gebhart/patrepeval huggingface dataset:
Nucleotide and Predicted Amino Acid Sequence-Based Analysis of the Avian Metapneumovirus Type C Cell Attachment Glycoprotein Gene: Phylogenetic Analysis and Molecular Epidemiology of U.S. Pneumoviruses (2003)

A serologically distinct avian metapneumovirus (aMPV) was isolated in the United States after an outbreak of turkey rhinotracheitis (TRT) in February 1997. The newly recognized U.S. virus was subsequently demonstrated to be genetically distinct from European subtypes and was designated aMPV serotype C (aMPV/C). We have determined the nucleotide sequence of the gene encoding the cell attachment glycoprotein (G) of aMPV/C (Colorado strain and three Minnesota isolates) and predicted amino acid sequence by sequencing cloned cDNAs synthesized from intracellular RNA of aMPV/C-infected cells. The nucleotide sequence comprised 1,321 nucleotides with only one predicted open reading frame encoding a protein of 435 amino acids, with a predicted M(r) of 48,840. The structural characteristics of the predicted G protein of aMPV/C were similar to those of the human respiratory syncytial virus (hRSV) attachment G protein, including two mucin-like regions (heparin-binding domains) flanking both sides of a CX3C chemokine motif present in a conserved hydrophobic pocket. Comparison of the deduced G-protein amino acid sequence of aMPV/C with those of aMPV serotypes A, B, and D, as well as hRSV revealed overall predicted amino acid sequence identities ranging from 4 to 16.5%, suggesting a distant relationship. However, G-protein sequence identities ranged from 72 to 97% when aMPV/C was compared to other members within the aMPV/C subtype or 21% for the recently identified human MPV (hMPV) G protein. Ratios of nonsynonymous to synonymous nucleotide changes were greater than one in the G gene when comparing the more recent Minnesota isolates to the original Colorado isolate. Epidemiologically, this indicates positive selection among U.S. isolates since the first outbreak of TRT in the United States.
Fusogenic selectivity of the envelope glycoprotein is a major determinant of human immunodeficiency virus type 1 tropism for CD4+ T-cell lines vs. primary macrophages. (1995)

We investigated the relationship between the fusion selectivity of the envelope glycoprotein (env) and the tropism of different human immunodeficiency virus type 1 (HIV-1) isolates for CD4+ human T-cell lines vs. primary macrophages. Recombinant vaccinia viruses were prepared encoding the envs from several well-characterized HIV-1 isolates with distinct cytotropisms. Cells expressing the recombinant envs were mixed with various CD4+ partner cell types; cell fusion was monitored by a quantitative reporter gene assay and by syncytia formation. With CD4+ continuous cell lines as partners (T-cell lines, HeLa cells expressing recombinant CD4), efficient fusion occurred with the envs from T-cell line-tropic isolates (IIIB, LAV, SF2, and RF) but not with the envs from macrophage-tropic isolates (JR-FL, SF162, ADA, and Ba-L). The opposite selectivity pattern was observed with primary macrophages as cell partners; stronger fusion occurred with the envs from the macrophage-tropic than from the T-cell line-tropic isolates. All the envs showed fusion activity with peripheral blood mononuclear cells as partners, consistent with the ability of this cell population to support replication of all the corresponding HIV-1 isolates. These fusion selectivities were maintained irrespective of the cell type used to express env, thereby excluding a role for differential host cell modification. We conclude that the intrinsic fusion selectivity of env plays a major role in the tropism of a HIV-1 isolate for infection of CD4+ T-cell lines vs. primary macrophages, presumably by determining the selectivity of virus entry and cell fusion.
DNA Aptamers Selected against the HIV-1 RNase H Display in Vitro Antiviral Activity (2001)

The DNA polymerase of the human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a target widely used to inhibit HIV-1 replication. In contrast, very few inhibitors of the RNase H activity associated with RT have been described, despite the crucial role played by this activity in viral proliferation. DNA ligands with a high affinity for the RNase H domain of HIV-1 RT were isolated by systematic evolution of ligands by an exponential enrichment strategy (SELEX), using recombinant RTs with or without the RNase H domain. The selected oligonucleotides (ODNs) were able to inhibit in vitro the HIV-1 RNase H activity, while no effect was observed on cellular RNase H. We focused our interest on two G-rich inhibitory oligonucleotides. Model studies of the secondary structure of these ODNs strongly suggested that they were able to form G-quartets. In addition to the inhibition of HIV-1 RNase H observed in a cell free system, these ODNs were able to strongly diminish the infectivity of HIV-1 in human infected cells. Oligonucleotides described here may serve as leading compounds for the development of specific inhibitors of this key retroviral enzyme activity.
Localization and Regulation of Thrombopoietin mRNA Expression in Human Kidney, Liver, Bone Marrow, and Spleen Using In Situ Hybridization (1997)

Thrombopoietin (TPO) is the primary hematopoietic growth factor involved in the regulation of platelet production. Although the kidney, liver, bone marrow (BM), and spleen have been identified as the major sources of TPO production, the precise cellular location of TPO mRNA expression in these tissues remains unknown. We have identified the cells expressing TPO mRNA in the human kidney, liver, and BM using an in situ hybridization assay. In the BM of individuals with normal platelet counts, the hybridization signal was too weak to allow identification of the TPO mRNA expressing cells. However, in thrombocytopenic subjects with aplastic anemia, postchemotherapy marrow aplasia, and immune thrombocytopenia, the stromal cells showed strong TPO mRNA expression. In the human subjects with normal platelet counts, the cells of the proximal convoluted tubules of the kidney showed consistent positive staining whereas the signal in the cells of the distal convoluted tubules was less consistent. Strong hybridization signal was also evident in the hepatocytes. The hybridization signal in the spleen, even in thrombocytopenic subjects, was too weak to allow confident identification of the cells expressing TPO mRNA. In all subjects, the interstitial cells and endothelial cells of the liver and spleen, the renal peritubular cells, and the hematopoietic precursor cells of the BM showed no TPO mRNA expression. Our data suggest that TPO mRNA expression in the human BM may be modulated by platelet mass.
Isolation and Characterization of a Disulfide-linked Human Stem Cell Factor Dimer (1996)

Distinct from the noncovalently linked recombinant human stem call factor (rhSCF) dimer, we report here the isolation and identification of an SDS-nondissociable dimer produced during folding/oxidation of rhSCF. Experimental evidence using various cleavage strategies and analyses shows that the isolated dimer is composed of two rhSCF monomers covalently linked by four disulfide bonds. The cysteines are paired as in the noncovalently associated dimer except that all pairings are intermolecular rather than intramolecular. Other structural models, involving intertwining of intramolecular disulfide loops, are ruled out. The molecule behaves similarly to the noncovalently associated dimer during ion-exchange or gel permeation chromatography. However, the disulfide-linked dimer exhibits increased hydrophobicity in reverse-phase columns and in the native state does not undergo spontaneous dimer dissociation-association as seen for the noncovalent dimer. Spectroscopic analyses indicate that the disulfide-linked and noncovalently associated rhSCF dimers have grossly similar secondary and tertiary structures. In vitro, the disulfide-linked dimer exhibits approximately 3-fold higher biological activity in supporting growth of a hematopoietic cell line and stimulating hematopoietic cell colony formation from enriched human CD34+ cells. The molecule binds to the rhSCF receptor, Kit, with an efficiency only half that of the noncovalently associated dimer. Formation of intermolecular disulfides in the disulfide-linked dimer with retention of biological activity has implications for the three-dimensional structure of noncovalently held dimer and disulfide-linked dimer.
A Requirement for Fibroblast Growth Factor in Regulation of Skeletal Muscle Growth and Differentiation Cannot Be Replaced by Activation of Platelet-Derived Growth Factor Signaling Pathways (1995)

The distinct effects of cytokines on cellular growth and differentiation suggest that specific signaling pathways mediate these diverse biological activities. Fibroblast growth factors (FGFs) are well-established inhibitors of skeletal muscle differentiation and may operate via activation of specific signaling pathways distinct from recently identified mitogen signaling pathways. We examined whether platelet-derived growth factor (PDGF)-activated signaling pathways are sufficient to mediate FGF-dependent repression of myogenesis by introducing the PDGF beta receptor into a mouse skeletal muscle cell line. Addition of PDGF-BB to cells expressing the PDGF beta receptor activated the PDGF beta receptor tyrosine kinase, stimulated mitogen-activated protein (MAP) kinase, and increased the steady-state levels of junB and c-fos mRNAs. Despite the activation of these intracellular signaling molecules, PDGF beta receptor activation elicited no detectable effect on cell proliferation or differentiation. In contrast to PDGF-BB, addition of FGF-2 to myoblasts activated signaling pathways that resulted in DNA synthesis and repression of differentiation. Because of the low number of endogenous FGF receptors expressed, FGF-stimulated signaling events, including tyrosine phosphorylation and activation of MAP kinase, could be detected only in cells expressing higher levels of a transfected FGF receptor cDNA. As the PDGF beta receptor- and FGF receptor-stimulated signaling pathways yield different biological responses in these skeletal muscle cells, we hypothesize that FGF-mediated repression of skeletal muscle differentiation activates signaling pathways distinct from those activated by the PDGF beta receptor. Activation of PDGF beta receptor tyrosine kinase activity, stimulation of MAP kinase, and upregulation of immediate-early gene expression are not sufficient to repress skeletal muscle differentiation.
SERCA Structural Dynamics Induced by ATP and Calcium (2004)

We have used time-resolved phosphorescence anisotropy (TPA) to probe rotational dynamics of the rabbit skeletal sarcoplasmic reticulum Ca-ATPase (SERCA), to test the hypothesis, generated from X-ray crystallography, that large-scale structural changes are induced by Ca in this system. Previous TPA studies on SERCA used primarily erythrosin 5'-isothiocyanate (ErITC), which binds to the nucleotide-binding domain and inactivates the enzyme. To investigate rotational dynamics of the active enzyme, we labeled SERCA with erythrosin 5'-iodoacetamide, which binds to the phosphorylation domain and has a minimal effect on the calcium-dependent ATPase activity. In the absence of nucleotide and the presence of calcium, TPA results were similar to those observed previously with ErITC, consistent with the global uniaxial rotation of SERCA monomers and oligomers and small amplitude internal protein dynamics. The removal of Ca had only a slight effect, while the addition of adenosine 5'-triphosphate (ATP) increased the amplitude of internal dynamics and changed the probe's orientation, corresponding to tilting of the phosphorylation domain by at least 20 degrees . Ca partially reversed the ATP effects. A nonhydrolyzable ATP analogue had the same effects as ATP, showing that the observed changes were not dependent on active ion transport. Computational analysis indicates that these ligands affect primarily the internal dynamics of the enzyme, with negligible effects on global dynamics and enzyme association. Melittin, which has been shown to aggregate and inhibit SERCA, eliminated the nucleotide-induced internal dynamics and increased the final anisotropy. We propose that (i) the large Ca-dependent structural changes suggested by SERCA crystallography are more dependent on ATP than on Ca and (ii) aggregation-induced inhibition of SERCA is due to the functional coupling between global and internal protein dynamics.
Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals (1995)

In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.
CKD and Sudden Cardiac Death (2012)

Multiple studies demonstrate a strong independent association between CKD and cardiovascular events including death, heart failure, and myocardial infarction. This review focuses on recent clinical studies that expand this spectrum of adverse cardiovascular events to include ventricular arrhythmias and sudden cardiac death. In addition, experimental models suggest structural remodeling of the heart and electrophysiologic changes in this population. These processes may explain the increased arrhythmic risk in kidney disease and aid in identifying patients who are at higher risk for sudden cardiac death. Finally, we review here the data to support the use of pharmacologic and device-based therapies for both the primary and secondary prevention of sudden cardiac death.
Sound preconditioning therapy inhibits ototoxic hearing loss in mice (2013)

Therapeutic drugs with ototoxic side effects cause significant hearing loss for thousands of patients annually. Two major classes of ototoxic drugs are cisplatin and the aminoglycoside antibiotics, both of which are toxic to mechanosensory hair cells, the receptor cells of the inner ear. A critical need exists for therapies that protect the inner ear without inhibiting the therapeutic efficacy of these drugs. The induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death and hearing loss. We hypothesized that exposure to sound that is titrated to stress the inner ear without causing permanent damage would induce HSPs in the cochlea and inhibit ototoxic drug–induced hearing loss. We developed a sound exposure protocol that induces HSPs without causing permanent hearing loss. We used this protocol in conjunction with a newly developed mouse model of cisplatin ototoxicity and found that preconditioning mouse inner ears with sound has a robust protective effect against cisplatin-induced hearing loss and hair cell death. Sound therapy also provided protection against aminoglycoside-induced hearing loss. These data indicate that sound preconditioning protects against both classes of ototoxic drugs, and they suggest that sound therapy holds promise for preventing hearing loss in patients receiving these drugs.
Severity of coronary atherosclerosis related to lipoprotein concentration. (1978)

The influence of individual lipoproteins on the severity of coronary atherosclerosis was studied in 41 patients undergoing coronary angiography. The extent of athero-sclerosis was quantified by a coronary atherosclerosis score (CAS) based on the number and severity of lesions in eight proximal segments of the coronary circulation. The concentration of high-density lipoprotein (HDL) showed a strong inverse association with CAS, which was independent of the effects of age and other lipoproteins. On multivariate analysis concentrations of other lipids--namely, total plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and the combined effect of LDL cholesterol plus very-low-density lipoprotein triglyceride--showed direct, significant correlations with CAS, but these were weaker than that of HDL. This study shows that concentrations of several circulating lipoproteins are related to the severity of coronary atherosclerosis, HDL having an apparent retarding effect. These findings may partly explain the influence of lipoproteins on the development of clinical coronary heart disease.
Model of accommodation: Contributions of lens geometry and mechanical properties to the development of presbyopia (2010)

The study results suggest that a significant amount of the loss of accommodation is due to changes in lens geometry.
Vagus Nerve Stimulation During Rehabilitative Training Improves Functional Recovery After Intracerebral Hemorrhage (2014)

VNS paired with rehabilitative training confers significantly improved forelimb recovery after ICH compared to rehabilitative training without VNS.
An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance (2009)

The HER2-targeted therapy trastuzumab is widely used for the treatment of patients with metastatic breast tumors overexpressing HER2. However, an objective response is observed in only 12% to 24% of patients treated with trastuzumab as a single agent and initial responders regress in <6 months (1-3). The reason for the clinical failure of trastuzumab in this setting remains unclear. Here we show that local lymph node-positive disease progression in 89% of breast cancer patients with HER2-positive tumors involves the HER2 oncogenic variant HER2Delta16. We further show that ectopic expression of HER2Delta16, but not wild-type HER2, promotes receptor dimerization, cell invasion, and trastuzumab resistance of NIH3T3 and MCF-7 tumor cell lines. The potentiated metastatic and oncogenic properties of HER2Delta16 were mediated through direct coupling of HER2Delta16 to Src kinase. Cotargeting of HER2Delta16 and Src kinase with the single-agent tyrosine kinase inhibitor dasatinib resulted in Src inactivation, destabilization of HER2Delta16, and suppressed tumorigenicity. Activated Src kinase was also observed in 44% of HER2Delta16-expressing breast carcinomas underscoring the potential clinical implications of coupled HER2Delta16 and Src signaling. Our results suggest that HER2Delta16 expression is an important genetic event driving trastuzumab-refractory breast cancer. We propose that successful targeted therapeutics for intervention of aggressive HER2-positive breast cancers will require a strategy to suppress HER2Delta16 oncogenic signaling. One possibility involves a therapeutic strategy employing single-agent tyrosine kinase inhibitors to disengage the functionally coupled oncogenic HER2Delta16 and Src tyrosine kinase pathways.
ASC Simulations of 2014 and 2015 2-shock campaign shots (2016)

We report on 1-D CASSIO 1 simulations of 2-shock capsules fielded by Los Alamos and Livermore from September 2014 through May 2015. These shots are part of a campaign to investigate the effect of various changes in the drive on mix with a simple capsule/hohlraum configuration. These are CH/CD shell capsules about 685 m OR and filled with D 2 or THD gas. We show that we can match the radius and velocity versus time, yield, burn averaged ion temperature, burn width and self emission image size well in 1-D for symmetry capsules. We can match the DT/TT yield ratio, but not the yields of the separated reactant capsules. The latter result suggests that surface imperfections and drive asymmetries that require at least 2-D models will be required for a complete understanding of 2-shock implosions.
DC coefficient restoration in transform image coding (1984)

In a transform coding system, a large number of bits have to be allocated to high-energy DC coefficients for both fine quantisation and good channel error immunity. Three schemes are proposed, in which the DC coefficients are not transmitted, but estimated at the receiver. This allows a reduction in bit rate, as well as the possibility of eliminating the serious effect of channel errors on those coefficients.
P2–194: Presymptomatic longitudinal decline in frontally mediated cognitive skills and memory in cognitively normal late middle aged APOE e4 carriers (2006)

APOE e4 is a major genetic risk factor for Alzheimer's disease (AD). Cross sectional studies suggest that frontally mediated cognitive skills decline with age in cognitively normal APOE e4 carriers more than in noncarriers (Caselli et al 1999; Caselli et al 2001) although longitudinal studies of late middle age APOE e4 carriers under 3 years in duration have failed to confirm this (Caselli et al, 2004). To assess frontally mediated cognitive skills in cognitively normal late middle age APOE e4 carriers and noncarriers who have undergone longitudinal neuropsychological testing for 6 years or more. Cognitively normal individuals age 50–65 years at entry underwent biannual neuropsychological testing for at least 6 years, and linear changes in cognitive skills were correlated with APOE e4 carrier status among those who remained healthy. We excluded anyone at entry, or who during the course of the study period, developed mild cognitive impairment (MCI), AD, any other form of symptomatic cognitive impairment, or anyone with more than 30% decline on any test score even in the absence of symptoms. 35 carriers and 33 noncarriers who completed at least six years of longitudinal neuropsychological assessment did not differ in entry age (56±4.2 years), education (16.3±2.3 years), gender (63% female), or duration of followup (77.8±6.9 months). Carriers performed slightly better on Auditory Verbal Learning Test (AVLT) memory measures at entry (p<0.05 on total learning, short term recall, long term recall, and % recall). Longitudinally, carriers declined significantly more than noncarriers on frontally mediated tests: WAIS–R mental arithmetic (p=0.04), digit symbol substitution (p=0.03), and on a composite Freedom from Distractibility measure (p=0.01) that includes mental arithmetic and digit span. Carriers also declined more on AVLT short term recall (p=0.009). There were no differences or declines in other cognitive domains. Longitudinal observation of late middle aged cognitively normal APOE e4 carriers confirms that in addition to memory, frontally mediated cognitive skills decline significantly more than in noncarriers even in the absence of emerging clinical symptoms or signs of MCI or AD.
rAAV.sFlt-1 Gene Therapy Achieves Lasting Reversal of Retinal Neovascularization in the Absence of a Strong Immune Response to the Viral Vector (2009)

The data support the notion that rAAV.sFlt-1 gene therapy is safe and effective for the long-term inhibition of deleterious blood vessel growth in the eye.