gebhart/patrepeval huggingface dataset:
The PROTEKT surveillance study: antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections (2002)

This paper presents data relating to Haemophilus influenzae and Moraxella catarrhalis from PROTEKT (1999-2000), a surveillance study that examined the susceptibility of respiratory pathogens to current and new antibacterials. Beta-lactamase production is the principal mechanism of resistance to ampicillin and other beta-lactam antibacterials in H. influenzae and M. catarrhalis. The PROTEKT study showed that globally, the prevalence of beta-lactamase production in H. influenzae varied considerably: of 2948 isolates, 489 (16.6%) were beta-lactamase-positive [range: 1.8% (Italy) to 65% (South Korea)]. Beta-lactamase-negative, ampicillin-resistant (BLNAR) strains of H. influenzae were uncommon (<0.1%) but their very detection highlights the need for continued vigilance. Overall, few isolates of H. influenzae showed resistance to either macrolides or telithromycin. The emergence of clarithromycin-resistant strains is worrying, however, as such isolates may also show resistance to other macrolides. There was a geographical correlation between beta-lactamase production and the prevalence of resistance to chloramphenicol and tetracycline among the H. influenzae isolates. Of 1131 M. catarrhalis isolates, 92% were beta-lactamase-positive. Most isolates, however, were fully susceptible to nearly all the antibacterials tested, except ampicillin. The most active were ciprofloxacin and levofloxacin (both having MIC(90) values of 0.03 mg/L), moxifloxacin (MIC(90) 0.06 mg/L), azithromycin (MIC(90) < or = 0.06 mg/L) and telithromycin (MIC(90) 0.12 mg/L). Overall, there were no concerns in terms of resistance to fluoroquinolones for both H. influenzae and M. catarrhalis. In summary, the PROTEKT surveillance study confirmed the problem of widespread prevalence of beta-lactamase-producing strains of H. influenzae and M. catarrhalis, although these pathogens generally remain susceptible to macrolides, fluoroquinolones and the new ketolide telithromycin.
Orientation Invariant Feature Embedding and Spatial Temporal Regularization for Vehicle Re-identification (2017)

In this paper, we tackle the vehicle Re-identification (ReID) problem which is of great importance in urban surveillance and can be used for multiple applications. In our vehicle ReID framework, an orientation invariant feature embedding module and a spatial-temporal regularization module are proposed. With orientation invariant feature embedding, local region features of different orientations can be extracted based on 20 key point locations and can be well aligned and combined. With spatial-temporal regularization, the log-normal distribution is adopted to model the spatial-temporal constraints and the retrieval results can be refined. Experiments are conducted on public vehicle ReID datasets and our proposed method achieves state-of-the-art performance. Investigations of the proposed framework is conducted, including the landmark regressor and comparisons with attention mechanism. Both the orientation invariant feature embedding and the spatio-temporal regularization achieve considerable improvements.
Fabrication of white organic light-emitting diodes by co-doping of emissive layer (2009)

Efficient white light emission by mixing of red emission from (Ir-BTPA) [bis(2-(2’-benzothienyl) pyridinato-N,C³’) (acetyl-acetonate) iridium(III) and greenish blue from (FIrPic) [bis(2-(4,6-difluorophenyl)pyridinato-N,C²’) iridium(III)] has been studied. Ir-BTPA and FIrPic are co-doped into a 4, 4’ bis 9 carbozyl (biphenyl) (CPB) host. The device emission colour is controlled by varying dopant concentration. Photoluminescence (PL), electroluminescence (EL) and colour coordinates have been studied as a function of applied voltage. The EL spectra of the devices with the co-doped emissive layer show three emission peaks at 469, 500 and 611 nm. Commission Internationale de l'Eclairage (CIE) coordinates of the devices are 0.27, 0.32 at 18 V and are well within the white region.
Bu-2470, a new peptide antibiotic complex. II. Structure determination of Bu-2470 A, B1, B2a and B2b. (1983)

The structures of Bu-2470 A, B1, B2a, and B2b have been determined. Bu-2470 A is a simple octapeptide having no fatty acid moiety, while Bu-2470 B1, B2a and B2b are octapeptides that have been acylated with a β-hydroxy C11 or C10 fatty acid. The octapeptide structure of Bu-2470 components was found identical with that of octapeptin C1, hence generic names of octapeptin C0, C2, C3 and C4 are proposed for Bu-2470 A, B1, B2a, and B2b, respectively.
Cloning and expression of two structurally distinct receptor-linked protein-tyrosine phosphatases generated by RNA processing from a single gene. (1993)

We describe here the first example of RNA processing generating two functional receptor-linked protein-tyrosine phosphatases (PTP) (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) that are structurally distinct within their catalytic domains. Two cDNAs, PTP-P1 and PTP-PS, were isolated from rat pheochromocytoma cells, which encode two receptor-linked protein-tyrosine-phosphatases and are produced by alternative splicing and differential use of polyadenylation sites. Both cDNAs share an identical extracellular domain and a single transmembrane domain, but differ within their cytoplasmic regions: PTP-P1 contains two tandem repeated PTPase catalytic domains, whereas PTP-PS contains only the amino-terminal domain. Bacterial expression of PTPase domains of both cDNAs demonstrates that PTP-P1 and PTP-PS contain tyrosine-phosphatase activity. PTP-P1 is encoded by three transcripts of approximately 8, 6, and 4 kilobases, whereas PTP-PS is encoded by a single 4.8-kilobase transcript. PTP-P1 (6 kilobases) and PTP-PS are mainly expressed within the brain and in neuronal and endocrine cells. These data suggest that PTP-P1 and PTP-PS may be involved in neuronal function.
Clonality and Longevity of CD4+CD28null T Cells Are Associated with Defects in Apoptotic Pathways (2000)

CD4(+)CD28(null) T cells are oligoclonal lymphocytes rarely found in healthy individuals younger than 40 yr, but are found in high frequencies in elderly individuals and in patients with chronic inflammatory diseases. Contrary to paradigm, they are functionally active and persist over many years. Such clonogenic potential and longevity suggest altered responses to apoptosis-inducing signals. In this study, we show that CD4(+)CD28(null) T cells are protected from undergoing activation-induced cell death. Whereas CD28(+) T cells underwent Fas-mediated apoptosis upon cross-linking of CD3, CD28(null) T cells were highly resistant. CD28(null) T cells were found to progress through the cell cycle, and cells at all stages of the cell cycle were resistant to apoptosis, unlike their CD28(+) counterparts. Neither the activation-induced up-regulation of the IL-2R alpha-chain (CD25) nor the addition of exogenous IL-2 renders them susceptible to Fas-mediated apoptosis. These properties of CD28(null) T cells were related to high levels of Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein, an inhibitor of Fas signaling that is normally degraded in T cells following activation in the presence of IL-2. Consistent with previous data showing protection of CD28(null) cells from spontaneous cell death, the present studies unequivocally show dysregulation of apoptotic pathways in CD4(+)CD28(null) T cells that favor their clonal outgrowth and maintenance in vivo.
Activation of Phosphotyrosine Phosphatase Activity Attenuates Mitogen-Activated Protein Kinase Signaling and Inhibits c-FOS and Nitric Oxide Synthase Expression in Macrophages Infected withLeishmania donovani (1999)

Intracellular protozoan parasites of the genus Leishmania antagonize host defense mechanisms by interfering with cell signaling in macrophages. In this report, the impact of Leishmania donovani on mitogen-activated protein (MAP) kinases and nitric oxide synthase (NOS) expression in the macrophage cell line RAW 264 was investigated. Overnight infection of cells with leishmania led to a significant decrease in phorbol-12-myristate-13-acetate (PMA)-stimulated MAP kinase activity and inhibited PMA-induced phosphorylation of the MAP kinase substrate and transcription factor Elk-1. Simultaneously, leishmania infection markedly attenuated the induction of c-FOS and inducible nitric oxide synthase (iNOS) expression in response to PMA and gamma interferon (IFN-gamma), respectively. These effects correlated with decreased phosphorylation of p44 and p42 MAP kinases on tyrosine residues. Consistent with the latter finding, lysates prepared from leishmania-infected cells contained an activity that dephosphorylated MAP kinase in vitro, suggesting the possibility of a phosphatase acting in vivo. Attenuation of both MAP kinase activity and c-FOS and iNOS expression was reversed by treatment of macrophages with sodium orthovanadate prior to infection. It was also found that the specific activity of the Src homology 2 domain containing tyrosine phosphatase (SHP-1) toward MAP kinase was markedly increased in leishmania-infected cells. These findings indicate that infection with L. donovani attenuates MAP kinase signaling and c-FOS and iNOS expression in macrophages by activating cellular phosphotyrosine phosphatases. This may represent a novel mechanism of macrophage deactivation during intracellular infection.
Progressing Stroke (2001)

Although many clinical trials in the acute phase of stroke have been performed during the past few years, none of them focused on the study of the very early stroke outcome. Therefore, more questions than answers remain on the underlying mechanisms, and treatment, of progressing stroke [1].KeywordsIschemic StrokeAcute StrokeAcute Ischemic StrokeInfarct VolumeStroke OnsetThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Neutral endopeptidase 24.11 is important for the degradation of both endogenous and exogenous glucagon in anesthetized pigs (2004)

Glucagon has a short plasma t(1/2) in vivo, with renal extraction playing a major role in its elimination. Glucagon is degraded by neutral endopeptidase (NEP) 24.11 in vitro, but the physiological relevance of NEP 24.11 in glucagon metabolism is unknown. Therefore, the influence of candoxatril, a selective NEP inhibitor, on plasma levels of endogenous and exogenous glucagon was examined in anesthetized pigs. Candoxatril increased endogenous glucagon concentrations, from 6.3 +/- 2.5 to 20.7 +/- 6.3 pmol/l [COOH-terminal (C)-RIA, P < 0.05]. During glucagon infusion, candoxatril increased the t(1/2) determined by C-RIA (from 3.0 +/- 0.5 to 17.0 +/- 2.5 min, P < 0.005) and midregion (M)-RIA (2.8 +/- 0.5 to 17.0 +/- 3.0 min, P < 0.01) and reduced metabolic clearance rates (MCR; 19.1 +/- 3.2 to 9.4 +/- 2.0 ml.kg(-1).min(-1), P < 0.02, C-RIA; 19.2 +/- 4.8 to 9.0 +/- 2.3 ml.kg(-1).min(-1), P < 0.05, M-RIA). However, neither t(1/2) nor MCR determined by NH2-terminal (N)-RIA were significantly affected (t(1/2), 2.7 +/- 0.4 to 4.5 +/- 1.6 min; MCR, 30.3 +/- 6.4 to 28.5 +/- 9.0 ml.kg(-1).min(-1)), suggesting that candoxatril had no effect on NH2-terminal degradation but leads to the accumulation of NH2-terminally truncated forms of glucagon. Determination of arteriovenous glucagon concentration differences revealed that renal glucagon extraction was reduced (but not eliminated) by candoxatril (from 40.4 +/- 3.8 to 18.6 +/- 4.1%, P < 0.02, C-RIA; 29.2 +/- 3.1 to 14.7 +/- 2.2%, P < 0.02, M-RIA; 26.5 +/- 4.0 to 19.7 +/- 3.5%, P < 0.06, N-RIA). Femoral extraction was reduced by candoxatril when determined by C-RIA (from 22.7 +/- 2.4 to 8.0 +/- 5.1%, P < 0.05) but was not changed significantly when determined using M- or N-RIAs (10.0 +/- 2.8 to 4.7 +/- 3.7%, M-RIA; 10.5 +/- 2.5 to 7.8 +/- 4.2%, N-RIA). This study provides evidence that NEP 24.11 is an important mediator of the degradation of both endogenous and exogenous glucagon in vivo.
Discontinuous epitopes of hepatitis B surface antigen derived from a filamentous phage peptide library. (1996)

The structure of the small hepatitis B virus surface antigen (HBsAg) was investigated by epitope mapping of four anti-HBsAg monoclonal antibodies (mAbs). Amino acid sequences of epitopes were derived from affinity-enrichment experiments (biopanning) using a filamentous phage peptide library. The library consists of 10(9) different clones bearing a 30-residue peptide fused to gene III. Sequence homologies between peptides obtained from panning the library against the antibodies and the native HBsAg sequence allowed for precise description of the binding regions. Three of four mAbs were found to bind to distinct discontinuous epitopes between amino acid residues 101 and 207 of HBsAg. The fourth mAb was demonstrated to bind to residues 121-124. The sequence data are supported by ELISA assays demonstrating the binding of the HBsAg-specific peptides on filamentous phage to mAbs. The sequence data were used to map the surface of HBsAg and to derive a topological model for the alpha-carbon trace of the 101-207 region of HBsAg. The approach should be useful for other proteins for which the crystal structure is not available but a representative set of mAbs can be obtained.
Tissue distribution of the AMP‐activated protein kinase, and lack of activation by cyclic‐AMP‐dependent protein kinase, studied using a specific and sensitive peptide assay (1989)

1. We have synthesized two peptides, one based on the exact sequence around the unique site (Ser79) for the AMP-activated protein kinase on rat acetyl-CoA carboxylase (SSMS peptide) and another in which the serine residue corresponding to the site for cyclic-AMP-dependent protein kinase (Ser77) was replaced by alanine (SAMS peptide). 2. Both peptides were phosphorylated with similar kinetics by the AMP-activated protein kinase, but only the SSMS peptide was a substrate for cyclic-AMP-dependent protein kinase. The SAMS peptide was not phosphorylated by any of five other purified protein kinases tested. 3. The Km of AMP-activated protein kinase for the SAMS peptide is higher than that for acetyl-CoA carboxylase, but the Vmax for peptide phosphorylation is 2.5 times higher than that of its parent protein. This peptide therefore gives a convenient and sensitive assay for the AMP-activated protein kinase. 4. Acetyl-CoA-carboxylase kinase and peptide kinase activities copurify through six steps from a post-mitochondrial supernatant of rat liver, showing that the SAMS peptide is a specific substrate for the AMP-activated protein kinase in this tissue. We could not demonstrate AMP-dependence of the kinase activity in crude preparations, apparently due to endogenous AMP remaining bound to the enzyme. However, 8-bromoadenosine 5-monophosphate (Br8AMP) is a partial agonist at the allosteric (AMP) site, and inhibition by 2 mM Br8AMP can be used to test that one is measuring the AMP-stimulated form of the kinase. 5. Using this approach, we have examined the kinase activity in nine different rat tissues, plus a mouse macrophage cell line, and find that there is a correlation between tissues expressing significant levels of peptide kinase activity and those active in the synthesis or storage of lipids. 6. We also use the peptide assay to show that cyclic AMP-dependent protein kinase does not activate purified AMP-activated protein kinase, and does not affect the activation of partially purified AMP-activated protein kinase by endogenous kinase kinase.
Modified Synthesis of 3′-OTBDPS-Protected Furanoid Glycal (2012)

Thermolytic cleavage of 3'-OH protected thymidine is the most common method of preparing furanoid glycals. We have observed that glycosidic bond cleavage is more facile when the 5'-OH of thymidine was also protected with a silyl group. Addition of trimethylsilyl chloride facilitated cleavage of the glycosidic bond; thus, both modifications are required for the formation of the furanoid glycal. Investigations into the selective deprotection of 5'-silyl versus 3'-silyl and subsequent glycosidic bond cleavage are reported herein.
The role of noise and positive feedback in the onset of autosomal dominant diseases (2010)

By identifying the intrinsic mechanisms involved in the onset of AD diseases, it may be possible to better assess risk factors as well as lead to potential new drug targets. To illustrate the applicability of this study of pathway dynamics, we simulated the primary pathways involved in two autosomal dominant diseases, Polycystic Kidney Disease (PKD) and mature onset diabetes of youth (MODY). Simulations demonstrate that some of the primary disease characteristics are consistent with the positive feedback-stochastic variation theory presented here. This has implications for new drug targets to control these diseases by blocking the positive feedback loop in the relevant pathways.
Loss of Wnt-5a protein is associated with early relapse in invasive ductal breast carcinomas. (2002)

Previous in vitro studies have implied that the Wnt-5a gene plays a role as a tumor suppressor. To explore the clinical relevance of this concept, 96 primary invasive breast carcinomas were stained with a novel anti-Wnt-5a antibody. Loss of Wnt-5a protein expression, evident in 44% of the invasive ductal carcinomas (n = 59), was significantly associated with higher histological grade (P = 0.01) and absence of estrogen (P = 0.003) and progesterone (P = 0.02) receptors. By contrast, loss of Wnt-5a protein in 24% of the invasive lobular carcinomas (n = 37) was not significantly related to any of the variables we investigated. The prognostic value of Wnt-5a for metastatic potential was evaluated by analyzing 83 additional invasive primary ductal carcinomas from patients with a longer follow-up time. We found that Wnt-5a expression was lost in tumors from 78% of the patients with recurrent disease (n = 32) compared with 35% of the recurrence-free patients (n = 51; P < 0.001), and that recurrence-free survival was significantly shorter in the Wnt-5a-negative group (P < 0.001). In multivariate analyses, loss of Wnt-5a expression proved to be an independent and powerful predictor of recurrence after adjustment for lymph node status and tumor size (hazard ratio = 4.8; P = 0.002). Our results show that loss of Wnt-5a increases the risk of early relapse and death because of recurrent ductal breast cancer, findings that support the notion that this protein retains tumor suppressor function by virtue of its effects on cell adhesion and motility.
Aldehyde–alcohol dehydrogenase and/or thiolase overexpression coupled with CoA transferase downregulation lead to higher alcohol titers and selectivity in Clostridium acetobutylicum fermentations (2008)

Metabolic engineering (ME) of Clostridium acetobutylicum has led to increased solvent (butanol, acetone, and ethanol) production and solvent tolerance, thus demonstrating that further efforts have the potential to create strains of industrial importance. With recently developed ME tools, it is now possible to combine genetic modifications and thus implement more advanced ME strategies. We have previously shown that antisense RNA (asRNA)-based downregulation of CoA transferase (CoAT, the first enzyme in the acetone-formation pathway) results in increased butanol to acetone selectivity, but overall reduced butanol yields and titers. In this study the alcohol/aldehyde dehydrogenase (aad) gene (encoding the bifunctional protein AAD responsible for butanol and ethanol production from butyryl-CoA and acetyl-CoA, respectively) was expressed from the phosphotransbutyrylase (ptb) promoter to enhance butanol formation and selectivity, while CoAT downregulation was used to minimize acetone production. This led to early production of high alcohol (butanol plus ethanol) titers, overall solvent titers of 30 g/L, and a higher alcohol/acetone ratio. Metabolic flux analysis revealed the likely depletion of butyryl-CoA. In order to increase then the flux towards butyryl-CoA, we examined the impact of thiolase (THL, thl) overexpression. THL converts acetyl-CoA to acetoacetyl-CoA, the first step of the pathway from acetyl-CoA to butyryl-CoA, and thus, combining thl overexpression with aad overexpression decreased, as expected, acetate and ethanol production while increasing acetone and butyrate formation. thl overexpression in strains with asRNA CoAT downregulation did not significantly alter product formation thus suggesting that a more complex metabolic engineering strategy is necessary to enhance the intracellular butyryl-CoA pool and reduce the acetyl-CoA pool in order to achieve improved butanol titers and selectivity.
Expression of a functional fungal polyketide synthase in the bacterium Streptomyces coelicolor A3(2) (1995)

The multifunctional 6-methylsalicylic acid synthase gene from Penicillium patulum was engineered for regulated expression in Streptomyces coelicolor. Production of significant amounts of 6-methylsalicylic acid by the recombinant strain was proven by nuclear magnetic resonance spectroscopy. These results suggest that it is possible to harness the molecular diversity of eukaryotic polyketide pathways by heterologous expression of biosynthetic genes in an easily manipulated model bacterial host in which prokaryotic aromatic and modular polyketide synthase genes are already expressed and recombined.
Copper(II)(3,5‐Diisopropylsalicylate)2 Accelerates Recovery of B and T Cell Reactivity Following Irradiation (1987)

Copper(II)(3,5-diisopropylsalicylate)2 (Cu-DIPS), administered subcutaneously to mice at 80 mg/kg body weight, had marked radioprotective activity. Given 3 h before exposure to 8.0 Gy (800 rad) irradiation, Cu-DIPS increased the 42-day survival from 40% to 86%. Seven days after exposure to 8.0 Gy, there were severe reductions in spleen weight (73%) and cellularity (98%) in both Cu-DIPS- and vehicle-treated mice. Viable spleen cells collected 7 days after irradiation were totally unresponsive to mitogenic or antigenic stimulation regardless of Cu-DIPS or vehicle treatment, suggesting that Cu-DIPS did not prevent radiation-induced damage to mature lymphocytes. At 14 days, when Cu-DIPS-treated mice started to show improved survival over vehicle-treated mice, spleen weights and cellularity were 2.5- and 3.5-fold higher, respectively, in Cu-DIPS-treated mice. Treatment with Cu-DIPS not only enhanced splenic repopulation, but also accelerated the reappearance of both B and T cell reactivities. Spleen cell responsiveness to the B cell mitogen, lipopolysaccharide (LPS), and the T cell mitogen, concanavalin A (Con A), regenerated significantly faster in Cu-DIPS-treated mice. Cu-DIPS also significantly accelerated the regeneration of T-dependent antibody induction. Based on these assays of immunocompetence, Cu-DIPS-treated mice had, on average, a seven-fold greater capacity to respond to immune stimulation than vehicle-treated mice 24 days after irradiation.