gebhart/patrepeval huggingface dataset:
Atomic‐resolution crystal structure of thioredoxin from the acidophilic bacterium Acetobacter aceti (2006)

The crystal structure of thioredoxin (AaTrx) from the acetic acid bacterium Acetobacter aceti was determined at 1 A resolution. This is currently the highest resolution crystal structure available for any thioredoxin. Thioredoxins facilitate thiol-disulfide exchange, a process that is expected to be slow at the low pH values encountered in the A. aceti cytoplasm. Despite the apparent need to function at low pH, neither the active site nor the surface charge distribution of AaTrx is notably different from that of Escherichia coli thioredoxin. Apparently the ancestral thioredoxin was sufficiently stable for use in A. aceti or the need to interact with multiple targets constrained the variation of surface residues. The AaTrx structure presented here provides a clear view of all ionizable protein moieties and waters, a first step in understanding how thiol-disulfide exchange might occur in a low pH cytoplasm, and is a basis for biophysical studies of the mechanism of acid-mediated unfolding. The high resolution of this structure should be useful for computational studies of thioredoxin function, protein structure and dynamics, and side-chain ionization.
Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover. (1980)

Ca2+-activated, phospholipid-dependent protein kinase from various mammalian tissues (Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T., and Nishizuka, Y (1979) J. Biol. Chem. 254, 3692-3695) was greatly stimulated by the addition of diacylglycerol at less than 5% (w/w) the concentration of phospholipid. This stimulation was due to an increase in the apparent affinity of enzyme for phospholipid and to a concomitant decrease in the Ka value for Ca2+ from about 1 x 10(-4) M to the micromolar range. Diacylglycerol alone showed little or no effect on enzymatic activity over a wide range of Ca2+ concentrations. This effect was greatest for diacylglycerol which contained unsaturated fatty acid at least at position 2. The active diacylglycerols so far tested included diolein, dilinolein, diarachidonin, 1-stearoyl-2-oleoyl diglyceride, and 1-stearoyl-2-linoleoyl diglyceride. In contrast, diacylglycerols containing saturated fatty acids such as dipalmitin and distearin were far less effective. Triacyl- and monoacylglycerols were totally ineffective, irrespective of the fatty acyl moieties. Cholesterol and free fatty acids were also ineffective. Based on these observations, a possible coupling is proposed between the protein kinase activation and phosphatidylinositol turnover which can be provoked by various extracellular messengers.
Dephosphorylation of Cell Cycle–regulated Proteins Correlates with Anoxia-induced Suspended Animation inCaenorhabditis elegans (2002)

Some metazoans have evolved the capacity to survive severe oxygen deprivation. The nematode, Caenorhabditis elegans, exposed to anoxia (0 kPa, 0% O(2)) enters into a recoverable state of suspended animation during all stages of the life cycle. That is, all microscopically observable movement ceases including cell division, developmental progression, feeding, and motility. To understand suspended animation, we compared oxygen-deprived embryos to nontreated embryos in both wild-type and hif-1 mutants. We found that hif-1 mutants survive anoxia, suggesting that the mechanisms for anoxia survival are different from those required for hypoxia. Examination of wild-type embryos exposed to anoxia show that blastomeres arrest in interphase, prophase, metaphase, and telophase but not anaphase. Analysis of the energetic state of anoxic embryos indicated a reversible depression in the ATP to ADP ratio. Given that a decrease in ATP concentrations likely affects a variety of cellular processes, including signal transduction, we compared the phosphorylation state of several proteins in anoxic embryos and normoxic embryos. We found that the phosphorylation state of histone H3 and cell cycle-regulated proteins recognized by the MPM-2 antibody were not detectable in anoxic embryos. Thus, dephosphorylation of specific proteins correlate with the establishment and/or maintenance of a state of anoxia-induced suspended animation.
Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles (2019)

We report a potent cationic lipid, SST-02 ((3-hydroxylpropyl)dilinoleylamine), which possesses a simple chemical structure and is synthesized just in one step. Cationic lipids are key components of siRNA-lipid nanoparticles (LNP), which may serve as potential therapeutic agents for various diseases. For a decade, chemists have given enhanced potency and new functions to cationic lipids along with structural complexity. In this study, we conducted a medicinal chemistry campaign pursuing chemical simplicity and found that even dilinoleylmethylamine (SST-01) and methylpalmitoleylamine could be used for the in vitro and in vivo siRNA delivery. Further optimization revealed that a hydroxyl group boosted potency, and SST-02 showed an ID<sub>50</sub> of 0.02 mg/kg in the factor VII (FVII) model. Rats administered with 3 mg/kg of SST-02 LNP did not show changes in body weight, blood chemistry, or hematological parameters, while the AST level decreased at a dose of 5 mg/kg. The use of SST-02 avoids a lengthy synthetic route and may thus decrease the future cost of nucleic acid therapeutics.
Small dual patch antenna (1999)

A novel two-layer rectangular patch antenna has been designed and tested. Compared with a basic single layer patch antenna with the same projection area, the resonant frequency is reduced by 39%. The bandwidth is 5%; the cross-polarisation level is less than –15 dB.
Five-year clinical results of zirconia frameworks for posterior fixed partial dentures. (2007)

Zirconia offers sufficient stability as a framework material for 3- and 4-unit posterior FPDs. The fit of the frameworks and veneering ceramics, however, should be improved.
Emerging Infections with Community-Associated Methicillin-Resistant Staphylococcus aureus in Outpatients at an Army Community Hospital (2005)

The incidence of MRSA at our institution is increasing. Isolates of MRSA show resistance patterns and microbiologic characteristics consistent with CA-MRSA isolates from the United States. Clinicians should consider the possibility of CA-MRSA in patients with soft-tissue infections who do not respond to initial therapy with beta-lactam antimicrobial agents.
Determination of two-dimensional planar displacement by moiré fringes of concentric-circle gratings (1994)

We investigate the moiré fringe pattern of two concentric-circle gratings with the aim of measuring the relative two-dimensional planar displacement induced between the gratings. In the first stage we give a comprehensive mathematical approach for the analysis of fringe patterns. Then we suggest a fast computational measurement algorithm that uses a Fourier transformation technique. Finally, our experimental results prove that a measuring accuracy of 0.01 µm can be achieved with this method.
The refractive index of AlxGa1−xAs below the band gap: Accurate determination and empirical modeling (2000)

The refractive indices of AlxGa1−xAs epitaxial layers (0.176⩽x⩽1) are accurately determined below the band gap to wavelengths, λ&amp;lt;3 μm. The layers are grown on GaAs substrates by molecular beam epitaxy metal organic and chemical vapor deposition with thicknesses ranging from 4 to 10 μm. They form improper waveguide structures with the GaAs substrate. The measurements are based on the excitation of the improper waveguide modes with grating couplers at 23 °C. The refractive indices of the layers are derived from the modal propagation constants in the range of 730 nm&amp;lt;λ&amp;lt;830 nm with an estimated uncertainty of Δn=5×10−4. The temperature coefficient of the refractive index is investigated in the same spectral range. From the effective indices of the TE and TM modes, we derive the strain-induced birefringence and the elasto-optic coefficients. High-resolution x-ray diffraction is used to determine the strain of the layers. The layer compositions are obtained with inductively coupled plasma atomic emission spectroscopy. The measurement range of the refractive index is extended from the direct gap to λ&amp;lt;3 μm by observing the Fabry-Pérot interference fringes of the transmission spectra of isolated layers. The measured values of the refractive index and the elasto-optic coefficient are compared to calculated data based on semiempirical models described in the literature. Published data of the index of refraction on GaAs, AlAs and GaP are analyzed to permit the development of a modified Sellmeier approximation. The experimental data on AlxGa1−xAs can be fitted over the entire composition range 0⩽x⩽1 to provide an accurate analytical description as a function of composition, wavelength, and temperature.
Heparin-Protamine Complexes in the Production of Heparin Rebound and Other Complications of Extracorporeal Bypass Procedures (1987)

Neutralization by protamine of the heparin activation of antithrombin III in plasma, in vitro, represents an equilibrium reaction in which by mass action heparin remains complexed only in the presence of an excess of protamine. Loss of this excess through enzymatic breakdown of the free protamine leads to instability of the complexes with liberation of the heparin, reestablishing antithrombin activity. This "heparin rebound" can also be produced by an increase in heparin levels or increased amounts of antithrombin III. These phenomena could occur after extracorporeal bypass procedures by an increase in heparin from whatever source or by added antithrombin III, through transfusions of fresh frozen plasma. A larger excess of protamine does not itself act as an anticoagulant but produces large heparin-protamine complexes that can still activate antithrombin III. Such large complexes, formed in vivo, could possibly block the pulmonary microcirculation and cause the acute pulmonary hypertension that has been reported after protamine infusions.
A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia (2004)

Preclinical studies with the histone deacetylase (HDAC) inhibitor depsipeptide (FK228) in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) have demonstrated that it effectively induces apoptosis at concentrations at which HDAC inhibition occurs. We initiated a minimum effective pharmacologic dose study of depsipeptide, targeting an in vivo dose at which acetylation of histone proteins H3 and H4 increased by 100% or more in vitro. Ten patients with CLL and 10 patients with AML were treated with 13 mg/m(2) depsipeptide intravenously days 1, 8, and 15 of therapy. Neither life-threatening toxicities nor cardiac toxicities were noted, although the majority of patients experienced progressive fatigue, nausea, and other constitutional symptoms that prevented repeated dosing. Several patients had evidence of antitumor activity following treatment, but no partial or complete responses were noted by National Cancer Institute criteria. HDAC inhibition and histone acetylation increases of at least 100% were noted, as well as increases in p21 promoter H4 acetylation, p21 protein, and 1D10 antigen expression. We conclude that depsipeptide effectively inhibits HDAC in vivo in patients with CLL and AML, but its use in the current schedule of administration is limited by progressive constitutional symptoms. Future studies with depsipeptide should examine alternative administration schedules.
Size-tagged preferred ends in maternal plasma DNA shed light on the production mechanism and show utility in noninvasive prenatal testing (2018)

Cell-free DNA in human plasma is nonrandomly fragmented and reflects genomewide nucleosomal organization. Previous studies had demonstrated tissue-specific preferred end sites in plasma DNA of pregnant women. In this study, we performed integrative analysis of preferred end sites with the size characteristics of plasma DNA fragments. We mined the preferred end sites in short and long plasma DNA molecules separately and found that these "size-tagged" ends showed improved accuracy in fetal DNA fraction estimation and enhanced noninvasive fetal trisomy 21 testing. Further analysis revealed that the fetal and maternal preferred ends were generated from different locations within the nucleosomal structure. Hence, fetal DNA was frequently cut within the nucleosome core while maternal DNA was mostly cut within the linker region. We further demonstrated that the nucleosome accessibility in placental cells was higher than that for white blood cells, which might explain the difference in the cutting positions and the shortness of fetal DNA in maternal plasma. Interestingly, short and long size-tagged ends were also observable in the plasma of nonpregnant healthy subjects and demonstrated size differences similar to those in the pregnant samples. Because the nonpregnant samples did not contain fetal DNA, the data suggested that the interrelationship of preferred DNA ends, chromatin accessibility, and plasma DNA size profile is likely a general one, extending beyond the context of pregnancy. Plasma DNA fragment end patterns have thus shed light on production mechanisms and show utility in future developments in plasma DNA-based noninvasive molecular diagnostics.
Are natural killer cells superior CAR drivers? (2014)

T lymphocytes engineered to express a chimeric antigen receptor (CAR) are being celebrated as a major breakthrough of anticancer immunotherapy. Natural killer cells have not received similar attention as CAR effectors, although the use of these relatively short-lived cytotoxic cells is associated with several advantages.
Multitest system for biochemical identification of Salmonella, Escherichia coli, and other Enterobacteriaceae isolated from foods: collaborative study. (1989)

Nine laboratories evaluated the ability of the MICRO-ID test system to correctly identify members of the Enterobacteriaceae. A total of 78 isolates representing 11 genera of enterics that had been previously isolated from foods were used in the collaborative study. The collaborators streaked each isolate on plate count agar and incubated the plates overnight at 35 degrees C to check purity of the isolates. Then they proceeded with the method in which an isolated colony is transferred to a plate count agar slant and is incubated 18-24 h at 35 degrees C. Growth from the slant is emulsified in 3.5 mL physiological saline to a density comparable to a McFarland No. 2 tube and is then used to inoculate the test (MICRO-ID) strip. The strip is incubated 4 h at 35 degrees C and the reactions are read and recorded. Isolates are identified by using an octal code and the test kit manual. The system correctly identified 98.8% of the Salmonella isolates, 97.7% of the E. coli isolates, and 84.6% of the other 9 enteric genera tested. The system has been approved interim official first action as an alternative to conventional biochemical tests (1) for presumptive generic identification of food-borne Salmonella and for screening and elimination of non-Salmonella isolates; (2) for identification of E. coli from foods; and (3) for presumptive generic identification of other Enterobacteriaceae isolated from foods.
Specific CP110 Phosphorylation Sites Mediate Anaphase Catastrophe after CDK2 Inhibition: Evidence for Cooperation with USP33 Knockdown (2015)

Chromosomal instability (CIN) is a hallmark of solid tumor biology and is implicated in carcinogenesis. Preferentially eliminating malignant cells by targeting CIN and aneuploidy is an attractive antineoplastic strategy. We previously reported that CDK2 antagonism causes lung cancer cells to undergo anaphase catastrophe and apoptosis through inhibition of phosphorylation of the centrosomal protein CP110. Cells with activating KRAS mutations were particularly sensitive to CDK2 inhibition due to downregulation of CP110 protein levels. This study investigated mechanisms of CDK2 antagonism that mediate anaphase catastrophe via changes in CP110 protein expression and how activated KRAS affects CP110 levels in lung cancers. Site-directed mutagenesis revealed candidate CDK phosphorylation sites of CP110 (residues Ser 170 and Thr 194) critical for conferring anaphase catastrophe by altering centrosome clustering in mitosis. Intriguingly, KRAS mutation can promote CP110 protein degradation by upregulating the ubiquitin ligase SCF(cyclinF), which targets CP110 protein for destabilization. Finally, CDK2 inhibitor response was enhanced when combined with knockdown of the deubiquitinase USP33 that in turn accelerates CP110 protein degradation. Thus, this study provides molecular pharmacologic insights into how CP110 expression regulates response to CDK2 inhibition. An improved understanding of in vitro antineoplastic mechanisms of combining CDK2 antagonism with induced CP110 repression provides a rationale for exploring clinical consequences of this strategy. Taken together, preclinical findings obtained from combining CDK2 inhibition with USP33 repression have implications for treating patients with non-small cell lung cancers.
Molecular Cloning and Characterization of Genes for Shigella sonnei Form I O Polysaccharide: Proposed Biosynthetic Pathway and Stable Expression in a Live Salmonella Vaccine Vector (2002)

The gene region for biosynthesis of Shigella sonnei form I O polysaccharide (O-Ps) and flanking sequences, totaling >18 kb, was characterized by deletion analysis to define a minimal construct for development of Salmonella-based live vaccine vector strains. Lipopolysaccharide (LPS) expression and DNA sequence studies of plasmid deletion derivatives indicated form I O-Ps expression from a 12.3-kb region containing a putative promoter and 10 contiguous open reading frames (ORFs), one of which is the transposase of IS630. A detailed biosynthetic pathway, consistent with the predicted functions of eight of the nine essential ORFs and the form I O-Ps structure, is proposed. Further sequencing identified partial IS elements (i.e., IS91 and IS630) and wzz upstream of the form I coding region and a fragment of aqpZ and additional full or partial IS elements (i.e., IS629, IS91, and IS911) downstream of this region. The stability of plasmid-based form I O-Ps expression was greater from low-copy vectors than from high-copy vectors and was enhanced by deletion of the downstream IS91 from plasmid inserts. Both core-linked (i.e., LPS) and non-core-linked (i.e., capsule-like) surface expression of form I O-Ps were detected by Western blotting and silver staining of polyacrylamide gel electrophoresis-separated Shigella and Escherichia coli extracts. However, salmonellae, which have a core that is chemically dissimilar to that of shigellae, expressed only non-core-linked surface-associated form I O-Ps. Finally, attenuated Salmonella enterica serovar Typhi live vaccine vector candidates, containing minimal-sized form I operon constructs, elicited immune protection in mice against virulent S. sonnei challenge, thereby supporting the promise of live, oral vaccines for the prevention of shigellosis.
Site-directed mutagenesis and the role of the oxyanion hole in subtilisin. (1986)

Oligonucleotide-directed mutagenesis was used to investigate the nature of transition state stabilization in the catalytic mechanism of the serine protease, subtilisin BPN'. The gene for this extracellular enzyme from Bacillus amyloliquefaciens has been cloned and expressed in Bacillus subtilis. In the transition state complex, the carbonyl group of the peptide bond to be hydrolyzed is believed to adopt a tetrahedral configuration rather than the ground-state planar configuration. Crystallographic studies suggest that stabilization of this activated complex is accomplished in part through the donation of a hydrogen bond from the amide side group of Asn-155 to the carbonyl oxygen of the peptide substrate. To specifically test this hypothesis, leucine was introduced at position 155. Leucine is isosteric with asparagine but is incapable of donating a hydrogen bond to the tetrahedral intermediate. The Leu-155 variant was found to have an unaltered Km but a greatly reduced catalytic rate constant, kcat, (factor of 200-300 smaller) when assayed with a peptide substrate. These kinetic results are consistent with the Asn-155 mediating stabilization of the activated complex and lend further experimental support for the transition-state stabilization hypothesis of enzyme catalysis.
Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects: a placebo-controlled parallel group study (1996)

The anti-inflammatory effects of oral theophylline on cells in bronchial biopsies of symptomatic atopic asthmatic subjects were investigated. Following a 2 week run-in period, asthmatic subjects were randomly assigned to either placebo (n=11) or theophylline (n=15). Bronchial biopsies were taken at fibre-optic bronchoscopy at the beginning and end of a 6 week period, during which subjects took placebo or theophylline medication at a dose intended to produce therapeutic concentrations. Nine of the placebo subjects and 12 of the theophylline subjects completed the study. Improvement in asthma control was seen in the theophylline-treated group. The mean (SD) theophylline blood level at the end of the study was 10.9 (6.0) microg x mL-1. A significant decrease in interleukin (IL)4 expression from 1.38 to 1.04 cells x mm-2 (<0.05) and a trend to a reduction in IL-5 from 1.29 to 0.48 cells x mm-2 (NS) were seen in biopsies from the theophylline-treated group compared with placebo, although there was no change in mast cell numbers (judged by tryptase expression). A decrease in epithelial CD8+ cells from 2.60 to 0.53 cells x mm-1 of surface (<0.05) was noted. This study shows an anti-inflammatory effect of theophylline in asthmatic bronchi, both in cell numbers and in the expression of IL-4, believed to be an important cytokine in the pathophysiology of asthmatic inflammation. We speculate that theophylline induces downregulation in vivo of cytokine production, accounting for the known inhibitory effect of theophylline on the late asthmatic reaction.
Lack of Effect of a High-Fiber Cereal Supplement on the Recurrence of Colorectal Adenomas (2000)

As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas.
Human Chromosome 21 Dosage: Effect on the Expression of the Interferon Induced Antiviral State (1974)

Human primary skin fibroblasts trisomic for chromosome 13, 18, or 21 and diploid human skin fibroblasts were induced for an antiviral response with human interferon. The cells that were trisomnic for chromosome 21 were three to seven times more sensitive to protection by human interferon than the normal diploid or trisomic 18 or 13 fibroblasts. The differential response in trisomnic 21 cells is consistent with the known assignment of the human antiviral gene to chromosome 21.
The recombination mechanisms leading to amplified spontaneous emission at the true-green wavelength in CH3NH3PbBr3 perovskites (2015)

We investigated the mechanisms of radiative recombination in a CH3NH3PbBr3 hybrid perovskite material using low-temperature, power-dependent (77 K), and temperature-dependent photoluminescence (PL) measurements. Two bound-excitonic radiative transitions related to grain size inhomogeneity were identified. Both transitions led to PL spectra broadening as a result of concurrent blue and red shifts of these excitonic peaks. The red-shifted bound-excitonic peak dominated at high PL excitation led to a true-green wavelength of 553 nm for CH3NH3PbBr3 powders that are encapsulated in polydimethylsiloxane. Amplified spontaneous emission was eventually achieved for an excitation threshold energy of approximately 350 μJ/cm2. Our results provide a platform for potential extension towards a true-green light-emitting device for solid-state lighting and display applications.