gebhart/patrepeval huggingface dataset:
Folding and Unfolding Kinetics of the Proline-to-Alanine Mutants of Bovine Pancreatic Ribonuclease A (1996)

Four single mutants (P42A, P93A, P114A, and P117A) of bovine pancreatic ribonuclease A (RNase A) in which each mutant has one of the four prolines of RNase A changed to alanine were prepared. The physical properties of these four mutants indicate that their native structure is essentially identical to that of wild-type RNase A. The disulfide-intact forms of these proteins were denatured in guanidine hydrochloride (Gdn.HCl) and then refolded by dilution of the Gdn.HCl. Single-jump folding, single-jump unfolding, and double-jump unfolding/folding stopped-flow experiments were carried out on wild-type and the four proline mutants of RNase A using absorption detection to follow the folding kinetics. The single-jump folding experiments carried out at six different final Gdn.HCl concentrations indicate that the folding rate constants of individual steps for the mutants are similar to those of wild-type RNase A. The Tyr92-Pro93 peptide bond has a cis conformation in native wild-type RNase A, and the results from our double-jump stopped-flow experiments indicate that the Tyr92-Ala93 peptide bond in the P93A mutant of RNase A is also cis in the native state. The existence of two cis peptide bonds (preceding Pro93 and Pro114) in wild-type RNase A is probably due to (as-yet-unidentified) long-range interactions, and such interactions are presumably the origin of a cis peptide bond even when alanine is substituted for Pro93. The data from the double-jump stopped-flow experiments are interpreted in terms of a folding/unfolding model. This model specifies the cis/trans isomerization state of the unfolded species (Uvf, Uf, Um, and Us) at each X-Pro peptide bond. Also, this model confirms the existence of several previously postulated chain-folding initiation sites.
Infections Caused by Pseudomonas aeruginosa (1983)

Pseudomonas aeruginosa has emerged as an important pathogen during the past two decades. It causes between 10% and 20% of infections in most hospitals. Pseudomonas infection is especially prevalent among patients with burn wounds, cystic fibrosis, acute leukemia, organ transplants, and intravenous-drug addiction. P. aeruginosa is a common nosocomial contaminant, and epidemics have been traced to many items in the hospital environment. Patients who are hospitalized for extended periods are frequently colonized by this organism and are at increased risk of developing infection. The most serious infections include malignant external otitis, endophthalmitis, endocarditis, meningitis, pneumonia, and septicemia. The likelihood of recovery from pseudomonas infection is related to the severity of the patient's underlying disease process. The introduction of the antipseudomonal aminoglycosides and penicillins has improved substantially the prognosis of these infections. Ticarcillin and carbenicillin have been especially beneficial in neutropenic patients; however, prompt institution of therapy is mandatory for optimal benefit. Many new drugs with antipseudomonal activity, including penicillins, cephalosporins, and other beta-lactams, have been introduced in recent years and offer the potential for new approaches to therapy for these infections.
Quantum Control of NaI Photodissociation Reaction Product States by Ultrafast Tailored Light Pulses (1997)

Recent experiments by Herek, Materny and Zewail [Chem. Phys. Lett. 1994, 228, 15] have demonstrated that the timing between two transform-limited, ultrafast laser pulses can be used to control the branching ratio of Na* (electronically excited atomic sodium) to Na in the photodissociation of NaI. In this work, we theoretically show that, by varying the linear chirp of the first pulse without changing its power spectrum or field strength versus time, the Na* to Na branching ratio can be controlled over a large range with a fixed interpulse delay time and a fixed form of the second pulse. Theory predicts that at 0 K the branching ratio can be varied by a factor of 3, while at high temperatures (1000 K), the factor drops to approximately 1.2 due to the effect of the wide distribution of initial states. Experimental results at 1000 K are presented and are found to be consistent with theory. Several possible experimental methods are discussed to overcome the effects of the thermal distribution of initial states.
The effects of the supplementation of Bacillus subtilis RX7 and B2A strains on the performance, blood profiles, intestinal Salmonella concentration, noxious gas emission, organ weight and breast meat quality of broiler challenged with Salmonella typhimurium (2014)

An experiment was conducted to evaluate the effects of B. subtilis RX7 and B. subtilis B2A on growth performance, blood profiles, intestinal Salmonella population, noxious gas emission, organ weight and breast meat quality of broilers under S. typhimurium challenge. A total of 120, one-day-old Ross 308 male broiler chicks were assigned to four dietary treatments, composed of six replications, with five birds per replication, for 10 day. The dietary treatment groups were negative control (NC; no antibiotic, no B. subtilis), positive control (PC; NC + 0.1% virginiamycin), B. subtilis RX7 (NC + 0.1% B. subtilis RX7 1.0 × 10(9) cfu/g) and B. subtilis B2A (NC + 0.1% B. subtilis 1.0 × 10(9) cfu/g). All birds were orally challenged with 2 ml suspension, containing 10(4) cfu/ml of S. typhimurium KCCM 40253. Results indicated that the body weight gain, feed intake and feed conversion did not differ, among all comparative treatments. Serum haptoglobin concentration was lower in Bacillus treatments (RX7 + B2A) than the NC treatment (p < 0.05). Intestinal and excreta Salmonella number, and excreta ammonia gas emission in the PC treatment or Bacillus treatments, was lower than the NC treatment (p < 0.05). Breast pH, colour and water-holding capacity were not affected by supplementation of B. subtilis RX7 and B2A. However, drip loss at 1 day post-slaughter from birds fed with B. subtilis RX7 and B2A decreased, compared with the positive control birds (p < 0.05). Relative gizzard weights of birds fed B. subtilis RX7 and B2A were significantly higher than the NC birds under S. typhimurium challenge. It is concluded from the results that B. subtilis RX7 and B2A increased the gizzard weight and decreased the intestinal and excreta Salmonella population and excreta ammonia gas, and drip loss of breast meat after being stored for 1 day, under stress caused by the S. typhimurium challenge.
Spiro‐Configured Bipolar Host Materials for Highly Efficient Electrophosphorescent Devices (2011)

In this study, we synthesized and characterized a series of spirobifluorene-based bipolar compounds (D2 ACN, DNPACN, DNTACN, and DCzACN) in which a dicyano-substituted biphenyl branch, linked orthogonally to a donor biphenyl branch bearing various diarylamines, acted as an acceptor unit allowing fine-tuning of the morphological stability, triplet energy, bipolar transport behavior, and the HOMO and LUMO energy levels. The promising physical properties of these new compounds, together with their ability to transport electrons and holes with balanced mobilities, made them suitable for use as host materials in highly efficient phosphorescent organic light-emitting diodes (PhOLEDs) with green iridium-based- or red osmium-based phosphors as the emitting layer (EML). We adopted a multilayer structure to efficiently confine holes and electrons within the EML, thus preventing exciton diffusion and improving device efficiency. The device incorporating D2 ACN doped with the red emitter [Os(bpftz)(2)(PPhMe(2))(2)] (bpftz=3-(trifluoromethyl)-5-(4-tert-butylpyridyl)-1,2,4-triazolate) gave a saturated red electrophosphorescence with CIE coordinates of (0.65, 0.35) and remarkably high efficiencies of 20.3 % (21 cd A(-1)) and 13.5 Lm W(-1) at a practical brightness of 1000 cd m(-2).
Inhibition and Role of let-7d in Idiopathic Pulmonary Fibrosis (2010)

Our results indicate a role for microRNAs in IPF. The down-regulation of let-7d in IPF and the profibrotic effects of this down-regulation in vitro and in vivo suggest a key regulatory role for this microRNA in preventing lung fibrosis. Clinical trial registered with www.clinicaltrials.gov (NCT 00258544).
Hematopoietic Stem Cell Defects in Mice with Deficiency of Fancd2 or Usp1 (2010)

Fanconi anemia (FA) is a human genetic disease characterized by a DNA repair defect and progressive bone marrow failure. Central events in the FA pathway are the monoubiquitination of the Fancd2 protein and the removal of ubiquitin by the deubiquitinating enzyme, Usp1. Here, we have investigated the role of Fancd2 and Usp1 in the maintenance and function of murine hematopoietic stem cells (HSCs). Bone marrow from Fancd2-/- mice and Usp1-/- mice exhibited marked hematopoietic defects. A decreased frequency of the HSC populations including Lin-Sca-1+Kit+ cells and cells enriched for dormant HSCs expressing signaling lymphocyte activation molecule (SLAM) markers, was observed in the bone marrow of Fancd2-deficient mice. In addition, bone marrow from Fancd2-/- mice contained significantly reduced frequencies of late-developing cobblestone area-forming cell activity in vitro compared to the bone marrow from wild-type mice. Furthermore, Fancd2-deficient and Usp1-deficient bone marrow had defective long-term in vivo repopulating ability. Collectively, our data reveal novel functions of Fancd2 and Usp1 in maintaining the bone marrow HSC compartment and suggest that FA pathway disruption may account for bone marrow failure in FA patients.
Inhibitors of human cathepsin L and cruzain as therapeutic agents. (2009)

Increased human cathepsin L activity is linked to invasive and metastatic cancers where it promotes degradation of the extracellular matrix. This major cysteine protease found in cell lysosomes and secreted from tissues, also plays a role in the pathology of degenerative cartilage and neurological disorders, and is reported to be required for the SARS coronavirus infection. A library of 59 small non-peptidic thiosemicarbazone and α, β-unsaturated carbonyl derivatives of benzophenone, propiophenone, α- and β-tetralone, 4-chromanone, and 4-thiochromenone were evaluated as inhibitors of human cathepsin L. While most of the compounds had IC50 values in the range of 0.4 µM or greater, four were very effective inhibitors of cathepsin L: the benzophenone thiosemicarbazones 2 (IC50= 1.5 nM), 55 (IC50= 44 nM), 38 (IC50= 60 nM), 32 (IC50= 66 nM), and 37 (IC50= 140 nM) and a sulfone analog of the bromo substituted thiochroman-4-one 22 (IC50= 1 nM). Kinetics studies were used to gain understanding in enzyme-inhibitor interactions of the most potent compounds (2 and 22) and they were found to be reversible, slow, tight binding inhibitors of cathepsin L. These data support formation of a transient covalent intermediate between thiosemicarbazone inhibitors and the cathepsin L active site thiolate. Ten of the most promising lead compounds were also tested for cytotoxicity in HEK-293 cells and generated no toxicity after 24 hours. Exposure of the prostate cancer cell line DU-145 to the most promising lead compounds successfully decreased the invasiveness and mobility properties of these cells in vitro. The non-peptidic nature of these inhibitors, coupled with their cell-based activity, makes these compounds very promising leads for the development of selective cathepsin L inhibitors. A separate research project consisted of recombinant cruzain purification and evaluation of thiosemicarbazone derivatives as potential inhibitors of this parasitic cysteine protease. Cruzain is the major cysteine protease of Trypanosoma cruzi organism and is a validated therapeutic target for the development of new chemotherapy. Chagas disease, a result of Trypanosoma cruzi infection, is the third largest parasitic disease challenge worldwide after malaria and leishmania and there is an urgent need for development of new therapeutic agents against Chagas disease. From the same library of thiosemicarbazone derivatives evaluated against cathepsin L, 25 compounds were evaluated against cruzain from which six compounds were in the nanomolar range with IC50 values ranging from 170 nM to 622 nM.
From Carbon Dioxide to Methane:  Homogeneous Reduction of Carbon Dioxide with Hydrosilanes Catalyzed by Zirconium−Borane Complexes (2006)

A mixture of a zirconium benzyl phenoxide complex and tris(pentafluorophenyl)borane is reported that catalyzes the hydrosilation reaction of carbon dioxide to generate methane via a bis(silyl)acetal intermediate.
Frequency domain optical reflectometer (1981)

A correlation reflectometer operating in the frequency domain is described. It is shown that such an instrument is well adapted to detecting weak discrete reflections. The detection of end reflections in a 2.2-km length of fiber whose end is index matched is demonstrated. A round-trip range of over 70 dB is obtained with a 1-mW optical source power. The method shows promise for characterizing the reflective properties of optical fiber elements, such as tapers, microbends, and splices, and may be useful in fault location.
Neuroblastoma tumour genetics: clinical and biological aspects (2001)

Neuroblastoma tumour cells show complex combinations of acquired genetic aberrations, including ploidy changes, deletions of chromosome arms 1p and 11q, amplification of the MYCN oncogene, and-most frequently-gains of chromosome arm 17q. Despite intensive investigation, the fundamental role of these features in neuroblastoma initiation and progression remains to be understood. Nonetheless, great progress has been made in relating tumour genetic abnormalities to tumour behaviour and to clinical outcome; indeed, neuroblastoma provides a paradigm for the clinical importance of tumour genetic abnormalities. Knowledge of MYCN status is increasingly being used in treatment decisions for individual children, and the clinical value of 1p and 17q data as adjuncts or refinements in risk stratification is under active investigation. Reliable detection of these molecular cytogenetic features should be regarded as mandatory for all new cases at presentation.
Coal Demethanation Principles And Field Experience (1982)

Abstract INTRODUCTION A program was initiated by Noval Technologies Ltd., a subsidiary of NOVA, An Alberta Corporation, in 1976 to develop coal demethanation technology and demonstrate its econonic viability. Theoretical studies and field experiments were started in Alberta in 1977 and are continuing. In 1979, in conjunction with Petro-Canada, Naval started a test program in Nova Scotia that is to lead to commercial development. This report is a brief coverage of the theoretical background, and the results of field experience, not only of the Naval project, but also of other major demethanation projects. The relations between basic physical parameters of the coal and their impact on the demethanation process are discussed, as are the results of the field experience using vertical boreholes and the effect of the various stimulation methods used, indicating the advantages and drawbacks of each. After over five years of experience, Noval feels that coal demethanation techniques are sufficiently advanced to make a commercial project feasible. INTRODUCTION Methane has been known to exist in association with coal beds for many years. It has been known under many names, such as firedamp, methane, coal gas, etc. Traditionally, the methane in the coal was only considered when the coal was being mined and then only as a hazard. Recently, mostly as a result of the energy shortage, methane in coal has been given attention as a potential energy source. Its use as a fuel is not entirely new or innovative because, mostly in Europe, collieries have used the gas for many years. However, its use in North America in large quantities is new. Two different methods are known for extracting methane from coal. One is an underground system operating within a mine, normally referred to simply as methane drainage. It was first applied about 50 years ago in Europe. The second takes place on the ground surface and is often referred to as Virgin Coal Demethanation (VCD). The extraction technology was started in the USA approximately 12 years ago. Both methods achieve the same goal, nevertheless they go about it in entirely different ways. The major aim of the methane drainage method has traditionally been to achieve an immediate impact on the mine ventilation system by decreasing the methane concentration in the mining operations. The use of methane as a potential energy source is only a secondary concern, even though many collieries end up utilizing it. VCD, which is independent of mining operations, also reduces the methane content of the coal and makes for safer mining operations. However, being independent of a mine, it can and has been used to obtain methane for use as a fuel, irrespective of whether or not the coal will be mined. This paper will briefly discuss the principles and field experience of VCD in general and relate it to Noval's experience. The terms ?gas? and ?methane? are used interchangeably in this paper, because gas from coal is almost 100% methane. In some cases, traces of other gases are present, such as CO2, Hz, N2 and 02, but these usually constitute less than 2%.
A Generalized Approach to the Modification of Solid Surfaces (2005)

Interfacial interactions underpin phenomena ranging from adhesion to surface wetting. Here, we describe a simple, rapid, and robust approach to modifying solid surfaces, based on an ultrathin cross-linkable film of a random copolymer, which does not rely on specific surface chemistries. Specifically, thin films of benzocyclobutene-functionalized random copolymers of styrene and methyl methacrylate were spin coated or transferred, then thermally cross-linked on a wide variety of metal, metal oxide, semiconductor, and polymeric surfaces, producing a coating with a controlled thickness and well-defined surface energy. The process described can be easily implemented and adapted to other systems.
Hybrid Speciation in Experimental Populations of Yeast (2002)

Most models of speciation require gradual change and geographic or ecological isolation for new species to arise. Homoploid hybrid speciation occurred readily between Saccharomyces cerevisiae and Saccharomyces paradoxus. Hybrids had high self-fertility (about 82%), low fertility when backcrossed to either parental species (about 7.5%), and vigorous growth under different thermal environments that favored one or the other of the parental species. Extensive karyotypic changes (tetrasomy) were observed in the hybrids, although genic incompatibilities accounted for 50% of the variation in self-fertility.
Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor (1999)

Immune mechanisms and the renin-angiotensin system are implicated in preeclampsia. We investigated 25 preeclamptic patients and compared them with 12 normotensive pregnant women and 10 pregnant patients with essential hypertension. Antibodies were detected by the chronotropic responses to AT1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists. Immunoglobulin from all preeclamptic patients stimulated the AT1 receptor, whereas immunoglobulin from controls had no effect. The increased autoimmune activity decreased after delivery. Affinity-column purification and anti-human IgG and IgM antibody exposure implicated an IgG antibody directed at the AT1 receptor. Peptides corresponding to sites on the AT1 receptor's second extracellular loop abolished the stimulatory effect. Western blotting with purified patient IgG and a commercially obtained AT1 receptor antibody produced bands of identical molecular weight. Furthermore, confocal microscopy of vascular smooth muscle cells showed colocalization of purified patient IgG and AT1 receptor antibody. The protein kinase C (PKC) inhibitor calphostin C prevented the stimulatory effect. Our results suggest that preeclamptic patients develop stimulatory autoantibodies against the second extracellular AT1 receptor loop. The effect appears to be PKC-mediated. These novel autoantibodies may participate in the angiotensin II-induced vascular lesions in these patients.
Chimeric antigen receptor T-cell therapy for solid tumors (2016)

Chimeric antigen receptor (CAR) T cells are engineered constructs composed of synthetic receptors that direct T cells to surface antigens for subsequent elimination. Many CAR constructs are also manufactured with elements that augment T-cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematological malignancies (e.g., CD19 CARs in leukemias). This success is not yet extrapolated to solid tumors, and the reasons for this are being actively investigated. Here in this mini-review, we discuss some of the key hurdles encountered by CAR T cells in the solid tumor microenvironment.
ISG15, a ubiquitin-like interferon-stimulated gene, promotes hepatitis C virus production in vitro: implications for chronic infection and response to treatment (2009)

Upregulation of interferon (IFN)-stimulated genes (ISGs), including IFN-stimulated gene 15 (ISG15) and other members of the ISG15 pathway, in pre-treatment liver tissue of patients chronically infected with hepatitis C virus (HCV) is associated with subsequent treatment failure (pegylated IFN-alpha/ribavirin). This study assessed the effect of ISG15 on HCV production in vitro. The levels of ISG15 and of its conjugation to target proteins (ISGylation) were increased by plasmid transfection, but ISGylation was inhibited by small interfering RNA directed against the E1 activating enzyme, Ube1L, in Huh7.5 cells. Cells were infected with HCV FL-J6/JFH virus, and HCV RNA and viral titres were determined. Levels of both HCV RNA and virus increased when levels of ISG15 and ISGylation were increased, and decreased when ISGylation was inhibited. The effects of ISGylation on HCV were independent of upstream IFN signalling: IFN-alpha-induced ISG expression was not altered by Ube1L knockdown. Thus, although ISG15 has antiviral activity against most viruses, ISG15 promotes HCV production. HCV might exploit ISG15 as a host immune evasion mechanism, and this may in part explain how increased expression of ISGs, especially ISG15, correlates with subsequent IFN-based treatment failure.
Development of color management system prototype (2002)

It is becoming popular to use a color monitor, color scanner, color printer, film recorder and other color devices with the increment of computing power as well as lowering the cost of hardware and software. When users develop a color image with their computer and print out that image with the color printer, the two images are different. Also when users develop a color image and send it to their friend or send it to the public domain, the image on the other user's screen is quite different from the original image. This kind of mismatching problem may cause serious problems when people purchase products through home shopping or remote medical diagnosis. We studied a color science based scanner and color monitor calibration and we developed a prototype color management system that can match between the original image and the scanned image displayed on the monitor. In addition, we developed a profile editor for making and modifying the ICC (International Color Consortium) profile. Our future research will focus on the calibration of other color devices such as color printers, digital cameras, etc., as well as the integration of our results to make a complete color management system. Also our research team will study the ICC profile and make more efficient profile tags to contribute an ICC as a member.