gebhart/patrepeval huggingface dataset:
Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair (2005)

Fanconi anemia (FA) is a recessive disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. Cells from FA patients are hypersensitive to agents that produce DNA crosslinks and, after treatment with these agents, have pronounced chromosome breakage and other cytogenetic abnormalities. Eight FANC genes have been cloned, and the encoded proteins interact in a common cellular pathway. DNA-damaging agents activate the monoubiquitination of FANCD2, resulting in its targeting to nuclear foci that also contain BRCA1 and BRCA2/FANCD1, proteins involved in homology-directed DNA repair. Given the interaction of the FANC proteins with BRCA1 and BRCA2, we tested whether cells from FA patients (groups A, G, and D2) and mouse Fanca-/- cells with a targeted mutation are impaired for this repair pathway. We find that both the upstream (FANCA and FANCG) and downstream (FANCD2) FA pathway components promote homology-directed repair of chromosomal double-strand breaks (DSBs). The FANCD2 monoubiquitination site is critical for normal levels of repair, whereas the ATM phosphorylation site is not. The defect in these cells, however, is mild, differentiating them from BRCA1 and BRCA2 mutant cells. Surprisingly, we provide evidence that these proteins, like BRCA1 but unlike BRCA2, promote a second DSB repair pathway involving homology, i.e., single-strand annealing. These results suggest an early role for the FANC proteins in homologous DSB repair pathway choice.
Novel role for the δ‐opioid receptor in hypoxic preconditioning in rat retinas (2008)

Delta-opioid receptor (DOR) is an oxygen-sensitive protein whose function in the rat retina is unknown. We examined whether DOR is involved in hypoxic preconditioning (HPC)-mediated retinoprotection following intraocular pressure (IOP) elevation. Rats were exposed to intermittent hypoxia (10% oxygen) to induce HPC. Unilateral retinal ischemia/reperfusion injury was induced by elevating IOP to 100 mmHg for 1 h. HPC attenuated the loss of neuronal marker expression and increased pro-apoptotic caspase 3 activity in the IOP retina. Excess superoxide production and 8-iso-prostaglandin F2alpha accumulation caused by enhanced oxidant protein expression and reduced antioxidant enzyme level after IOP elevation were largely abrogated by HPC. HPC markedly increased the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and DOR, but intravitreal administration of HIF-1alpha-specific small interfering RNA abrogated the up-regulation of DOR. This suggested that DOR functions downstream of HIF-1alpha. However, the endogenous content of leucine enkephalin in retinas was not affected by HPC or IOP. Treatment of retinas with the DOR antagonist naltrindole attenuated the HPC-induced protection and activation of extracellular signal-regulated kinase. These results suggest a novel mechanism of HPC-mediated retinoprotection whereby HIF-1alpha induces the expression of DOR, and DOR-mediated activation of extracellular signal-regulated kinase triggers cellular events that correct the redox imbalance in the post-ischemic retina.
Protein-Protein Interactions in Colicin E9 DNase-Immunity Protein Complexes. 1. Diffusion-Controlled Association and Femtomolar Binding for the Cognate Complex (1995)

The cytotoxic activity of the secreted bacterial toxin colicin E9 is due to a nonspecific DNase housed in the C-terminus of the protein. A kinetic and thermodynamic analysis of complex formation for both the holotoxin and the isolated DNase domain with the cytoplasmic inhibitor of this enzyme, the immunity protein Im9, is presented. The dissociation constant for each complex was calculated from the ratio of the association and dissociation rate constants. Association was monitored by stopped-flow fluorescence and comprises at least two steps for both complexes, an initial fluorescence enhancement followed by a fluorescence quench. The data are consistent with a two-step binding mechanism in which the rate of formation of an encounter complex (k1) is rate determining and essentially diffusion controlled (4.0 x 10(9) M-1 s-1 for colicin E9) in buffer of low ionic strength. This encounter complex then rearranges to the final stable complex. Sequential stopped-flow experiments using 5-hydroxy-L-tryptophan labeled DNase domain support the two-step mechanism and further show that the rate of encounter complex rearrangement is significantly faster than its dissociation. The overall rate of dissociation of the colicin E9-Im9 complex (k(off)) was determined by radioactive subunit exchange to be 3.7 x 10(-7) s-1. Thus, the Kd for the complex (k(off)/k1) is 9.3 x 10(-17) M, which corresponds to a change in free energy on binding of -21.9 kcal mol-1 at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Fermented dairy products, calcium, and colorectal cancer in The Netherlands Cohort Study. (1994)

Fermented dairy products, calcium, and colorectal cancer in The Netherlands Cohort Study.<br/><br/>Kampman E, Goldbohm RA, van den Brandt PA, van 't Veer P.<br/><br/>Department of Epidemiology, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.<br/><br/>Experimental studies suggest that an increased consumption of fermented dairy products and calcium might decrease the risk of colorectal cancer. The associations between fermented dairy products, dietary calcium, and colorectal cancer risk were investigated in a population with a wide variation in intake of dairy products. The Netherlands Cohort Study of diet and cancer started in 1986 when 120,852 Dutch men and women, ages 55-69, filled out a questionnaire concerning dietary patterns and lifestyle. The present analysis is based on 3.3 years of follow-up and includes 215 incident cases of colon cancer and 111 incident cases of rectal cancer, excluding cases diagnosed in the first year of follow-up. After adjustment for potential confounding variables, colorectal cancer risk was weakly inversely associated with the consumption of fermented milk [relative rate (RR) in the highest category of intake compared to nonusers, 0.89; 95% confidence interval (CI), 0.60, 1.33], unfermented milk (RR, 0.86; 95% CI, 0.57, 1.29), and cheese (RR, 0.88; 95% CI, 0.59, 1.33). However, category-specific relative rates and tests for trends were not statistically significant. For fermented milk, the inverse association was limited to colon cancer (RR, 0.70; 95% CI, 0.43, 1.15; trend, P = 0.33). In crude and multivariate models, total dietary calcium intake (highest versus lowest quintile, RR, 0.92; 95% CI, 0.64, 1.34) and calcium from fermented dairy products (RR, 1.14; 95% CI, 0.77, 1.68) were not significantly associated with colorectal cancer risk. Calcium from unfermented dairy products was inversely associated with rectal cancer risk (RR, 0.55; 95% CI, 0.30, 1.04; trend, P = 0.03). After 3.3 years of follow-up, these data are not consistent with a substantially decreased risk of colorectal cancer with increased intake of fermented dairy products and dietary calcium
Coronary Bypass Graft Patency in Patients With Diabetes in the Bypass Angioplasty Revascularization Investigation (BARI) (2002)

Despite diabetic patients' having smaller distal vessels and vessels judged to be of poorer quality, diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up. Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes.
The effect of recombinant human (1-84) or synthetic human (1-34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats. (1993)

The purpose of this study was to evaluate the dose-effect relationship of recombinant human PTH [hPTH-(1-84)] and synthetic human PTH [sPTH-(1-34)] for the skeleton of estrogen-deplete osteopenic rats. Ex vivo densitometry of regionalized whole femurs and histomorphometry of proximal tibial cancellous bone were the end points. Retired breeder female rats, aged 6-7 months, were used. Ten were killed at baseline, and the rest were ovariectomized (OVX). On day 42, a pre-PTH treatment OVX group was killed. The rest were then treated by daily sc injection with hPTH (0, 1.55, 15.5, or 155 micrograms/kg BW.day) or sPTH (0.55, 5.5, or 55 micrograms/kg BW.day) and killed on day 70. The level of cancellous bone mineral was lower in pretreatment OVX rats than at baseline. It was higher in rats treated with 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH than in pretreatment and vehicle-treated OVX rats. Cancellous bone volume was also lower both 42 and 70 days after OVX. Although hPTH did not affect cancellous bone volume, treatment with 5.5-55 micrograms/kg.day sPTH caused higher bone volume than in either pretreatment or vehicle-treated OVX rats. Trabecular number declined after OVX and did not change with PTH treatment. In contrast, trabecular thickness declined after OVX, but was higher after 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH treatment. In OVX rats, the amount of mineralizing surface was greater by day 42 and fell toward control levels by day 70. It was greater in rats treated with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH than in vehicle-treated OVX rats. On a molar basis, sPTH was modestly more potent than hPTH. Osteoclast surface was not affected by PTH treatment. Treating estrogen-deplete osteopenic adult rats for 28 days with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH increases trabecular thickness, but not trabecular number, to cause a rise in bone mass. The extent of mineralizing surface rises without a change in resorption surface. The marked rise in mineralizing surfaces suggests that extended in vivo treatment with PTH activates osteogenic precursor cells near once quiescent surfaces to become osteoblasts.
Two cytosolic components of the human neutrophil respiratory burst oxidase translocate to the plasma membrane during cell activation. (1990)

The superoxide-forming respiratory burst oxidase of human neutrophils is composed of membrane-associated catalytic components and cytosolic constituents required for oxidase activation. This study concerns the hypothesis that cytosolic oxidase components translocate to a membrane fraction when neutrophils are stimulated and the oxidase is activated. A polyclonal antiserum that recognizes two discrete cytosolic oxidase components of 47 and 67 kD was used to probe transfer blots of electrophoresed membrane and cytosol fractions of resting and stimulated neutrophils. In contrast to their strictly cytosolic localization in unstimulated cells, both proteins were detected in membrane fractions of neutrophils activated by phorbol esters and other stimuli. This translocation event was a function of stimulus concentration as well as time and temperature of exposure to the stimulus. It was inhibited by concentrations of N-ethylmaleimide that blocked superoxide formation but was unaffected by 2-deoxyglucose. There was a correlation between translocation of the cytosolic proteins and activation of the oxidase as determined by superoxide formation. Quantitative analyses suggested that approximately 10% of total cellular p47 and p67 became membrane-associated during phorbol ester activation of the oxidase. Analysis of Percoll density gradient fractions indicated that the target membrane for translocation of both proteins was the plasma membrane rather than membranes of either specific or azurophilic granules. In the cell-free oxidase system arachidonate-dependent but membrane-independent precipitation of the cytosolic oxidase proteins was demonstrated. The data show that activation of the respiratory burst oxidase in stimulated human neutrophils is closely associated with translocation of the 47- and 67-kD cytosolic oxidase components to the plasma membrane. We suggest that this translocation event is important in oxidase activation.
Characterization of MB-102, a New Fluorescent Tracer Agent for Point-of-Care Renal Function Monitoring (2019)

MB-102 is a fluorescent tracer agent designed for measurement of point-of-care glomerular filtration rate (GFR) and is currently in clinical studies. MB-102 possesses a strong UV absorbance at 266 nm and 435 nm, and broad fluorescent emission at ~560 nm when excited at ~440 nm. The MB-102 formulation is stable at 2°C-8°C for >3 years. The pK<sub>a</sub>'s of the 2 acid groups are 2.71 and 3.40. Both X-ray crystallography and HPLC confirmed the D, D chirality of MB-102 in solid, in solution, and in the drug formulation. Initial safety and toxicity was published previously [Bugaj and Dorshow, 2015], which enabled the commencement of clinical studies. In vitro studies showed that 4.1% of MB-102 is bound to human plasma proteins, compared to 6.0% for the accepted standard GFR agent iohexol. The blood-to-plasma ratio for MB-102 was 0.590, illustrating minimal distribution of MB-102 into red blood cells. The manufacture of MB-102 under good manufacturing practice yields the designed molecular structure at high purity (>95% wt/wt).
Evidence for association of the cloned liver growth hormone receptor with a tyrosine kinase. (1992)

The ability of the cloned liver growth hormone (GH) receptor, when expressed in mammalian cell lines, to copurify with tyrosine kinase activity and be tyrosyl phosphorylated was examined. 125I-human growth hormone-GH receptor complexes isolated from COS-7 cells transiently expressing high levels of the cloned liver GH receptor bound to anti-phosphotyrosine antibody, suggesting that the cloned GH receptor is tyrosyl phosphorylated in vivo. GH-GH receptor complexes purified from transfected COS-7 cells using anti-GH antibody incorporated 32P when incubated with [gamma-32P]ATP, indicating association of tyrosine kinase activity with cloned liver GH receptor. The level of phosphorylation of the GH receptor was very low, as compared with the endogenous GH receptor in 3T3-F442A cells, suggesting that tyrosine kinase activity is not intrinsic to the cloned GH receptor but rather resides with a kinase present at low levels in the COS-7 cells. To test whether a higher level of GH receptor phosphorylation would be observed when the GH receptor was expressed in a different cell line, GH receptor cDNAs were stably transfected into mouse L and CHO cells, which have few or no endogenous GH receptors, and RIN5-AH cells, which do express endogenous GH receptors. In vivo tyrosyl phosphorylation of the cloned GH receptor in mouse L cells and in vitro phosphorylation of the cloned GH receptor in both L and CHO cells were higher than in transfected COS-7 cells but still substantially lower than in untransfected 3T3-F442A cells. Significantly increased 32P incorporation into tyrosyl residues in GH receptors in the in vitro kinase assay was demonstrated for GH receptors isolated from the transfected RIN5-AH cells. These studies show that the cloned liver GH receptor can be tyrosyl phosphorylated when expressed in a variety of cell types. The finding that the level of phosphorylation of GH receptor appears to vary with cell type is consistent with the cloned liver GH receptor being a substrate for an associated tyrosine kinase and with the amount of such a GH receptor-associated tyrosine kinase being cell type-specific.
MULTICOMPONENT DISTILLATION CONFIGURATIONS WITH LARGE ENERGY SAVINGS (2010)

In industry, many separation processes involve the separation of multicomponent mixtures using distillation. There are many distillation configurations that can carry out the same overall separation process. These configurations use an equal number of distillation columns, but they differ significantly in energy consumption. Therefore a major challenge for a practitioner is the identification of energy-optimal configurations for a given application. We describe an easy-to-use matrix-based framework to identify all feasible candidate configurations for the separation of any non-azeotropic multicomponent mixture. We also describe an optimization framework to rank-list all feasible configurations with respect to energy consumption. We have demonstrated the efficacy of these frameworks by identifying more than 70 new configurations that can lower the energy consumption for petroleum crude distillation by 5 – 48%. We also present a framework to analyze operability of distillation sequences.
Automatic Reporting of Estimated Glomerular Filtration Rate—Just What the Doctor Ordered (2006)

Chronic kidney disease (CKD) is a recently recognized public health problem. CKD is defined as the presence of markers of kidney damage or of glomerular filtration rate (GFR) <60 mL · min−1 · (1.73 m−2) [<1 mLs−1 · (1.73 m−2)−1] for three months or more (1)(2)(3). According to these definitions, the prevalence of CKD in noninstitutionalized US adults is estimated as ∼11%, or ∼20 million people (4). CKD is associated with poor outcomes and high cost, disproportionately affecting the elderly and racial and ethnic minorities. Thus, new public health campaigns focus on early detection of CKD, especially in patients at increased risk, including those with hypertension, diabetes, cardiovascular disease, or a family history of CKD (5).

To facilitate early detection of CKD, many national and international organizations now recommend automatic reporting of estimated glomerular filtration rate (eGFR) whenever serum creatinine is measured (1)(2)(3)(5)(6)(7)(8)(9)(10)(11)(12). Approximately 20% of participants in the College of American Pathologists’ chemistry survey were reporting eGFR calculations in 2005 (13). In this issue of Clinical Chemistry , Dr. Rainey offers a dissenting view, likening automatic eGFR reporting to “jumping the gun”. A careful examination of the arguments reveals, in our view, that reporting eGFR whenever a serum creatinine is requested is “just what the doctor ordered”.

Dr. Rainey asserts that “Most creatinine measurements are not made to assess renal function in persons who have CKD or are at high risk for CKD. The great majority of creatinine measurements are ordered as part of a Basic Metabolic Panel”.

The serum creatinine level holds no clinically useful meaning other than to serve as an index of kidney function. …
Characterization of a Proteolytically Stable D-Peptide That Suppresses Herpes Simplex Virus 1 Infection: Implications for the Development of Entry-Based Antiviral Therapy (2014)

Uncontrolled herpes simplex virus 1 (HSV-1) infection can advance to serious conditions, including corneal blindness or fatal encephalitis. Here, we describe a highly potent anti-HSV-1 peptide (DG2) that inhibits HSV-1 entry into host cells and blocks all aspects of infection. Importantly, DG2 is highly resistant to proteases and shows minimal toxicity, paving the way for prophylactic or therapeutic application of the peptide in vivo.
High energy density proton exchange membrane fuel cell with dry reactant gases (1996)

Proton exchange membrane fuel cells (PEMFC) require careful control of humidity levels in the cell stack to achieve a high and stable level of performance. External humidification of the reactant gases, as in the state-of-the-art PEMFCs, increases the complexity, the weight, and the volume of the fuel cell power plant. A method for the operation of PEMFCs without external humidification (i.e., self-humidified PEMFCs) was first developed and tested by Dhar at BCS Technology. A project is underway in our Center to develop a PEMFC cell stack, which can work without external humidification and attain a performance level of a current density of 0.7 A/cm{sup 2} at a cell potential of 0.7 V, with hydrogen/air as reactants at 1 atm pressure. In this paper, the results of our efforts to design and develop a PEMFC stack requiring no external humidification will be presented. This paper focuses on determining the effects of type of electrodes, the methods of their preparation, as well as that of the membrane and electrode assembly (MEA), platinum loading and types of electrocatalyst on the performance of the PEMFC will be illustrated.
Fabrication and analysis of deep submicron strained-Si n-MOSFET's (2000)

Deep submicron strained-Si n-MOSFETs were fabricated on strained Si/relaxed Si/sub 0.8/Ge/sub 0.2/ heterostructures. Epitaxial layer structures were designed to yield well-matched channel doping profiles after processing, allowing comparison of strained and unstrained Si surface channel devices. In spite of the high substrate doping and high vertical fields, the MOSFET mobility of the strained-Si devices is enhanced by 75% compared to that of the unstrained-Si control devices and the state-of-the-art universal MOSFET mobility. Although the strained and unstrained-Si MOSFETs exhibit very similar short-channel effects, the intrinsic transconductance of the strained Si devices is enhanced by roughly 60% for the entire channel length range investigated (1 to 0.1 /spl mu/m) when self-heating is reduced by an ac measurement technique. Comparison of the measured transconductance to hydrodynamic device simulations indicates that in addition to the increased low-field mobility, improved high-field transport in strained Si is necessary to explain the observed performance improvement. Reduced carrier-phonon scattering for electrons with average energies less than a few hundred meV accounts for the enhanced high-field electron transport in strained Si. Since strained Si provides device performance enhancements through changes in material properties rather than changes in device geometry and doping, strained Si is a promising candidate for improving the performance of Si CMOS technology without compromising the control of short channel effects.
A self-clocked fair queueing scheme for broadband applications (2002)

An efficient fair queueing scheme which is feasible for broadband implementation is proposed and its performance is analyzed. The author defines fairness in a self-contained manner, eliminating the need for the hypothetical fluid-flow reference system used in the present state of art and thereby removing the associated computational complexity. The scheme is based on the adoption of an internally generated virtual time as the index of work progress, hence the name self-clocked fair queueing. The author proves that the scheme possesses the desired fairness property and is nearly optimal, in the sense that the maximum permissible disparity among the normalized services offered to the backlogged sessions is never more than two times the corresponding figure in any packet-based queueing system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Schlemm's Canal Becomes Smaller After Successful Filtration Surgery (2000)

The decrease in size of Schlemm's canal after successful filtration surgery could make glaucoma more difficult to control if the filter ultimately fails. Arch Ophthalmol. 2000;118:1251-1256