gebhart/patrepeval huggingface dataset:
The integrin superfamily and the eye. (1996)

Integrins may have many different roles in the eye, from influencing ocular development, cell migration in wound healing or pathologic processes, and modulating inflammation and thrombosis in ocular tissue. With the variety of integrins expressed on ocular cells, great versatility and redundancy are afforded in integrin interactions. Elucidation of the functional roles of specific integrins may answer important questions regarding tumor invasion, metastasis, and ocular development. The roles of integrins in inflammation is a rapidly advancing field that soon may lead to anti-inflammatory pharmacologic agents. Potent integrin antagonists, such as cyclic RGD peptides isolated from viper venom, may prove to be useful as anti-inflammatory, anti-metastatic, or anti-thrombotic agents for the treatment of ocular disease.
THE RECOMBINANT 23-kDa N-TERMINAL FRAGMENT OF BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN (rBPI23) DECREASES ESCHERICHIA COLI-INDUCED MORTALITY AND ORGAN INJURY DURING IMMUNOSUPPRESSION-RELATED NEUTROPENIA (1995)

Cyclophosphamide-induced neutropenia exacerbates septic shock and multiple organ injury in conscious rats during Escherichia coli (EC) bacteremia despite antibiotics and fluid administration. We hypothesized that such shock and inflammatory organ injury would be mitigated by rBPI23's microbicidal activity and/or binding of EC endotoxins. Four days after 100 mg cyclophosphamide/kg, catheterized rats with < 300 PMNs/microL were pretreated with rBPI23 or the irrelevant 22 kDa protein thaumatin [3.3-6.6 mg/kg, i.v. in 0.9% NaCl (NS)] 5 min before graded i.v. infection with 5 x 10(9) or 1 x 10(10) cfu of EC serotype 055:B5 ending at t = 0. Posttreatment with each protein continued (3.3-6.6 mg/kg in 1 mL NS/h) through 8 h, in addition to penicillin plus amikacin sulfate at t = 1.5 and 8 h. Arterial samples were obtained before pretreatment and at t = 1.5, 4.5, 8, and 24 h when animals were necropsied. One of eight thaumatin + 5 x 10(9) EC rats and none of six thaumatin + 10(10) EC rats survived 24 h. In contrast, rBPI23 significantly reduced mortality after either inoculum, improved bacterial clearance, and led to renormalization of early EC-induced hypotension, hypothermia, tachypnea, hyperoxemia, and hypocarbia. Compared with thaumatin, however, rBPI23 did not reduce circulating endotoxin or bioactive and antigenic tumor necrosis factor-alpha. Sepsis-induced severe neutropenia (< 50 PMNs/microL) evident in all EC rats by t = 1.5 h was reversed with rBPI23 by t = 8 h, but thrombocytopenia (< 5 x 10(4) platelets/microL) evident in all groups by t = 4.5 h was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Acylation of Human Insulin With Palmitic Acid Extends the Time Action of Human Insulin in Diabetic Dogs (1997)

To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilon-amino group of Lys(B29) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N(epsilon)-palmitoyl Lys(B29)] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N(epsilon)-palmitoyl Lys(B29)] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N(epsilon)-palmitoyl Lys(B29)] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N(epsilon)-palmitoyl Lys(B29)] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy.
Mortalin is over‐expressed by colorectal adenocarcinomas and correlates with poor survival (2004)

Using comparative proteomic analysis we have identified over-expression of mortalin in colorectal adenocarcinomas. Mortalin, also known as mitochondrial heat-shock protein 70 (mhsp 70), is involved in cell cycle regulation with important roles in cellular senescence and immortalization pathways. It is known to bind to and inactivate wild-type tumour suppressor protein p53 and influences the Ras-Raf-MAPK pathway. By immunostaining a colorectal cancer tissue microarray linked to a patient database, we further found that mortalin over-expression correlates with poor patient survival and, in multivariate analysis, is independent of standard prognostic variables (p = 0.04). Our findings demonstrate that mortalin over-expression may predict outcome in colorectal cancer and suggest that this protein is involved in colorectal neoplasia. Our experimental approach emphasises the analytical power of combining proteomics with tissue microarray analysis in the context of a well-defined tumour database.
Regulation of cellular glutathione (1989)

In addition to its participation in a variety of other biochemical reactions, glutathione (GSH) is a major antioxidant. It is regularly generated intracellularly from its oxidized form by glutathione reductase activity that is coupled with a series of interrelated reactions. Synthesis of GSH also takes place intracellularly by a two-step reaction, the first of which is catalyzed by rate-limiting gamma-glutamylcysteine synthetase activity. Intracellular substrates for GSH are provided both by direct amino acid transport and by a gamma-glutamyl transpeptidase reaction that salvages circulating GSH by coupling the gamma-glutamyl moiety to a suitable amino acid acceptor for transport into the cell. Although the liver is a net synthesizer of circulating GSH, organs such as the kidney salvage GSH through the gamma-glutamyl transpeptidase reaction. Intracellular GSH may be consumed by GSH transferase reactions that conjugate GSH with certain xenobiotics. Elevation of cellular GSH levels in cultured cells in response to hyperoxia or electrophilic agents such as diethylmaleate is coupled with an increase in activity of the Xc- transport system for the amino acids cystine and glutamate. Strategies may be developed for protection against oxidant injury by enhancement of transport systems for precursor amino acids of GSH or by providing substrate that circumvents feedback inhibition of GSH synthesis.
Milbourne Redux? (1991)

Milbourne Redux? Get access H. A. Mason H. A. Mason Search for other works by this author on: Oxford Academic Google Scholar The Cambridge Quarterly, Volume XX, Issue 3, 1991, Pages 223–257, https://doi.org/10.1093/camqtly/XX.3.223 Published: 01 March 1991
1,25‐dihydroxyvitamin D3 and PI3K/AKT inhibitors synergistically inhibit growth and induce senescence in prostate cancer cells (2010)

These findings provide the rationale for the development of therapies utilizing 1,25(OH)(2)D(3) or its analogs combined with inhibition of PI3K/AKT for the treatment of prostate cancer.
Mapping the time course of nonconscious and conscious perception of fear: An integration of central and peripheral measures (2003)

Neuroimaging studies using backward masking suggest that conscious and nonconscious responses to complex signals of fear (facial expressions) occur via parallel cortical and subcortical circuits. Little is known, however, about the temporal differentiation of these responses. Psychophysics procedures were first used to determine objective thresholds for both nonconscious detection (face vs. blank screen) and discrimination (fear vs. neutral face) in a backward masking paradigm. Event-related potentials (ERPs) were then recorded (n = 20) using these thresholds. Ten blocks of masked fear and neutral faces were presented under each threshold condition. Simultaneously recorded skin conductance responses (SCRs) provided an independent index of stimulus perception. It was found that Fear stimuli evoked faster SCR rise times than did neutral stimuli across all conditions, indicating that emotional content influenced responses, regardless of awareness. In the first 400 msec of processing, ERPs dissociated the time course of conscious (enhanced N4 component) from nonconscious (enhanced N2 component) perception of fear, relative to neutral. Nonconscious detection of fear also elicited relatively faster P1 responses within 100 msec post-stimulus. The N2 may provide a temporal correlate of the initial sensory processing of salient facial configurations, which is enhanced when top-down cortical feedback is precluded. By contrast, the N4 may index the conscious integration of emotion stimuli in working memory, subserved by greater cortical engagement. Hum. Brain Mapping 21:64-74, 2004.
Dose--response curve for ethylnitrosourea-induced specific-locus mutations in mouse spermatogonia. (1982)

The extreme mutagenic effectiveness of N-ethyl-N-nitrosourea in the mouse has permitted the accumulation of the most extensive dose--response data yet obtained for chemical induction of specific-locus mutations in spermatogonia. In the lower portion of the curve, below a dose of 100 mg/kg, the data fall statistically significantly below a maximum likelihood fit to a straight line. Independent evidence indicates that, over this dose range, ethylnitrosourea reaches the testis in amounts directly proportional to the injected dose. It is concluded that, despite the mutagenic effectiveness of ethylnitrosourea, the spermatogonia are apparently capable of repairing at least a major part of the mutational damage when the repair process is not swamped by a high dose. This finding is important both in basic studied on the mutagenic action of chemicals in mammals and in risk estimation.
Rates of protein synthesis and turnover in fetal life (1981)

Uniformly labeled [14C]lysine was infused at constant rate into the inferior vena cava of eight ovine fetuses with gestational ages ranging from 110 to 145 days. The infusion lasted 9 to 13 h and produced a steady-state specific activity of free lysine in the fetal plasma. In the steady state, approximately 9% of the infused radioactivity was excreted by the fetus as 14CO2, indicating fetal catabolism of lysine. At the end of the infusion, the fetal carcass was analyzed for its total content of labeled and unlabeled lysine. The rate of protein synthesis was calculated from the carcass-to-plasma lysine specific activity ratio. The fractional rate constant (Ks) for the unidirectional flux of lysine into fetal proteins was inversely related (r = -0.88) to fetal age: Ks = 0.584 - 0.0036 age (days). In each fetus, Ks was 2-4 times greater than the estimated fractional rate of fetal protein accretion (KG). The discrepancy between Ks and KG demonstrates that a large fraction of protein synthesis in the ovine fetus is devoted to protein turnover.
Large E1B proteins of adenovirus types 5 and 12 have different effects on p53 and distinct roles in cell transformation (1993)

The formation of complexes between oncoproteins of DNA tumor viruses and the cellular protein p53 is thought to result in inactivation of the growth suppressor function of p53. In cells transformed by nononcogenic human adenovirus type 5 (Ad5), the 55-kDa protein encoded by E1B forms a stable complex with p53 and sequesters it in the cytoplasm. However, the homologous 54-kDa protein of highly oncogenic Ad12 does not detectably associate with p53. Yet in Ad12-transformed cells, p53 is metabolically stable, is present at high levels in the nucleus, and contributes to the oncogenicity of the cells. Such properties have previously been described for mutant forms of p53. Here, we show that stable p53 in Ad12-transformed cells is wild type rather than mutant and that stabilization of p53 is a direct consequence of the expression of the Ad12 E1B protein. We also compared the effects of the E1B proteins on transformation of rodent cells by different combinations of oncogenes. A synergistic interaction was observed for the gene encoding the 54-kDa E1B protein of Ad12 with myc plus ras oncogenes, resembling the effect of mutant p53 on myc plus ras. In contrast, the Ad5 55-kDa E1B protein strongly inhibited transformation by myc plus ras but stimulated transformation by E1A plus ras. The data are explained in terms of different interactions of the two E1B proteins with endogenous p53. The results suggest that in cultured rat cells, endogenous wild-type p53 plays an essential role in cell proliferation, even in the presence of myc plus ras. The dependence on p53 is lost, however, when the adenovirus E1A oncogene is present.
Preparation and physical and chemical properties of silk fibroin peptide (2007)

To study the preparation technics,and physical and chemical properties of silk fibroin peptide,refined waste silk was dissolved in 40% calcium chloride solution.The solution obtained was hydrolyzed with alcalase,then ultrafiltrated,and after these processes,desalted by nanofiltration(NF).Finally the desalted solution was sprayed dry.The physical and chemical properties of silk fibroin peptide powder were determined.The results showed that the content of silk fibroin peptide in silk fibroin peptide powder was 929.6 g/kg.The relative molecular weights of the main components of silk fibroin hydrolysate with DH 17% were 249 and 762,respectively,and the water contents took up about 72.9% and 15.5%,respectively.The relative molecular weights of the main components of silk fibroin hydrolysate with DH 21% were 209 and 668,respectively,the contents taking up about 84.4% and 7.2%,respectively.The main amino acids of silk fibroin peptide were glycine,alanine,serine and tyrosine,taking up 85% of a total amount of amino acid.The average hydrophobicity was 2.29 kJ/residues.The solubility of silk fibroin peptide was very good in the pH ranging from 2 to 10.The viscosity of silk fibroin peptide solution was low,and increased lentamente with the concentration increased.So silk fibroin peptide had good physical,chemical and nutrient properties,and would have a wide application foreground.
Structural analysis of peptides capable of binding to more than one Ia antigen. (1989)

The Ia binding regions were analyzed for three unrelated peptide Ag (sperm whale myoglobin 106-118, influenza hemagglutinin 130-142, and lambda repressor protein 12-26) for which binding to more than one Ia molecule has previously been demonstrated. By determining the binding profile of three separate series of truncated synthetic peptides, it was found that in all three cases the different Ia reactivities mapped to largely overlapping regions of the peptides; although, for two of the peptides, the regions involved in binding the different Ia specificities were distinct. Moreover, subtle differences were found to dramatically influence some, but not other, Ia reactivities. Using a large panel of synthetic peptides it was found that a significant correlation exists between the capacity of peptides to interact with different alleles of the same molecule (i.e., IAd and IAk), but no correlation was found with the capacity of peptides to interact with different isotypes within the same haplotype (i.e., IAd and IEd). These data suggest that different alleles of the same MHC molecule may actually recognize closely related structures, whereas different isotypes may recognize unrelated, albeit non-mutually exclusive, structures on an Ag molecule.
Time reversal techniques for wireless communications (2005)

The application of the time reversal (TR) technique in a multiple input-single output (MISO) configuration can reduce the delay spread of the channel impulse response by a factor of 2-3, depending on the power allocation scheme. Moreover, this technique provides a gain of about 20 dB in peak signal power. These effects are demonstrated with measurements of fixed wireless access channels in the 5 GHz band. The measurements were performed at 3 different locations in downtown Toronto, and the channel has been measured with 8 element uniform linear antenna arrays at both ends, thus providing an 8/spl times/8 configuration.
Interleukin 3 stimulates proliferation and triggers endothelial-leukocyte adhesion molecule 1 gene activation of human endothelial cells. (1993)

Proliferation and functional activation of endothelial cells within a tissue site of inflammation are regulated by humoral factors released by cells, such as T lymphocytes and monocytes, infiltrating the perivascular space. In the present study we investigated the effects of interleukin 3 (IL-3), an activated T lymphocyte-derived cytokine, on cultured human umbilical vein endothelial cells (HUVEC). Proliferative activity, evaluated both by estimation of the fraction of cells in the S phase and by direct cell count demonstrated that IL-3, at the dose of 25 ng/ml, enhances more than threefold both DNA synthesis and cell proliferation above baseline control conditions. Binding studies with radioiodinated ligand demonstrated that HUVEC constitutively express a smaller number of IL-3 binding sites (approximately 99 binding sites per cell, with an apparent Kd of 149 pM). Accordingly, molecular analysis showed the presence of transcripts for both alpha and beta subunits of the IL-3 receptor. Functional activation of endothelial cells was evaluated by the expression of the endothelial-leukocyte adhesion molecule 1 (ELAM-1) transcript and by leukocyte adhesion. The ELAM-1 gene transcript was clearly detectable 4 h after IL-3 addition and started to decrease after 12 h. Moreover, IL-3-induced ELAM-1 transcription was followed by enhanced adhesion of neutrophils and CD4+ T cells to HUVEC. The findings that IL-3 can stimulate both proliferation and functional activation of endothelial cells suggest that this cytokine can be involved in sustaining the process of chronic inflammation.
Neurologic Function and Health-Related Quality of Life in Patients Following Targeted Temperature Management at 33°C vs 36°C After Out-of-Hospital Cardiac Arrest (2015)

ClinicalTrials.gov NCT01020916.
Rapid Diversity‐Oriented Synthesis in Microtiter Plates for In Situ Screening of HIV Protease Inhibitors (2003)

Click and go: By using click chemistry based on a new triazole forming reaction condition (see scheme), over 100 triazole compounds generated in microtiter plates from a core structure were screened for HIV protease inhibition in situ without product isolation. Potent inhibitors, active at nanomolar concentrations, against the wild type and drug resistant mutants were identified.
[Role of bortezomib in the treatment of multiple myeloma]. (2007)

The proteasome inhibitor bortezomib is approved for the treatment of patients with relapsed/refractory multiple myeloma. Botezomib represents a new generation of treatments for multiple myeloma that affects both specific intracellular signaling pathways and the tumor microenvironment. There is a growing body of clinical evidence showing its effectiveness alone and in combination not only in relapsed/refractory cases but also in the front line setting. Regimens incorporating bortezomib and other novel agents such as immunomodulatory derivatives of thalidomide together with commonly used conventional drugs show considerable high response rates including complete response that resulting in improving survival, with or without following stem cell transplantation. Thus these approaches represent a promising future direction in myeloma treatment.
Design of fan-out kinoforms in the entire scalar diffraction regime with an optimal-rotation-angle method (1997)

An algorithm for the design of diffractive optical phase elements (kinoforms) that give rise to fan-out (i.e., spot) patterns was developed and tested. The algorithm is based on the Helmholtz-Kirchhoff rigorous scalar diffraction integral for the evaluation of the electric field behind the kinoform. The optimization of the kinoform phase modulation is performed with an efficient optimal-rotation-angle method. The algorithm permits any spatial configuration of the locations of the desired spots. For example, the spots (all or some) can be located at large angles to the optical axis (nonparaxial case) or they can be located in the near near field of the kinoform, i.e., where the Fresnel approximation is no longer valid. Two examples of fabricated kinoforms designed with this algorithm are presented.
Unique carbohydrate–carbohydrate interactions are required for high affinity binding between FcγRIII and antibodies lacking core fucose (2011)

Antibody-mediated cellular cytotoxicity (ADCC), a key immune effector mechanism, relies on the binding of antigen-antibody complexes to Fcγ receptors expressed on immune cells. Antibodies lacking core fucosylation show a large increase in affinity for FcγRIIIa leading to an improved receptor-mediated effector function. Although afucosylated IgGs exist naturally, a next generation of recombinant therapeutic, glycoenginereed antibodies is currently being developed to exploit this finding. In this study, the crystal structures of a glycosylated Fcγ receptor complexed with either afucosylated or fucosylated Fc were determined allowing a detailed, molecular understanding of the regulatory role of Fc-oligosaccharide core fucosylation in improving ADCC. The structures reveal a unique type of interface consisting of carbohydrate-carbohydrate interactions between glycans of the receptor and the afucosylated Fc. In contrast, in the complex structure with fucosylated Fc, these contacts are weakened or nonexistent, explaining the decreased affinity for the receptor. These findings allow us to understand the higher efficacy of therapeutic antibodies lacking the core fucose and also suggest a unique mechanism by which the immune system can regulate antibody-mediated effector functions.
Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders (2017)

Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n = 3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n = 1) who underwent HCT on a prospective, phase II, multicenter clinical trial. Patients were given HLA-matched related (n = 2) or unrelated (n = 12) grafts after conditioning with treosulfan (42 g/m<sup>2</sup>), fludarabine (150 mg/m<sup>2</sup>), ± thymoglobulin (n = 11; 6 mg/kg). All patients engrafted. At a median follow-up of 3 years, 13 patients are alive with complete correction of their underlying disease. These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with a low toxicity profile and excellent disease-free survival in patients with marrow failure disorders.