gebhart/patrepeval huggingface dataset:
<title>Matrix-assisted laser-desorption mass spectrometry of DNA using an infrared free-electron laser</title> (1993)

Sequencing the human genome requires an interdisciplinary approach combining aspects of biology, chemistry, physics, and engineering applied at the molecular level. One potentially interesting approach involves the use of matrix-assisted laser desorption-ionization mass spectroscopy (MALDI-MS), because of its high sensitivity, high speed, great accuracy, and ease of automation. However, while MALDI-MS has been successful in mass analysis of proteins and many large biomolecules, attempts to apply the technique to DNA sequencing have proven notoriously difficult. Because the choice of matrix materials for MALDI-MS is severely constrained by the application of conventional UV and visible laser sources, we are investigating the application of a tunable infrared free-electron laser to test the potential of infrared MALDI-MS for DNA sequencing. We describe the advantages of using tunable IR laser sources to choose matrix materials with optimal desorption, ionization, and thermomechanical properties, while avoiding the photochemical effects induced by ultraviolet and visible lasers. We also show the results of preliminary MALDI-MS experiments on small organic molecules using the Vanderbilt free-electron laser.
Biophysical properties of human astrocytic brain tumor cells in cell culture (1980)

For malignant cells cultured from a human astrocytoma, electrophysiological characteristics of the plasma membrane included specific resistivity of 446.82 +/- 279.5 ohm . cm2, specific capacitance of 0.758 +/- 0.52 microfarads/cm2, time constant 0.318 +/- 0.10 msec. The resting membrane potential averaged--14.07 +/- 7.4 mV; the mean input resistance 8.1 +/- 4.0 megohms. The average cell area was 1638 +/- 585 mu2 for contactual and and 1919 +/- 989 mu2 for noncontactual cells. Changes in input resistance and resting membrane potential were observed with increasing time in culture, possibly reflecting cel cycling. There did not appear to be electrical coupling in this cell line.
Division behavior and shape changes in isogenic ftsZ, ftsQ, ftsA, pbpB, and ftsE cell division mutants of Escherichia coli during temperature shift experiments (1988)

Isogenic ftsZ, ftsQ, ftsA, pbpB, and ftsE cell division mutants of Escherichia coli were compared with their parent strain in temperature shift experiments. To improve detection of phenotypic differences in division behavior and cell shape, the strains were grown in glucose-minimal medium with a decreased osmolality (about 100 mosM). Already at the premissive temperature, all mutants, particularly the pbpB and ftsQ mutants, showed an increased average cell length and cell mass. The pbpB and ftsQ mutants also exhibited a prolonged duration of the constriction period. All strains, except ftsZ, continued to initiate new constrictions at 42 degrees C, suggesting the involvement of FtsZ in an early step of the constriction process. The new constrictions were blunt in ftsQ and more pronounced in ftsA and pbpB filaments, which also had elongated median constrictions. Whereas the latter strains showed a slow recovery of cell division after a shift back to the permissive temperature, ftsZ and ftsQ filaments recovered quickly. Recovery of filaments occurred in all strains by the separation of newborn cells with an average length of two times LO, the length of newborn cells at the permissive temperature. The increased size of the newborn cells could indicate that the cell division machinery recovers too slowly to create normal-sized cells. Our results indicate a phenotypic resemblance between ftsA and pbpB mutants and suggest that the cell division gene products function in the order FtsZ-FtsQ-FtsA, PBP3. The ftsE mutant continued to constrict and divide at 42 degrees C, forming short filaments, which recovered quickly after a shift back to the permissive temperature. After prolonged growth at 42 degree C, chains of cells, which eventually swelled up, were formed. Although the ftsE mutant produced filaments in broth medium at the restrictive temperature, it cannot be considered a cell division mutant under the presently applied conditions.
Phosphorylation-dephosphorylation of the CD6 glycoprotein renders two isoforms of 130 and 105 kilodaltons. Effect of serum and protein kinase C activators. (1990)

The molecular nature of the structural changes on the T cell-CD6 glycoprotein upon cell activation has been investigated. Cell surface 125I labeling and immunoprecipitation studies from PBMC revealed that after stimulation by different activators of protein kinase C, or after exposure to either human or FCS, the anti-CD6 mAb precipitated an additional protein of 130 kDa, together with the 105-kDa protein present in resting cells. Cell surface expression of this 130-kDa CD6 protein form could be detected as early as 15 min after PKC activation, without requiring de novo protein synthesis. Pulse and chase activation experiments of radioiodinated cells suggested that the 130-kDa molecule is the result of a posttranslational modification of the 105-kDa protein and that this conversion is a reversible process. Studies of 32P-cell labeling and immunoprecipitation by anti-CD6 mAb revealed that only the 130-kDa form was phosphorylated, whereas the 105-kDa protein was unphosphorylated both in resting and activated cells. Moreover, the removal of phosphate groups from the 130-kDa CD6-form by enzymatic treatment with alkaline phosphatase resulted in its conversion to the 105-kDa form. Taken together, these results demonstrate the existence of two CD6 molecular forms that are in a dynamic equilibrium and differ only at their degree of phosphorylation: a 105-kDa unphosphorylated form present in resting T cells that changes very rapidly to a 130-kDa phosphorylated form by exposure of cells either to serum or to activators of PKC.
GaN HFET digital circuit technology for harsh environments (2003)

The first demonstration of GaN digital circuits is reported. First‐generation GaN digital technology has already shown high yields for circuits of considerable complexity. Specifically, a 31-stage ring oscillator was implemented using 217 transistors. Properties of the AlGaN/GaN material system that enable outstanding power handling capabilities of GaN heterojunction field effect transistors (HFETs), i.e. large bandgap, high breakdown field and high saturation velocity, also make it attractive for digital applications in harsh environments. Because of these unique material characteristics GaN digital control circuits have the potential to operate in high radiation environments, at elevated temperature, and directly from high voltage rails. Successful operation of GaN 31-stage ring oscillators at the highest base-plate temperature attainable by test setup of 265°C, indicates these circuits can operate at significantly higher temperatures.
Preservation of Bacteria by Circulating-Gas Freeze Drying (1963)

Water-washed Serratia marcescens and Escherichia coli were freeze dried in a circulating-gas system at atmospheric pressure. This convective procedure resulted in a substantially higher survival of organisms than could be obtained by the vacuum method of freeze drying. There was little or no decrease in cell viability during convective drying when the residual moisture content was 15% or higher. Below this level, survival declined with decreasing moisture content. A detailed comparison of the convective and vacuum methods indicated that the advantage gained by freeze drying bacteria in air accrues in the early period of sublimation, at which time cells were found to be sensitive to vacuum drying but insensitive to air drying. An explanation for this difference is proposed, based upon the kinetics of water removal in the two processes. In brief, it is suggested that the convective method permits samples to be dried more uniformly; and regional over-drying, which may be deleterious even if transient, is thus avoided in achieving the optimal level of moisture.
Lack of Protective Osmolytes Limits Final Cell Density and Volumetric Productivity of Ethanologenic Escherichia coli KO11 during Xylose Fermentation (2004)

Limited cell growth and the resulting low volumetric productivity of ethanologenic Escherichia coli KO11 in mineral salts medium containing xylose have been attributed to inadequate partitioning of carbon skeletons into the synthesis of glutamate and other products derived from the citrate arm of the anaerobic tricarboxylic acid pathway. The results of nuclear magnetic resonance investigations of intracellular osmolytes under different growth conditions coupled with those of studies using genetically modified strains have confirmed and extended this hypothesis. During anaerobic growth in mineral salts medium containing 9% xylose (600 mM) and 1% corn steep liquor, proline was the only abundant osmolyte (71.9 nmol x ml(-1) optical density at 550 nm [OD(550)] unit(-1)), and growth was limited. Under aerobic conditions in the same medium, twice the cell mass was produced, and cells contained a mixture of osmolytes: glutamate (17.0 nmol x ml(-1) OD(550) unit(-1)), trehalose (9.9 nmol x ml(-1) OD(550) unit(-1)), and betaine (19.8 nmol x ml(-1) OD(550) unit(-1)). Two independent genetic modifications of E. coli KO11 (functional expression of Bacillus subtilis citZ encoding NADH-insensitive citrate synthase; deletion of ackA encoding acetate kinase) and the addition of a metabolite, such as glutamate (11 mM) or acetate (24 mM), as a supplement each increased the intracellular glutamate pool during fermentation, doubled cell growth, and increased volumetric productivity. This apparent requirement for a larger glutamate pool for increased growth and volumetric productivity was completely eliminated by the addition of a protective osmolyte (2 mM betaine or 0.25 mM dimethylsulfoniopropionate), consistent with adaptation to osmotic stress rather than relief of a specific biosynthetic requirement.
Family care in the intensive care unit: The Golden Rule, evidence, and resources* (2007)

Critical Care Medicine, St. John Medical Center, Tulsa, OK, Department of Pulmonary/Critical Care, University of Oklahoma–Tulsa, Tulsa, OK (Plost) St. John Medical Center, Tulsa, OK (Nelson) The authors have not disclosed any potential conflicts of interest.
Sagnac effect in fiber gyroscopes (1981)

We review the kinematic explanation of the Sagnac effect in fiber gyroscopes and recall that the index of the dielectric medium does not have any influence. Furthermore, we present a novel electrodynamic approach that confirms in more detail that the Sagnac phase shift of a ring-waveguide interferometer is the same as for the original Sagnac experiment with plane waves in a vacuum.
Induction of Spermatogenesis and Fertility during Gonadotropin Treatment of Gonadotropin-Deficient Infertile Men: Predictors of Fertility Outcome (2008)

Larger testis volume is a useful prognostic indicator of response. The association of slower responses after prior androgen therapy suggests that faster pregnancy rates might be achieved by substituting gonadotropin for androgen therapy for pubertal induction, although a prospective randomized trial will be required to prove this.
Functional Reconnection of Severed Mammalian Spinal Cord Axons with Polyethylene Glycol (1999)

We describe a technique using the water-soluble polymer polyethylene glycol (PEG) to reconnect the two segments of completely transected mammalian spinal axons within minutes. This was accomplished by fusing completely severed strips of isolated guinea pig thoracic white matter maintained in vitro in a double sucrose gap recording chamber. The faces of the severed segments were pressed together, and PEG (MW 1,400-3,500 d; approximately 50% by weight in distilled water) was applied directly to this region through a micropipette and removed by aspiration within 2 min. Successful fusion was documented by the immediate restored conduction of compound action potentials through the original transection and by the variable numbers of fused axons in which anatomical continuity was shown to be restored by high-resolution light microscopy and by the diffusion of intracellular fluorescent dyes through fused axons. These data support the conclusion that some severed and subsequently PEG-fused spinal axons both demonstrate restored anatomical continuity and also are physiologically competent to conduct action potentials. This work adds to our previous demonstration that PEG application can immediately repair severely crushed, rather than cut, spinal cord white matter, and may lead to novel treatments for acute trauma to the central and peripheral nervous systems.
Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy (2006)

This data set represents the first description of signalling pathways associated with the functional recovery of end-stage human heart failure and the identification of new targets in the human heart that are modified by this combination therapy.
MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells (2017)

Programmed death ligand-1 (PD-L1) is a critical regulator of T cell function contributing to peripheral immune tolerance. Although it has been shown that posttranscriptional regulatory mechanisms control PD-L1 expression in cancer, it remains unknown whether such regulatory loops operate also in non-transformed cells. Here we studied PD-L1 expression in human dermal lymphatic endothelial cells (HDLECs), which play key roles in immunity and cancer. Treatment of HDLECs with the pro-inflammatory cytokines IFN-γ and TNF-α synergistically up-regulated PD-L1 expression. IFN-γ and TNF-α also affected expression of several microRNAs (miRNAs) that have the potential to suppress PD-L1 expression. The most highly up-regulated miRNA following IFN-γ and TNF-α treatment in HDLECs was miR-155, which has a central role in the immune system and cancer. Induction of miR-155 was driven by TNF-α, the effect of which was significantly enhanced by IFN-γ. The PD-L1 3'-UTR contains two functional miR-155-binding sites. Endogenous miR-155 controlled the kinetics and maximal levels of PD-L1 induction upon IFN-γ and TNF-α treatments. We obtained similar findings in dermal fibroblasts, demonstrating that the IFN-γ/TNF-α/miR-155/PD-L1 pathway is not restricted to HDLECs. These results reveal miR-155 as a critical component of an inflammation-induced regulatory loop controlling PD-L1 expression in primary cells.
Using the yeast two‐hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth (1998)

Neisseria gonorrhoeae opacity-associated (Opa) proteins are a family of outer membrane proteins involved in gonococcal adherence to and invasion of human cells. We wanted to identify additional roles for Opa in the infectious process and used the yeast two-hybrid system to identify human epithelial cell proteins that interact with Opa proteins. Although this system has been used successfully to identify many types of interacting proteins, it has not been used to screen a human cell cDNA library for binding partners of a prokaryotic outer membrane protein. Therefore, we were also interested in exploring the versatility of the yeast two-hybrid system in identifying bacteria-host interactions. Using OpaP from strain F62SF as bait, we screened a HeLa cell cDNA library for Opa-interacting proteins (OIPs). We identified five different OIPs, designated OIP1-OIP5, two of which are homologous to human proteins--thyroid hormone receptor interacting protein (TRIP6) and pyruvate kinase isoenzyme M2 (PK). In the studies presented here, we investigated the interaction between Opa proteins and PK in more depth. Opa-PK interactions were confirmed by in vitro and in vivo assays independent of the yeast two-hybrid system. Escherichia coli expressing six different Opa proteins from gonococcal strain FA1090 all bound more PK than Opa-negative E. coli in in vitro binding assays. Using anti-PK antibody and fluorescence microscopy, we showed that human epithelial cell PK co-localizes with intracellular Opa+ gonococci and E. coli expressing Opa proteins. Using a mutant of N. gonorrhoeae unable to grow on pyruvate or lactate, it appears that intracellular pyruvate is essential for gonococcal growth and survival. These results suggest a novel mechanism in bacterial pathogenesis, i.e. the requirement for direct molecular interaction with a host metabolic enzyme (PK) for the acquisition of an essential intracellular carbon source and growth substrate (pyruvate). These results demonstrate that the yeast two-hybrid system is a valuable tool for identifying biologically relevant interactions between bacteria and host proteins, providing valuable leads for further investigations into novel mechanisms of bacterial pathogenesis.
Different Equilibrium Stability Behavior of ScFv Fragments:  Identification, Classification, and Improvement by Protein Engineering (1999)

A classification of scFv fragments concerning their unfolding/refolding equilibria is proposed. It is based on the analysis of different mutants of the levan-binding A48 scFv fragment and the HER-2 binding 4D5 scFv fragment as well as a "hybrid" scFv carrying the VL domain of 4D5 and the VH domain of an A48 mutant. The denaturant-induced unfolding curves of the corresponding scFv fragments were measured and, if necessary for the classification, compared with the denaturation of the isolated domains. Depending on the relative intrinsic stabilities of the domains and the stability of the interface, the different scFv fragments were grouped into different classes. We also demonstrate with several examples how such a classification can be used to improve the stability of a given scFv fragment, by concentrating engineering efforts on the "weak part" of the particular molecule, which may either be the intrinsic stability of VL, of VH, or the stability of the interface. One of the scFv fragments obtained by this kind of approach is extremely stable, starting denaturation only at about 7 M urea. We believe that such extremely stable frameworks may be very suitable recipients in CDR grafting experiments. In addition, the thermodynamic equilibrium stabilities of seven related A48 scFv mutants covering a broad range of stabilities in urea unfolding were shown to be well correlated with thermal aggregation properties measured by light scattering and analytical gel filtration.
LONG‐TERM POTASSIUM SUPPLEMENTATION LOWERS BLOOD PRESSURE IN ELDERLY HYPERTENSIVE SUBJECTS (1997)

Following a randomised cross-over trial of the effect of a four-week 60 mmol/day potassium supplement versus placebo on blood pressure (BP), eight of the original 18 hypertensive subjects continued with a 48 mmol daily potassium supplement for four months. For these eight subjects 24-h potassium excretion during placebo, one month of 60 mmol and four months of 48 mmol daily potassium supplementation phases was 56 +/- 23, 102 +/- 28 and 90 +/- 35 mmol/24 hours, respectively, and mean 24-h BP following each phase was 160 +/- 16/89 +/- 11, 147 +/- 13/83 +/- 12 and 145 +/- 14/81+/- 9 mmHg respectively, a significant fall in mean 24-h SBP between four months of potassium supplement and placebo period of 15 +/- 13 mmHg (95% CI: 4, 26 mmHg, p = 0.02), although the fall in 24-h DBP was not significant (8 +/- 11 mmHg, 95% CI: 0, 17 mmHg, p = 0.08). Modest increases in dietary potassium intake could have significant effects on lowering BP in the large proportion of elderly subjects with hypertension.
Hepatitis B Virus-Induced Calreticulin Protein Is Involved in IFN Resistance (2012)

IFN-α is a widely used treatment for hepatitis B virus (HBV) infection, and IFN resistance caused by viral and/or host factors is currently a challenging clinical problem. A better understanding of the molecular mechanisms underlying IFN immunotherapy in the treatment of viral infection would be very beneficial clinically and is of immense clinical importance. Calreticulin (CRT) is an endoplasmic reticulum luminal calcium-binding chaperone that is involved in the regulation of calcium homoeostasis, the folding of newly synthesized proteins, and many other cellular functions. However, little is known about the role of CRT in HBV infection. In this study, we observed high levels of CRT expression in the sera and PBMCs of patients with HBV relative to those of healthy individuals. HBV upregulated the expression of CRT at the transcriptional level. Further investigation showed that HBV-induced CRT enhanced HBV replication by antagonizing the IFN pathway. CRT suppressed the production of endogenous IFN-α by reducing the nuclear translocation of IFN regulatory factor-7 but not IFN regulatory factor-3. Furthermore, CRT also suppressed the antiviral activity of IFN-α by inhibiting the phosphorylation of STAT1 and decreasing the expression of two IFN-α downstream effectors, protein kinase R and 2',5'-oligoadenylate synthetase. Our results offer new insights into the pathogenesis of HBV infection and may provide potential targets for anti-HBV therapy.
ε-Sarcoglycan Replaces α-Sarcoglycan in Smooth Muscle to Form a Unique Dystrophin-Glycoprotein Complex (1999)

The sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that epsilon-sarcoglycan is an integral component of the smooth muscle sarcoglycan complex along with beta- and delta-sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle sarcoglycan complex, whereas the complex was unaffected in alpha-sarcoglycan null mice in agreement with the finding that alpha-sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle sarcoglycan complex, containing epsilon-sarcoglycan, was fully restored following intramuscular injection of recombinant delta-sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the sarcoglycan complex and show that epsilon-sarcoglycan replaces alpha-sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in sarcoglycan-deficient patients.