gebhart/patrepeval huggingface dataset:
Detection and Characterization of Circulating Tumour Cells from Frozen Peripheral Blood Mononuclear Cells (2015)

Retrospective analysis of patient tumour samples is a cornerstone of clinical research. CTC biomarker characterization offers a non-invasive method to analyse patient samples. However, current CTC technologies require prospective blood collection, thereby reducing the ability to utilize archived clinical cohorts with long-term outcome data. We sought to investigate CTC recovery from frozen, archived patient PBMC pellets. Matched samples from both mCRPC patients and mock samples, which were prepared by spiking healthy donor blood with cultured prostate cancer cell line cells, were processed "fresh" via Epic CTC Platform or from "frozen" PBMC pellets. Samples were analysed for CTC enumeration and biomarker characterization via immunofluorescent (IF) biomarkers, fluorescence in-situ hybridization (FISH) and CTC morphology. In the frozen patient PMBC samples, the median CTC recovery was 18%, compared to the freshly processed blood. However, abundance and localization of cytokeratin (CK) and androgen receptor (AR) protein, as measured by IF, were largely concordant between the fresh and frozen CTCs. Furthermore, a FISH analysis of PTEN loss showed high concordance in fresh vs. frozen. The observed data indicate that CTC biomarker characterization from frozen archival samples is feasible and representative of prospectively collected samples.
Bactericidal Effects of 405 nm Light Exposure Demonstrated by Inactivation ofEscherichia, Salmonella, Shigella, Listeria, and MycobacteriumSpecies in Liquid Suspensions and on Exposed Surfaces (2012)

The bactericidal effect of 405 nm light was investigated on taxonomically diverse bacterial pathogens from the genera Salmonella, Shigella, Escherichia, Listeria, and Mycobacterium. High-intensity 405 nm light, generated from an array of 405-nm light-emitting diodes (LEDs), was used to inactivate bacteria in liquid suspension and on exposed surfaces. L. monocytogenes was most readily inactivated in suspension, whereas S. enterica was most resistant. In surface exposure tests, L. monocytogenes was more susceptible than Gram-negative enteric bacteria to 405 nm light when exposed on an agar surface but interestingly less susceptible than S. enterica after drying onto PVC and acrylic surfaces. The study findings, that 405 nm light inactivates diverse types of bacteria in liquids and on surfaces, in addition to the safety advantages of this visible (non-UV wavelength) light, indicate the potential of this technology for a range of decontamination applications.
Studies of immunomodulating actions of carotenoids. II. astaxanthin enhancesin vitroantibody production to T‐dependent antigens without facilitating polyclonal B‐cell activation (1993)

Previously we have shown that astaxanthin, a carotenoid without provitamin A activity, enhances in vitro antibody (Ab) production to sheep red blood cells in normal B6 mice. In this study, we further attempted to examine the mechanisms of this enhancing action of carotenoids on specific Ab production in vitro in relation to different antigen (Ag) stimuli, cytokine production, and T- and B-cell interactions in both normal and autoimmune strains of mice. When the actions of carotenoids were tested in normal strains of mice, we found that astaxanthin enhanced in vitro Ab production to T cell-dependent Ag, but not to T-independent Ag, and did not augment total immunoglobulin production. Astaxanthin exerted maximum enhancing actions when it was present at the initial period of Ag priming. This action of astaxanthin was abolished when T cells were depleted from spleen cell suspensions and appeared to require direct interactions between T and B cells. The results also indicated that carotenoids may modulate the production of interferon-tau in this assay system. When the actions of carotenoids were tested in autoimmune-prone MRL and NZB mice, the enhancing action of astaxanthin on in vitro Ab production was less significant. Furthermore, carotenoids did not potentiate or augment spontaneous Ab and immunoglobulin production by spleen cells in these strains. Taken together, carotenoids without provitamin A activity may be able to augment in vitro specific Ab production to T cell-dependent Ag partly through affecting the initial stage of Ag presentation without facilitating polyclonal B-cell activation or autoantibody production.
Proliferative responses to interleukin-3 and granulocyte colony- stimulating factor distinguish a minor subpopulation of CD34-positive marrow progenitors that do not express CD33 and a novel antigen, 7B9 (1991)

Human hematopoietic colony-forming cells (CFC) express the CD34 antigen (CD34+) as well as differentiation antigens such as CD33 and HLA-DR. CD34+ cells that do not express these latter differentiation antigens have been shown to contain few CFC in direct culture, but generate increasing numbers of CFC when cultured over a marrow stromal cell layer in the long-term culture system. In this study we determined if CD34+ cells with low or absent expression of CD33 and a novel antigen, 7B9 (CD34+CD33–7B9-), could be distinguished from CD34+ cells expressing these antigens (CD34+CD33+7B9+) based on their proliferative responses to interleukin-3 (IL-3) and granulocyte colony-stimulating factor (G-CSF) in a short-term liquid culture system. These two populations were separated by fluorescence-activated cell sorting, cultured with IL-3 (10 ng/mL), G-CSF (100 ng/mL), or IL-3 and G-CSF, and 3H-thymidine uptake was measured. CD34+CD33–7B9- cells proliferated in the presence of IL-3, but not G-CSF. However, a synergistic response to the combination of IL-3 and G-CSF was seen in most experiments. In contrast, CD34+CD33+7B9+ cells proliferated in the presence of either IL-3 or G-CSF but did not display an additive or synergistic response to the combination of IL-3 and G-CSF. In colony-forming assays performed before and after liquid culture, the CD34+CD33–7B9- cells in two experiments contained 0.3% and 2.2% of all sorted marrow CFC before liquid culture and generated 40-fold and ninefold increases in the number of granulocyte-macrophage colony-forming units (CFU-GM), respectively, after liquid culture with IL-3 and G-CSF. In contrast, the CD34+CD33+7B9+ cells contained 99.7% and 97.8% of all sorted marrow CFC before liquid culture and had no change or a threefold increase in the number of CFU-GM, respectively, after liquid culture with IL-3 and G-CSF. Single-cell liquid cultures containing IL-3 and G-CSF with cells that were either CD34+CD33–7B9- and depleted of mature lymphoid cells (CD34+lin-) or were CD34+lin+ showed that a higher proportion of wells containing a CD34+lin- cell gave rise to one or more CFC (8.7%) than did wells containing a CD34+lin+ cell (2.9%), with the responding cells in the former population giving rise to an average of 2.9 +/- 0.6 CFC and in the latter population, 2.0 +/- 1.0 CFC.(ABSTRACT TRUNCATED AT 400 WORDS)
T cell receptor β chain usage in myelin basic protein‐specific rat T lymphocytes (1989)

Abstract Myelin basic protein (MBP)‐specific T cell lines and clones have been established from rats of the major histocompatibility complex (MHC)‐compatible Lewis and BS strains. All lines and clones are MHC class II restricted and share the CD 4 phenotype. The cells proliferate specifically in response to either a peptide representing amino acids #68–88 of guinea pig MBP, to residues #47–67 or to an unidentified myelin antigen which is distinct from MBP. All lines and clones specific for MBP express the same T cell receptor (TcR) variable (V) β chain element, which is homologous to the mouse Vβ8.2 gene segment. Three lines/clones with the same antigen fine specificity have identical V β D β J β junctions on the protein level, a region which represents part of the potential antigen‐binding protion of the TcR; two of the lines express members of the V α 2 family. These results suggest biased usage of TcR V β elements in rat T cells specific for MBP. Our findings broaden the basis for a rational therapeutic strategy to specifically intervene in the rodent model system of experimental allergic encephalomyelitis.
A cyclic peptidylic inhibitor of murine urokinase-type plasminogen activator: changing species specificity by substitution of a single residue (2008)

uPA (urokinase-type plasminogen activator) is a potential therapeutic target in a variety of pathological conditions, including cancer. In order to find new principles for inhibiting uPA in murine cancer models, we screened a phage-displayed peptide library with murine uPA as bait. We thereby isolated several murine uPA-binding peptide sequences, the predominant of which was the disulfide-bridged constrained sequence CPAYSRYLDC, which we will refer to as mupain-1. A chemically synthesized peptide corresponding to this sequence was found to be a competitive inhibitor of murine uPA, inhibiting its activity towards a low-molecular-mass chromogenic substrate as well as towards its natural substrate plasminogen. The K(i) value for inhibition as well as the K(D) value for binding were approx. 400 nM. Among a variety of other murine and human serine proteases, including trypsin, mupain-1 was found to be highly selective for murine uPA and did not even measurably inhibit human uPA. The cyclic structure of mupain-1 was indispensable for binding. Alanine scanning mutagenesis identified Arg(6) of mupain-1 as the P1 residue and indicated an extended binding interaction including the P5, P3, P2, P1 and P1' residues of mupain-1 and the specificity pocket, the catalytic triad and amino acids 41, 99 and 192 located in and around the active site of murine uPA. Exchanging His(99) of human uPA by a tyrosine residue, the corresponding residue in murine uPA, conferred mupain-1 susceptibility on to the latter. Peptide-derived inhibitors, such as mupain-1, may provide novel mechanistic information about enzyme-inhibitor interactions, provide alternative methodologies for designing effective protease inhibitors, and be used for target validation in murine model systems.
An Experimental Study of Thermal Aspects of Cylindrical Plunge Grinding (1972)

The workpiece temperature in cylindrical plunge grinding is considered as a superposition of a base temperature and an interference zone temperature. A solution for the transient base temperature distribution is derived. A two-part experiment for determining thermal effects is described. The heat transfer coefficient at the workpiece surface is measured in the first part, and specific grinding energy and workpiece temperature are measured in the second part. The energy entering the workpiece during grinding is determined from the base temperature solution and experimental data. Results obtained with several grinding fluids and application systems are presented. The energy entering the workpiece was found to be 75 to 85 percent of the total grinding energy during dry grinding and 25 to 35 percent during wet grinding.
Gelatin‐based sprayable foam as a skin substitute (1981)

Physical and antimicrobial properties of a newly developed gelatin based spray-on foam bandage for use on skin wounds have been evaluated. The aqueous foam is sprayed from aerosol containers and effectively covers and washes uneven wound surfaces. The foam dries to form an adherent and stable three-dimensional matrix which diminishes evaporative water losses. The foam possesses antimicrobial activity against gram-positive, gram-negative, and fungal contaminants.
Mechanism of action of inter-.alpha.-trypsin inhibitor (1987)

Inter-alpha-trypsin inhibitor (I alpha I) is a unique proteinase inhibitor that can be proteolyzed by the same enzymes that are inhibited, to generate smaller inhibitors. This study examines the reactions of I alpha I with trypsin, chymotrypsin, plasmin, and leukocyte elastase. Complexes of I alpha I and proteinase were demonstrated by gel filtration chromatography. Complete digestion of I alpha I by each proteinase was not accompanied by a comparable loss of inhibition of that enzyme or a different enzyme. Following proteolysis, inhibitory activity was identified in I alpha I fragments of molecular weight 50,000-100,000 and less than 40,000. Addition of a second proteinase inhibitor prevented proteolysis. Both I alpha I and its complex with proteinase were susceptible to degradation. Kinetic parameters for both the inhibition and proteolysis reactions of I alpha I with four proteinases were measured under physiological conditions. On the basis of these results, a model for the mechanism of action of I alpha I is proposed: Proteinase can react with either of two independent sites on I alpha I to form an inhibitory complex or a complex that leads to proteolysis. Both reactions occur simultaneously, but the inhibitory capacity of I alpha I is not significantly affected by proteolysis since the product of proteolysis is also an inhibitor. For a given proteinase, the inhibition equilibrium constant and the Michaelis constant for proteolysis describe the relative stability of the inhibition and proteolysis complexes; the second-order rate constants for inhibition and proteolysis indicate the likelihood of either reaction. The incidence of inhibition or proteolysis reactions involving I alpha I in vivo cannot be assessed without knowledge of the exact concentrations of inhibitor and proteinases; however, analysis of inhibition rate constants suggests that I alpha I might be involved in plasmin inhibition.
Convenient Preparation of Dialkyl Diselenides: A Large Scale Synthesis ofbis-(2-Hydroxyethyl) Diselenide (1993)

Abstract A convenient and economic large scale preparation of bis-(2-hydroxyethyl) diselenide is reported. The title compound is a useful source of nucleophilic 2-hydroxyethyl selenolate anion or electrophilic 2-hydroxyethyl selenenyl halides or pseudohalides.
Dynamic headspace capillary gas chromatography: A versatile analytical technique (1988)

Abstract The applicability of dynamic headspace analyses for viscous liquids and solid samples is demonstrated. Some comments on the usefulness of this technique for quantifying volatiles in polymeric matrices are made.
Roles of the WHHL Rabbit in Translational Research on Hypercholesterolemia and Cardiovascular Diseases (2011)

Conquering cardiovascular diseases is one of the most important problems in human health. To overcome cardiovascular diseases, animal models have played important roles. Although the prevalence of genetically modified animals, particularly mice and rats, has contributed greatly to biomedical research, not all human diseases can be investigated in this way. In the study of cardiovascular diseases, mice and rats are inappropriate because of marked differences in lipoprotein metabolism, pathophysiological findings of atherosclerosis, and cardiac function. On the other hand, since lipoprotein metabolism and atherosclerotic lesions in rabbits closely resemble those in humans, several useful animal models for these diseases have been developed in rabbits. One of the most famous of these is the Watanabe heritable hyperlipidemic (WHHL) rabbit, which develops hypercholesterolemia and atherosclerosis spontaneously due to genetic and functional deficiencies of the low-density lipoprotein (LDL) receptor. The WHHL rabbit has been improved to develop myocardial infarction, and the new strain was designated the myocardial infarction-prone WHHL (WHHLMI) rabbit. This review summarizes the importance of selecting animal species for translational research in biomedical science, the development of WHHL and WHHLMI rabbits, their application to the development of hypocholesterolemic and/or antiatherosclerotic drugs, and future prospects regarding WHHL and WHHLMI rabbits.
Synthesis of a tritium-labeled indolidan analog and its use as a radioligand for phosphodiesterase-inhibitor cardiotonic binding sites (1989)

We have radiolabeled a structural analogue of indolidan, a potent phosphodiesterase-inhibitor cardiotonic, to permit biochemical studies regarding the interaction of this class of drugs with their pharmacological receptor. [3H]-LY186126 (1,3-dihydro-3,3-dimethyl-1-[3H3]methyl-5-(1,4,5,6-tetrahydro-4-me thyl-6- oxo-3-pyridazinyl)-2H-indol-2-one; [3H]-3) was selected as a synthetic target because of its potency as a cardiotonic and the ability to readily incorporate three tritia via the indolone N-CH3 substituent. Alkylation of a desmethyl precursor with tritium-labeled iodomethane resulted in [3H]-3 with a radiochemical purity of 98% and a specific activity of 79.2 Ci/mmol. This radioligand binds with high affinity to myocardial membrane vesicles. The binding was saturable, and Kd and Bmax values of 4.1 nM and 383 fmol/mg protein were obtained. A series of indolidan congeners displaced [3H]-3 bound to myocardial vesicles, and Ki values for inhibition of binding were highly correlated with canine inotropic ED50 values, suggesting the specific binding of [3H]-3 to cardiac vesicles is pharmacologically relevant.
Implication of transcription factor E2F in regulation of DNA replication (1999)

The transcription factor E2F plays crucial roles in induction of S phase in mammalian cells by regulating the expression of genes that encode molecules involved in cell cycle progression. E2F exerts a repressive effect on E2F-responsive genes in G0/G1 phase by associating with the retinoblastoma tumor suppressor gene product pRb and the related protein p130. This repression is relieved by phosphorylation of the pRb family proteins by G1 cyclin (cyclin D and cyclin E) -dependent kinases, resulting in expression of E2F-responsive genes in late G1 with a peak at the G1/S boundary. One group of genes influenced by E2F encode cell cycle regulatory molecules, including members of the E2F family and cyclin E, demonstrating a loop-type regulation of activities of E2F and cyclin E-dependent kinase at this stage in the cell cycle. Another group is involved in DNA replication, including genes for molecules regulating initiation of DNA replication. Overexpression of E2F is sufficient to induce DNA synthesis in serum starved fibroblasts. In addition, overexpression of cyclin E, which is essential for entry into S phase, overcomes G1 arrest caused by inhibition of E2F activity without resuming E2F mediated transcription, suggesting the mergence of the two pathways. Thus, E2F target-gene products and cyclin E-dependent kinase activity apparently co-operate to initiate replication of DNA.
Surrogate End Points in Clinical Trials: Are We Being Misled? (1996)

Phase 3 clinical trials, which evaluate the effect that new interventions have on the clinical outcomes of particular relevance to the patient (such as death, loss of vision, or other major symptomatic event), often require many participants to be followed for a long time.There has recently been great interest in using surrogate end points, such as tumor shrinkage or changes in cholesterol level, blood pressure, CD4 cell count, or other laboratory measures, to reduce the cost and duration of clinical trials. In theory, for a surrogate end point to be an effective substitute for the clinical outcome, effects of the intervention on the surrogate must reliably predict the overall effect on the clinical outcome. In practice, this requirement frequently fails. Among several explanations for this failure is the possibility that the disease process could affect the clinical outcome through several causal pathways that are not mediated through the surrogate, with the intervention's effect on these pathways differing from its effect on the surrogate. Even more likely, the intervention might also affect the clinical outcome by unintended, unanticipated, and unrecognized mechanisms of action that operate independently of the disease process. We use examples from several disease areas to illustrate how surrogate end points have been misleading about the actual effects that treatments have on the health of patients. Surrogate end points can be useful in phase 2 screening trials for identifying whether a new intervention is biologically active and for guiding decisions about whether the intervention is promising enough to justify a large definitive trial with clinically meaningful outcomes.In definitive phase 3 trials, except for rare circumstances in which the validity of the surrogate end point has already been rigorously established, the primary end point should be the true clinical outcome.
N-Acylvanillamides:  Development of an Expeditious Synthesis and Discovery of New Acyl Templates for Powerful Activation of the Vanilloid Receptor (2002)

A simple and general synthesis of vanillamides was developed and employed to screen acids from the fatty and isoprenoid pools for new acyl templates of biological relevance as capsaicin analogues. Potent activation of the human vanilloid receptor 1 (VR1) was observed for the vanillamides of certain polyfunctional acids from both pools, showing that the vanilloid activity of capsaicinoids can be substantially improved by introducing polar groups and/or unsaturations on the acyl moiety. The activity of the unsaturated analogues was maintained or even increased by cyclopropanation, while omega dimerization led to a substantial increase of activity. Because of the wide structural diversity of the library of compounds screened, these observations could not be translated into a single framework of structure-activity relationships. Nevertheless, a series of new highly active leads was identified, validating the pharmacological potential of the unnatural combination of natural building blocks to provide new bioactive compounds.
Comparison of Systemic Resistance Induced by Avirulent and NonpathogenicPseudomonasSpecies (1996)

The plant growth-promoting rhizobacterium (PGPR) Pseudomonas fluorescens strain WCS417 has been shown to induce systemic resistance against Fusarium oxysporum in several plant species without inducing synthesis of pathogenesis-related proteins (PR). The aim of this study was to establish the spectrum of protection achieved by P fluorescens-mediated induced resistance and to compare its effectiveness with pathogen-mediated systemic acquired resistance, which is associated with necrosis and induction of PR synthesis. We demonstrated that pretreatment with P. fluorescens protects radish (Raphanus sativus) through induction of systemic resistance not only against the fungal root pathogen F. oxysporum f. sp. raphani, but also against the avirulent bacterial leaf pathogen P syringae pv. tomato and the fungal leaf pathogens Alternaria brassicicola and F. oxysporum. We thus demonstrated, for the first time, that one PGPR strain can induce resistance against multiple pathogens. The level of protection was at least as high as that achieved by the necrotizing, PR-inducing P. syringae pv. tomato, and the spectrum was even broader indicating that i) necrosis is not a prerequisite for effective, biological induction of resistance and ii) the absence of PR after induction by P. fluorescens does not lower the level of protection.