gebhart/patrepeval huggingface dataset:
The exoA gene of Streptococcus pneumoniae and its product, a DNA exonuclease with apurinic endonuclease activity (1989)

The gene encoding the major DNA exonuclease of Streptococcus pneumoniae, exoA, was cloned in a streptococcal host vector system. Its location was determined by subcloning and by insertion mutations. Transfer of a DNA segment containing the gene to an Escherichia coli expression vector showed that exoA was the structural gene for the enzyme and that it was adjacent to its promoter. DNA sequence determination indicated that the gene encoded a protein, ExoA, of molecular weight 31,263. Under hyperexpression conditions, the ExoA protein constituted 10% of total cellular protein. In addition to previously demonstrated 3' to 5' exonuclease and 3'-phosphatase activities, ExoA was shown to make single-strand breaks at apurinic sites in DNA. Its enzymatic activities are thus similar to those of exonuclease III of E. coli and other gram-negative bacteria. The nucleotide sequence of exoA revealed it to be homologous to xth of E. coli, with 26% identity of amino acid residues in the predicted proteins. So far, no null chromosomal mutants of exoA have been obtained, and the biological function of ExoA remains unknown.
RAC1 Inhibition Targets Amyloid Precursor Protein Processing by γ-Secretase and Decreases Aβ Production in Vitro and in Vivo (2005)

beta-Amyloid peptides (Abeta) that form the senile plaques of Alzheimer disease consist mainly of 40- and 42-amino acid (Abeta 40 and Abeta 42) peptides generated from the cleavage of the amyloid precursor protein (APP). Generation of Abeta involves beta-secretase and gamma-secretase activities and is regulated by membrane trafficking of the proteins involved in Abeta production. Here we describe a new small molecule, EHT 1864, which blocks the Rac1 signaling pathways. In vitro, EHT 1864 blocks Abeta 40 and Abeta 42 production but does not impact sAPPalpha levels and does not inhibit beta-secretase. Rather, EHT 1864 modulates APP processing at the level of gamma-secretase to prevent Abeta 40 and Abeta 42 generation. This effect does not result from a direct inhibition of the gamma-secretase activity and is specific for APP cleavage, since EHT 1864 does not affect Notch cleavage. In vivo, EHT 1864 significantly reduces Abeta 40 and Abeta 42 levels in guinea pig brains at a threshold that is compatible with delaying plaque accumulation and/or clearing the existing plaque in brain. EHT 1864 is the first derivative of a new chemical series that consists of candidates for inhibiting Abeta formation in the brain of AD patients. Our findings represent the first pharmacological validation of Rac1 signaling as a target for developing novel therapies for Alzheimer disease.
Population Pharmacokinetics of Tenofovir in HIV-1–Infected Pediatric Patients (2011)

Children without LPV/r should receive: 150 mg TDF from 20 to 30 kg, 225 mg TDF from 30 to 40 kg, and the adult dosage of 300 mg TDF over 40 kg. To avoid risk of renal toxicity, TDF dose should be decreased when coadministrated with LPV/r, children should receive 150 mg TDF from 20 to 40 kg, 225 mg TDF from 40 to 55 kg, and the adult dosage of 300 mg TDF over 55 kg.
Respiratory viruses and exacerbations of asthma in adults. (1993)

These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.
Bovine β‐lactoglobulin: Interaction studies with palmitic acid (2000)

Bovine beta-lactoglobulin (BLG) in vivo has been found complexed with fatty acids, especially palmitic and oleic acid. To elucidate the still unknown structure-function relationship in this protein, the interactions between 13C enriched palmitic acid (PA) and BLG were investigated by means of one-, two-, and three-dimensional NMR spectroscopy in the pH range 8.4-2.1. The NMR spectra revealed that at neutral pH the ligand is bound within the central cavity of BLG, with the methyl end deeply buried within the protein. The analysis of 13C spectra of the holo protein revealed the presence of conformational variability of bound PA carboxyl end in the pH range 8.4-5.9, related to the Tanford transition. The release of PA starts at pH lower than 6.0, and it is nearly complete at acidic pH. This finding is relevant in relation to the widely reported hypothesis that this protein can act as a transporter through the acidic gastric tract. Ligand binding and release is shown to be completely reversible over the entire pH range examined, differently from other fatty acid binding proteins whose behavior is analyzed throughout the paper. The mode of interaction of BLG is compatible with the proposed function of facilitating the digestion of milk fat during the neonatal period of calves.
Functional Implications of a Newly Characterized Pathway of 11,12-Epoxyeicosatrienoic Acid Metabolism in Arterial Smooth Muscle (1996)

Epoxyeicosatrienoic acids (EETs) are potent vasodilators derived from cytochrome P-450 metabolism of arachidonic acid. The rapid conversion of EETs to their corresponding dihydroxyeicosatrienoic acids (DHETs) has been proposed as a process whereby EETs are rendered biologically inactive. However, the vascular metabolism of EETs and the vasoactivities of EET metabolites have not been extensively studied. Accordingly, 11,12-EET metabolism was characterized in porcine aortic smooth muscle cells. The cells converted [3H]11,12-EET to 11,12-DHET and to a newly identified metabolite, 7,8-dihydroxy-hexadecadienoic acid (DHHD). 11,12-DHET accumulation in the medium reached a maximum in 2 to 4 hours and then declined, whereas 7,8-DHHD accumulation increased continuously and exceeded the amount of 11,12-DHET by 8 hours. [3H]11,12-EET conversion to radiolabeled 7,8-DHHD was reduced in the presence of unlabeled 11,12-DHET, indicating that 11,12-DHET is an intermediate in the conversion of 11,12-EET to 7,8-DHHD. This is consistent with a pathway whereby 11,12-EET is converted by an epoxide hydrolase to 11,12-DHET, which then undergoes two beta-oxidations to form 7,8-DHHD. In porcine coronary artery rings contracted with a thromboxane mimetic, 11,12-DHET produced relaxation similar in magnitude to that produced by 11,12-EET (77% versus 64% relaxation at 5 mumol/L, respectively). 7,8-DHHD also produced vasorelaxation. Thus, the vasoactivity of 11,12-EET is not eliminated by conversion to 11,12-DHET and 7,8-DHHD. These results suggest that 11,12-DHET and its metabolite, 7,8-DHHD, may contribute to the regulation of vascular tone in the porcine coronary artery and possibly other vascular tissues.
L2-Net: Deep Learning of Discriminative Patch Descriptor in Euclidean Space (2017)

The research focus of designing local patch descriptors has gradually shifted from handcrafted ones (e.g., SIFT) to learned ones. In this paper, we propose to learn high performance descriptor in Euclidean space via the Convolutional Neural Network (CNN). Our method is distinctive in four aspects: (i) We propose a progressive sampling strategy which enables the network to access billions of training samples in a few epochs. (ii) Derived from the basic concept of local patch matching problem, we empha-size the relative distance between descriptors. (iii) Extra supervision is imposed on the intermediate feature maps. (iv) Compactness of the descriptor is taken into account. The proposed network is named as L2-Net since the output descriptor can be matched in Euclidean space by L2 distance. L2-Net achieves state-of-the-art performance on the Brown datasets [16], Oxford dataset [18] and the newly proposed Hpatches dataset [11]. The good generalization ability shown by experiments indicates that L2-Net can serve as a direct substitution of the existing handcrafted descriptors. The pre-trained L2-Net is publicly available.
Bellcore Metrocore network-a test-bed for metropolitan area network research (2003)

The authors describe the Bellcore Metrocore network, a testbed prototype of a metropolitan area network (MAN) for exploring network concepts and technology applications in broadband communications. This system operates at 150 Mb/s with the potential for upgrading to multi-Gb/s. A basic hardware architecture has been designed which consists of a network interface (media access control (MAC) layer), and several independent, modular units that interface to various services. At the MAC layer, integrated services are supported by giving priority to those traffic types requiring bounded delay. The software network architecture includes a network controller to configure, monitor, and administer the network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An analysis of simultaneous variation in protein structures (1997)

The simultaneous substitution of pairs of buried amino acid side chains during divergent evolution has been examined in a set of protein families with known crystal structures. A weak signal is found that shows that amino acid pairs near in space in the folded structure preferentially undergo substitution in a compensatory way. Three different physicochemical types of covariation 'signals' were then examined separately, with consideration given to the evolutionary distance at which different types of compensation occur. Where the compensatory covariation tends towards retaining the combined residue volumes, the signal is significant only at very low evolutionary distances. Where the covariation compensates for changes in the hydrogen bonding, the signal is strongest at intermediate evolutionary distances. Covariations that compensate for charge variations appeared with equal strength at all the evolutionary distances examined. A recipe is suggested for using the weak covariation signal to assemble the predicted secondary structural elements, where the evolutionary distance, covariation type and weighting are considered together with the tertiary structural context (interior or surface) of the residues being examined.
Selective Primary Health Care: Strategies for Control of Disease in the Developing World. V. Leprosy (1983)

Leprosy afflicts 10-15 million people in the world, primarily in tropical and subtropical developing countries. In areas endemic for leprosy, the incidence may reach four to six cases per 1,000 population, and the prevalence of the disease frequently exceeds 10 per 1,000 population in parts of Africa and Asia. While these figures are not high in relation to those for other tropical diseases, many developing countries consider leprosy a major health problem because a significant proportion of cases result in deformity and subsequent social stigmatization. Leprosy comprises a wide spectrum of clinical and pathologic stages that have been classified histopathologically. In polar lepromatous disease there is specific immunologic unresponsiveness of cell-mediated immunity to Mycobacterium leprae antigens, while, in the tuberculoid form of the disease, strong cell-mediated immunity is present but tissue damage seems to be a consequence. This review discusses the detailed immunologic analyses of the histopathology and pathogenesis of the various stages of leprosy. It will be argued that lepromatous leprosy presents an extraordinary model for understanding the mechanisms of immunologic unresponsiveness in humans. The present effectiveness and limitations of chemotherapy in the face of emerging resistance to dapsone are briefly discussed. Recent advances in the development of vaccines are discussed in terms of their immunologic potential and epidemiologic necessity. The implications of an effective prophylactic or immunotherapeutic vaccine used in combination with chemotherapy are also presented.
Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors (2002)

Treatment of advanced, poorly immunogenic tumors in animal models, considered the closest simulation available thus far for conditions observed in cancer patients, remains a major challenge for cancer immunotherapy. We reported previously that established tumors in mice receiving an agonistic mAb to the T cell costimulatory molecule 4-1BB (CD137) regress due to enhanced tumor antigen–specific cytotoxic T lymphocyte responses. In this study, we demonstrate that several poorly immunogenic tumors, including C3 tumor, TC-1 lung carcinoma, and B16-F10 melanoma, once established as solid tumors or metastases, are refractory to treatment by anti–4-1BB mAb. We provide evidence that immunological ignorance, rather than anergy or deletion, of tumor antigen–specific CTLs during the progressive growth of tumors prevents costimulation by anti–4-1BB mAb. Breaking CTL ignorance by immunization with a tumor antigen–derived peptide, although insufficient to stimulate a curative CTL response, is necessary for anti–4-1BB mAb to induce a CTL response leading to the regression of established tumors. Our results suggest a new approach for immunotherapy of human cancers.
Biologic Agents in the Treatment of Rheumatoid Arthritis (2000)

Advances in the understanding of the pathogenesis of rheumatoid arthritis (RA) as well as improved biotechnology has enabled selective targeting of the pathogenic elements of disease. Targeting cell recruitment through adhesion molecules has been shown to be successful in pre-clinical murine models. Results of studies of an anti-ICAM-1 monoclonal antibody and anti-sense oligonucleotides have been encouraging. An alternate approach to inhibiting recruitment has been the targeting of chemoattractant molecules ie. chemokines. Important advances have been made in cytokine directed therapy targeting TNFalpha and IL-1. TNF antagonists (anti-TNF monoclonal antibody/soluble TNF receptor Fc fusion protein) have resulted in rapid and substantial improvement in signs and symptoms of disease as well as disease modification, shown by slowing of radiological progression. IL-1 receptor antagonist protein appears to have a significant effect on radiological progression despite a modest effect on symptoms and signs. Studies using anti-inflammatory cytokines such as IL-10 are in progress. A more recent therapeutic approach has been to target T-cell activation by interfering with co-stimulatory complexes such as CD40L/CD40 and CD28/CD80 and CD86. Both pre-clinical and preliminary clinical studies in human subjects support the concept. Another approach involving T-cell receptor peptide vaccination with VB peptides over-utilized in RA synovium has shown to be beneficial. Targeting the cytokines driving T-cells in the RA synovium ie. IL-12 & IL-15 has also proven beneficial in animal studies. Recent attention has also been directed toward the invading synovial fibroblast using Fas-FasL mediated apoptosis. Pre-clinical studies in which angiogenesis and osteoclast activation are targeted have been encouraging. In conclusion, the proof of principle has been established that selective targeting of pathogenic elements of disease results in substantial improvement in signs and symptoms as well as disease progression. Improved efficacy is expected with more aggressive targeting of the pathogenic elements.
Functional analysis of the methylmalonyl‐CoA epimerase from Caenorhabditis elegans (2005)

Methylmalonyl-CoA epimerase (MCE) is an enzyme involved in the propionyl-CoA metabolism that is responsible for the degradation of branched amino acids and odd-chain fatty acids. This pathway typically functions in the reversible conversion of propionyl-CoA to succinyl-CoA. The Caenorhabditis elegans genome contains a single gene encoding MCE (mce-1) corresponding to a 15 kDa protein. This was expressed in Escherichia coli and the enzymatic activity was determined. Analysis of the protein expression pattern at both the tissue and subcellular level by microinjection of green fluorescent protein constructs revealed expression in the pharynx, hypodermis and, most prominently in body wall muscles. The subcellular pattern agrees with predictions of mitochondrial localization. The sequence similarity to an MCE of known structure was high enough to permit a three-dimensional model to be built, suggesting conservation of ligand and metal binding sites. Comparison with corresponding sequences from a variety of organisms shows more than 1/6 of the sequence is completely conserved. Mutants allelic to mce-1 showed no obvious phenotypic alterations, demonstrating that the enzyme is not essential for normal worm development under laboratory conditions. However, survival of the knockout mutants was altered when exposed to stress conditions, with mutants surprisingly showing an increased resistance to oxidative stress.
Cooperative bimanual action (1997)

We present an experiment on cooperative bimanual action. Right-handed subjects manipulated a pair of physical objects, a tool and a target object, so that the tool would touch a target on the object @g. 1). For this task, there is a marked specialization of the hands. Performance is best when the left hand orients the target object and the right hand manipulates the tool, but is significantly reduced when these roles are reversed. This suggests that the right hand operates relative to the frame-of-reference of the left hand.
156. The relation between configuration and conjugation in diphenyl derivatives. Part I. The enantiomorphism and ultra-violet absorption spectra of some 2 : 2′-bridged compounds (1952)

G. H. Beaven, D. M. Hall, M. S. Lesslie and E. E. Turner, J. Chem. Soc., 1952, 854 DOI: 10.1039/JR9520000854
Sympathetic overactivity as a cause of hypertension in chronic renal failure (2002)

Sympathetic overactivity in chronic renal failure is caused by neurohormonal mechanisms arising in the failing kidney. Future clinical studies are needed to determine whether normalization of sympathetic activity should constitute an important therapeutic goal in this high-risk patient population.
Derivation of High-Purity Oligodendroglial Progenitors (2009)

Oligodendrocytes are a type of glial cells that play a critical role in supporting the central nervous system (CNS), in particular insulating axons within the CNS by wrapping them with a myelin sheath, thereby enabling saltatory conduction. They are lost, and myelin damaged - demyelination - in a wide variety of neurological disorders. Replacing depleted cell types within demyelinated areas, however, has been shown experimentally to achieve remyelination and so help restore function. One method to produce oligodendrocytes for cellular replacement therapies is through the use of progenitor or stem cells. The ability to differentiate progenitor or stem cells into high-purity fates not only permits the generation of specific cells for transplantation therapies, but also provides powerful tools for studying cellular mechanisms of development. This chapter outlines methods of generating high-purity OPCs from multipotent neonatal progenitor or human embryonic stem cells.
Cytoplasmic Male Sterility of Rice with Boro II Cytoplasm Is Caused by a Cytotoxic Peptide and Is Restored by Two Related PPR Motif Genes via Distinct Modes of mRNA Silencing (2006)

Cytoplasmic male sterility (CMS) and nucleus-controlled fertility restoration are widespread plant reproductive features that provide useful tools to exploit heterosis in crops. However, the molecular mechanism underlying this kind of cytoplasmic-nuclear interaction remains unclear. Here, we show in rice (Oryza sativa) with Boro II cytoplasm that an abnormal mitochondrial open reading frame, orf79, is cotranscribed with a duplicated atp6 (B-atp6) gene and encodes a cytotoxic peptide. Expression of orf79 in CMS lines and transgenic rice plants caused gametophytic male sterility. Immunoblot analysis showed that the ORF79 protein accumulates specifically in microspores. Two fertility restorer genes, Rf1a and Rf1b, were identified at the classical locus Rf-1 as members of a multigene cluster that encode pentatricopeptide repeat proteins. RF1A and RF1B are both targeted to mitochondria and can restore male fertility by blocking ORF79 production via endonucleolytic cleavage (RF1A) or degradation (RF1B) of dicistronic B-atp6/orf79 mRNA. In the presence of both restorers, RF1A was epistatic over RF1B in the mRNA processing. We have also shown that RF1A plays an additional role in promoting the editing of atp6 mRNAs, independent of its cleavage function.
Preparation and Characterization of Light-Sensitive Microcapsules Based on a Liquid Crystalline Polyester (2012)

Photosensitive microcapsules and membranes based on poly(α-methylstilbenesebacoate-co-α-methylstilbeneisophthalate), containing the photosensitive α-methylstilbene moiety, were prepared by a phase-inversion precipitation process. In order to simulate the morphology and behavior of the microcapsule shell under UV irradiation, an exhaustive characterization of a membrane was first performed by ESEM, POM, AFM, and contact angle measurements. The prepared microcapsules contained either chloroform or a concentrated solution of vanillin in chloroform as the core; in all cases, before UV irradiation, their outer surface appeared smooth and dense. The influence of vanillin on microcapsule cross-section morphology was observed by ESEM microscopy. Release of vanillin in water, at room temperature, was markedly influenced by UV irradiation: in the absence of irradiation, it was practically negligible, while when microcapsules were submitted to continuous irradiation with UV light, the surface morphology of the capsules changed drastically and vanillin started to be released after ca. 20 min of irradiation.
Subcritical co‐solvents extraction of lipid from wet microalgae pastes of Nannochloropsis sp. (2011)

In this paper subcritical co-solvents extraction (SCE) of algal lipid from wet pastes of Nannochloropsis sp. is examined. The influences of five operating parameters including the ratio between ethanol to hexane, the ratio of mixed solvents to algal biomass (dry weight), extraction temperature, pressure, and time were investigated. The determined optimum extraction conditions were 3:1 (hexane to ethanol ratio), 10:1 ratio (co-solvents to microalgae (dry weight) ratio), 90°C, 1.4 MPa, and 50 min, which could produce 88% recovery rate of the total lipids. In addition, electron micrographs of transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were conducted to show that the algal cell presented shrunken, collapsed with some wrinkles and microholes after SCE extraction. The main composition of total lipids extracted under the optimum conditions was TAG which represented more than 80%. And the fatty acid profile of triglycerides revealed that C16:0 (35.67 ± 0.2%), C18:1 (26.84 ± 0.044%) and C16:1 (25.96 ± 0.011%) were dominant. PRACTICAL APPLICATIONS: The reported method could save energy consumption significantly through avoiding deep dewatering (for example drying). The composition of the extracted lipid is suitable for the production of high quality biodiesel.
Ireland: HIV and hepatitis C in prisons. (2002)

Two studies from the Department of Community Health and General Practice at Trinity College, Dublin, have highlighted the extent of the HIV and hepatitis C (HCV) crisis in Irish prisons. The studies confirm that rates of HIV and HCV are disproportionately high in Irish prisons, and that high risk behaviours are commonplace.