gebhart/patrepeval huggingface dataset:
Thermoplastic Polyurethane Elastomers Made from High Molecular Weight POLY-L® Polyols (1992)

High molecular weight polyether polyols formed by the poly merization of epoxides, especially propylene oxide, using conventional KOH catalysis contain high levels of unsaturation. This unsaturation is in the form of allyl and isopropenyl end groups and results in a loss of functionality. A diol that ideally has a functionality of 2.0 can be as low as 1.70 for a conventional 4000 molecular weight polyol. As the molecular weight increases the func tionality decreases. Since the unsaturation is a function of molecular weight, a limiting molecular weight will be reached where further propylene oxide fails to add to the chain and to increase molecular weight. High molecular weight polyether diols containing low unsaturation were pre pared using double metal cyanide catalysts. With these catalysts ultra high molecular weight polyols can be made without a concomitant increase in the rate of formation of unsaturated end groups. A 4000 molecular weight diol was made that had unsaturation levels five times lower than a comparable polyol prepared by conventional KOH catalysis. Additionally, 5500 and 6600 molec ular weight diols containing very low unsaturation levels were also made. All of the polyols were capped with ethylene oxide to give high levels of primary hydroxyl groups. These polyols were evaluated in thermoplastic polyurethane elastomer formulations. The thermoplastic polyurethane elastomers were based on MDI and chain ex tended with butanediol. Those prepared from polyols with low unsaturation levels had significantly higher physical properties than thermoplastic polyurethane elastomers prepared with conventionally made polyols. Soft ther moplastic polyurethane elastomers were made from high molecular weight polyols containing low unsaturation levels. These soft thermoplastic polyure thane elastomers are softer than any currently commercially available. They exhibited good tensile strength, excellent elongation and high resilience prop erties.
Cloning of cDNA coding for connective tissue activating peptide III from a human platelet-derived lambda gt11 expression library (1989)

We report here the cloning of the cDNA coding for platelet connective tissue-activating peptide-III (CTAP-III) from a lambda gt11 expression library prepared using messenger RNA (mRNA) isolated from human platelets. The open reading frame of the clone coded for a protein with 128 amino acid residues. Since the precursor of CTAP-III, platelet basic protein (PBP is 94 amino acids long, the 5'-translated region of the cDNA codes for a leader sequence 34 amino acids long. This leader sequence, like the sequence of mature CTAP-III, shows significant homology to the sequence of platelet factor 4 (PF4), the only other platelet specific alpha-granule protein cloned until now, from a human erythroleukemic (HEL) cell line-derived cDNA library. These leader sequences are probably critical for targeting such proteins to the alpha-granule. Northern blot hybridization with platelet and megakaryocyte mRNA shows a single species mRNA of approximately 0.8 kb, suggesting that the corresponding cDNA is full length. The cloning of platelet specific CTAP-III provides additional evidence for the platelet specificity of the cDNA library used.
Low-Dose Radiation-Induced Senescent Stromal Fibroblasts Render Nearby Breast Cancer Cells Radioresistant (2009)

In addition to cell cycle arrest, DNA repair or/and apoptosis, ionizing radiation can also induce premature senescence, which could lead to very different biological consequences depending on the cell type. We show in this report that low-dose radiation-induced senescent stromal fibroblasts stimulate proliferation of cocultured breast carcinoma cells. Such effects of senescent fibroblasts appear to result from their ability to induce the expression in carcinoma cells of mitotic genes and subsequent mitotic division. The elevated proliferation of breast carcinoma cells correlates with resistance to radiation as well as to adriamycin. Of interest is the observation that exposure to lower doses (<20 cGy) augments the ability of senescent fibroblasts to promote the survival of cocultured breast carcinoma cells. The resistance appears to be mediated partially by the Akt pathway, because expression of a dominant negative Akt mutant in breast carcinoma cells results in a partial reversal of the radioresistance. The ability of fibroblasts to modulate the radiosensitivity of nearby carcinoma cells implicates the importance of targeting the stroma during therapy.
The significance of the late fall in myocardial PCO2 and its relationship to myocardial pH after regional coronary occlusion in the dog. (1985)

After acute regional coronary occlusion, myocardial tissue PCO2, as measured by mass spectrometry, rises, reaches a peak, and then gradually falls. This late fall in myocardial tissue PCO2 could be due to (1) a gradual increase in tissue blood flow (and hence improved carbon dioxide washout), (2) a gradual consumption of tissue bicarbonate, (3) a gradual reduction in the production of carbon dioxide due to progressive cellular damage, or (4) an artifact caused by the continued presence of the mass spectrometer probe in the ischemic tissue. To determine which of these four mechanisms is responsible for the late fall in myocardial tissue PCO2, we subjected 27 anesthetized open-chest dogs to 3-hour occlusion of the left anterior descending coronary artery. Both myocardial tissue PCO2 and intramyocardial hydrogen ion concentration were measured in the myocardial segment supplied by the left anterior descending coronary artery. Ten dogs (group 1) were killed after the occlusion (occlusion I), and 11 dogs (group 2) underwent reocclusion (occlusion II) at the same site after a 45-minute period of reflow. Regional myocardial blood flow was measured periodically by the intramural injection of 127Xe. Changes in myocardial tissue PCO2 and hydrogen ion concentration were related to ultrastructural changes in the tissues adjacent to the myocardial tissue PCO2 probe. Regional myocardial blood flow remained unchanged throughout the 3-hour occlusion, ruling out increased carbon dioxide washout as a cause for its late fall. Tissue hydrogen ion concentration, as measured by a new lead glass electrode, correlated well with myocardial tissue PCO2, with the reduction in regional myocardial blood flow, and with ischemic damage assessed histologically. Myocardial hydrogen ion concentration also exhibited a late fall after the occlusion, from a peak of 199.8 +/- 27.8 nmol/liter to 91.9 +/- 12.1 nmol/liter (mean +/- SEM). This ruled out consumption of tissue bicarbonate as the cause for the late fall in myocardial tissue PCO2. Peak rise in myocardial tissue PCO2 after occlusion II (71.2 +/- 7.9 mm Hg) was significantly lower than peak myocardial tissue PCO2 after occlusion I (116.7 +/- 13.9 mm Hg, P less than 0.001). The difference between these latter two values, as well as the magnitude of fall in myocardial tissue PCO2 during occlusion I, related directly to the degree of histological damage observed.(ABSTRACT TRUNCATED AT 400 WORDS)
Epitope studies indicate that histidyl‐tRNA synthetase is a stimulating antigen in idiopathic myositis (1995)

The most frequently found myositis-specific antibody, the anti-Jo-1 antibody (anti-HRS), binds to histidyl-tRNA synthetase (HRS). Although this antibody reacts with HRS, it is unclear whether HRS is the stimulating antigen or is merely a protein that cross-reacts with a yet undefined antigen. Because antibody directed against an unrelated antigen would not be expected to cross-react with HRS at multiple sites, we mapped the epitopes on HRS to resolve this issue. We found by Western blot analyses that immunoglobulins G (IgG) from 18 of 19 anti-HRS positive patient sera react with amino acids 2-44 and 286-509 of HRS. Patient IgG specific for these two epitopes were found not to inhibit HRS enzyme activity. Instead, the inhibitory property of anti-HRS was found to be associated with antibodies that do not react to HRS in immunoblots, indicating the presence of other epitopes. In addition, antibodies that react in immunoblots were found to represent only a small fraction of total anti-HRS antibody. Our finding that patient IgG recognized at least three distinct epitopes on HRS strongly suggests that the immunological response at some point in the disease is directed against HRS and not against a cross-reactive antigen.
The Chemistry of the Morphine Alkaloids (1954)

Journal Article The Chemistry of the Morphine Alkaloids Get access The Chemistry of the Morphine Alkaloids. Bentley K. W.. 433 pages. Oxford University Press, 114 Fifth Avenue, New York 11, N. Y. ( 1954) $8.00. AIBS Bulletin, Volume 4, Issue 3, July 1954, Page 13, https://doi.org/10.1093/aibsbulletin/4.3.13-e Published: 01 July 1954
A toxic fragment from the entomocidal crystal protein of Bacillus thuringiensis. (1984)

Purified crystal protein from Bacillus thuringiensis subsp. dendrolimus strain T84A1gave a single polypeptide band (apparent mol. wt 145, 000) on SDS-PAGEand the only N-terminal amino acid sequence was Met-Asp-Asn-Asn-Pro-Asn-Ile-. No pentose or hexose was detected. Solid phase tryptic digestion of the solubilized crystal protein bound on a DEAE-cellulose column was found to be a successful method to prepare a toxic fragment without denaturation. The resulting fragment (fragment T) was slightly basic (pI 8.9) and the molecular weight was estimated as 58, 000 on SDS-PAGEand by gel filtration without denaturing agents. The apparent number of the amono acid residues was 516 and the N- and C-terminal sequences were determined as Ile-Glu-X-Gly- Tyr-Thr- and -Leu-Arg, respectively. The molar specific toxicities of the solubilized crystal protein and fragment T were nearly identical. The fragment T retained the full toxicity and selectivity of the intact crystal protein. Location of the fragment T in the crystal protein is also discussed.
The two homologous domains of human angiotensin I-converting enzyme are both catalytically active (1991)

Molecular cloning of human endothelial angiotensin I-converting enzyme (kininase II; EC 3.4.15.1) (ACE) has recently shown that the enzyme contains two large homologous domains (called here the N and C domains), each bearing a putative active site, identified by sequence comparisons with the active sites of other zinc metallopeptidases. However, the previous experiments with zinc or competitive ACE inhibitors suggested a single active site in ACE. To establish whether both domains of ACE are enzymatically active, a series of ACE mutants, each containing only one intact domain, were constructed by deletion or point mutations of putative critical residues of the other domain, and expressed in heterologous Chinese hamster ovary cells. Both domains are enzymatically active and cleave the C-terminal dipeptide of hippuryl-His-Leu or angiotensin I. Moreover, both domains have an absolute zinc requirement for activity, are activated by chloride and are sensitive to competitive ACE inhibitors, and appear to function independently. However, the two domains display different catalytic constants and different patterns of chloride activation. At high chloride concentrations, the C domain hydrolyzes the two substrates tested faster than does the N domain. His-361,365 and His-959,963 are established as essential residues in the N and C domains, respectively, most likely involved in zinc binding, and Glu-362 in the N domain and Glu-960 in the C domain are essential catalytic residues. These observations provide strong evidence that ACE possesses two independent catalytic domains and suggest that they may have different functions.
A study of the role of ATM mutations in the pathogenesis of B-cell chronic lymphocytic leukaemia (2007)

Mutations in the ATM gene have previously been identified in CLL tumours. In this project, I have demonstrated that their detection would have prognostic value. With a prevalence of 12%, ATM mutations represent the commonest single gene defect to be detected in CLL tumours and they identified a subgroup of CLL patients that had a significant reduction in both treatment free and overall survival. Furthermore, ATM mutations provided prognostic information that was independent of age, clinical stage, the mutation status of the IGVH genes and TP53 mutations. The temporal acquisition of the ATM mutations and their relationship with loss of an ATM allele via a chromosomal 11q deletion provides clues into their mechanism of action. There was only a partial correlation between CLL tumours with mutations in the ATM gene and those with a chromosome 11q deletion. In certain cases, the ATM mutations represented germ-line changes and in others were acquired very early in the disease course raising the possibility that they might contribute to the initial clonal transformation process. However, in some CLL tumours, the ATM mutations had been acquired after the development of the tumour clone during disease progression indicating that there may be a step-wise acquisition of ATM allelic defects during the ontogeny of CLL. The ATM protein is the key coordinator of the cellular response to DNA double strand breaks. In this study, I showed that bi-allelic defects in the ATM gene lead to deficient ATM dependent responses, including the up regulation of p53, following both ionising irradiation and also treatment with the chemotherapeutic drug, Fludarabine. Thus an important mechanism accounting for the poor outcome in CLL patients with ATM mutations is likely to relate to chemo-resistance. Interestingly, there were differential responses to DNA damage with both irradiation and fludarabine amongst the category of tumours with an 11q deletion according to the status of the remaining ATM allele. Therefore, ATM mutations can stratify tumours with a chromosome 11q deletion into two functional subgroups. The identification of CLL tumours with ATM mutations would therefore predict those patients that will have a poor clinical outcome and be both more likely to require early treatment for their disease. Patients whose tumours had bi-allelic ATM defects will be expected to have deficient responses to DNA damaging chemotherapeutic drugs, while those with mono-allelic ATM defects might identify a group in whom the use of DNA damaging agents could provide selective pressure for the emergence of sub-clones that have subsequently acquired bi-allelic ATM defects.
cDNA Amplification Using One‐Sided (Anchored) PCR (1992)

The polymerase chain reaction (PCR) offers an opportunity to directly select, amplify, and isolate a message of interest. This unit describes anchored PCR, a modification of the standard reaction that allows amplification of full-length mRNA when only a small amount of sequence information is available. Anchored PCR can be employed when only a small region of sequence lying within the mRNA is known in advance, unlike the amplification of RNA or cDNA by conventional PCR which requires prior knowledge of the sequences flanking the region of interest to design the PCR primers.
Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin (2007)

Metastasis is a multi-step process wherein tumour cells detach from the primary mass, migrate through barrier matrices, gain access to conduits to disseminate, and subsequently survive and proliferate in an ectopic site. During the initial invasion stage, prostate carcinoma cells undergo epithelial-mesenchymal-like transition with gain of autocrine signalling and loss of E-cadherin, hallmarks that appear to enable invasion and dissemination. However, some metastases express E-cadherin, and we found close connections between prostate carcinoma cells and hepatocytes in a liver microtissue bioreactor. We hypothesise that phenotypic plasticity occurs late in prostate cancer progression at the site of ectopic seeding. Immunofluorescence staining for E-cadherin in co-cultures of hepatocytes and DU-145 prostate cancer cells revealed E-cadherin upregulation at peripheral sites of contact by day 2 of co-culture; E-cadherin expression also increased in PC-3 cells in co-culture. These carcinoma cells bound to hepatocytes in an E-cadherin-dependent manner. Although the signals by which the hepatocytes elicited E-cadherin expression remain undetermined, it appeared related to downregulation of epidermal growth factor receptor (EGFR) signalling. Inhibition of autocrine EGFR signalling increased E-cadherin expression and cell-cell heterotypic adhesion; further, expression of a downregulation-resistant EGFR variant prevented E-cadherin upregulation. These findings were supported by finding E-cadherin and catenins but not activated EGFR in human prostate metastases to the liver. We conclude that the term epithelial-mesenchymal transition only summarises the transient downregulation of E-cadherin for invasion with re-expression of E-cadherin being a physiological consequence of metastatic seeding.
Resistance of human hematopoietic stem cells to a monoclonal antibody recognizing CD43 (1997)

Hematopoietic progenitor cells (HPC) interact with bone marrow stroma by adhesion molecules which are thought to be critically important to the regulation of hematopoiesis. The specific roles of individual adhesion molecules involved in these interactions remain poorly understood. A monoclonal antibody (mAb) recognizing CD43, an adhesion molecule highly expressed by HPC, induces apoptosis in CD34hiLin- marrow cells. This process operates at a single-cell level, and the initiation of apoptosis requires crosslinking of surface CD43 and the presence of cytokines. In contrast to HPC, more differentiated hematopoietic cells do not undergo apoptosis in response to the CD43-mediated stimulation. Not all progenitor cells undergo apoptosis upon stimulation of CD43. Dividing progenitor cells are most affected, whereas more primitive, quiescent cells survive anti-CD43 mAb treatment. These surviving cells: A) are enriched for cobblestone area-forming cells; B) repopulate fragments of human fetal bone implanted into CX.B-17 severe combined immunodeficiency (SCID/hu) mice; C) have a potential to differentiate in vivo to myeloid and lymphoid cells, and D) have a high proliferative potential in long-term stromal cell-free liquid culture. These data indicate tha cells with hematopoietic stem cell characteristics are relatively resistant to CD43-mediated apoptosis compared to HPC and that CD43 may function as a negative regulator of early events occurring during hematopoiesis.
IL-15 Enables Septic Shock by Maintaining NK Cell Integrity and Function (2016)

Interleukin 15 is essential for the development and differentiation of NK and memory CD8<sup>+</sup> (mCD8<sup>+</sup>) T cells. Our laboratory previously showed that NK and CD8<sup>+</sup> T lymphocytes facilitate the pathobiology of septic shock. However, factors that regulate NK and CD8<sup>+</sup> T lymphocyte functions during sepsis are not well characterized. We hypothesized that IL-15 promotes the pathogenesis of sepsis by maintaining NK and mCD8<sup>+</sup> T cell integrity. To test our hypothesis, the pathogenesis of sepsis was assessed in IL-15-deficient (IL-15 knockout, KO) mice. IL-15 KO mice showed improved survival, attenuated hypothermia, and less proinflammatory cytokine production during septic shock caused by cecal ligation and puncture or endotoxin-induced shock. Treatment with IL-15 superagonist (IL-15 SA, IL-15/IL-15Rα complex) regenerated NK and mCD8<sup>+</sup> T cells and re-established mortality of IL-15 KO mice during septic shock. Preventing NK cell regeneration attenuated the restoration of mortality caused by IL-15 SA. If given immediately prior to septic challenge, IL-15-neutralizing IgG M96 failed to protect against septic shock. However, M96 caused NK cell depletion if given 4 d prior to septic challenge and conferred protection. IL-15 SA treatment amplified endotoxin shock, which was prevented by NK cell or IFN-γ depletion. IL-15 SA treatment also exacerbated septic shock caused by cecal ligation and puncture when given after the onset of sepsis. In conclusion, endogenous IL-15 does not directly augment the pathogenesis of sepsis but enables the development of septic shock by maintaining NK cell numbers and integrity. Exogenous IL-15 exacerbates the severity of sepsis by activating NK cells and facilitating IFN-γ production.
Preferential binding of ATR protein to UV-damaged DNA (2002)

The ATR protein is a member of the phosphoinositide 3-kinase-related kinase family and plays an important role in UV-induced DNA damage checkpoint response. Its role as a signal transducer in cell cycle checkpoint is well established, but it is currently unclear whether ATR functions as a damage sensor as well. Here we have purified the ATR protein and investigated its interaction with DNA by using biochemical analysis and electron microscopy. We find that ATR is a DNA-binding protein with higher affinity to UV-damaged than undamaged DNA. In addition, damaged DNA stimulates the kinase activity of ATR to a significantly higher level than undamaged DNA. Our data suggest that ATR may function as an initial sensor in the DNA damage checkpoint response.
Unliganded Epidermal Growth Factor Receptor Dimerization Induced by Direct Interaction of Quinazolines with the ATP Binding Site (1997)

Receptor dimerization is critical for signaling by the epidermal growth factor receptor (EGFR) tyrosine kinase. This occurs after binding of the receptor's extracellular domain by ligand or bivalent antibodies. The role of other receptor domains in dimerization is less clear, and there are no examples of dimers induced by direct perturbation of the EGFR kinase domain. Submicromolar concentrations of AG-1478 and AG-1517, quinazolines specific for inhibition of the EGFR kinase, induced reversible receptor dimerization in vitro and in intact A431 cells. Consistent with the inhibitory effect of quinazolines on receptor kinase activity, the dimers formed lacked a detectable Tyr(P) signal. Quinazoline-induced EGFR dimerization was abrogated in vitro by ATP and the ATP analog adenyl-5'-yl imidodiphosphate. Receptors with a single-point mutation in the ATP binding site as well as wild-type EGFR with a covalent modification of the ATP site failed to dimerize in response to AG-1478 and AG-1517. These data suggest that EGFR dimerization can be induced by the interaction of quinazolines at the ATP site in the absence of receptor ligand binding. In SKBR-3 cells, the quinazolines induced the formation of inactive EGFR/ErbB-2 heterodimers, potentially sequestering ErbB-2 from interacting with other coreceptors of the ErbB family. Structural studies of the quinazoline interaction with the EGFR tyrosine kinase domain should allow for an analysis of receptor-specific chemical features required for binding to the ATP site and disruption of signaling, a strategy that can be perhaps applied to other tumor cell receptor systems.