gebhart/patrepeval huggingface dataset:
Hepatitis C virus-encoded NS2-3 protease: cleavage-site mutagenesis and requirements for bimolecular cleavage (1995)

Cleavage at the 2/3 site of hepatitis C virus (HCV) is thought to be mediated by a virus-encoded protease composed of the region of the polyprotein encoding NS2 and the N-terminal one-third of NS3. This protease is distinct from the NS3 serine protease, which is responsible for downstream cleavages in the nonstructural region. Site-directed mutagenesis of residues surrounding the 2/3 cleavage site showed that cleavage is remarkably resistant to single-amino-acid substitutions from P5 to P3' (GWRLL decreases API). The only mutations which dramatically inhibited cleavage were the ones most likely to alter the conformation of the region, such as Pro substitutions at the P1 or P1' position, deletion of both amino acids at P1 and P1', or simultaneous substitution of multiple Ala residues. Cotransfection experiments were done to provide additional information on the polypeptide requirements for bimolecular cleavage. Polypeptides used in these experiments contained amino acid substitutions and/or deletions in NS2 and/or the N-terminal one-third of NS3. Polypeptides with defects in either NS2 or the N-terminal portion of NS3 but not both were cleaved when cotransfected with constructs expressing intact versions of the defective region. Cotransfection experiments also showed that certain defective NS2-3 constructs partially inhibited cleavage of wild-type polypeptides. Although these results show that inefficient cleavage can occur in a bimolecular reaction, they suggest that both molecules must contribute a functional subunit to allow formation of a protease which is capable of cleavage at the 2/3 site. This reaction may resemble the cis cleavage thought to occur at the 2/3 site during processing of the wild-type HCV polyprotein.
Neuropsychology of learning disabilities: Essentials of subtype analysis. (1985)

Part I: Introduction. Rourke, Overview of Learning Disability Subtypes. Part II: Theory and Methodology. Adams, Theoretical, Methodological, and Statistical Issues. Fletcher, Satz, Cluster Analysis and the Search for Learning Disability Subtypes. Joschko, Rourke, Neuropsychological Subtypes of Learning-Disabled Children Who Exhibit the ACID Pattern on the WISC. Del Dotto, Rourke, Subtypes of Left-Handed Learning-Disabled Children. Part III: Reading, Spelling, and Arithmetic Disability Subtypes. Doehring, Reading Disability Subtypes: Interactions of Reading and Nonreading Deficits. Sweeney, Rourke, Spelling Disability Subtypes. Strang, Rourke, Arithmetic Disability Subtypes: The Neuropsychological Significance of Specific Arithmetical Impairment in Childhood. Part IV: Validity Studies of Learning Disability Subtypes. Fletcher, External Validation of Learning Disability Typologies. Van der Vlugt, Satz, Subgroups and Subtypes of Learning-Disabled and Normal Children: A Cross-Cultural Replication. Lyon, Educational Validation Studies of Learning Disability Subtypes. Part V: Personality and Socioemotional Dimensions of Learning Disabilities in Children. Porter, Rourke, Socioemotional Functioning of Learning-Disabled Children: A Subtypal Analysis of Personality Patterns. Ozols, Rourke, Dimensions of Social Sensitivity in Two Types of Learning-Disabled Children. Strang, Rourke, Adaptive Behavior of Children Who Exhibit Specific Arithmetic Disabilities and Associated Neuropsychological Abilities and Deficits. Part VI: Summary and Conclusions. Fisk, Finnell, Rourke, Major Findings and Future Directions for Learning Disability Subtype Analyses.
A decapeptide (Gln-Asp-Leu-Thr-Met-Lys-Tyr-Gln-Ile-Phe) from human melanoma is recognized by CTL in melanoma patients. (1994)

The decapeptide 810 (QDLTMKYQIF) contains the antigenic epitope (KYQI) recognized by human mAb L92. This sequence is found in a 43-kDa protein associated with human melanoma M14. We examined the expression of 810 in human cells and its involvement in the cellular immune responses of melanoma patients. Nineteen stage III melanoma patients and 19 normal donors were studied for their responses to 810. All patients were immunized in vivo with an allogeneic melanoma cell vaccine. PBMC cytotoxicity was tested on autologous EBV-transformed B lymphoblastoid cell lines (BCL) pulsed with 810 and autologous melanomas. Proliferative responses of PBMC to 810 were evaluated by using [3H]Tdr incorporation assays. Western blotting revealed that the 43-kDa protein was not specific to melanoma but was common to various cells. However, the percentage of cytotoxicity of PBMC against autologous 810-pulsed BCL was significantly greater in melanoma patients than in normal controls (p < 0.005). Cytotoxicity was increased after melanoma cell vaccine immunization in 15 patients (78%). Proliferative responses to 810 were observed only in melanoma patients and were enhanced in 12 patients (63%) after vaccination. Restimulation of PBMC from vaccinated patients with 810 increased cytotoxicity against both autologous 810-pulsed BCL and melanomas. These targets were lysed by CD8+ T lymphocytes in an HLA class I-restricted manner. HLA-A2 and -A11 seemed to serve as the 810-presenting molecule. Our findings indicate that 810 may function as an epitope for CTL on human melanoma and can be used as a vaccine.
Limitations of Screening for Lung Cancer with Low-Dose Spiral Computed Tomography (2005)

Past lung cancer screening trials in the United States with chest X-ray and sputum cytology were not able to show any decrease in lung cancer mortality; however, these trials are over 20 years old. Recent follow-up of the Mayo Lung Project showed a better survival from lung cancer in the screened arm, but no difference in overall mortality, suggesting an overdiagnosis of nonfatal cancers. Recent reports of low radiation dose spiral computed tomography (CT) chest screening for lung cancer have shown that CT screening detects cancers at a smaller size than chest X-rays. To date, there have been no randomized trials of CT versus observation or chest radiographs for screening purposes. All data available thus far on CT screening are from phase II proof-of-principle trials. The major limitations of CT screening, discussed here, include (a) a high rate of nodule detection: over 50% of participants will have at least one noncalcified nodule; (b) resulting follow-up CT scans, associated with increased costs; (c) cost and morbidity of biopsy or resection of benign noncalcified nodule (20-25% of such procedures in several trials); and (d) a small, but difficult to quantify, risk of cancer associated with multiple follow-up CT scans.
Bone morphogenetic protein-2 exhibits therapeutic benefits for osteonecrosis of the femoral head through induction of cartilage and bone cells (2018)

Osteonecrosis of the femoral head is an orthopedic disease caused by femoral head damage or insufficient blood supply, which leads to the death of bone cells and bone marrow. Osteonecrosis of the femoral head leads to changes in the structure of the femoral head, femoral head collapse and joint dysfunction. Bone morphogenetic protein-2 (BMP-2) exhibits beneficial effects on bone formation, repair and angiogenesis at the femoral head. In the present study, the therapeutic effects of recombinant human BMP-2 containing an Fc fragment (rBMP-2/Fc) were investigated on a steroid induced mouse model of osteonecrosis of the femoral head. Bone cell viability was used to determine the <i>in vitro</i> effects of rBMP-2/Fc. The therapeutic efficacies of rBMP-2/Fc on mice with osteonecrosis of the femoral head were evaluated using clinical arthritis scores. The expression levels of inflammatory factors in the mice were analyzed by reverse transcription-quantitative polymerase chain reaction. Histological analysis was used to evaluate the effects of rBMP-2/Fc on the femoral head. The results revealed that rBMP-2/Fc treatment significantly increased the IL-6, IL-10, vascular endothelial growth factor and macrophage colony-stimulating factor expression levels in synovial cells compared with the control group (P<0.01). Furthermore, it was observed that rBMP-2/Fc significantly improved the viability and growth of synovial cells (P<0.01) through the nuclear factor (NF)-κB signaling pathway. Treatment with rBMP-2/Fc significantly decreased receptor activator of NF-κB ligand expression levels. Furthermore, <i>in vivo</i> experiments demonstrated that rBMP-2/Fc treatment markedly relieved the arthralgia and damage caused by osteonecrosis of the femoral head. In conclusion, rBMP-2/Fc treatment may be beneficial for articular cartilage repair by the upregulation of angiogenesis factors through the down regulation of the NF-κB signaling pathway in mice with osteonecrosis of the femoral head. This preclinical data suggests that rBMP-2/Fc may be a promising novel agent for treatment of osteonecrosis of the femoral head.
A post‐natal decrease in acetylcholine channel open time at rat end‐plates. (1980)

1. The mean channel open time (tau) of ACh receptors in adult developing rat skeletal muscle was estimated by analysis of ACh current fluctuations. 2. At adult end-plates, tau was 1.4 msec at 21 degrees C. Time constants of miniature end-plate current decays (taus) were equally brief. 3. On the other hand, tau and taus were long (4.5 msec, 21 degrees C) at neonatal rat end-plates. These estimates are comparable to values obtained at extrajunctional sites on embryonic rat myotubes grown in culture and on adult denervated muscle fibres. 4. Both tau and taus decreased to values characteristic of adult end-plates during the first 2 weeks after birth. 5. Complex ACh power spectra were obtained at most end-plates during the transition period and at some, miniature synaptic current decays were doubly exponential. End-plates in transition might contain a mixture of slow, neonatal channels and fast, adult channels.
Motility of dendritic spines in visual cortex in vivo : Changes during the critical period and effects of visual deprivation (2003)

Cortical dendritic spines are highly motile postsynaptic structures onto which most excitatory synapses are formed. It has been postulated that spine dynamics might reflect synaptic plasticity of cortical neurons. To test this hypothesis, we have investigated spine dynamics during the critical period in mouse visual cortex in vivo with and without sensory deprivation. The motility of spines on apical dendrites of layer 5 neurons was assayed by time-lapse two-photon microscopy. Spines were motile at the ages examined, postnatal days (P)21-P42, although motility decreased between P21 and P28 and then remained stable through P42. Binocular deprivation from before the time of eye-opening up-regulated spine motility during the peak of the critical period (P28), without affecting average spine length, class distribution, or density. Deprivation at the start of the critical period had no effect on spine motility, whereas continued deprivation through the end of the critical period appeared to reduce spine motility slightly. We conclude that spine motility might be involved in critical-period plasticity and that reduction of activity during the critical period enhances spine dynamics.
Inflammatory Mediators in Uveitis: Differential Induction of Cytokines and Chemokines in Th1- Versus Th2-Mediated Ocular Inflammation (2002)

Ocular inflammation leads to vision loss through the destruction and scarring of delicate tissues along the visual axis. To identify inflammatory mediators involved in this process, we used real time RT-PCR to quantify the expression of mRNA transcripts of 34 cytokines, 26 chemokines, and 14 chemokine receptors at certain time points during T cell-mediated ocular inflammation. We induced disease by adoptive transfer of Ag-specific Th1 or Th2 cells into recipients expressing the target Ag in their eyes. We also compared the mediator expression patterns seen in adoptive transfer-induced inflammation with that seen in mouse eyes developing experimental autoimmune uveoretinitis. In addition, we used laser capture microdissection to examine chemokine mRNA production by both retinal pigment epithelium cells and infiltrating leukocytes in inflamed eyes. Major findings included the following: 1) Three patterns of expression of the inflammation-related molecules were seen in recipients of adoptively transferred Th cells: preferential expression in Th1 recipients, or in Th2 recipients, or similar expression in both recipient groups. 2) In experimental autoimmune uveoretinitis, the inflammatory mediator expression pattern largely paralleled that seen in Th1-induced disease. 3) Both retinal pigment epithelium and infiltrating leukocytes expressed chemokine transcripts in distinct, but overlapping patterns in inflamed eyes. 4) Interestingly, transcripts of multiple cytokines, chemokines, and chemokine receptors were constitutively expressed in high levels in mouse eyes. Seven of these molecules have not been previously associated with the eye. These data underscore the multiplicity of mediators that participate in the pathogenesis of eye inflammation and point to upstream cytokines as potential therapeutic targets.
Enzymology and Evolution of the Pyruvate Pathway to 2-Oxobutyrate in Methanocaldococcus jannaschii (2007)

The archaeon Methanocaldococcus jannaschii uses three different 2-oxoacid elongation pathways, which extend the chain length of precursors in leucine, isoleucine, and coenzyme B biosyntheses. In each of these pathways an aconitase-type hydrolyase catalyzes an hydroxyacid isomerization reaction. The genome sequence of M. jannaschii encodes two homologs of each large and small subunit that forms the hydrolyase, but the genes are not cotranscribed. The genes are more similar to each other than to previously characterized isopropylmalate isomerase or homoaconitase enzyme genes. To identify the functions of these homologs, the four combinations of subunits were heterologously expressed in Escherichia coli, purified, and reconstituted to generate the iron-sulfur center of the holoenzyme. Only the combination of MJ0499 and MJ1277 proteins catalyzed isopropylmalate and citramalate isomerization reactions. This pair also catalyzed hydration half-reactions using citraconate and maleate. Another broad-specificity enzyme, isopropylmalate dehydrogenase (MJ0720), catalyzed the oxidative decarboxylation of beta-isopropylmalate, beta-methylmalate, and d-malate. Combined with these results, phylogenetic analysis suggests that the pyruvate pathway to 2-oxobutyrate (an alternative to threonine dehydratase in isoleucine biosynthesis) evolved several times in bacteria and archaea. The enzymes in the isopropylmalate pathway of leucine biosynthesis facilitated the evolution of 2-oxobutyrate biosynthesis through the introduction of a citramalate synthase, either by gene recruitment or gene duplication and functional divergence.
The behaviour of 9 stored product beetles at pitfall trap arenas and their capture in millet (1993)

Abstract Pitfall trap capture for Sitophilus oryzae (L.), S. zeamais (Motschulsky), S. granarius (L.), Tribolium confusum (Duval), T. castaneum (Herbst); Oryzaephilus surinamensis (L.), Cryptolestes pusillus (Schonherr), Rhyzopertha dominica (Fabr.), and Prostephanus truncatus (Horn) in millet was assessed by visual and time‐lapse video recordings. The behaviour of different beetle species in arenas containing millet was monitored over 24 h and the frequency of encounters with the trap rim resulting in capture recorded. The capture efficiency of four types of pitfall traps (i.e. polystyrene, polythene, glass and tin‐plated steel can) with rims exposed or submerged below the millet surface level were compared. Capture was related to beetle size, locomotory rate, and beetle behaviour at the trap rim as well as trap design and placement. The lighter and smaller species were least captured. Glass jars were more effective than plastic and metal containers. Traps placed with their rims submerged below the grain surface level were more efficient than those with rims exposed. Capture rate was unrelated to trap size. The frequency of encounters with trap rims was not correlated with capture rate. Three types of avoidance behaviours at the trap rims i.e. probing, skirting and spontaneous retreat, were related to capture rate, spontaneous retreat being the most effective escape mechanism and probing least.
Specular reflection cancellation/enhancement in the presence of a phase-conjugate mirror (1987)

Experimental results are presented showing both cancellation and enhancement of the specular reflection off a partially transparent ordinary plane mirror in the presence of a phase-conjugate mirror. The intensities measured lay in the range 6–513% of the original specular reflection, the maximum extent of cancellation occurring for a phase-conjugate reflectivity of unity. Single-domain photorefractive crystals of barium titanate operating by means of degenerate four-wave mixing acted as the phase-conjugate mirrors.
Pathogenesis and treatment of Ph+ leukemia: recent insights from mouse models (2001)

Several methods to model human Ph+ leukemia in laboratory mice are available, including propagation of BCR/ABL-expressing cells in mice, xenotransplantation of primary Ph+ leukemia cells into immunodeficient mice, BCR/ABL transgenic mice, and BCR/ABL retroviral bone marrow transduction and transplantation. Recent studies in these different model systems have yielded important advances in our knowledge of the pathogenesis and therapy of human chronic myeloid leukemia and Ph+ B-lymphoblastic leukemia, and are the subject of this review.
Increased expression of the ETS-related transcription factor FLI-1/ERGB correlates with and can induce the megakaryocytic phenotype. (1996)

The human leukemia cell line K562 can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the megakaryocytic pathway, generating morphological changes and increased expression of lineage-specific surface markers. We report that TPA-treated K562 cells also express higher levels of FLI-1/ERGB, a member of the ETS family of transcription factors. Furthermore, introduction of a retroviral construct expressing human FLI-1/ERGB into K562 cells induces changes similar to those seen following TPA treatment, including increased adherence to the surface of the culture vessel and altered size and morphology. Infected cells exhibit higher levels of the megakaryocyte marker CD41a and, to a lesser extent, CD49b. These markers, as well as virally encoded FLI-1/ERGB-specific RNA and protein, are expressed at the highest levels in the attached cell population, while the growth rate of adherent cells is reduced, and the fraction of cells in G0-G1 is increased. FLI-1/ERGB virus-infected cells also exhibit increased expression of hemoglobin, a marker of erythroid differentiation. Our results suggest FLI-1/ERGB plays a role in controlling differentiation and gene expression along the megakaryocyte/platelet pathway, and further implicate ETS-related genes in the control of multiple developmentally regulated hematopoietic genes.
Observer Variability for Classification of Pulmonary Nodules on Low-Dose CT Images and Its Effect on Nodule Management (2015)

There is moderate inter- and intraobserver agreement for nodule classification by using current recommendations for low-radiation-dose CT examinations of the chest. Discrepancies in nodule categorization were mainly caused by disagreement on the size and presence of a solid component, which may lead to different management in the majority of cases with such discrepancies. (©) RSNA, 2015.
Nasal pH measurement: a reliable and repeatable parameter (1999)

The nasal mucosal pH is approximately 5.5-6.5, and increases in rhinitis to 7.2-8.3. This knowledge has not led to the widespread measurement of the nasal mucosal pH as an objective clinical parameter. The purpose of this study was to assess whether repeatable measures of nasal mucosal pH could be obtained in the clinical setting. Fifty-four adults without nasal symptoms were prospectively recruited. Using a semi-disposable antimony pH catheter, the nasal mucosal pH was measured in four specific areas of the nose and each reading repeated three times. The patients' age, sex, smoking habits, nasal anatomical variation and clearest nostril at the time of measurement were also recorded. The data shows that it is possible to obtain reliable and repeatable values for the pH of the nasal mucosa (Spearman-Brown R = 0.84). Analysis shows there is no significant difference between septal and turbinate mucosal pH. Subset analysis implies that nasal mucosal pH is higher in men then women (P < 0.05). The other variables did not affect the nasal mucosal pH significantly.
Pressure-volume relationship and pressure-induced electronic and structural transformations in Eu and Yb monochalcogenides (1974)

The pressure-volume relationships for EuSe, EuS, YbSe, and YbS have been obtained from high-pressure x-ray-diffraction studies to nearly 300 kbar. Like EuTe, EuSe and EuS exhibit normal compression and undergo the NaCl-to-CsCl-type transition at about 145 and 215 kbar. The compression curves of YbSe and YbS are anomalous in the 150-200-kbar region, which we believe is because of a change in the valence state of Yb from ${2}^{+}$ towards the ${3}^{+}$ state. Among the Eu monochalcogenides EuO is the only substance that shows a valence transformation (\ensuremath{\sim}300 kbar) followed by a NaCl-to-CsCl-type transition (\ensuremath{\sim}400 kbar). However, all the Yb monochalcogenides undergo the valence transformation continuously with pressure. The bulk moduli evaluated from the experimental $P\ensuremath{-}V$ data and the measured pressure coefficients of the energy gap between the $4f$ level and the conduction-band edge from optical-absorption studies of divalent rare-earth monochalcogenides are compared. These data are used to rationalize the occurrence or nonoccurrence of the valence transitions in this series of compounds.
Gene therapy for cystic fibrosis: challenges and future directions. (1995)

The initial concept of human gene therapy was permanent cor- rection of a recessive disease by transplantation of ex vivo manipulated stem cells (1). An early and still important model for this strategy is treatment of severe combined immunodeficiency due to adenosine deaminase deficiency by bone marrow- directed gene therapy (2). The autosomal recessive disease cystic fibrosis (CF)' was subsequently considered a candidate for gene therapy when the gene responsible for the disease was isolated in 1989 (3-5). The wide distribution of possible cellular targets for gene transfer in the CF lung and the absence of a known lung epithelial stem cell suggested that an ex vivo approach to gene therapy would not be feasible (6, 7). Research immediately focused on in vivo approaches for gene transfer that could conveniently be delivered into the airway via aerosols. The ensuing research effort has literally dominated the field of human gene therapy of genetic diseases while establishing the basic principles of in vivo gene delivery. This review summarizes critical scientific issues that have emerged in the develop- ment of in vivo gene therapy for CF using adenoviral vectors as a model.
A better understanding and an improved solution to the specific problems of stereophonic acoustic echo cancellation (1998)

Teleconferencing systems employ acoustic echo cancelers to reduce echoes that result from coupling between the loudspeaker and microphone. To enhance the sound realism, two-channel audio is necessary. However, in this case (stereophonic sound) the acoustic echo cancellation problem is more difficult to solve because of the necessity to uniquely identify two acoustic paths. We explain these problems in detail and give an interesting solution which is much better than previously known solutions. The basic idea is to introduce a small nonlinearity into each channel that has the effect of reducing the interchannel coherence while not being noticeable for speech due to self masking.