gebhart/patrepeval huggingface dataset:
Mutations spectrum ofGNE in hereditary inclusion body myopathy sparing the quadriceps (2002)

Hereditary Inclusion Body Myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult onset and a typical muscle pathology. We have recently identified the gene encoding for a bifunctional enzyme, UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE), as the mutated gene in the prototype form of the disease presenting quadriceps sparing, particularly common in Middle Eastern Jews. Interestingly, we have identified the homozygous M712T Middle Eastern Jewish mutation also in two unrelated Middle Eastern Moslem families. We have also evaluated the involvement of GNE in several families from worldwide non-Jewish ethnic origins presenting symptoms similar to the Middle Eastern HIBM prototype. A total of 14 GNE mutations were identified (one nonsense and 13 missense), of which six are novel: an homozygous missense mutation in a consanguineous family from Italy and in a non consanguineous family from USA, and distinct compound heterozygotes in families from Germany, Italy, Ireland, Bahamas, USA and East India. This study brings to 17 the number of reported GNE mutations in quadriceps sparing myopathy, occurring either in the epimerase or the kinase domain of the enzyme. The mechanism leading to this unique phenotype still remains to be elucidated. © 2002 Wiley-Liss, Inc.
Comparative value of cyanamid in fertilization of apple trees : soil changes and tree response (1938)

Quantitative determinations for nitrate and ammonia nitrogen content were made on soil samples taken at various depths under mature apple trees growing in sod and fertilized with Cyanamid, ammonium sulfate, and sodium nitrate in the fall and spring.With ~igh moisture conditions the decomposition of Cyanamid was rapid and in a f ew days the ammonia concentration in the soil was almost as high as from fertilization with ammonium sulfate.When no rain fell soon after the Cyanamid was applied, the quantity of available nitrogen in the soil was reduced below that found from the use of the two other materials.This seemed to indicate that a portion of the Cyanamid nitrogen either had been lost or tied up by some biological or physical process.There was a significant and quite similar soil penetration of am-: monia from Cyanamid and ammonium sulfate under optimal weather conditions.Very little variation was observed in rates of nitrification of nitrogen from Cyanamid and sulfate of ammonia, but the rapiq absorption of nitrogen by the trees from these materials indicated that this transformation may not be necessary.If the ammonia content resulting from the application of fertilizers is taken as a measure of the residual effect, then greater soil r etention of nitrogen results from fertilization with ammonium sulfate than from application of Cyanamid.The nitrate form of nitrogen was taken up more r apidly by the trees than the ammonia form , but the ammonia continued to be absorbed over a longer period.Sod was a serious competitor for nitrogen applied in the spring.This was in part responsible for the efficient utilization of nitrate of soda in the fall and the good results obtained from the spring application of Cyanamid, which has a temporary caustic effect on grass.Differences in growth and in nitrogen content of the developing parts of the fertilized trees were small but correlated well with variations in the available nitrogen of the soil.Fall applications of all forms of nitrogen fertilizers used gave equally good, if not better, results than spring applications.There was little difference in growth and nitrogen recovery from the three materials under favorable conditions and, with proper use, Cyanamid was as satisfactory as sulfate of ammonia and nitrate of soda for fertilization of apple trees.
A Formulated TLR7/8 Agonist is a Flexible, Highly Potent and Effective Adjuvant for Pandemic Influenza Vaccines (2017)

Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models. However, many of these agonist molecules have proven difficult to develop clinically. Here, we describe comprehensive adjuvant formulation development of the imidazoquinoline TLR-7/8 agonist 3M-052, in combination with H5N1 hemagglutinin (HA) based antigens. We find that 3M-052 in multiple formulations protects both mice and ferrets from lethal H5N1 homologous virus challenge. Furthermore, we conclusively demonstrate the ability of 3M-052 adjuvant formulations to broaden responses to H5N1 HA based antigens, and show that this broadening is functional using a heterologous lethal virus challenge in ferrets. Given the extensive clinical use of imidazoquinoline TLR agonists for other indications, these studies identify multiple adjuvant formulations which may be rapidly advanced into clinical trials in an H5N1 vaccine.
Statin Therapy-Evidence Beyond Lipid Lowering Contributing to Plaque Stability (2006)

Primarily statin drugs inhibit hepatic 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is responsible for the reduction in circulating low-density lipoprotein (LDL) cholesterol. Several findings from recent research studies indicate that statins have multiple actions that favorably influence key factors involved in the atherogenic process. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL cholesterol reduction or via a direct effect on cellular functions. Such actions may contribute to the early cardiovascular benefit observed in several outcome trials with statin drugs therapy. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. This review summarise the results of the major outcome trials of statins and non-statins therapy and the possible mechanisms beyond lipid lowering contributing to plaque stability.
Immunological Relationship between the Class I Epitope of Streptococcal M Protein and Myosin (1998)

The class I epitope of streptococcal M protein is an epidemiological marker for acute rheumatic fever (ARF)-associated serotypes of group A streptococci and is recognized by anti-M protein monoclonal antibody (MAb) 10B6. Using MAb 10B6, we determined the relationship between the class I epitope of M protein and the alpha-helical coiled-coil protein myosin. MAb 10B6 reacted by enzyme-linked immunosorbent assay and Western blotting with human cardiac myosin and rabbit skeletal myosin and its heavy meromyosin (HMM) subfragment. Overlapping synthetic peptides of M5 protein were used to identify the region of M5 protein recognized by MAb 10B6. Two C repeat peptides (C2A and C3) containing the amino acid sequence KGLRRDLDASREAK reacted with MAb 10B6. Partial sequence identity, RRDL, was found in the HMM fragment of myosin, which reacted with MAb 10B6. However, not all peptides of M5 protein and myosin containing the RRDL sequence reacted with MAb 10B6. ARF sera and sera from uncomplicated pharyngitis (UNC) reacted with C repeat region peptides of M protein, while acute glomerulonephritis sera were not as reactive. Affinity-purified human antibody to peptide C3 reacted with myosin. The data demonstrate that the class I epitope of M protein is immunologically cross-reactive with myosin and the HMM subfragment, and antibodies to peptide C3 and myosin were present in ARF and UNC sera.
Preparation and Enhancement of Thermal Conductivity of Heat Transfer Oil‐Based MoS2 Nanofluids (2013)

The lipophilic MoS 2 nanoparticles are synthesized by surface modification with stearic acid (SA). The heat transfer oil‐based nanofluids, with the mass fraction of lipophilic nanoparticles varying from 0.25% up to 1.0%, are prepared and their thermal conductivity is determined at temperatures ranging from 40 to 200°C using an apparatus based on the laser flash method. It has been found that the nanofluids have higher thermal conductivity and the thermal conductivity enhancement increased not only with increasing mass fraction of nanoparticles, but also with increasing temperature in the range 40–180°C The results show a 38.7% enhancement of the thermal conductivity of MoS 2 nanofluid with only 1.0% mass fraction at 180°C.
Hassles with Taking Out the Garbage: Aggravating Aggresomes (2002)

Diverse human diseases ranging from amyloidosis to neurodegenerative diseases are now recognized as 'conformational diseases' caused by protein misfolding and protein aggregation. Misfolded and aggregated proteins are usually handled in the cell through chaperone-mediated refolding, or when that is impossible, destroyed by proteasomal degradation. Recent evidence suggests that cells might have evolved a third pathway that involves the sequestration of aggregated proteins into specialized 'holding stations' called aggresomes. The aggresomal pathway provides a mechanism by which aggregated proteins form particulate (approximately 200 nm) mini-aggregates that are transported on microtubules (MTs) towards the MT organizing center (MTOC) by a process mediated by the minus-end motor protein dynein. Once at the MTOC, the individual particles pack into a single, usually spherical aggresome (1-3 microm) that surrounds the MTOC. Aggresomes are dynamic: they recruit various chaperones and proteasomes, presumably to aid in the disposal of the aggregated proteins. In addition, the formation of an aggresome is likely to activate the autophagic clearance mechanism that terminates in lysosomal degradation. Hence, the aggresome pathway may provide a novel system to deliver aggregated proteins from the cytoplasm to lysosomes for degradation. Although it is clear that many pathological states correlate with the formation of aggresomes, their causal relationships remain hotly debated. Here, we describe the current state of our knowledge of the aggresome pathway and outline the open questions that provide the focus of current research.
Axotomy-Induced miR-21 Promotes Axon Growth in Adult Dorsal Root Ganglion Neurons (2011)

Following injury, dorsal root ganglion (DRG) neurons undergo transcriptional changes so as to adopt phenotypic changes that promote cell survival and axonal regeneration. Here we used a microarray approach to profile changes in a population of small noncoding RNAs known as microRNAs (miRNAs) in the L4 and L5 DRG following sciatic nerve transection. Results showed that 20 miRNA transcripts displayed a significant change in expression levels, with 8 miRNAs transcripts being altered by more than 1.5-fold. Using quantitative reverse transcription PCR, we demonstrated that one of these miRNAs, miR-21, was upregulated by 7-fold in the DRG at 7 days post-axotomy. In dissociated adult rat DRG neurons lentiviral vector-mediated overexpression of miR-21 promoted neurite outgrowth on a reduced laminin substrate. miR-21 directly downregulated expression of Sprouty2 protein, as confirmed by Western blot analysis and 3' untranslated region (UTR) luciferase assays. Our data show that miR-21 is an axotomy-induced miRNA that enhances axon growth, and suggest that miRNAs are important players in regulating growth pathways following peripheral nerve injury.
Health and human behavior (1993)

Part 1 Methods and issues behavioural epidemiology understanding and changing health behaviours the health care system compliance with medical regimens. Part 2 Life stress stress and coping social support. Part 3 Chronic illnesses pain and arthritis diabetes cardiovascular disease cancer the Acquired Immune Defiency Syndrome (AIDS) injury, violence, and substance abuse. Part 4 Health behaviour and health promotion dietary risk factors and interventions physical activity smoking obesity person factors - personality and demographic influences on health community interventions. Part 5 Summary - for those interested in more information about the field of health psychology.
DOUBLE-BLIND MULTICENTER STUDY COMPARING ALPROSTADIL α-CYCLODEXTRIN WITH MOXISYLYTE CHLORHYDRATE IN PATIENTS WITH CHRONIC ERECTILE DYSFUNCTION (1998)

Alprostadil alpha-cyclodextrin is significantly more effective than moxisylyte chlorhydrate in producing full penile rigidity in office and at home. Injection related side effects occur with the same frequency but moxisylyte results in more systemic side effects and alprostadil results in more painful and prolonged erections. Patients and partners are significantly more satisfied with alprostadil alpha-cyclodextrin.
Next-generation sequencing for cancer diagnostics: a practical perspective. (2011)

Next-generation sequencing (NGS) is arguably one of the most significant technological advances in the biological sciences of the last 30 years. The second generation sequencing platforms have advanced rapidly to the point that several genomes can now be sequenced simultaneously in a single instrument run in under two weeks. Targeted DNA enrichment methods allow even higher genome throughput at a reduced cost per sample. Medical research has embraced the technology and the cancer field is at the forefront of these efforts given the genetic aspects of the disease. World-wide efforts to catalogue mutations in multiple cancer types are underway and this is likely to lead to new discoveries that will be translated to new diagnostic, prognostic and therapeutic targets. NGS is now maturing to the point where it is being considered by many laboratories for routine diagnostic use. The sensitivity, speed and reduced cost per sample make it a highly attractive platform compared to other sequencing modalities. Moreover, as we identify more genetic determinants of cancer there is a greater need to adopt multi-gene assays that can quickly and reliably sequence complete genes from individual patient samples. Whilst widespread and routine use of whole genome sequencing is likely to be a few years away, there are immediate opportunities to implement NGS for clinical use. Here we review the technology, methods and applications that can be immediately considered and some of the challenges that lie ahead.
A novel nozzle for more efficient sperm orientation to improve sorting efficiency of X and Y chromosome-bearing sperm (1998)

Efficient high-resolution detection of DNA for flow cytometric sorting of X and Y chromosome-bearing sperm is dependent on effectively orientating the sperm head to the laser beam in orthogonally configured flow systems. Normally, a beveled needle is required to enlarge the fraction of properly orientated sperm (flat side facing the laser beam). In this report, a modification to a standard jet-in-air nozzle for improved sperm orientation is presented. Inside the modified nozzle (novel nozzle), orientation forces are applied lower in the nozzle than in the current beveled injection needle system. The nozzle was tested with sperm heads from several species. This study shows that use of the nozzle to orientate cattle, swine, rabbit, mouse, and human sperm effectively improves the percentage of sperm that are properly oriented. The percentage of sperm heads oriented by use of the former system (beveled needle) ranges around 30% for most species. With the newly designed nozzle, that percentage ranges around 60%. At least a twofold increase in analysis is achieved. It was found that, unlike results with the beveled needle, the percentage of properly oriented sperm was independent of the sample rate. The introduced nozzle is a significant improvement over the beveled needle system for the analysis and sorting of sperm on the basis of DNA content. In addition to the improvement in sorted sperm production brought about by the novel nozzle when fitted to standard-speed cell sorters, it clearly also has significant potential for improving the efficiency of the Beltsville Sperm Sexing Technology for separating X and Y chromosome-bearing sperm when adapted to high-speed cell-sorting systems.
Simultaneous measurement of position and color of single fluorescent emitters using diffractive optics (2014)

We propose a method for simultaneously measuring the position and emission color of single fluorescent emitters based on the use of a large pitch diffraction grating in the emission light path. The grating produces satellite spots adjacent to the main spot; the relative distance between the spots is a measure for the emission wavelength. We present proof-of-principle experiments on beads and mixtures of quantum dots using a spatial light modulator for making a programmable diffraction grating. A wavelength precision of around 10 nm can be achieved for 1000 signal photons and practical background levels, while maintaining a localization precision of around 10 nm.
In vitrocultivation ofTrypanosoma congolensebloodstream forms in the absence of feeder cell layers (1991)

Bloodstream forms of Trypanosoma congolense (2 clones: ILNat3.1 and IL3000, and 4 stocks: IL2079, IL2466, IL3266 and CP-81) were continuously cultivated in vitro at 34-36 degrees C in the absence of feeder cell layers, using HMI-93 medium which was modified from Iscove's modified Dulbecco's MEM (Flow Laboratories, Irvine, Scotland). The modification was done by supplementing the medium with 0.05 mM bathocuproine sulphonate, 1.5 mM L-cysteine, 0.5 mM hypoxanthine, 0.12 mM 2-mercaptoethanol, 1 mM sodium pyruvate, 0.16 mM thymidine, 20% (v/v) heat-inactivated young goat serum and 5% (v/v) Serum Plus (Hazleton Biologics, Lenaxa, KS, USA). Trypanosomes obtained from two different sources were used to initiate primary cultures: (1) metacyclic forms which were produced in vitro at 27 degrees C, and (2) bloodstream forms obtained from Balb/c mice which had been infected with the bloodstream forms transformed in vitro from the metacyclic forms. Metacyclic forms placed in 25 cm2 T-type (T-25) flasks rapidly attached to the bottom of the flasks and transformed to bloodstream forms during the initial 24 h and continued to proliferate. The bloodstream forms isolated from the infected mouse blood by means of diethylaminoethyl cellulose (DE52) column chromatography also continued to proliferate in the flasks. Cultures were maintained by replacing the medium every 24 h. Every 4-5 days, the attached bloodstream forms were resuspended in fresh medium by gentle pipetting and then were subcultured. The method was further simplified by initiating primary cultures directly with 10 microliters of the tail blood of infected mice in 24-well culture plates and then by subcultivating either in wells or in T-25 flasks. The shortest population doubling time, 9 h, was achieved by seeding subcultures with 10(6) bloodstream forms/ml. The bloodstream forms propagated in this system were morphologically similar to those seen in infected mouse blood, they were covered with a surface coat as examined by electron microscopy and they were infective to mice.
Trifunctional IrIII ppy-type asymmetric phosphorescent emitters with ambipolar features for highly efficient electroluminescent devices (2014)

Simple trifunctional IrIII ppy-type asymmetric phosphorescent emitters with ambipolar character are reported, which afford highly efficient OLEDs.
Erythropoietin regulates endothelial progenitor cells (2003)

Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular reparative processes and neoangiogenesis, and their number in peripheral blood correlates with endothelial function and cardiovascular risk. We tested the hypothesis that the cytokine erythropoietin (EPO) stimulates EPCs in humans. We studied 11 patients with renal anemia and 4 healthy subjects who received standard doses of recombinant human EPO (rhEPO). Treatment with rhEPO caused a significant mobilization of CD34(+)/CD45(+) circulating progenitor cells in peripheral blood (measured by flow cytometry), and increased the number of functionally active EPCs (measured by in vitro assay) in patients (week 2, 312% +/- 31%; week 8, 308% +/- 40%; both P <.01 versus baseline) as well as in healthy subjects (week 8, 194% +/- 15%; P <.05 versus baseline). The effect on EPCs was already observed with an rhEPO dose of about 30 IU/kg per week. Administration of rhEPO increased the number of functionally active EPCs by differentiation in vitro in a dose-dependent manner, assessed in cell culture and by tube formation assay. Furthermore, rhEPO activates the Akt protein kinase pathway in EPCs. Erythropoietin increases the number of functionally active EPCs in humans. Administration of rhEPO or EPO analogs may open new therapeutic strategies in regenerative cardiovascular medicine.
Green's function representations for seismic interferometry (2006)

Abstract The term seismic interferometry refers to the principle of generating new seismic responses by crosscorrelating seismic observations at different receiver locations. The first version of this principle was derived by Claerbout (1968), who showed that the reflection response of a horizontally layered medium can be synthesized from the autocorrelation of its transmission response. For an arbitrary 3D inhomogeneous lossless medium it follows from Rayleigh's reciprocity theorem and the principle of time-reversal invariance that the acoustic Green's function between any two points in the medium can be represented by an integral of crosscorrelations of wavefield observations at those two points. The integral is along sources on an arbitrarily shaped surface enclosing these points. No assumptions are made with respect to the diffusivity of the wavefield. The Rayleigh-Betti reciprocity theorem leads to a similar representation of the elastodynamic Green's function. When a part of the enclosing surface is the earth's free surface, the integral needs only to be evaluated over the remaining part of the closed surface. In practice, not all sources are equally important: The main contributions to the reconstructed Green's function come from sources at stationary points. When the sources emit transient signals, a shaping filter can be applied to correct for the differences in source wavelets. When the sources are uncorrelated noise sources, the representation simplifies to a direct crosscorrelation of wavefield observations at two points, similar as in methods that retrieve Green's functions from diffuse wavefields in disordered media or in finite media with an irregular bounding surface.
The Effect of Inhibitors on Sulphate Reducing Bacteria: a Compilation (1964)

Summary: The effects of about 200 bacteriostatic and bactericidal agents on sulphate reducing bacteria, including some hitherto unpublished results, are tabulated.
Discovery of a Potent and Selective EGFR Inhibitor (AZD9291) of Both Sensitizing and T790M Resistance Mutations That Spares the Wild Type Form of the Receptor (2014)

Epidermal growth factor receptor (EGFR) inhibitors have been used clinically in the treatment of non-small-cell lung cancer (NSCLC) patients harboring sensitizing (or activating) mutations for a number of years. Despite encouraging clinical efficacy with these agents, in many patients resistance develops leading to disease progression. In most cases, this resistance is in the form of the T790M mutation. In addition, EGFR wild type receptor inhibition inherent with these agents can lead to dose limiting toxicities of rash and diarrhea. We describe herein the evolution of an early, mutant selective lead to the clinical candidate AZD9291, an irreversible inhibitor of both EGFR sensitizing (EGFRm+) and T790M resistance mutations with selectivity over the wild type form of the receptor. Following observations of significant tumor inhibition in preclinical models, the clinical candidate was administered clinically to patients with T790M positive EGFR-TKI resistant NSCLC and early efficacy has been observed, accompanied by an encouraging safety profile.