gebhart/patrepeval huggingface dataset:
Cytochrome c activation of CPP32-like proteolysis plays a critical role in a Xenopus cell-free apoptosis system (1997)

In a cell-free system based on Xenopus egg extracts, Bcl-2 blocks apoptotic activity by preventing cytochrome c release from mitochondria. We now describe in detail the crucial role of cytochrome c in this system. The mitochondrial fraction, when incubated with cytosol, releases cytochrome c. Cytochrome c in turn induces the activation of protease(s) resembling caspase-3 (CPP32), leading to downstream apoptotic events, including the cleavage of fodrin and lamin B1. CPP32-like protease activity plays an essential role in this system, as the caspase inhibitor, Ac-DEVD-CHO, strongly inhibited fodrin and lamin B1 cleavage, as well as nuclear morphology changes. Cytochrome c preparations from various vertebrate species, but not from Saccharomyces cerevisiae, were able to initiate all signs of apoptosis. Cytochrome c by itself was unable to process the precursor form of CPP32; the presence of cytosol was required. The electron transport activity of cytochrome c is not required for its pro-apoptotic function, as Cu- and Zn-substituted cytochrome c had strong pro-apoptotic activity, despite being redox-inactive. However, certain structural features of the molecule were required for this activity. Thus, in the Xenopus cell-free system, cytosol-dependent mitochondrial release of cytochrome c induces apoptosis by activating CPP32-like caspases, via unknown cytosolic factors.
The Arabidopsis Homolog of Yeast TAP42 and Mammalian α4 Binds to the Catalytic Subunit of Protein Phosphatase 2A and Is Induced by Chilling (1999)

Type 2A serine/threonine protein phosphatases (PP2A) have been implicated as important mediators of a number of plant growth and developmental processes. In an effort to identify plant PP2A substrates and/or regulators, we performed a yeast two-hybrid screen using an Arabidopsis PP2A catalytic subunit cDNA as bait. All true positives identified by this screen were derived from the same gene, which we have named TAP46 (2A phosphatase associated protein of 46 kD). The TAP46 gene appears to be a single-copy gene and is expressed in all Arabidopsis organs. Transcripts derived from this gene are induced by chilling treatment but not by heat or anaerobic stress. Immunoprecipitation assays using antibodies generated to a peptide spanning amino acids 356 to 366 of TAP46 indicate that TAP46 is associated with a type 2A protein phosphatase in vivo. A search of the database identified TAP46 as a homolog of Saccharomyces cerevisiae TAP42 and mammalian alpha4. These two proteins are known to bind to the catalytic subunit of PP2A and to function in the target-of-rapamycin signaling pathway. Our results identify TAP46 as a plant PP2A-associated protein, with a possible function in the chilling response, and suggest that a target-of-rapamycin-like signaling pathway may exist in plants.
Prevalence of Enterotoxin and Toxic Shock Syndrome Toxin Genes in Staphylococcus aureus Isolated from Milk of Cows with Mastitis (2006)

Staphylococcus aureus isolated from milk of cows with mastitis were evaluated for the prevalence of 16 enterotoxin genes (sea-see and seg-seq) and toxic shock syndrome toxin gene (tsst-1). Of 78 S. aureus examined, 73 (93.6%) were positive for one or more enterotoxin genes and these were divided into 36 groups by the presence of different enterotoxin genes. Enterotoxin genes including sen (84.6%), sem (71.8%), sei (60.3%) and sed (52.6%) were found frequently, while seg (24.4%), seq (16.7%), seo (12.8%), and seb (1.3%) were found at lower frequencies. Toxic shock syndrome toxin (tsst-1) gene was detected in 20 (25.6%) isolates and was always found in combination with other enterotoxin genes. The majority (88.5%) harbored more than one enterotoxin gene in different combinations. Eight S. aureus isolates (10.3%) were positive for sed, sei, sem, and sen; six (7.7%) possessed sed, seg, sei, sem, sen, and tsst-1; five (6.4%) had sei, sem, and sen; and four (5.1%) had sei, and sen. One isolate was positive for seb along with other SE genes including sed, seh, sem, sen, seq, and tsst-1. None of the isolates carried other enterotoxin genes (sea, sec, see, sej, sek, sel, and sep). PFGE profiles revealed 15 distinct pulsotypes among the 78 S. aureus isolates evaluated. PFGE and enterotoxin gene profiles did not match with each other because a single pulsotype carried different combinations of enterotoxin genes. The majority of S. aureus isolated from milk of mastitic cows carried newly described SE genes sem, sen and sei along with classical SE genes, sed and tsst-1. This is the first report describing the high prevalence of newly described enterotoxin genes, sem and sen in S. aureus from bovine mastitis. The high prevalence of enterotoxin genes and tsst-1 in S. aureus may be important as it is relevant to udder pathogenicity and food hygiene.
Capture management efficacy in children and young adults with endocardial and unipolar epicardial systems (2004)

Although not an IDE (Investigation Device Exemption) study, this study showed acceptable VCM performance in "Monitor Only" mode in 13/15 patients with unipolar epicardial leads. A 2-month "Monitor Only" observation period helps screen patients who might not benefit from VCM. VCM may provide substantial energy savings and extended battery life for children and young adults.
Phosphane‐Free Green Protocol for Selective Nitro Reduction with an Iron‐Based Catalyst (2011)

Iron phthalocyanine with iron sulfate has been successfully applied for high chemo- and regioselective reduction of aromatic nitro compounds to give the corresponding amines in a green solvent system without using any toxic ligand. The catalytic systems were also compatible with a large range of other reducible functional groups, such as keto, acid, amide, ester, halogen, lactone, nitrile, N-benzyl, O-benzyl, hydroxy, and heterocycles. In the present study, dinitro compounds have been regioselectively reduced to the corresponding amines with high yield. In most of the cases the conversion and selectivity was greater than 99% as determined by GC-MS analysis.
Cloning and Characterization of the xyl1 Gene, Encoding an NADH-Preferring Xylose Reductase from Candida parapsilosis , and Its Functional Expression in Candida tropicalis (2003)

Xylose reductase (XR) is a key enzyme in D-xylose metabolism, catalyzing the reduction of D-xylose to xylitol. An NADH-preferring XR was purified to homogeneity from Candida parapsilosis KFCC-10875, and the xyl1 gene encoding a 324-amino-acid polypeptide with a molecular mass of 36,629 Da was subsequently isolated using internal amino acid sequences and 5' and 3' rapid amplification of cDNA ends. The C. parapsilosis XR showed high catalytic efficiency (kcat/Km = 1.46 s(-1) mM(-1)) for D-xylose and showed unusual coenzyme specificity, with greater catalytic efficiency with NADH (kcat/Km = 1.39 x 10(4) s(-1) mM(-1)) than with NADPH (kcat/Km = 1.27 x 10(2) s(-1) mM(-1)), unlike all other aldose reductases characterized. Studies of initial velocity and product inhibition suggest that the reaction proceeds via a sequentially ordered Bi Bi mechanism, which is typical of XRs. Candida tropicalis KFCC-10960 has been reported to have the highest xylitol production yield and rate. It has been suggested, however, that NADPH-dependent XRs, including the XR of C. tropicalis, are limited by the coenzyme availability and thus limit the production of xylitol. The C. parapsilosis xyl1 gene was placed under the control of an alcohol dehydrogenase promoter and integrated into the genome of C. tropicalis. The resulting recombinant yeast, C. tropicalis BN-1, showed higher yield and productivity (by 5 and 25%, respectively) than the wild strain and lower production of by-products, thus facilitating the purification process. The XRs partially purified from C. tropicalis BN-1 exhibited dual coenzyme specificity for both NADH and NADPH, indicating the functional expression of the C. parapsilosis xyl1 gene in C. tropicalis BN-1. This is the first report of the cloning of an xyl1 gene encoding an NADH-preferring XR and its functional expression in C. tropicalis, a yeast currently used for industrial production of xylitol.
High-Resolution DNA Melting Analysis for Simultaneous Mutation Scanning and Genotyping in Solution (2005)

When DNA melting is performed rapidly and observed at high resolution with saturating DNA dyes, it is possible to scan for mutations and genotype at the same time within a few minutes after amplification. The method is no more complex than PCR and may reduce the need for resequencing.
The high-throughput protein-to-structure pipeline at SECSG (2005)

Using a high degree of automation, the crystallography core at the Southeast Collaboratory for Structural Genomics (SECSG) has developed a high-throughput protein-to-structure pipeline. Various robots and automation procedures have been adopted and integrated into a pipeline that is capable of screening 40 proteins for crystallization and solving four protein structures per week. This pipeline is composed of three major units: crystallization, structure determination/validation and crystallomics. Coupled with the protein-production cores at SECSG, the protein-to-structure pipeline provides a two-tiered approach for protein production at SECSG. In tier 1, all protein samples supplied by the protein-production cores pass through the pipeline using standard crystallization screening and optimization procedures. The protein targets that failed to yield diffraction-quality crystals (resolution better than 3.0 A) become tier 2 or salvaging targets. The goal of tier 2 target salvaging, carried out by the crystallomics core, is to produce the target proteins with increased purity and homogeneity, which would render them more likely to yield well diffracting crystals. This is performed by alternative purification procedures and/or the introduction of chemical modifications to the proteins (such as tag removal, methylation, surface mutagenesis, selenomethionine labelling etc.). Details of the various procedures in the pipeline for protein crystallization, target salvaging, data collection/processing and high-throughput structure determination/validation, as well as some examples, are described.
Sulfonic acid dyes: inhibition of the human immunodeficiency virus and mechanism of action. (1992)

Over 50 different commercially available sulfonic acid-containing dyes were analyzed for their ability to prevent HIV-1-induced cell killing and in inhibiting HIV-1 replication. Compounds of remarkably similar structure, but with differing patterns of sulfonic acid group substitutions, had a wide range of potency in inhibiting HIV-1. Chicago sky blue (CSB) was highly effective in the inhibition of HIV-1 with less toxicity to CEM-SS cells than most of the other sulfonated dyes tested. Synthesis of CSB was undertaken to produce a product greater than 98% pure and this compound was used to elucidate the possible mechanisms by which this class of structurally related compounds inhibits HIV-1. Addition of CSB to cells infected at high multiplicity at any time up to 24 h after infection, unlike dideoxycytidine (ddC) or oxathiin carboxanilide (OC), inhibited HIV-1-induced cell killing. Other postinfection time course studies revealed that CSB had to be present for 24 h or longer immediately after infection to be protective. Virus binding to cells occurred in the presence of CSB, but the requirement for virion envelope-cell membrane fusion was delayed. CSB was a potent inhibitor of the reverse transcriptase (RT) of both HIV-1 and HIV-2, although it was less active against HIV-2 in a cell killing-based assay. CSB also inhibited Rauscher and LP-BM5 murine leukemia viruses. CSB appears to disrupt the interaction between viral proteins and cell membranes, both in the fusion step early in the infection cycle and in the development of syncytia in the late stages of virus infection.
SDN-based network orchestration for new dynamic Enterprise Networking services (2017)

Enterprise Networking (EN) services are source of high revenues for carriers. However, the traditional way of providing and selling those to enterprise and business customers is ossified and unsatisfactory for users. High prices, static connections and slow time to provision, make enterprise users doubtful about whether guaranteed connectivity is worth the price and push them to look for alternative solutions. That poses carriers at high risk of customer leak. This paper explains how SDN can foster the evolution of EN services in order to make them appealing again to enterprises. We propose an approach based on an SDN orchestrator as the enabling component of EN “4.0” services that are rapidly deployable, tailored to users' needs and dynamically configured. By global optimization of the core and the edge, a carrier can cut OpEx and increase margins. We present an early implementation of this concept, describing a demo-test in a simple virtualised but realistic network environment, showing new features and advantages for the carrier in terms of resource optimization.
Halofuginone, A Specific Collagen Type I Inhibitor, Reduces Anastomotic Intimal Hyperplasia (1995)

Oral administration of halofuginone inhibits intimal hyperplasia at vascular anastomoses. Intimal hyperplasia inhibition by halofuginone may be a therapeutic option for preventing arterial stenosis in vascular surgery.
A phase Ib trial of Bcl-2 inhibitor obatoclax in combination with carboplatin and etoposide for previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC) (2009)

3576 Background: Obatoclax (Ob) is a small-molecule antagonist of all the Bcl-2 prosurvival proteins. In vitro it enhances the effects of the drugs cisplatin and etoposide. Bcl-2 family proteins are frequently expressed in SCLC, and SCLC cell lines are sensitive to Ob. Methods: This study was designed to find the maximal tolerated doses (MTD) of oOb when given on a 21 day (D) cycle together with carboplatin (AUC 5 D1) and etoposide (100 mg/m2 D1–3), in separate dose escalations using Ob as a 3-hr infusion D1–3 and as a 24-hr infusion D1–3. Eligible patients had ES-SCLC, measurable disease, ≤1 prior therapy, ECOG PS ≤1, and adequate hematological, renal and hepatic function. 3- 6 patients were enrolled into ascending dose cohorts with standard DLT rules evaluating safety in C1 to determine dose escalation. Results: 24 patients were enrolled into 5 dosing cohorts (14 males; median age 67). A total of 66 cycles (C) have been administered to date. There were no DLTs in the initial cohorts using Ob 15 mg over 3 hr or Ob 30 mg over 24 hr. Two DLTs occurred in the Ob 30 mg over 3 hr cohort - both due to myelosuppression in previously treated patients. As a result, the trial was amended to exclude previously treated patients. 5 previously untreated patients receiving Ob 30 over 3 hr had no DLTs. There were no DLTs in the Ob 45 mg over 24 hr cohort but 2 patients in the Ob 24-hr infusion cohorts had infusion pump malfunctions while at home. There were 2 DLTs in the Ob 45 mg over 3 hr cohort (somnolence, euphoria, &amp; disorientation) establishing MTD of Ob 30 mg over 3 hr daily x 3. After C2 the 6 previously untreated patients on Ob 24-hr infusion cohorts had 3 PRs, 1 SD, 1 PD, and 1 Unk; the 2 previously treated patients had PRs. After C2 all 7 previously-untreated patients at 15 or 30 mg in the 3-hr infusion cohorts have PR; the 3 previously treated patients had SD. Conclusions: Ob can be combined with carboplatin and etoposide using either a 3-hr or a 24-hr infusion, and both regimens are associated with high early response rates in ES-SCLC, perhaps due to inhibition of mcl-1. Due to practical issues with the 24-hr infusion arm, the 3-hr 30 mg MTD dose will be utilized in a randomized phase II versus carboplatin and etoposide alone. [Table: see text]
Patterned Colloidal Deposition Controlled by Electrostatic and Capillary Forces (2000)

We use substrates chemically micropatterned with anionic and cationic regions to govern the deposition of charged colloidal particles. The direct observation of the colloidal assembly suggests that this process includes two steps: an initial patterned attachment of colloids to the substrate and an additional ordering of the structure upon drying. The driving forces of the process, i.e. , screened electrostatic and lateral capillary interactions, are discussed. This approach makes it possible to fabricate complex, high-resolution two-dimensional arrays of colloidal particles.
On clinical trials with a high placebo response rate (2015)

The basic problem that causes the frequent failure of a standard randomized parallel placebo-controlled clinical trial with a high placebo response rate is the underestimation of the treatment effect by the observed relative treatment difference. A two-period sequential parallel enrichment design has been proposed where the first period is a standard parallel design and at the end of the first period, the placebo non-responders are identified and re-randomized in the second period. Based on such a design, available methods have primarily focused on testing either the first period treatment null hypothesis or the global null hypothesis defined as the joint period 1 and period 2 treatment effect null hypothesis by a test statistic which is either derived from a combined statistic or defined directly as a weighted z-score where the weights are functions of some population and design parameters satisfying certain power optimality criterion. However, in some cases, it is not clear what their combined statistics are estimating and in others, the combined statistics are estimating the apparent treatment effect; but generally, there is no discussion of the need to provide a proper assessment of the treatment effect for the intended study population. It should be clear that an appropriate assessment of the treatment effect for the intended study population is critical for the benefit/risk analysis as well as the proper dosage recommendation. Any benefit/risk analysis and dosage recommendation that are based on an apparent treatment effect from a standard parallel design such as the first period of a sequential parallel enrichment design tend to underestimate the benefit/risk ratio which in turn may lead to overdosing recommendation. It is the purpose of this paper to introduce the concept of an adjusted treatment effect which is derived by adjusting the apparent treatment effect from the first period of a sequential parallel enrichment design with information from the second period subject to a consistency condition. The adjustment properly compensates for the high placebo response rate. It is proposed that this adjusted treatment effect should be used to assess the treatment effect for the intended study population and should be the basis for the benefit/risk analysis and the dosage recommendation.
Sulfated blood group Lewis(a). A superior oligosaccharide ligand for human E-selectin. (1994)

In earlier studies of oligosaccharide probes (neoglycolipids) generated from an ovarian cystadenoma glycoprotein, one of the components that strongly supported binding of the endothelial adhesion molecule, E-selectin, was identified as an equimolar mixture of tetrasaccharides of blood group Le(a) and Le(x) type sulfated at position 3 of the outer galactose (C.-T. Yuen, A. M. Lawson, W. Chai, M. Larkin, M. S. Stoll, A. C. Stuart, F. X. Sullivan, T. J. Ahern, and T. Feizi (1992) Biochemistry 31, 9126-9131). In the present studies, the individual sulfated Le(a) and sulfated Le(x) oligosaccharides synthesized chemically have been investigated, first, for their ability to support E-selectin binding when converted into neoglycolipids, and second, for their ability to inhibit E-selectin binding to immobilized lipid-linked sialyl-Le(a), sialyl-Le(x), or sulfated Le(a) pentasaccharides; their activities have been compared with those of the sialyl-Le(a) and sialyl-Le(x) analogues. From these studies, the sulfated Le(a) tetra- and pentasaccharides emerge as the most potent E-selectin ligands so far. In particular, the inhibitory activity of the sulfated Le(a) pentasaccharide is substantially greater than that of the sialyl-Le(x) trisaccharide, which is currently the most widely used inhibitor of E-selectin binding: 45-, 35-, or 15-fold greater depending on whether adhesion is to sialyl-Le(a), sulfated Le(a), or sialyl-Le(x) pentasaccharides, respectively. These findings have an important bearing on design of new generations of inhibitors of E-selectin binding as antiinflammatory compounds.
Toxin Gene Analysis of a Variant Strain of Clostridium difficile That Causes Human Clinical Disease (2000)

A toxin variant strain of Clostridium difficile was isolated from two patients with C. difficile-associated disease (CDAD), one of whom died from extensive pseudomembranous colitis. This strain, identified by restriction endonuclease analysis (REA) as type CF2, was not detected by an immunoassay for C. difficile toxin A. Culture supernatants of CF2 failed to elicit significant enterotoxic activity in the rabbit ileal loop assay but did produce atypical cytopathic effects in cell culture assay. Southern hybridization, PCR amplification, and DNA sequence analyses were performed on the toxin A (tcdA) and toxin B (tcdB) genes of type CF2 isolate 5340. Type CF2 5340 tcdA exhibited a 1,821-bp truncation, due to three deletions in the 3' end of the gene, and a point mutation in the 5' end of the gene, resulting in a premature stop codon at tcdA position 139. Type CF2 5340 tcdB exhibited multiple nucleotide base substitutions in the 5' end of the gene compared to tcdB of the standard toxigenic strain VPI 10463. Type CF2 5340 toxin gene nucleotide sequences and deduced amino acid sequences showed a strong resemblance to those of the previously described variant C. difficile strain 1470, a strain reported to have reduced pathogenicity and no association with clinical illness in humans. REA of strain 1470 identified this strain as a distinct type (CF1) within the same REA group as the closely related type CF2. A review of our clinical-isolate collection identified five additional patients infected with type CF2, three of whom had documented CDAD. PCR amplification of the 3' end of tcdA demonstrated identical 1. 8-kb deletions in all seven type CF2 isolates. REA type CF2 is a toxin variant strain of C. difficile that retains the ability to cause disease in humans but is not detected in clinical immunoassays for toxin A.