gebhart/patrepeval huggingface dataset:
Cleavage of FLICE (caspase‐8) by granzyme B during cytotoxic T lymphocyte‐induced apoptosis (1997)

Cytotoxic T lymphocytes induce apoptosis in target cells through the CD95(APO-1/Fas) and the perforin/granzyme B (GrB) pathway. The exact substrate of GrB in vivo is still unknown, but to induce apoptosis GrB requires the activity of caspases in target cells. We show here that in HeLa target cells induction of apoptosis through the perforin/GrB pathway resulted in minor direct cleavage of CPP32 (caspase-3) by GrB. Most caspase-3 cleavage resulted from activation of an upstream caspase. Moreover, target cells derived from caspase-3(-/-) mice displayed GrB-induced poly(ADP-ribose) polymerase (PARP) cleavage with only partially reduced efficiency compared to wild-type target cells. This indicates that other PARP-cleaving caspases can be activated during perforin/GrB-induced cell death. In contrast to caspase-3, FLICE (caspase-8) was directly cleaved by GrB in HeLa cells. We therefore conclude that FLICE not only plays a central role in CD95(APO-1/Fas)-induced apoptosis but can also be directly activated during perforin/GrB-induced apoptosis.
Progression of Systolic Abnormalities in Patients With “Isolated” Diastolic Heart Failure and Diastolic Dysfunction (2002)

Through the use of tissue Doppler imaging, systolic abnormalities were evident in patients previously labeled as DHF and to a much lesser extent, isolated DD. This indicates the common coexistence of systolic and diastolic dysfunction in a spectrum of different severity in the pathophysiological process of heart failure.
Response Characterization of Electroactive Polymers as Mechanical Sensors (2008)

The characterization of the dynamic response (including transfer function identification) of trilayer polypyrrole (PPy) type conducting polymer sensors is presented. The sensor was built like a cantilever beam with the free end stimulated through a mechanical lever system, which provided displacement inputs. The voltage generated and current passing between the two outer PPy layers as a result of the input was measured to model the output/input behavior of the sensors based on their experimental current/displacement and voltage/displacement frequency responses. We specifically targeted the low-frequency behavior of the sensor as it is a relatively slow system. Experimental transfer function models were generated and verified experimentally for sensors with different dimensions. The models can be used to understand the dynamic behavior and sensing ability of the polymers as mechanical sensors. The effect of the active sensor length on the voltage and current outputs has demonstrated that the shorter is the sensor length, the higher are the voltage output and the current passed for the same mechanical input. Also, their current and voltage responses under an impulse displacement stimulus were experimentally measured to show their dynamic sensing response and to estimate the current and voltage sensing bandwidths. Further, an energy balance method has been proposed to estimate the sensor output. Based on the novel experimental and analytical results, the contribution of this study is the first comprehensive investigation into the response analysis and characterization of the PPy-type conducting polymers as mechanical sensors, to the best of authors' knowledge.
Model eyes for evaluation of intraocular lenses (2007)

In accordance with the present international standard for intraocular lenses (IOLs), their imaging performance should be measured in a model eye having an aberration-free cornea. This was an acceptable setup when IOLs had all surfaces spherical and hence the measured result reflected the spherical aberration of the IOL. With newer IOLs designed to compensate for the spherical aberration of the cornea there is a need for a model eye with a physiological level of spherical aberration in the cornea. A literature review of recent studies indicated a fairly high amount of spherical aberration in human corneas. Two model eyes are proposed. One is a modification of the present ISO standard, replacing the current achromat doublet with an aspheric singlet cut in poly(methyl methacrylate) (PMMA). The other also has an aspheric singlet cut in PMMA, but the dimensions of it and the entire model eye are close to the physiological dimensions of the eye. They give equivalent results when the object is at infinity, but for finite object distances only the latter is correct. The two models are analyzed by calculation assuming IOLs with different degrees of asphericity to elucidate their sensitivity to variation and propose tolerances. Measured results in a variant of the modified ISO model eye are presented.
Expression of p53 protein in psoriasis. (2005)

P53 protein appears to be an important factor in the pathogenesis of psoriasis.
Prediction of the three-dimensional structure of human interleukin-7 by homology modeling (1996)

The three-dimensional structure of human interleukin (IL)-7 has been predicted based on homology to human IL-2, IL-4, granulocyte-macrophage colony stimulating factor and growth hormone. The model has a topology common to other cytokines and displays a unique disulfide pattern. Knowledge of the tertiary structure of IL-7 has implications for analysis of key binding regions, suggestions for mutagenesis experiments and design of (ant)agonists. In this context, the model is discussed and compared with other cytokine structures.
Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver (2001)

The rate of reconstitution following hematopoietic stem cell (HSC) transplantation differs widely depending on the tissue source of the cells infused. To test the hypothesis that variability in engraftment kinetics is related to differences in the efficiency with which intravenously transplanted HSCs "home" to the bone marrow (BM), the homing properties of murine fetal liver (FL), adult BM, and mobilized peripheral blood (MPB) cells were compared. Lethally irradiated mice transplanted with 2 x 10(6) FL, BM, or MPB cells exhibited sequentially slower recovery of circulating leukocytes and platelets that correlates with the progressively lower frequency of colony-forming cells (CFCs) in these tissues. However, differences in the rate and degree of early and long-term reconstitution were maintained even after infusing equal numbers of CFCs derived from FL, BM, and MPB. To compare the homing of progenitors from these tissues, cells were labeled with fluorescent PKH26 dye and injected into lethally irradiated hosts. Three hours later, PKH26(+) cells were reisolated from the BM and spleen by fluorescence-activated cell sorting and assayed for in vitro CFCs. Despite the higher level of very late antigen (VLA)-2, VLA-4, and VLA-5 on Sca-1(+)c-kit(+) cells from FL compared to BM, 10-fold fewer FL CFCs homed to hematopoietic organs than those from BM. MPB cells homed slightly better, but still less efficiently than BM cells. Therefore, clonogenic cells from different tissues exhibit striking variations in homing efficiency that does not necessarily correlate with engraftment kinetics. Homing is likely counterbalanced by intrinsic differences in proliferative potential that ultimately determine the rate of hematopoietic reconstitution.
Evaluation of a dipstick method for the detection of human immunodeficiency virus infection (1995)

Serology has been a fundamental tool to prevent post-transfusional infection with human immunodeficiency virus (HIV) and for epidemiological surveys, the first step to attempt control of the pandemia. Enzyme immunoassay is in widespread use. Nevertheless, simpler methods are needed in many countries, where laboratory facilities and trained personnel are limited, and HIV prevalence is high. The evaluation of a simple and noninstrumented HIV antibody test is presented here. The test employs synthetic antigens of HIV-1 and HIV-2 attached to the teeth of a polystyrene comb, which fit into the wells of standard microtiter plates where samples are diluted. Captured antibodies are developed with colloidal gold-labeled Protein A. Three seroconversion panels plus 662 samples were tested, including HIV-1 and HIV-2-infected individuals, normal blood donors, and a noninfected baby born to a seroreactive mother. When compared with enzyme-linked immunosorbent assay (ELISA) and Western blot, the dipstick showed 100% sensitivity and 98.7% specificity. The simplicity of result evaluations and excellent reagent stability make the dipstick suitable for small blood banks and for epidemiological surveys.
Does patient age impact outcomes of neuromodulation? (2012)

These data suggest that neuromodulation success is not age dependent, however continued study is needed to confirm findings.
Pathophysiology and Pharmacological Treatment of Insulin Resistance* (2000)

Diabetes mellitus type 2 is a world-wide growing health problem affecting more than 150 million people at the beginning of the new millennium. It is believed that this number will double in the next 25 yr. The pathophysiological hallmarks of type 2 diabetes mellitus consist of insulin resistance, pancreatic beta-cell dysfunction, and increased endogenous glucose production. To reduce the marked increase of cardiovascular mortality of type 2 diabetic subjects, optimal treatment aims at normalization of body weight, glycemia, blood pressure, and lipidemia. This review focuses on the pathophysiology and molecular pathogenesis of insulin resistance and on the capability of antihyperglycemic pharmacological agents to treat insulin resistance, i.e., a-glucosidase inhibitors, biguanides, thiazolidinediones, sulfonylureas, and insulin. Finally, a rational treatment approach is proposed based on the dynamic pathophysiological abnormalities of this highly heterogeneous and progressive disease.
The serum concentrations of TAG-72 antigen measured with CA 72-4 IRMA in patients with ovarian carcinoma. Preliminary data. (1989)

The Authors assayed CA 125 (cut-off value: 65 and 35 U/ml), CA 19.9 (cut-off value: 40 U/ml) and CA 72.4 (cut-off value 3.8 U/ml) immunoreactivity in blood samples drawn before surgery in 34 patients with ovarian carcinoma and in 47 patients with benign ovarian pathology. With a cut-off value of 65 U/ml, CA 125 had a sensitivity (SE) for ovarian carcinoma of 85.3%, a specificity (SP) of 89.4%, a diagnostic accuracy (DA) of 87.7%; with a cut-off value of 35 U/ml CA 125 had a SE of 88.2%, a SP of 66.0%, a DA of 75.3%; CA 19.9 had a SE of 20.6%, a SP of 70.2%, a DA of 49.4%; CA 72.4 had a SE of 64.7%, a SP of 93.6%, a DA of 81.5%. CA 125 was expressed by all ovarian carcinoma histotypes. CA 72.4 seems to have a high correlation with mucinous histotype, analogously to CA 19.9. However CA 72.4 seems to be preferable to CA 19.9 for its greater sensitivity and specificity.
Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis (2015)

Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326.).
A Development of the Evaluation Index for UTIS Traffic Information Service (2010)

Road Traffic Authority and National Police Agency is currently managing the development of an integrated metropolitan traffic information infrastructure that installs of facilities for a traffic information infrastructures, such as Local Traffic Information Center, UTIS(Urban Traffic Information System), CCTV, VMS and etc. CTIC was established in 2005 to act as an traffic information hub and to provide integrated UTIS traffic information without regional barriers. This study was carried out to seek for solution to improve quality of UTIS traffic information service for the Central Traffic Information Center(CTIC). In this study, the Evaluation index for UTIS traffic information service was developed and the implementation plan was established by using requirement analysis method, case study and AHP(Analytic Hierarchy Process) technique. The Evaluation index consist of 5 fields and 20 index, it make possible evaluation of direct/indirect effect for UTIS traffic information service. In conclusion, It is expected that quality of UTIS traffic information service will be improved by using developed evaluation index and also can be applied for performance evaluation of other traffic information systems.
Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. (1994)

Both positive and negative signals govern the progression of cells from G1 into S phase, and a variety of data implicate the E2F transcription factor as a target for the action of one class of negative regulators, the Rb family of growth suppressors. We now find that the E2F1 gene, which encodes one of the components of E2F activity, is subject to autoregulatory control during progression from G0 to S phase and that this primarily reflects a negative control in G0 and early G1, a time when the majority of E2F activity exits as a complex with Rb family members. In addition, we find that deregulated expression of G1 cyclins in quiescent cells stimulates the E2F1 promoter and that this is augmented by coexpression of cyclin-dependent kinases in an E2F-dependent manner. We conclude that the E2F1 gene is a downstream target for G1 cyclin-dependent kinase activity, most likely as a consequence of phosphorylation of Rb family members, and that the autoregulation of E2F1 transcription may provide a sensitive switch for regulating the accumulation of E2F activity during the transition from G1 to S phase.
Differential Cold Tolerance of Quackgrass and Johnsongrass Rhizomes (1977)

Rhizomes of quackgrass [ Agropyron repens (L.) Beauv.] and johnsongrass [ Sorghum halepense (L.) Pers.] were buried at various depths in the soil in the fall of 1972 and 1973, then removed at different times for viability tests. Quackgrass rhizomes retained viability at 2 cm where the coldest temperatures were −17 C. Johnsongrass rhizomes survived the winter at depths of 20 cm or more, and were killed at temperatures below about −9 C. Quackgrass rhizomes had a higher concentration of lipids and higher proportions of unsaturated fatty acids than did johnsongrass rhizomes. This difference may contribute to the superior cold tolerance of the quackgrass rhizomes.
Copper microcircuit repair of opens using thermally driven exchange plating (1990)

A two-step method for the repair of circuit board defects consisting of complete opens is described. First, a small copper bridge is grown in unacidified copper sulfate solution by passing a few milliamperes of ac current at a frequency of 2–2000 kHz through the break. Local Joule heating results in copper deposition and bridging of the open via thermally driven exchange plating. For the second step, the cross section of the repair is increased by exchange plating in acid copper, using up to ∼1 A of ac current at a frequency on the order of 60 Hz or greater.
Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas. (1991)

Phospholipase C-gamma 1 (PLC-gamma 1) is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. However, the biological significance of this molecule in normal or malignant human epithelial cell proliferation is unknown. We determined the relative content of PLC-gamma 1 in primary human mammary carcinomas and in nonmalignant mammary tissues. By Western blot and immunohistochemistry, considerably higher levels of PLC-gamma 1 protein were detectable in the majority of carcinomas and in one of two benign fibroadenomas compared to normal breast tissues. In 18 of 21 carcinomas that contained high levels of PLC-gamma 1, the presence of phosphotyrosine on PLC-gamma 1 could also be detected. All carcinomas in which tyrosine phosphorylated PLC-gamma 1 was present also expressed detectable levels of the epidermal growth factor receptor or erbB-2, two tyrosine kinases known to phosphorylate this enzyme. Thus, a high percentage of mammary carcinomas concomitantly display increased levels of receptor tyrosine kinases and a direct tyrosine phosphorylation substrate, thereby potentially amplifying two successive steps in a signal transduction pathway.
Inhibition of Mnk kinase activity by cercosporamide and suppressive effects on acute myeloid leukemia precursors (2013)

Mnk kinases regulate the phosphorylation and activation of the eukaryotic initiation factor 4E (eIF4E), a protein that plays key roles in the initiation of messenger RNA translation and whose activity is critical for various cellular functions. eIF4E is deregulated in acute myeloid leukemia (AML), and its aberrant activity contributes to leukemogenesis. We determined whether cercosporamide, an antifungal agent that was recently shown to act as a unique Mnk inhibitor, exhibits antileukemic properties. Treatment of AML cells with cercosporamide resulted in a dose-dependent suppression of eIF4E phosphorylation. Such suppression of Mnk kinase activity and eIF4E phosphorylation by cercosporamide resulted in dose-dependent suppressive effects on primitive leukemic progenitors (CFU-L) from AML patients and enhanced the antileukemic properties of cytarabine (Ara-C) or mammalian target of rapamycin (mTOR) complex 1 inhibition. Similarly, the combination of cercosporamide with cytarabine resulted in enhanced antileukemic responses in a xenograft mouse model in vivo. Altogether, this work demonstrates that the unique Mnk inhibitor cercosporamide suppresses phosphorylation of eIF4E and exhibits antileukemic effects, in support of future clinical-translational efforts involving combinations of Mnk inhibitors with cytarabine and/or mTOR inhibitors for the treatment of AML.
On-chip immunoprecipitation for protein purification (2010)

Immunoprecipitation (IP) is one of the most widely used and selective techniques for protein purification. Here, a miniaturised, polymer-supported immunoprecipitation (µIP) method for the on-chip purification of proteins from complex mixtures is described. A 4 µl PDMS column functionalised with covalently bound antibodies was created and all critical aspects of the µIP protocol (antibody immobilisation, blocking of potential non-specific adsorption sites, sample incubation and washing conditions) were assessed and optimised. The optimised µIP method was used to obtain purified fractions of affinity-tagged protein from a bacterial lysate.
U. S. reformulated gasoline rule complex, confusing (1994)

Refiners are in for a worse ride than they feared under the US Environmental Protection Agency's final rule for reformulated gasoline. Last Dec. 15 EPA issued the long-awaited rule required by 1990 Clean Air Act amendments. The complexity of the final rule, which immediately drew fire from the petroleum industry, leaves it open to interpretation, further increasing the likelihood that refiners will face as yet unseen hardships. Refiners have withstood a 2 year delay in the finalization of the complex model only to learn that 20--30% of all gasoline made in the US cannot be produced within the confines of this model, and they have less than 1 year to find a solution. This paper gives background to the legislation, then discusses baseline reports and audits, compliance, the ethanol issue, other provisions, distribution, and future requirements.
Modular Engineering of l -Tyrosine Production in Escherichia coli (2011)

Efficient biosynthesis of L-tyrosine from glucose is necessary to make biological production economically viable. To this end, we designed and constructed a modular biosynthetic pathway for L-tyrosine production in E. coli MG1655 by encoding the enzymes for converting erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to L-tyrosine on two plasmids. Rational engineering to improve L-tyrosine production and to identify pathway bottlenecks was directed by targeted proteomics and metabolite profiling. The bottlenecks in the pathway were relieved by modifications in plasmid copy numbers, promoter strength, gene codon usage, and the placement of genes in operons. One major bottleneck was due to the bifunctional activities of quinate/shikimate dehydrogenase (YdiB), which caused accumulation of the intermediates dehydroquinate (DHQ) and dehydroshikimate (DHS) and the side product quinate; this bottleneck was relieved by replacing YdiB with its paralog AroE, resulting in the production of over 700 mg/liter of shikimate. Another bottleneck in shikimate production, due to low expression of the dehydroquinate synthase (AroB), was alleviated by optimizing the first 15 codons of the gene. Shikimate conversion to L-tyrosine was improved by replacing the shikimate kinase AroK with its isozyme, AroL, which effectively consumed all intermediates formed in the first half of the pathway. Guided by the protein and metabolite measurements, the best producer, consisting of two medium-copy-number, dual-operon plasmids, was optimized to produce >2 g/liter L-tyrosine at 80% of the theoretical yield. This work demonstrates the utility of targeted proteomics and metabolite profiling in pathway construction and optimization, which should be applicable to other metabolic pathways.
Evaluation of different methods of inactivation of Newcastle disease virus and avian influenza virus in egg fluids and serum. (1991)

Viruses conveyed in shipments of eggs, viral diagnostic reagents, or avian serum samples are a potential hazard for susceptible poultry. Different methods of treatment of those materials to eliminate the hazard of virulent and avirulent strains of Newcastle disease virus (NDV) or avian influenza virus (AIV) were evaluated. The NDV strains tested were more thermostable than the AIV strains. The results suggest that standard pasteurization methods would not reliably inactivate the concentrations of NDV used. beta-Propiolactone (BPL) (greater than or equal to 0.025%) inactivated NDV or AIV in allantoic fluid, but higher concentrations were needed to inactivate virus diluted in serum. Hemagglutination (HA) of NDV and AIV and hemolysis (HL) activity of NDV were reduced or eliminated by 0.4% BPL. Formalin (greater than or equal to 0.04%) inactivated either virus but adversely affected HA and HL activity. NDV or AIV was inactivated by binary ethylenimine (BEI) (0.01 M) with no adverse effect on HA or HL. Heat (56 C) or BEI (0.01 M) had no apparent effect on hemagglutination-inhibition (HI) titers of NDV and AIV antisera, the effect of formalin (0.1%) was variable, and BPL (greater than or equal to 0.25%) depressed the HI titers of both antisera. The optimum method should achieve virus inactivation without harming the treated material.
Probing DNA sequences in solution with a monomer-excimer fluorescence color change (1998)

The use of a simple fluorescent nucleoside analogue in detection of point mutations by hybridization in solution is described. Pyrene is placed at 3' and 5' ends of a pair of oligodeoxynucleotide probes via a phosphoramidite derivative of deoxyribose with this fluorophore attached at the 1' position, replacing a DNA base. Adjacent binding of dual probes containing this fluorophore to a complementary target sequence results in a pronounced spectral change from blue pyrene monomer emission (lambdamax= 381 398 nm) to green-white excimer emission (lambdamax= 490 nm). Optimization of the relative binding positions of the two probes shows that the greatest spectral change occurs when they bind with partial end overlap. In optimum orientation, the monomer emission band for the probes decreases intensity by as much as a factor of seven and the excimer band increases up to 40-fold on binding a complementary target. Application to the detection of a single-base point mutation in solution is described.