenvironment but not in normal tissues. CAB-Axl antibodies were then conjugated to a model toxin payload to generate CAB-Axl-ADCs. The CAB-Axl-ADCs were active against Axl positive human tumor xenografts with tumor stasis observed at 1mg/kg weekly and tumor regressions observed at 1 mg/kg twice a week dose levels. A non-specific IgG-ADC showed minimal efficacy at the same dose levels. Single dose studies in cynomolgus macaques have demonstrated that CAB-Axl-ADC has reduced liver toxicity and immune system effects compared to Axl-ADCs that bind to Axl under normal conditions. In conclusion, our data is consistent with our work on CAB-EGFR antibodies, and suggests that ADCs generated using the CAB technology provides biologics with increased therapeutic index. Specifically, the CAB-Axl-ADC is an excellent candidate for evaluation as a treatment for human cancers that are Axl positive. Citation Format: Cathy Chang, Gerhard Frey, William J. Boyle, Leslie L. Sharp, Jay M. Short. Novel conditionally active biologic anti-Axl antibody-drug conjugate demonstrates anti-tumor efficacy and improved safety profile. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3836.
Analysis of the catalytic domain of the lysin of the lactococcal bacteriophage Tuc2009 by chimeric gene assembling (1996)

An active chimeric cell wall lytic enzyme (Tsl) has been constructed by fusing the region coding for the N-terminal half of the lactococcal phage Tuc2009 lysin and the region coding for the C-terminal domain of the major pneumococcal autolysin. The chimeric enzyme exhibited a glycosidase activity capable of hydrolysing choline-containing pneumococcal cell walls. This experimental approach demonstrated that the Tuc2009 lysin possesses a modular structure and further supports the hypothesis that many cell wall lytic enzymes have evolved by the fusion of preexisting catalytic and peptidoglycan-binding domains.
Value-relevance of nonfinancial information: The wireless communications industry (1996)

We examine the value-relevance to investors of financial (accounting) and nonfinancial information of independent cellular companies and find that, on a stand-alone basis, financial information (earnings, book values, and cash flows) are largely irrelevant for security valuation. Nonfinancial indicators, such as POPS (a growth proxy) and Market Penetration (an operating performance measure), are highly value-relevant. However, combined with nonfinancial information, earnings do contribute to the explanation of prices. The complementarity between financial and nonfinancial data is highlighted in this study.
Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria (2008)

Bacteria are capable of "communicating" their local population densities via a process termed quorum sensing (QS). Gram-negative bacteria use N-acylated l-homoserine lactones (AHLs), in conjunction with their cognate LuxR-type receptors, as their primary signalling circuit for QS. In this critical review, we examine AHL signalling in Gram-negative bacteria with a primary focus on the design of non-natural AHLs, their structure-activity relationships, and their application in chemical biological approaches to study QS (72 references).
A multi-robot cooperative task achievement system (2002)

Discusses a general architecture where various schemes for multi-robot task achievement can be integrated called "M+ Cooperative task achievement". The main originality comes from its ability to allow the robots to detect-in distributed and cooperative manner-resource conflict situations as well as sub-optimalities. Different decisions are performed by the robots such as actions re-scheduling, suppression of redundancies and opportunistic enhancement of the global performance. Finally, we illustrate its use through a simulated system, which allows a number of robots to plan and perform cooperatively a set of tasks in a hospital environment.
Studies of the Metabolism and Distribution of Fibrinogen in Patients with Hemophilia A* (1967)

Using autologous (131)I-fibrinogen, we made studies of the metabolism and distribution of fibrinogen in 10 patients with hemophilia A. In two patients simultaneous studies of autologous (131)I-fibrinogen and homologous (125)I-fibrinogen prepared from healthy donors' plasma were carried out. The average value for the plasma volume was 42.1 +/- 8.8 ml/kg; for the plasma fibrinogen concentration, 349 +/- 90 mg/100 ml; for the intravascular fibrinogen, 144 +/- 32 mg/kg; for the interstitial fibrinogen, 30 +/- 11 mg/kg; for the slower half-life of (131)I-fibrinogen, 2.34 +/- 0.17 days; for the transcapillary transfer rate of fibrinogen, 109 +/- 37 mg/kg per day; and for the catabolic and synthetic rates of fibrinogen, 51.7 +/- 13.1 mg/kg per day. Comparison of these results with those of the previous study in healthy male subjects showed that in patients with hemophilia A the catabolic and synthetic rates of fibrinogen are markedly increased, whereas the plasma fibrinogen concentration, intravascular and interstitial fibrinogen, and the transcapillary transfer rate of fibrinogen are not significantly different. The simultaneous studies of autologous (131)I-fibrinogen and normal homologous (125)I-fibrinogen in two subjects revealed that the two preparations behaved very similarly. Based on these findings, we concluded that our present findings are not due to the qualitative difference between the hemophilia A and normal fibrinogens, but that they are due to the difference in the host condition with respect to the fibrinogen metabolism, which is either an increased rate of direct breakdown of fibrinogen or an increased rate of fibrinogen breakdown after fibrin formation, or both.
Anastomotic Leakage Is Predictive of Diminished Survival After Potentially Curative Resection for Colorectal Cancer (2004)

Apart from its immediate clinical consequences, anastomotic leakage also has an independent negative association with survival.
Local fluorescent probes for the fluorescence resonance energy transfer scanning near-field optical microscopy (2002)

We present fluorescence resonance energy transfer (FRET) images of donor dye molecule clusters recorded using a local fluorescence probe for scanning near-field optical microscopy (SNOM): standard apertured SNOM fiber tip coated with the 30–100-nm-thick polymer layer stained with the acceptor dye molecules. The tip works as a “self-sharpening pencil”: the apical layers of the FRET-active tip coating are mechanically worn out during scanning thus continuously exposing a fresh active apex to continue imaging. Only a few tens of acceptor molecules are used to form the optical images, and using such an approach spatial resolution better than the size of the aperture is achievable.
Social class and minor psychiatric disorder in British Civil Servants: a validated screening survey using the General Health Questionnaire (1992)

Major psychiatric disorder is more common in people of lower rather than higher socioeconomic status. This is less clear for the commoner, so-called minor psychiatric disorders, but these are more affected by tendency to report symptoms. To examine this the distribution of minor psychiatric disorder by employment grade measured by the 30-item General Health Questionnaire is reported from the first cross-sectional phase of the Whitehall II Study of 10,314 London-based civil servants, men and women between 35 and 55 years. Validation of the GHQ in a random subsample stratified by grade and sex (N = 201) suggested that people in lower employment grades tend to under-report minor psychiatric disorder on the GHQ relative to those in higher employment grades. The prevalence of minor psychiatric disorder corrected by the coefficients from the validity study was greater in the lower employment grades than the higher employment grades particularly for men. This was echoed in grade differences in well-being measured by the Affect Balance Scale, and in symptoms and recurrent health problems. Overall, for women there were few clear-cut differences in minor psychiatric disorder by employment grade. The lack of social class gradient in women suggests that further exploration should examine women's role at work and their personal lives for the aetiology of minor psychiatric disorder.