gebhart/patrepeval huggingface dataset:
Use of simian virus 40 replication to amplify Epstein-Barr virus shuttle vectors in human cells (1988)

We have increased the copy number of Epstein-Barr virus vectors that also carry the origin of replication of simian virus 40 (SV40) by providing a transient dose of SV40 T antigen. T antigen was supplied in trans by transfection of a nonreplicating plasmid which expresses T antigen into cells carrying Epstein-Barr virus-SV40 vectors. A significant increase in vector copy number occurred over the next few days. We also observed a high frequency of intramolecular recombination when the vector carried a repeat segment in direct orientation, but not when the repeat was in inverted orientation or absent. Furthermore, by following the mutation frequency for a marker on the vector after induction of SV40 replication, it was determined that SV40 replication generates a detectable increase in the deletion frequency but no measurable increase in the frequency of point mutations.
Purification and Properties of Alanine Dehydrogenase from Bacillus sphaericus (1979)

1. The bacterial distribution of alanine dehydrogenase (L-alanine:NAD+ oxidoreductase, deaminating, EC 1.4.1.1) was investigated, and high activity was found in Bacillus species. The enzyme has been purified to homogeneity and crystallized from B. sphaericus (IFO 3525), in which the highest activity occurs. 2. The enzyme has a molecular weight of about 230 000, and is composed of six identical subunits (Mr 38 000). 3. The enzyme acts almost specifically on L-alanine, but shows low amino-acceptor specificity; pyruvate and 2-oxobutyrate are the most preferable substrates, and 2-oxovalerate is also animated. The enzyme requires NAD+ as a cofactor, which cannot be replaced by NADP+. 4. The enzyme is stable over a wide pH range (pH 6.0--10.0), and shows maximum reactivity at approximately pH 10.5 and 9.0 for the deamination and amination reactions, respectively. 5. Alanine dehydrogenase is inhibited significantly by HgCl2, p-chloromercuribenzoate and other metals, but none of purine and pyrimidine bases, nucleosides, nucleotides, flavine compounds and pyridoxal 5'-phosphate influence the activity. 6. The reductive amination proceeds through a sequential ordered ternary-binary mechanism. NADH binds first to the enzyme followed by ammonia and pyruvate, and the products are released in the order of L-ALANINE AND NAD+. The Michaelis constants are as follows: NADH (10 microM), ammonia (28.2 mM), pyruvate (1.7 mM), L-alanine (18.9 mM) and NAD+ (0.23 mM). 7. The pro-R hydrogen at C-4 of the reduced nicotinamide ring of NADH is exclusively transferred to pyruvate; the enzyme is A-stereospecific.
Challenges in rheumatoid arthritis (1999)

Pathogenesis of Rheumatoid disease: 1 Is rheumatic factor relevant? 2 Is apoptosis relevant? 3 Do cytokines have direct involvement in Pathogenesis? 4 Is it a T cell or a B cell disease? 5 Is enzymatic Chondrolysis specific? Disease Progression and Management: 1 Are measures of outcome helpful indicators? 2 The case for early aggressive therapy 3 The case for conservative therapy 4 Does histology or arthroscopy predict outcome? 5 How valuable is imaging? Drug Treatment: 1 Do early systemic steroids prevent disease? 2 Are intra-articular steroids as effective as systemic? 3 Should disease-modifying drugs be used alone or in combination? 4 Does immunotherapy have a role? 5 Is stem cell transplantation ethical and of value? 6 Will there be a role for gene therapy? Benefits and Risks: 1 Do prosthese last longer? Should joints be replaced earlier? 2 Are Occupational therapy and Physiotherapy cost-effective? 3 Is rheumatoid arthritis becoming a milder disease? 4 Should limited funds go to patient care or to research?.
Blood-brain interfaces in vertebrates: a comparative approach (1984)

The neuronal microenvironment in the vertebrate brain is isolated from plasma by a series of selective membranes, including the blood-brain barrier, the choroid plexus, and the meningeal barrier. This review deals with the structure and function of these selective membranes in the different vertebrate classes. Present knowledge indicates that all vertebrates have brain barrier membranes and, further, that functional characteristics of these membranes are basically similar in all the vertebrate classes. The blood-brain barrier (or capillary-glial complex) and the meningeal barrier have many of the properties of a tight epithelium, including the presence of tight junctions and specific transport mechanisms. The choroidal epithelium is a typical secretory epithelium. The functional significance of the specialized membranes located at the blood-brain interface is considered, and we suggest that the phylogenetic development of a blood-brain barrier provided neurons of the vertebrate brain with a unique extracellular milieu optimal both for synaptic communication and for nonsynaptic communication via the entire extracellular space.
Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. (1994)

Familial amyotrophic lateral sclerosis (FALS) has been linked to mutations in the homodimeric enzyme Cu/Zn superoxide dismutase 1 (SOD1). Assay by transient expression in primate cells of six FALS mutant enzymes revealed a continuum of enzymatic activity bounded by the enzyme carrying the mutation Gly-85-->Arg, which was inactive, and mutant enzyme G37R carrying the Gly-37-->Arg change, which retained full specific activity but displayed a 2-fold reduction in polypeptide stability. The G37R mutant displayed similar properties in transformed lymphocytes from an individual heterozygous for the G37R and wild-type SOD1 genes; heterodimeric enzymes composed of mutant and wild-type subunits were detected, but there was no measurable diminution in the stability and activity of the wild-type subunits. Thus, for mutants such as G37R, either surprisingly modest losses in activity (involving only the mutant subunit) can yield motor neuron death, or alternatively, mutant SOD1 may acquire properties that injure motor neurons by one or more mechanisms unrelated to the metabolism of oxygen radicals.
A mitotic kinesin-like protein required for normal karyokinesis, myosin localization to the furrow, and cytokinesis in Dictyostelium (2004)

Dictyostelium mitotic kinesin Kif12 is required for cytokinesis. Myosin II localization to the cleavage furrow is severely depressed in Kif12-null (Deltakif12) cells, which accounts in part for the cytokinesis failure. Myosin II-null cells, however, undergo mitosis-coupled cytokinesis when adhering to a surface, whereas the Deltakif12 cells cannot. During mitosis, the rate of change of internuclear separation in Deltakif12 cells is reduced compared with wild-type cells, indicating multiple roles of this molecular motor during mitosis and cytokinesis. GFP-Kif12, which rescues wild-type behavior when expressed in the Deltakif12 strain, is concentrated in the nucleus in interphase cells, translocates to the cytoplasm at the onset of mitosis, appears in the centrosomes and spindle, and later is concentrated in the spindle midbody. Given these results, we hypothesize a mechanism for myosin II translocation to the furrow to set up the contractile ring.
BMP9 and BMP10 are critical for postnatal retinal vascular remodeling (2012)

ALK1 is a type I receptor of the TGF-β family that is involved in angiogenesis. Circulating BMP9 was identified as a specific ligand for ALK1 inducing vascular quiescence. In this work, we found that blocking BMP9 with a neutralizing antibody in newborn mice significantly increased retinal vascular density. Surprisingly, Bmp9-KO mice did not show any defect in retinal vascularization. However, injection of the extracellular domain of ALK1 impaired retinal vascularization in Bmp9-KO mice, implicating another ligand for ALK1. Interestingly, we detected a high level of circulating BMP10 in WT and Bmp9-KO pups. Further, we found that injection of a neutralizing anti-BMP10 antibody to Bmp9-KO pups reduced retinal vascular expansion and increased vascular density, whereas injection of this antibody to WT pups did not affect the retinal vasculature. These data suggested that BMP9 and BMP10 are important in postnatal vascular remodeling of the retina and that BMP10 can substitute for BMP9. In vitro stimulation of endothelial cells by BMP9 and BMP10 increased the expression of genes involved in the Notch signaling pathway (Jagged1, Dll4, Hey1, Hey2, Hes1) and decreased apelin expression, suggesting a possible cross-talk between these pathways and the BMP pathway.
Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection (2003)

Human immunodeficiency virus type 1 (HIV-1)-associated dementia is a neuroinflammatory brain disorder that is fueled by viral infection and immune activation of brain mononuclear phagocytes (MP; macrophages and microglia). MP serve as a reservoir for persistent viral infection, a vehicle for viral dissemination throughout the brain, and a major source of neurotoxic products that when produced in abundance, affect neuronal function. Such neurotoxic substances secreted by MP lead to clinical neurological impairment (cognitive, behavior, and motor abnormalities), which occurs usually years after the initial viral infection. How HIV-1 evades the immune function characteristic for MP as a first line of defense, including phagocytosis and intracellular killing, is not well understood despite more than two decades of study. In this report, we review the complex role(s) played by MP in the neuropathogenesis of HIV-1 infection. The clinical manifestations, pathology and pathogenesis, and treatment options are discussed in relationship to innate and adaptive immunity. Particular emphasis is given to the diversity of MP functions and how it may affect the disease process and manifestations. New insights into disease mechanisms are provided by advances in enhanced magnetic resonance imaging and proteomics to identify cell movement and genetic profiles of disease. New therapeutic strategies are discussed based on current knowledge of HIV-1-associated dementia pathogenesis.
Synthesis and Antitumor Activity of Fused Quinoline Derivatives. III. Novel N-Glycosylaminoindolo(3,2-b)quinolines. (1992)

Novel indolo[3,2-b]quinolines (1b-k), having a nitro, amino, acetamido, methanesulfonamido, or glycosylamino group at the 2, 7, or 8-position, were prepared and their antitumor activities against P388 leukemia in mice were examined. The 7-galactopyranosylamino derivative (1g) showed the most potent activity (optimal dose = 25 mg/kg, T/C greater than 333%, cure rate 5/6).
rRNA complementarity within mRNAs: A possible basis for mRNA-ribosome interactions and translational control (1998)

Our recent demonstration that many eukaryotic mRNAs contain sequences complementary to rRNA led to the hypothesis that these sequences might mediate specific interactions between mRNAs and ribosomes and thereby affect translation. In the present experiments, the ability of complementary sequences to bind to rRNA was investigated by using photochemical cross-linking. RNA probes with perfect complementarity to 18S or 28S rRNA were shown to cross-link specifically to the corresponding rRNA within intact ribosomal subunits. Similar results were obtained by using probes based on natural mRNA sequences with varying degrees of complementarity to the 18S rRNA. RNase H cleavage localized four such probes to complementary regions of the 18S rRNA. The effects of complementarity on translation were assessed by using the mRNA encoding ribosomal protein S15. This mRNA contains a sequence within its coding region that is complementary to the 18S rRNA at 20 of 22 nucleotides. RNA from an S15-luciferase fusion construct was translated in a cell-free lysate and compared with the translation of four related constructs that were mutated to decrease complementarity to the 18S rRNA. These mutations did not alter the amino acid sequence or the codon bias. A correlation between complementarity and translation was observed; constructs with less complementarity increased the amount of translation up to 54%. These findings raised the possibility that direct base-pairing of particular mRNAs to rRNAs within ribosomes may function as a mechanism of translational control.
Epithelial cell proliferation and islet neogenesis in IFN-g transgenic mice (1993)

We have identified a model system for the study of pancreatic islet development and regeneration in transgenic mice bearing the interferon-gamma (IFN-g) gene expressed in the pancreatic islets. Previous studies showed that the locally produced IFN-g causes lymphocyte infiltration and islet cell destruction. Here we demonstrate that new islet cells are formed continuously from duct cells as evidenced by (1) the dramatic proliferation of duct cells, (2) the appearance of primitive cells and (3) their subsequent differentiation to endocrine cells. The IFN-g induced islet neogenesis is similar to embryonic islet morphogenesis and offers a model system for studying factors modulating islet development. Additionally, the duct cells occasionally transdifferentiate to gastrointestinal-like cell types and hepatocytes. These results underscore the lymphokine's ability to initiate a complex 'transdifferentiation' pathway, providing a window for understanding lineage interrelationships within a terminally differentiated structure.
Massively Parallel Methods for Deep Reinforcement Learning (2015)

We present the first massively distributed architecture for deep reinforcement learning. This architecture uses four main components: parallel actors that generate new behaviour; parallel learners that are trained from stored experience; a distributed neural network to represent the value function or behaviour policy; and a distributed store of experience. We used our architecture to implement the Deep Q-Network algorithm (DQN). Our distributed algorithm was applied to 49 games from Atari 2600 games from the Arcade Learning Environment, using identical hyperparameters. Our performance surpassed non-distributed DQN in 41 of the 49 games and also reduced the wall-time required to achieve these results by an order of magnitude on most games.
Validation of RNA interference in western corn rootworm Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) adults (2011)

This research clearly demonstrates the effect of RNAi on WCR adults that have been exposed to dsRNA by feeding and establishes a tool to screen dsRNAs of potential target genes in adults. This technique may serve as an alternative to target screening of larvae which are difficult to maintain on artificial diets.
Literary Aspects of Urban Culture in Rouen, c.1500-c.1640 (1997)

In the century after 1450, the cities of France experienced a period of prosperity and autonomy, which led to the development of a thriving urban culture.In Rouen, one of France's largest cities, this urban culture was highly developed.This thesis examines Rouen's urban culture and places it in its historical context, with reference to the social, political and religious environment.In the process, the thesis addresses two important questions-the nature of the relationship between popular and high culture within the city, and the relationship between the provincial culture of Rouen and national cultural developments.Before about 1530, Rouen's culture can be described as communal.All of the different forms of cultural activity shared the same basic mentality.With continuing prosperity and new cultural and technological developments, different aspects of Rouen' s cultural life developed in different directions.Rouen' s festive life developed into a thriving popular culture centred around the Abbaye des Conards, which was made up of artisans and merchants.Initially operating fairly freely, it developed a symbiotic relationship with Rouen's Parlement during the religious wars, before declining due to internal and external factors.
Imperatoxin A, a Cell-Penetrating Peptide from Scorpion Venom, as a Probe of Ca2+-Release Channels/Ryanodine Receptors (2010)

Scorpion venoms are rich in ion channel-modifying peptides, which have proven to be invaluable probes of ion channel structure-function relationship. We previously isolated imperatoxin A (IpTxa), a 3.7 kDa peptide activator of Ca(2+)-release channels/ryanodine receptors (RyRs) [1,2,3] and founding member of the calcin family of scorpion peptides. IpTxa folds into a compact, mostly hydrophobic molecule with a cluster of positively-charged, basic residues polarized on one side of the molecule that possibly interacts with the phospholipids of cell membranes. To investigate whether IpTxa permeates external cellular membranes and targets RyRs in vivo, we perfused IpTxa on intact cardiomyocytes while recording field-stimulated intracellular Ca(2+) transients. To further investigate the cell-penetrating capabilities of the toxin, we prepared thiolated, fluorescent derivatives of IpTxa. Biological activity and spectroscopic properties indicate that these derivatives retain high affinity for RyRs and are only 5- to 10-fold less active than native IpTxa. Our results demonstrate that IpTxa is capable of crossing cell membranes to alter the release of Ca(2+)in vivo, and has the capacity to carry a large, membrane-impermeable cargo across the plasma membrane, a finding with exciting implications for novel drug delivery.
Fabrication of Interpenetrating Semilayered Structure of Conducting Polymer and Fullerene by Solvent Corrosion Method and Its Photovoltaic Properties (2005)

Photovoltaic cells with an interpenetrating interface between a conducting polymer layer and a fullerene layer fabricated by a solvent corrosion method have been investigated. Using a weakly dissoluble combination of a solvent and an underlayer film, we fabricated a “semilayered” structure that maintained a bilayer structure and interpenetrated at the interface of the conducting polymer and the fullerene layers. Poly(3-hexylthiophene) (PAT6) or poly(2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV) were used as the conducting polymer layer and C 60 was used as the fullerene layer. In these cells, high external quantum efficiencies (EQEs) were obtained because of efficient exciton dissociations at the interpenetrating interface and efficient carrier transports by each continuous pathway between fullerene molecules of electrons and between conducting polymers of holes. An improvement was achieved by inserting a zinc oxide layer with an appropriate thickness between ITO and fullerene layer. From the comparison between the absorption spectra and the obtained EQE, the ratio of the contribution of each absorption to photocurrent was estimated. The photovoltaic properties were found to be dependent on the solvent used and corrosion time, which have been discussed by taking the form and the degree of corroded interpenetrating interface into consideration.
The biology of fracture healing. An overview for clinicians. Part II. (1989)

Bone healing problems can be divided into: technical failures, when treatment problems have impaired normal biologic potential; biologic failures, when biologic malfunctions have made the correct treatment ineffective; and combinations of the two. Biologic failures include inadequate callus formation or lack of a normal regional acceleratory phenomenon (RAP), normal modeling or remodeling, or maldifferentiation of the healing tissues, plus combinations. The most common biologic failures involve the inability to form callus and/or a normal RAP. When an inadequate RAP combines with inadequate callus production, then chronic infection, nonunion, multiple failed bone grafts and fixation procedures, and even amputation can ensue. Accumulating evidence suggests that most biologic failures stem from problems attributable to mitogens, differentiating and priming agents, growth factors, and other labile biochemical and biophysical messengers and signals in the region of the fracture itself. The ability of bone to heal can differ in different parts of the bony skeleton at a given moment. Until the basic causes of such problems can be corrected, present-day clinicians must manage them by presently available treatments while conducting research that might resolve them. The causes of most biologic failures probably act within the first weeks after the fracture, although it may take months for clinical roentgenograms to show their effects.
Music therapy as procedural support for invasive medical procedures: toward the development of music therapy theory (2011)

In partial response to the demand for evidence-based practice, there is an increasing interest in the use of music therapy as procedural support for both invasive and non-invasive medical procedures. Clinicians and researchers are attempting to define how music therapy functions as procedural support in order to advance clinical practice and research, but concepts remain inadequately specified in the literature. The current philosophical inquiry used qualitative document analysis to critically examine the extant literature in music therapy as procedural support during invasive medical procedures. The aims of the analysis were to identify key concepts, provide definitions of those concepts, and begin to explicate the interrelationships among concepts related to music therapy as procedural support. A total of 19 clinical practice articles, clinical practice book chapters, and research articles met the criteria for inclusion in the analysis. Data analysis and synthesis resulted in a working model of music therapy as procedural support, in which the music therapist engages in a reflexive process of continually assessing the patient's responses in order to refocus the intervention lens (e.g., altering aspects of the music, of focus of attention, and of patient/therapist interaction) to positively influence outcomes. It is hoped that the working model of music therapy as procedural support may stimulate clinical dialogue and serve as an initial systematic step toward theory construction in this area.
Diagnosis of Infectious Bronchitis (IB) by Examination of Tracheal Mucus for IB-Precipitating Antigens (1981)

The use of tracheal exudates for detecting precipitating infectious bronchitis (IB) antigen by the agar-gel precipitin (AGP) technique is described. Of 47 experimentally infected tracheas, 24 gave positive precipitin lines between the second and 12th day postinfection; 9 out of 18 tracheas from birds from natural outbreaks of IB were also positive. Tests can be read within 18-24 hr. For best results, several antisera or an antiserum at various concentrations should be used.
Autoantibodies to tyrosinase (1997)

The appearance of antityrosinase autoantibodies in the serum of patients with metastatic melanoma and diffuse vitiligo is characterized by these two pathologies. The changes in the serum level of these autoantibodies in patients with melanoma after immunization with another antigen (HMW MAA) may have diagnostic and therapeutic implications.
A conversational system for the computer analysis of nucleic acid sequences (1981)

We present a conversational system for the computer analysis of nucleic acid and protein sequences based on the well-known Queen and Korn program (1). The system can be used by persons with only minimal knowledge of computers.
Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis (1997)

Gelsolin depletion occurs in a variety of tissue injury syndromes. Depletion of actin-scavenger capacity in the presence of continued actin release may affect outcome in situations of severe organ damage.
Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response. (2010)

Oblimersen was shown to increase in vitro and in vivo effect of RT on SCLC cell lines. Radiation increases intracellular and intratumoural penetration of ODN. This pre-clinical study argues in favour of clinical development in localised SCLC.