gebhart/patrepeval huggingface dataset:
Accumulation of Mutant Huntingtin Fragments in Aggresome-like Inclusion Bodies as a Result of Insufficient Protein Degradation (2001)

The huntingtin exon 1 proteins with a polyglutamine repeat in the pathological range (51 or 83 glutamines), but not with a polyglutamine tract in the normal range (20 glutamines), form aggresome-like perinuclear inclusions in human 293 Tet-Off cells. These structures contain aggregated, ubiquitinated huntingtin exon 1 protein with a characteristic fibrillar morphology. Inclusion bodies with truncated huntingtin protein are formed at centrosomes and are surrounded by vimentin filaments. Inhibition of proteasome activity resulted in a twofold increase in the amount of ubiquitinated, SDS-resistant aggregates, indicating that inclusion bodies accumulate when the capacity of the ubiquitin-proteasome system to degrade aggregation-prone huntingtin protein is exhausted. Immunofluorescence and electron microscopy with immunogold labeling revealed that the 20S, 19S, and 11S subunits of the 26S proteasome, the molecular chaperones BiP/GRP78, Hsp70, and Hsp40, as well as the RNA-binding protein TIA-1, the potential chaperone 14-3-3, and alpha-synuclein colocalize with the perinuclear inclusions. In 293 Tet-Off cells, inclusion body formation also resulted in cell toxicity and dramatic ultrastructural changes such as indentations and disruption of the nuclear envelope. Concentration of mitochondria around the inclusions and cytoplasmic vacuolation were also observed. Together these findings support the hypothesis that the ATP-dependent ubiquitin-proteasome system is a potential target for therapeutic interventions in glutamine repeat disorders.
Eine neueSchefflera (Sch. Sarasinorum) aus Celébes (1906)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Video Captioning with Transferred Semantic Attributes (2017)

Automatically generating natural language descriptions of videos plays a fundamental challenge for computer vision community. Most recent progress in this problem has been achieved through employing 2-D and/or 3-D Convolutional Neural Networks (CNNs) to encode video content and Recurrent Neural Networks (RNNs) to decode a sentence. In this paper, we present Long Short-Term Memory with Transferred Semantic Attributes (LSTM-TSA) - a novel deep architecture that incorporates the transferred semantic attributes learnt from images and videos into the CNN plus RNN framework, by training them in an end-to-end manner. The design of LSTM-TSA is highly inspired by the facts that 1) semantic attributes play a significant contribution to captioning, and 2) images and videos carry complementary semantics and thus can reinforce each other for captioning. To boost video captioning, we propose a novel transfer unit to model the mutually correlated attributes learnt from images and videos. Extensive experiments are conducted on three public datasets, i.e., MSVD, M-VAD and MPIIMD. Our proposed LSTM-TSA achieves to-date the best published performance in sentence generation on MSVD: 52.8% and 74.0% in terms of BLEU@4 and CIDEr-D. Superior results are also reported on M-VAD and MPII-MD when compared to state-of-the-art methods.
PT‐141: A Melanocortin Agonist for the Treatment of Sexual Dysfunction (2003)

PT-141, a synthetic peptide analogue of alpha-MSH, is an agonist at melanocortin receptors including the MC3R and MC4R, which are expressed primarily in the central nervous system. Administration of PT-141 to rats and nonhuman primates results in penile erections. Systemic administration of PT-141 to rats activates neurons in the hypothalamus as shown by an increase in c-Fos immunoreactivity. Neurons in the same region of the central nervous system take up pseudorabies virus injected into the corpus cavernosum of the rat penis. Administration of PT-141 to normal men and to patients with erectile dysfunction resulted in a rapid dose-dependent increase in erectile activity. The results suggest that PT-141 holds promise as a new treatment for sexual dysfunction.
Improving Site‐Directed RNA Editing In Vitro and in Cell Culture by Chemical Modification of the GuideRNA (2014)

Adenosine-to-inosine deamination can be re-addressed to user-defined mRNAs by applying phosphothioate/2'-methoxy-modified guideRNAs. Dense chemical modification of the guideRNA clearly improves performance of the covalent conjugates inside the living cell. Furthermore, careful positioning of a few modifications controls editing selectivity in vitro and was exploited for the challenging repair of the Factor 5 Leiden missense mutation.
CVD in Stagnation Point Flow: An Evaluation of the Classical 1D Treatment (1986)

There has been considerable interest in CVD to utilize rotating disk, stagnation point, and impinging jet flows to achieve large area film thickness and composition uniformity, as well as to conduct kinetic experiments. The present study explores the limits of the classical one‐dimensional treatment for typical CVD reactor configurations and flows by comparison with the complete two‐dimensional axisymmetric description. The one and two‐dimensional balance equations for flow, energy, and chemical species are solved numerically by the Galerkin finite element method. The comparisons are presented in terms of the size of the deposition surface where the classical analysis is correct within 5% for varying reactor size parameters, flow rates, pressures, and gases. The results demonstrate that the one‐dimensional treatment is valid over a wide range of conditions and radial distances. When it fails, the primary reasons are thermal recirculation and edge effects. The general results should provide guidelines for designing kinetic studies as well as commercial CVD reactor equipment.
Salivary proteins and glycoproteins in phlebotomine sandflies of various species, sex and age (2000)

Salivary gland proteins were studied in sandflies (Diptera: Psychodidae: Phlebotominae) by electrophoretic techniques. In Phlebotomus duboscqi Neveu-Lemaire the protein concentration was about 30 times higher in females than in males. SDS PAGE revealed eight major bands of 29-62 kDa in salivary gland extracts (SGE) from females, whereas only one band of 57kDa was detected in males. The number of protein components in SGE gradually increased with the age of females. In P. papatasi (Scopoli) the typical electrophoretic pattern was reached in 3-5 days after imago emergence, depending on the temperature at which females were maintained. All major protein components of the female SGE were present in the content of glands. Female SGE were compared in seven colonies of five Phlebotomus and Lutzomyia species; electrophoretic profiles distinguished between species and even between colonies of different geographical origin. In general, the highest variability of major protein components was observed in the 38-48kDa region. Four colonies of the subgenus Phlebotomus (P. duboscqi and P. papatasi) possessed common mobility polypeptides, the highest similarity was found between two colonies of P. papatasi. Other species tested significantly differed, specific prominent bands of 33, 35 and 38kDa were found in P. halepensis Theodor, P. perniciosus Newstead and Lutzomyia longipalpis (Lutz & Neiva), respectively. Glycoproteins in SGE of Lu. longipalpis and P. duboscqi females were identified and analysed using blotting with five lectin conjugates. Specific reaction of lectins ConA and WGA revealed the complex type of N-glycans in the 48 and 53-54kDa glycoproteins present in both species. Similar glycosylation was detected in species-specific bands of the 57-60 and 65-67 kDa in P. duboscqi and Lu. longipalpis, respectively. The high mannose type of glycosylation was found in the 20 and 39 kDa polypeptides of Lu. longipalpis and the 40-42 kDa polypeptides of P. duboscqi. Innate lectin activity specific for aminosugars was detected in SGE of P. duboscqi females using haemagglutination tests with rabbit erythrocytes.
Strategies to Reduce Mortality in Adult and Neonatal Candidemia in Developing Countries (2017)

Candidemia, the commonest invasive fungal infection, is associated with high morbidity and mortality in developing countries, though the exact prevalence is not known due to lack of systematic epidemiological data from those countries. The limited studies report a very high incidence of candidemia and unique epidemiology with a different spectrum of <i>Candida</i> species. The recent global emergence of multi-drug resistant <i>Candida auris</i> is looming large as an important threat in hospitalized patients of developing countries. While managing candidemia cases in those countries several challenges are faced, which include poor infrastructure; compromised healthcare and infection control practices; misuse and overuse of antibiotics and steroids; lack of awareness in fungal infections; non-availability of advance diagnostic tests and antifungal drugs in many areas; poor compliance to antifungal therapy and stewardship program. Considering the above limitations, innovative strategies are required to reduce mortality due to candidemia in adults and neonates. In the present review, we have unraveled the challenges of candidemia faced by low resource countries and propose a ten part strategy to reduce mortality due candidemia.
Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives (2005)

The continually increasing wealth of knowledge about the role of genes involved in acquired or hereditary diseases renders the delivery of regulatory genes or nucleic acids into affected cells a potentially promising strategy. Apart from viral vectors, non-viral gene delivery systems have recently received increasing interest, due to safety concerns associated with insertional mutagenesis of retro-viral vectors. Especially cationic polymers may be particularly attractive for the delivery of nucleic acids, since they allow a vast synthetic modification of their structure enabling the investigation of structure-function relationships. Successful clinical application of synthetic polycations for gene delivery will depend primarily on three factors, namely (1) an enhancement of the transfection efficiency, (2) a reduction in toxicity and (3) an ability of the vectors to overcome numerous biological barriers after systemic or local administration. Among the polycations presently used for gene delivery, poly(ethylene imine), PEI, takes a prominent position, due to its potential for endosomal escape. PEI as well as derivatives of PEI currently under investigation for DNA and RNA delivery will be discussed. This review focuses on structure-function relationships and the physicochemical aspects of polyplexes which influence basic characteristics, such as complex formation, stability or in vitro cytotoxicity, to provide a basis for their application under in vivo conditions. Rational design of optimized polycations is an objective for further research and may provide the basis for a successful cationic polymer-based gene delivery system in the future.
Measurement of whole body interleukin-6 (IL-6) production: prediction of the efficacy of anti-IL-6 treatments (1995)

A major limitation on the therapeutic use of cytokine antagonists is that the amount of cytokine to be neutralized in vivo is not presently known. We previously reported that anti-interleukin-6 (IL-6) monoclonal antibody (MoAb) administered to a patient with multiple myeloma (MM) induced high amounts of IL-6 to circulate in the form of monomeric immune complexes. Based on this observation, the present study developed a new methodology to estimate daily IL-6 production in 13 patients with MM or renal cancer who received anti-IL-6 MoAb. Treatment was considered effective when the production of C-reactive protein (CRP) was inhibited. The production of this acute-phase protein by hepatocytes is dependent on the activation of IL-6 gp130 transducer. Inhibition of tumor proliferation was also evaluated in patients with MM. In 7 of 13 patients whose CRP production was completely inhibited (> 96%) and who showed some antitumoral effects, whole-body IL-6 production in vivo was less than 18 micrograms/d (median, 5.7 micrograms/d; range, 0.5 to 17.5 micrograms/d). In the other 6 patients, subtotal inhibition of CRP production and a lack of antitumoral response were associated with high IL-6 production (median, 180 micrograms/d; range, 18 to 358 micrograms/d). These in vivo observations were consistent with mathematical modeling that predicted that anti-IL-6 MoAb treatment would be efficient only in low IL-6 producers. These data indicate the difficulty of neutralizing IL-6 with a single anti-IL-6 MoAb in vivo and call for new strategies to avoid accumulation of IL-6 in the form of stable immune complexes.
Contemporary Management of Fibroids (2003)

The management of uterine fibroids has undergone a revolution in the past few decades with better understanding of its impact on fertility and technical advances in endoscopy and radiologic embolisation techniques and also pharmaceutical alternatives such as gonadotrophin-releasing hormone agonist and progesterone intrauterine contraceptive devices. Advances in molecular biology may provide an opportunity to manipulate receptors and cellular biology in order to arrest tumourigenesis altogether.
A new type of mutation in the plant photoreceptor phytochrome B causes loss of photoreversibility and an extremely enhanced light sensitivity (2000)

Photoreversibility, reversion of the inductive effect of a brief red light pulse by a subsequent far-red light pulse, is a property of photoresponses regulated by the plant photoreceptor phytochrome B (phyB). We screened for mutants with impaired photoreversibility to gain better insight into the phyB-specific signalling cascade. The phenotype of the mutant described is caused by a single amino acid exchange in a phyB subdomain that is highly conserved in all phytochromes but whose functional significance was unknown. The mutated phyB showed a slower dark reversion but no major alterations in its spectral properties. In addition to its loss of photoreversibility, the mutant also exhibited a hypersensitivity towards continuous red-light irradiation and an altered phenotype of adult plants under short-day conditions.
Expression of IL-10 family cytokines in rheumatoid arthritis: elevated levels of IL-19 in the joints (2009)

The majority of the IL-10 family cytokines are expressed in RA. IL-19 demonstrated the highest expression in rheumatoid joints, and could thus be involved in the regulation of synovial inflammation in RA.
Total sequence, flanking regions, and transcripts of bacteriophage T4 nrdA gene, coding for alpha chain of ribonucleoside diphosphate reductase. (1988)

As a part of a study of the role of bacteriophage T4-coded ribonucleoside diphosphate reductase in the switch-on and regulation of T4 DNA replication, we report the cloning and sequencing of the nrdA gene, coding for the alpha protein chain of the enzyme. The open reading frame of the nrdA gene begins 558 base pairs downstream of the 3' terminus of the td gene (thymidylate synthase). nrdB, encoding the beta chain of the enzyme, initiates 700 base pairs from the termination of nrdA. A high degree of similarity is found between the deduced amino acid sequence of the 754-residue alpha chain and the corresponding chain reported for nrdA of Escherichia coli; 56% of the residues are identical, with some segments reaching 84%. Some structural aspects of the derived alpha 2 subunit of the T4 enzyme are explored. By the S1 nuclease protection method, the RNA formed after T4 infection contains two prereplicative transcripts for nrdA, T3 and TU, and one postreplicative transcript, TL. T3 is found in low concentration. While the 5' termini of T3 and TL occur at sites near nrdA, TU apparently is a multicistronic transcript initiating farther upstream. The regulation of nrdA expression is examined in light of these findings.
Annexin V as a probe of the contribution of anionic phospholipids to the procoagulant activity of tumour cell surfaces. (1994)

The ability of anionic phospholipids (especially phosphatidylserine, PS) on the outer membrane leaflet of four tumour cell lines to support different stages of the extrinsic pathway of coagulation was probed using annexin V as an inhibitor. The procoagulant activity of two tumorigenic (MKN-28, human gastric carcinoma, Hep3B, human hepatoblastoma) and two non-tumorigenic (HepG2, human hepatocellular, HOC-1, human ovarian carcinoma) cell lines were observed to be inhibited by annexin V, although significant differences (observed as IC50 with respect to annexin V) were noted for each stage of coagulation and between different cell types. This was considered to suggest a restricted accessibility of PS in the vicinity of coagulation factors on the surface of the cell. PS levels, as estimated by binding of 125I-annexin V, were high on two of the cell lines tested, equivalent to 24 x 10(6) sites per cell for HepG2 (Kd 128 nM) and 6.5 x 10(6) sites per cell for MKN-28 (Kd 50 nM). During 9 days' culturing of HepG2 and MKN-28, the number of sites per cell remained constant. However, perhaps supporting a proposal of reduced availability, there was an observed fall in PS-dependent procoagulant activity of HepG2 and MKN-28 cells, subsequent to a peak on reaching confluency at 3 days. Both prothrombinase activity and total procoagulant activity fell, even though the number of 125I-annexin V binding sites remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Neutral and Cationic Group 13 Phosphinimine and Phosphinimide Complexes (1999)

Reactions of the silylphosphimines R3PNSiMe3 (R = i-Pr, Ph, Cy) with AlCl3, AlMeCl2, AlMe2Cl, and AlMe3 afford the compounds (i-Pr3PNSiMe3)AlCl3 (1), (R3PNSiMe3)AlMeCl2 (R = i-Pr, 2; Ph, 3; Cy, 4), (R3PNSiMe3)AlMe2Cl (R = i-Pr, 5; Ph, 6; Cy, 7), and (R3PNSiMe3)AlMe3 (R = i-Pr, 8; Ph, 9; Cy, 10). Reaction of R3PNH (R = t-Bu, Cy, Ph) with AlMe2Cl and AlMe3 afforded (R3PNH)AlMe2Cl (R = Cy, 11; t-Bu, 12) and (Ph3PNH)AlMe3 (13), respectively. The dimeric species [Me2Al(μ-NPt-Bu3)]2 (14) [AlCl2(μ-NPt-Bu3)]2 (15) were derived from reactions of (t-Bu3PNH) and AlMe3 and t-Bu3PNLi and MeAlCl2, respectively. Reaction of the bisphosphinimine salt LiCH(PPh2(NSiMe3))2 (16) with aluminum, gallium, and indium halides yielded [CH(PPh2(NSiMe3))2]MCl2 (M = Al, 17; Ga, 18; In, 19) while the analogous species [CH(PPh2(NSiMe3))2]AlMe2 (20) was prepared via reaction of 16 with Me2AlCl. The compounds [CH(PPh2(NSiMe3))2]MR2 (M = Al, Bz, 21; M = Ga, R = Me, 22; Bz, 23; M = In, R = Me, 24; Bz, 25) were readily prepared by treatment of 17−19 with the appropriate alkylating reagents. The borane B(C6F5)3 reacts stoichiometrically with the adducts 8−10 to give the products [(R3PNSiMe3)AlMe2][MeB(C6F5)3] (R = i-Pr, 26; Ph, 27; Cy, 28) while treatment of 27 with PMe3 affords clean conversion to the salt [(Ph3PNSiMe3)2AlMe(PMe3)][(MeB(C6F5)3)] (29). Similarly, species [Me2Al(μ-NPt-Bu3)2AlMe][MeB(C6F5)3] (30) and [Me2Al(μ-NPt-Bu3)2AlMe(PMe3)][MeB(C6F5)3] (31) were obtained from 14. Attempts to generate the related ionic derivatives from 20−25 yielded unstable mixtures of products. Under mild conditions these group 13 ionic species did not effect the polymerization of ethylene. Crystallographic data are reported for compounds 1, 3, 6, 8, 11, 13−15, 18, and 20.
The role of letters in reviewing research (1994)

unknown referee as any evidence of these could then be referred back to the referee's institution.The bench test of a piece of research is its shelf life: will it still be of interest or relevant in 10 years' time?This test could equally well apply to negative findings.Many important discoveries throughout history have initially been considered to be unacceptable on religious or cultural grounds.As the ultimate peer reviewer is the wider medical audience, the medical referee should perhaps just
Input variable selection for neural networks: application to predicting the U.S. business cycle (2002)

Selecting a "best subset" of input variables is a critical issue in forecasting. This is especially true when the number of available input series is large, and an exhaustive search through all combinations of variables is computationally infeasible. Inclusion of irrelevant variables not only doesn't help prediction, but can reduce forecasting accuracy through added noise or systematic bias. We demonstrate a technique called "sensitivity-based pruning" (SBP) that removes irrelevant input variables from a nonlinear forecasting or regression model. The technique makes use of a saliency measure computed for each input variable and uses estimates of prediction risk for determining the number of input variables to prune. We present preliminary results of the SBP technique applied to neural network predictors of a key business cycle measure, the US Index of Industrial Production.
Glycomimetic drugs--a new source of therapeutic opportunities. (2009)

Carbohydrates are ubiquitous and represent the most abundant class of molecules in nature. All cell surfaces are coated with complex carbohydrates where they act as recognition molecules for other cells, functional molecules, and pathogens. Consequently, they are involved in disease indications as diverse as inflammation, cancer, and infectious disease. In general, native carbohydrates lack the properties necessary for efficacious drugs and historically have not been successful candidates to capitalize on these applications. Understanding the bioactive conformation and molecular interactions of functional carbohydrates, however, allows the rational design of small molecule glycomimetics that exhibit improved drug-like properties such as increased affinity, serum half-life, stability, and bioavailability. Recent advances in analytical techniques (i.e., NMR, x-ray crystallization), molecular modeling, and synthetic organic chemistry allow the design of potent glycomimetic compounds, which opens the door to a new class of therapeutic drugs to target molecular mechanisms that can address many of the current unmet needs in the treatment of disease.
Development and Application of Molecular Markers to Problems in Plant Genetics (1989)

Proceedings of a Cold Spring Harbor Lab. meeting Nov. 1988. Topics addressed include: the use of cytogenetic tools to relate physical and genetics maps, the molecular nature of genetic polymorphism and its relationships to speciation, statistical methods for mapping quantitative trait loci, the natu