gebhart/patrepeval huggingface dataset:
Emerging Cystic Fibrosis Transmembrane Conductance Regulator Modulators as New Drugs for Cystic Fibrosis: A Portrait of <i>in Vitro</i> Pharmacology and Clinical Translation (2019)

Pharmacological correction of the defective ion channel with cystic fibrosis transmembrane conductance regulator (CFTR) has become an attractive approach to therapy directed at the root cause of the life-limiting disease cystic fibrosis (CF). CFTR defects range from absence, misfolding, and resulting degradation to functional defects of the CFTR protein. The discovery and development of the CFTR potentiator ivacaftor was a major break-through in CF therapy and has triggered an enormous incentive for seeking effective modulators such as lumacaftor, tezacaftor or elexacaftor for all patients with CF. A number of emerging CFTR modulators are currently in the development pipeline, and rescue levels of CFTR protein approach a cure for cystic fibrosis. In this review, we identify and characterize all preclinical and clinical emerging CFTR modulators and discuss the <i>in vitro</i> pharmacology, looking at CFTR protein expression and chloride transport and the translation to the clinic. The new emerging CFTR modulators could offer new therapeutic solutions for CF patients.
Unique modifications with phosphocholine and phosphoethanolamine define alternate antigenic forms of <i>Neisseria gonorrhoeae</i> type IV pili (2004)

Several major bacterial pathogens and related commensal species colonizing the human mucosa express phosphocholine (PC) at their cell surfaces. PC appears to impact host-microbe biology by serving as a ligand for both C-reactive protein and the receptor for platelet-activating factor. Type IV pili of Neisseria gonorrhoeae (Ng) and Neisseria meningitidis, filamentous protein structures critical to the colonization of their human hosts, are known to react variably with monoclonal antibodies recognizing a PC epitope. However, the structural basis for this reactivity has remained elusive. To address this matter, we exploited the finding that the PilE pilin subunit in Ng mutants lacking the PilV protein acquired the PC epitope independent of changes in pilin primary structure. Specifically, we show by using mass spectrometry that PilE derived from the pilV background is composed of a mixture of subunits bearing O-linked forms of either phosphoethanolamine (PE) or PC at the same residue, whereas the wild-type background carries only PE at that same site. Therefore, PilV can influence pilin structure and antigenicity by modulating the incorporation of these alternative modifications. The disaccharide covalently linked to Ng pilin was also characterized because it is present on the same peptides bearing the PE and PC modifications and, contrary to previous reports, was found to be linked by means of 2,4-diacetamido-2,4,6-trideoxyhexose. Taken together, these findings provide new insights into Ng type IV pilus structure and antigenicity and resolve long-standing issues regarding the nature of both the PC epitope and the pilin glycan.
Low Voltage Optical Modulator Using Electrooptically Induced Phase Gratings (1973)

An optical modulator with square phase gratings, which are induced by a mosaic structure of electrooptic crystals, is proposed. Analysis and experiments show its utility and the possibility of fabricating it by binding several crystals. An experimental device is built by an array structure using eight 0.9(z) x 0.9(y) x 12.5(x)-mm LiNbO(3) rods. Its 100% modulation voltage is 68 V, and its capacitance is 18 pF. Experimental results, such as modulation transfer function and angle of diffraction, agree well with the analysis, and the farfield patterns obtained are fairly good. This type of modulator offers a low voltage operation, which is about 40% of that of a conventional one for LiNbO(3)crystals. Furthermore, it has the advantage of insensitivity to temperature change.
A Newer Short Synthesis of dl-Muscone(I) (1996)

New routes have been developed for the practical syntheses of dl-Muscone(1) employing cyclopentadecanone(2) as the starting material. In this experiment, addition of bromine to cyclopentadecanone in dried E. Ether solution with a trace of as the catalyst were produced 2-bromocyclopentadecanone(3). This process was enhanced formation of regioselective enolate anion at position. 2-Bromocyclopentadecanone was put into -LiBr-DMF solution at 140∼150, were produced trans- and cis-2-cyclopentadecen-1-one(4) mixture. Other by-products were reduced by control of reaction temperature and time. Trans- and cis-2-cyclopentadecen-1-one(4) mixture was directly put into dried E. Ether solvent and induce to react dropwise with complex, all of them got into 1,4-addition, dl-Muscone (1) was formed as the result. Conculsion, through three steps procedure from cyclopentadecanone(2) to dl-Muscone(1), the pure dl-Muscone was obtained with the high proportion of 85%, and synthetic cost was able to be much lower than any other conventional methods as there were no chemical separating steps.
Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in the mouse (2004)

Cyclooxygenase (COX)-2 is expressed in the heart in animal models of ischemic injury. Recent studies have suggested that COX-2 products are involved in inflammatory cell infiltration and fibroblast proliferation in the heart. Using a mouse model, we questioned whether 1). myocardial infarction (MI) in vivo induces COX-2 expression chronically, and 2). COX-2 inhibition reduces collagen content and improves cardiac function in mice with MI. MI was produced by ligation of the left anterior descending coronary artery in mice. Two days later, mice were treated with 3 mg/kg NS-398, a selective COX-2 inhibitor, or vehicle in drinking water for 2 wk. After the treatment period, mice were subjected to two-dimensional M-mode echocardiography to determine cardiac function. Hearts were then analyzed for determination of infarct size, interstitial collagen content, brain natriuretic peptide (BNP) mRNA, myocyte cross-sectional area, and immunohistochemical staining for transforming growth factor (TGF)-beta and COX-2. COX-2 protein, detected by immunohistochemistry, was increased in MI versus sham hearts. MI resulted in increased left ventricular systolic and diastolic dimension and decreased ejection fraction, fractional shortening, and cardiac output. NS-398 treatment partly reversed these detrimental changes. Myocyte cross-sectional area, a measure of hypertrophy, was decreased by 30% in the NS-398 versus vehicle group, but there was no effect on BNP mRNA. The interstitial collagen fraction increased from 5.4 +/- 0.4% in sham hearts to 10.4 +/- 0.9% in MI hearts and was decreased to 7.9 +/- 0.6% in NS-398-treated hearts. A second COX-2 inhibitor, rofecoxib (MK-0966), also decreased myocyte cross-sectional area and interstitial collagen fraction. TGF-beta, a key regulator of collagen synthesis, was increased in MI hearts. NS-398 treatment reduced TGF-beta immunostaining by 40%. NS-398 treatment had no effect on infarct size. These results suggest that COX-2 products contribute to cardiac remodeling and functional deficits after MI. Thus selected inhibition of COX-2 may be a therapeutic target for reducing myocyte damage after MI.
Purification and Characterization of<i>Aspergillus niger</i>Lipase (1988)

Purification and Characterization of Aspergillus niger Lipase Get access Akio Sugihara, Akio Sugihara Osaka Municipal Technical Research Institute, 6–50, 1–chome, Morinomiya, Joto-ku, Osaka 536, Japan Search for other works by this author on: Oxford Academic Google Scholar Yuji Shimada, Yuji Shimada Osaka Municipal Technical Research Institute, 6–50, 1–chome, Morinomiya, Joto-ku, Osaka 536, Japan Search for other works by this author on: Oxford Academic Google Scholar Yoshio Tominaga Yoshio Tominaga Osaka Municipal Technical Research Institute, 6–50, 1–chome, Morinomiya, Joto-ku, Osaka 536, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 52, Issue 6, 1 June 1988, Pages 1591–1592, https://doi.org/10.1080/00021369.1988.10868874 Published: 01 June 1988 Article history Received: 07 December 1987 Published: 01 June 1988
A New Concept of Calcium Carbonate Concrete using Demolished Concrete and CO<sub>2</sub> (2021)

Countermeasures against carbon dioxide emissions are a concern in the construction field as well as in society. To solve this problem, a concept for new calcium carbonate concrete is proposed, and this concept is validated experimentally. In the proposed concept, calcium carbonate comprising Ca originating from demolished concrete or other Ca-containing industrial wastes and HCO3- from CO2 gas collected from the air or emitted by industrial plants acts as a binder for aggregates, which can be natural rocks or crushed demolished concrete. This short paper describes the details of the process of making calcium carbonate concrete and discusses future perspectives.
Asynchronous transcriptional silencing of individual retroviral genomes in embryonic cells (2014)

Our data suggest that retroviral silencing occurs stochastically, in an individual locus-specific fashion, and often without synchronous silencing of both viruses in the same cells. Surprisingly, the chromatin modifications that mark the silenced proviruses are unchanged even in cells that temporarily escape silencing. This local silencing effect is a feature of stem cell epigenomic regulation that has not previously been revealed.
Microporous Polysaccharide Hemospheres Do Not Inhibit Bone Healing Compared to Bone Wax or Microfibrillar Collagen (2008)

Topical hemostats may reduce bone bleeding but the presence of residual matter may inhibit bone growth. We compared a recently approved hemostat, microporous polysaccharide hemospheres (Arista AH, Medafor Inc, Minneapolis, Minnesota), with conventional hemostatic agents in a rabbit calvarial model. Standard defects were created and microfibrillar collagen (Avitene; C.R. Bard Inc, Murray Hill, New Jersey), bonewax, or microporous polysaccharide hemospheres was applied. Bone growth was evaluated after fluorescent labeling the mineralization front. At 7 weeks bonewax and microfibrillar collagen had reduced bone growth compared to control or microporous polysaccharide hemospheres. Microporous polysaccharide hemospheres and control animals also had reduced rabbit calvarial defects compared to bonewax or microfibrillar collagen.
Effects of various metal substrata on accumulation of<i>Pseudomonas aeruginosa</i>biofilms and the efficacy of monochloramine as a biocide (1993)

Monochloramine at 4 mg·l−1 was used to treat biofilms of Pseudomonas aeruginosa grown in annular reactors on various metal substrata, including stainless steel, mild steel and copper. Disinfection of in situ biofilms was most efficient on the stainless steel slides. The treatment reduced viable cells in the biofilm on the stainless steel slides by more than 4 orders of magnitude after 60 min, while the same treatment reduced viable cells in the biofilms on the other slides (mild steel and copper) by only 2 orders of magnitude. Mild steel corrosion products retarded the disinfection of homogenized biofilm cells. The composition of steady state biofilms on the various substrata (before biocide treatment) differed. Biofilm on stainless steel slides had more viable cells but less extracellular polymeric substance (EPS). Biofilms on mild steel and copper slides had fewer viable cells but more EPS. Almost 95% of total cells in the biofilm on the copper slides were dead cells. The lower efficacy of disinfection of in situ biofilms on mild steel and copper is hypothesized to be due to the higher EPS content of biofilms on those substrata.
cDNA cloning reveals a tissue specific expression of alternatively spliced transcripts of the ryanodine receptor type 3 (RyR3) calcium release channel (1996)

Ryanodine receptors (RyRs) are a family of intracellular calcium release channels. Three cDNAs encoding different isoforms of RyR have been identified and cloned. We report the complete sequence of the mink RyR3 cDNA and the characterization of three alternative spliced regions. The first two splicing sites are represented by insertions of five and six amino acids, respectively. The third site is represented by a mutually exclusive splicing. The tissue distribution of the alternatively spliced transcripts revealed a ubiquitous expression of splicing site I and a differential distribution of sites II and III, indicating that a further level of complexity in RyR3 expression may result from alternative splicings in this gene.
抗老化、耐臭氧、耐油的硫化橡胶组成物 (2000)

本专利介绍了一种具有抗老化、耐臭氧、耐油的硫化橡胶组成物的制备。该组成物组分为：有机过氧化物；比例为1～99：1～99的二烯烃和其它共聚物所组成的混合物。其它共聚物包括：C2H4，C3-20α-烯烃和末端乙烯其降冰片烯QR^1R^2[Q=降冰片烯，R^1=H或C1-10芳香基，R^2=CH2或(C2)nCHR^3CH；
Novel Approach to the Detection of Triacetone Triperoxide (TATP):  Its Structure and Its Complexes with Ions (2002)

Vapors of chemical substances may be detected with a solid-state sensor coated with a layer that selectively and specifically forms a bond with the vapor, leading to changes in the physicochemical properties of the sensor device. Triacetone triperoxide (TATP) is a homemade explosive that may evade detection by most commonly used detectors but could be detected by a sensor with the proper coating. The conformation and the strength of the bond formed between TATP and several ionsLi+, Cu+, Zn2+, Cd2+, In3+, Sb3+, Sc3+, and Ti4+have been calculated by quantum chemical methods. It was found that of the ions tested in the present work the bonds formed between TATP and Zn2+ and In3+ were the strongest and the interaction with Sb3+, Sc3+, and Ti4+ leads to cleavage of the TATP ring. Thus, in principle, a coating with a suitable ion may serve as the key element for detection of concealed TATP.
High‐risk childhood acute lymphoblastic leukemia in China: Factors influencing the treatment and outcome (2008)

A decreased treatment-related death frequency was associated with an improved outcome of leukemia. This emphasizes the importance of improving supportive care in developing countries for children with high-risk ALL who receive very intensive chemotherapy. Treatment abandonment remains a prominent reason for treatment failure in China.
Total isomerization gains flexibility (1983)

Isomerization extends refinery flexibility to meet changing markets. TIP (Total Isomerization Process) allows conversion of paraffin fractions in the gasoline boiling region including straight run naptha, light reformate, aromatic unit raffinate, and hydrocrackate. The hysomer isomerization is compared to catalytic reforming. Isomerization routes are graphed. Cost estimates and suggestions on the use of other feedstocks are given. TIP can maximize gas production, reduce crude runs, and complement cat reforming. In four examples, TIP reduces reformer severity and increases reformer yield.
Gellan gum biosynthetic enzymes in producing and nonproducing variants of Pseudomonas elodea (1991)

A pathway for the synthesis of the repeating tetrasaccharide units in gellan gum from Pseudomonas elodea is proposed. The enzymes presumed to be involved in the synthesis of the activated precursors UDP‐glucose, TDP‐rhamnose, and UDP‐glucuronic acid were detected and assayed in crude cell extracts of the gellan‐producing (Gel+) P. elodea ATCC 31461. The levels of UDP‐glucose pyrophosphorylase and TDP‐glucose pyrophosphorylase were higher in cells grown in media leading to higher gellan yields. Moreover, these enzymes exhibited lower values in cells of a Gel‐ variant, spontaneously obtained from the Gel+ wild type. The activation or repression of their synthesis is thought to be involved in the expression of the mucoid phenotype. Nevertheless, based on results here reported, the involvement of other enzymes, that catalyze steps downstream from the formation of the precursors cannot be excluded.
Genetic variants in the KIF6 region and coronary event reduction from statin therapy (2010)

A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with differential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with differential event reduction from statin therapy (P (interaction) < 01 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS). These analyses revealed that two SNPs (rs9462535 and rs9471077), in addition to rs20455, were associated with event reduction from statin therapy (P (interaction) < 0.1 in each of the three studies). The relative risk reduction ranged from 37 to 50% (P < 0.01) in carriers of the minor alleles of these SNPs and from -4 to 13% (P > 0.4) in non-carriers. These three SNPs are in high linkage disequilibrium with one another (r (2) > 0.84). Functional studies of these variants may help to understand the role of KIF6 in the pathogenesis of CHD and differential response to statin therapy.
A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients (2008)

The proposed clinical scoring can predict NASH in morbidly obese persons with sufficient accuracy to be considered for clinical use, identifying a very high-risk group in whom liver biopsy would be very likely to detect NASH, as well as a low-risk group in whom biopsy can be safely delayed or avoided.
New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis). (2015)

A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.
Application of symbolic computer algebra in high-level data-flow synthesis (2003)

The growing market of multimedia applications has required the development of complex application-specified integrated circuits with significant data-path portions. Unfortunately, most high-level synthesis tools and methods cannot automatically synthesize data paths such that complex arithmetic library blocks are intelligently used. Namely, most arithmetic-level optimizations are not supported and they are left to the designer's ingenuity. In this paper, we show how symbolic algebra can be used to construct arithmetic-level decomposition algorithms. We introduce our tool, SymSyn, that optimizes and maps data flow descriptions into data paths using complex arithmetic components. SymSyn uses two new algorithms to find either minimal component mapping or minimal critical path delay (CPD) mapping of the data flow. In this paper, we give an overview of the proposed algorithms. We also show how symbolic manipulations such as tree-height-reduction, factorization, expansion, and Horner transformation are incorporated in the preprocessing step. Such manipulations are used as guidelines in initial library element selection to accelerate the proposed algorithms. Furthermore, we demonstrate how substitution can be used for multiexpression component sharing and CPD optimization.
Characterization of the protein-synthesis dependent adaptive acid tolerance response in Lactobacillus acidophilus. (2002)

Exposure of L. acidophilus CRL 639 cells to sublethal adaptive acid conditions (pH 5.0 for 60 min) was found to confer protection against subsequent exposure to lethal pH (pH 3.0). Adaptation, which only occurred in complex media, was dependent on de novo protein synthesis and was inhibited by amino acid analogues. There was no modification in the protein synthesis rate during adaptation, but the protein degradation rate decreased. Synthesis of acid stress proteins may increase the stability of pre-existing proteins. By 2D-PAGE, induction of nine acid stress proteins and repression of several housekeeping proteins was observed. Putative heat shock proteins DnaK, DnaJ, GrpE, GroES and GroEL (70, 43, 24, 10 and 55 kDa, respectively) were among the proteins whose synthesis was induced in response to acid adaptation.
Epstein–Barr Virus Replication in Oropharyngeal Epithelial Cells (1984)

Despite the well-established tropism of the Epstein–Barr virus (EBV) for human B lymphocytes, the cell type within the oropharynx capable of allowing EBV replication has never been conclusively identified. Using in situ cytohybridization, we demonstrated EBV DNA in oropharyngeal epithelial cells from 10 of 12 patients with infectious mononucleosis. In duplicates of specimens found to contain cell-associated EBV DNA, we detected EBV RNA in two of four samples, using a biotin-labeled EBV DNA probe, thereby confirming the intracellular location of the viral genome. In 20 of 28 throat washings analyzed, cytohybridization results and assays for cell-free infectious virus were in agreement. In seven of the eight remaining specimens, cytohybridization identified intracellular EBV DNA in the absence of detectable extracellular virus. We conclude that the oropharyngeal epithelial cell may be the target cell type that is productively infected in infectious mononucleosis. (N Engl J Med 1984; 310:1225–30.)
<i>Methanosarcina acetivorans</i> sp. nov., an Acetotrophic Methane-Producing Bacterium Isolated from Marine Sediments (1984)

A new acetotrophic marine methane-producing bacterium that was isolated from the methane-evolving sediments of a marine canyon is described. Exponential phase cultures grown with sodium acetate contained irregularly shaped cocci that aggregated in the early stationary phase and finally differentiated into communal cysts that released individual cocci when ruptured or transferred to fresh medium. The irregularly shaped cocci (1.9 +/- 0.2 mm in diameter) were gram negative and occurred singly or in pairs. Cells were nonmotile, but possessed a single fimbria-like structure. Micrographs of thin sections showed a monolayered cell wall approximately 10 nm thick that consisted of protein subunits. The cells in aggregates were separated by visible septation. The communal cysts contained several single cocci encased in a common envelope. An amorphous form of the communal cyst that had incomplete septation and internal membrane-like vesicles was also present in late exponential phase cultures. Sodium acetate, methanol, methylamine, dimethylamine, and trimethylamine were substrates for growth and methanogenesis; H(2)-CO(2) (80:20) and sodium formate were not. The optimal growth temperature was 35 to 40 degrees C. The optimal pH range was 6.5 to 7.0. Both NaCl and Mg were required for growth, with maximum growth rates at 0.2 M NaCl and 0.05 M MgSO(4). The DNA base composition was 41 +/- 1% guanine plus cytosine. Methanosarcina acetivorans is the proposed species. C2A is the type strain (DSM 2834, ATCC 35395).