gebhart/patrepeval huggingface dataset:
Non-A.beta. Component of Alzheimer's Disease Amyloid (NAC) is Amyloidogenic (1995)

The non-A beta component of Alzheimer's disease (AD) amyloid (NAC) was identified biochemically as the second major component in the amyloid purified from brain tissue of AD patients. NAC, derived from its 140 amino acid long precursor, NACP, is at least 35 amino acids long (NAC35) although its amino terminus is not definitely determined. An antiserum, anti-NAC-X1, was raised against the amino-terminal 9 amino acid sequence of NAC35 and purified on a peptide affinity column. This affinity-purified anti-NAC-X1 antibody immunostained amyloid in AD brain sections and recognized NAC35 but not NACP on Western or dot blot. In aqueous solutions, synthetic NAC35 self-aggregated in a time-, concentration-, and temperature-dependent manner. NAC35 was detected initially as a monomer with a molecular mass of 3500 Da but became aggregated as a function of time into a higher molecular mass component that could not migrate into the gel. The aggregate of NAC35 showed green-gold birefringence after Congo red staining when analyzed under polarized light and fiber-like structure when analyzed ultrastructurally. These results suggest that NAC can form amyloid after it has been cleaved out of its precursor and may be a crucial factor in amyloidosis in the AD brain.
Photo-cross-linking reaction of benzophenone-containing polyimide and its model compounds (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhoto-cross-linking reaction of benzophenone-containing polyimide and its model compoundsHiroyuki Higuchi, Takashi Yamashita, Kazuyuki Horie, and Itaru MitaCite this: Chem. Mater. 1991, 3, 1, 188–194Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/cm00013a038https://doi.org/10.1021/cm00013a038research-articleACS PublicationsRequest reuse permissionsArticle Views1233Altmetric-Citations57LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis (2012)

Development of effective neuroprotective therapies resulting in clinically meaningful results is hampered by several factors in all research stages, both conceptual and methodological. Novel solutions might be offered by evaluation of new targets throughout clinical studies, therapies emerging from drug repositioning approaches, multi-target approaches and network pharmacology.
Interleukin-10 Prevents Glutamate-Mediated Cerebellar Granule Cell Death by Blocking Caspase-3-Like Activity (2001)

Interleukin-10 (IL-10) has been shown to reduce neuronal degeneration after CNS injury. However, the molecular mechanisms underlying the neuroprotective properties of this cytokine are still under investigation. Glutamate exacerbates secondary injury caused by trauma. Thus, we examined whether IL-10 prevents glutamate-mediated cell death. We used rat cerebellar granule cells in culture because these neurons undergo apoptosis upon exposure to toxic concentrations of glutamate (100-500 microm) or NMDA (300 microm). Pretreatment of cerebellar granule cells with IL-10 (1-50 ng/ml) elicited a dose- and time-dependent reduction of glutamate-induced excitotoxicity. Most importantly, IL-10 reduced the number of apoptotic cells when added to the cultures together or 1 hr after glutamate. Using patch-clamping and fluorescence Ca(2+) imaging techniques, we examined whether IL-10 prevents glutamate toxicity by blocking the function of NMDA channel. IL-10 failed to affect NMDA channel properties and to reduce NMDA-mediated rise in intracellular Ca(2+). Thus, this cytokine appears to prevent glutamate toxicity by a mechanism unrelated to a blockade of NMDA receptor function. Various proteases, such as caspase-3, and transcription factors, such as nuclear factor kappaB (NF-kappaB), have been proposed to participate in glutamate-mediated apoptosis. Thus, we examined whether IL-10 modulates the activity of these apoptotic markers. IL-10 blocked both the glutamate-mediated induction of caspase-3 as well as NF-kappaB DNA binding activity, suggesting that the neuroprotective properties of IL-10 may rely on its ability to block the activity of proapoptotic proteins.
Bank Receivership and Conservatorship (1994)

A history of regulatory and statutory responses to failing banks, with special focus on changes since 1987 affecting receiverships, conservatorships, and bridge banks. The author argues that some of these changes, including depositor preference legislation enacted in 1993, have had unintended and still-uncertain consequences.
Response of human artery, vein, and cultured smooth muscle cells to atrial and C-type natriuretic peptides (1996)

These results indicated that human smooth muscle cells in arteries and veins express both forms of natriuretic peptide receptors but that atrial natriuretic peptide acts primarily on the artery and C-type natriuretic peptide acts predominantly on the vein. Increased concentrations of C-type natriuretic peptide could contribute to venous pooling in septic shock.
Nucleotide sequence variation in salmonid alphaviruses from outbreaks of salmon pancreas disease and sleeping disease (2005)

We compared 18 salmonid alphaviruses (SAV) including the reference F93-125 salmon pancreas disease virus (SPDV) and S49p sleeping disease virus (SDV) isolates by nucleotide sequence analyses of regions within the E1, nsP4 and nsP3 genes, and found these to comprise 3 distinct groups, which we have designated Subtypes 1, 2 and 3: Subtype 1, which comprised SAVs with sequences closely similar to the reference SPDV isolate, included SAVs from pancreas disease (PD) outbreaks in farmed salmon in Ireland and Scotland over a 10 yr period; viruses from recent outbreaks of sleeping disease (SD) in freshwater-reared trout farmed in England, Scotland and France were closely similar to and were grouped with the reference SDV isolate in Subtype 2; 3 viruses isolated from PD-affected salmon in Norway were genetically different from viruses belonging to Subtypes 1 and 2 and have been assigned to Subtype 3; 1 virus isolated from PD-affected salmon in the Western Isles, Scotland, in 2003 showed consistent nucleotide sequence differences from SAV Subtypes 1, 2 and 3, but was more closely related to the Subtype 1 SAVs. The occurrence of the different subtype SAVs appeared to have a geographical basis, which may prove useful in future molecular epidemiology studies of SAV-induced disease outbreaks.
Current state and recent advances in biopharmaceutical production in Escherichia coli, yeasts and mammalian cells (2013)

Almost all of the 200 or so approved biopharmaceuticals have been produced in one of three host systems: the bacterium Escherichia coli, yeasts (Saccharomyces cerevisiae, Pichia pastoris) and mammalian cells. We describe the most widely used methods for the expression of recombinant proteins in the cytoplasm or periplasm of E. coli, as well as strategies for secreting the product to the growth medium. Recombinant expression in E. coli influences the cell physiology and triggers a stress response, which has to be considered in process development. Increased expression of a functional protein can be achieved by optimizing the gene, plasmid, host cell, and fermentation process. Relevant properties of two yeast expression systems, S. cerevisiae and P. pastoris, are summarized. Optimization of expression in S. cerevisiae has focused mainly on increasing the secretion, which is otherwise limiting. P. pastoris was recently approved as a host for biopharmaceutical production for the first time. It enables high-level protein production and secretion. Additionally, genetic engineering has resulted in its ability to produce recombinant proteins with humanized glycosylation patterns. Several mammalian cell lines of either rodent or human origin are also used in biopharmaceutical production. Optimization of their expression has focused on clonal selection, interference with epigenetic factors and genetic engineering. Systemic optimization approaches are applied to all cell expression systems. They feature parallel high-throughput techniques, such as DNA microarray, next-generation sequencing and proteomics, and enable simultaneous monitoring of multiple parameters. Systemic approaches, together with technological advances such as disposable bioreactors and microbioreactors, are expected to lead to increased quality and quantity of biopharmaceuticals, as well as to reduced product development times.
High resolution passive facial performance capture (2010)

We introduce a purely passive facial capture approach that uses only an array of video cameras, but requires no template facial geometry, no special makeup or markers, and no active lighting. We obtain initial geometry using multi-view stereo, and then use a novel approach for automatically tracking texture detail across the frames. As a result, we obtain a high-resolution sequence of compatibly triangulated and parameterized meshes. The resulting sequence can be rendered with dynamically captured textures, while also consistently applying texture changes such as virtual makeup.
Expression of P1-450 and P3-450 DNA coding sequences as enzymatically active cytochromes P-450 in mammalian cells. (1987)

Two cDNA clones representing the mRNA coding sequences for mouse cytochromes P1-450 and P3-450 were inserted into the thymidine kinase gene of the wild-type vaccinia virus under the control of the vaccinia virus promoter. Murine and human cells infected with each of the resulting infectious recombinant viruses efficiently expressed their respective P-450 proteins. The newly synthesized protein products are translocated into the microsomes, and their characterization by immunochemical analysis indicates that the sizes of the polypeptides expressed were indistinguishable from their cytochrome P-450 counterparts found in mammalian liver microsomes. Functional analysis of each of the proteins by spectral and enzymatic analysis indicates that the expressed proteins have incorporated heme, and the holoenzymes displayed catalytic activities characteristic of their respective cytochrome P-450 enzymes. Thus, this system can be used to produce properly processed and catalytically active P-450 gene products in a wide variety of cells. The remarkable fidelity of expression and processing of these enzymes suggests that the vaccinia virus recombinants can be used for a wide variety of studies, including analysis of the effects of defined mutations produced in vitro, and directly correlate the structure/activity relationships of the cytochrome P-450 enzymes.
Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma (2011)

Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.
Magnetic tunnel junctions using B2-ordered Co2MnAl Heusler alloy epitaxial electrode (2006)

Magnetic tunnel junctions were fabricated with epitaxially grown Co2MnAl bottom electrodes combined with an Al–O tunnel barrier using a magnetron sputtering system. The epitaxial Co2MnAl electrode had very low surface roughness of 0.2nm and a highly ordered B2 structure. Magnetic tunnel junctions (MTJs) with a stacking structure of epitaxial-Co2MnAl∕Al–O∕CoFe∕IrMn exhibited large tunnel magnetoresistance (TMR) ratios of 65% at room temperature and 83% at 10K. The TMR ratios were larger than those of a MTJ with a Co2MnAl polycrystalline electrode.
An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids (2001)

Hepatic hydroxylation is an essential step in the metabolism and excretion of bile acids and is necessary to avoid pathologic conditions such as cholestasis and liver damage. In this report, we demonstrate that the human xenobiotic receptor SXR (steroid and xenobiotic receptor) and its rodent homolog PXR (pregnane X receptor) serve as functional bile acid receptors in both cultured cells and animals. In particular, the secondary bile acid derivative lithocholic acid (LCA) is highly hepatotoxic and, as we show here, a metabolic substrate for CYP3A hydroxylation. By using combinations of knockout and transgenic animals, we show that activation of SXR/PXR is necessary and sufficient to both induce CYP3A enzymes and confer resistance to toxicity by LCA, as well as other xenotoxicants such as tribromoethanol and zoxazolamine. Therefore, we establish SXR and PXR as bile acid receptors and a role for the xenobiotic response in the detoxification of bile acids.
Applied Discriminant Analysis. (1995)

Partial table of contents: Discriminant Analysis in Research. PREDICTION. Basic Ideas of Classification. Multivariate Normal Rules. Classification Results. Hit Rate Estimation. Nonnormal Rules. Reporting Results of a PDA. Applications of PDA. DESCRIPTION. Group Separation. Assessing Effects. Describing Effects. Selecting and Ordering Variables. Reporting Results of a DDA. Applications of DDA. ISSUES AND PROBLEMS. Special Problems. Appendices. Answers to Exercises. References. Index.
Comparison of multivariate calibration methods for quantitative spectral analysis (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComparison of multivariate calibration methods for quantitative spectral analysisEdward V. Thomas and David M. HaalandCite this: Anal. Chem. 1990, 62, 10, 1091–1099Publication Date (Print):May 15, 1990Publication History Published online1 May 2002Published inissue 15 May 1990https://pubs.acs.org/doi/10.1021/ac00209a024https://doi.org/10.1021/ac00209a024research-articleACS PublicationsRequest reuse permissionsArticle Views1486Altmetric-Citations386LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Genetic Correction of Tauopathy Phenotypes in Neurons Derived from Human Induced Pluripotent Stem Cells (2013)

Tauopathies represent a group of neurodegenerative disorders characterized by the accumulation of pathological TAU protein in brains. We report a human neuronal model of tauopathy derived from induced pluripotent stem cells (iPSCs) carrying a TAU-A152T mutation. Using zinc-finger nuclease-mediated gene editing, we generated two isogenic iPSC lines: one with the mutation corrected, and another with the homozygous mutation engineered. The A152T mutation increased TAU fragmentation and phosphorylation, leading to neurodegeneration and especially axonal degeneration. These cellular phenotypes were consistent with those observed in a patient with TAU-A152T. Upon mutation correction, normal neuronal and axonal morphologies were restored, accompanied by decreases in TAU fragmentation and phosphorylation, whereas the severity of tauopathy was intensified in neurons with the homozygous mutation. These isogenic TAU-iPSC lines represent a critical advancement toward the accurate modeling and mechanistic study of tauopathies with human neurons and will be invaluable for drug-screening efforts and future cell-based therapies.
The Relationship Between Proliferating Cell Nuclear Antigen (PCNA), Nuclear DNA Content and Mutant p53 During Genesis of Cervical Carcinoma (1995)

Proliferating cell nuclear antigen (PCNA), nuclear DNA content and mutant p53 overexpression were studied by means of image cytometry and immunohistochemistry respectively in normal mucosa (n = 10), in mild (n = 16), moderate (n = 9) and severe (n = 17) atypical lesions, as well as in squamous cell carcinomas (n = 36) of the cervix uteri. The results show that increasing histopathological atypia in the cervical mucosa was correlated to an initial increase of PCNA followed by distinct aneuploidy and p53 overexpression. The data are suggested to contribute to a better understanding of the genesis of cervical carcinoma, and to indicate that the coexistence of both distinct aneuploidy and p53 immunoreactivity can be used to decide if a cell population is neoplastic, whereas the absence of p53 overexpression does not necessarily exclude neoplasia. This diagnostic procedure can be suggested to improve early detection of intraepithelial squamous neoplasia.
Clinical Evaluation of a Noninvasive Alarm System for Nocturnal Hypoglycemia (2010)

The prototype HypoMon shows potential as an adjunct method for noninvasive overnight monitoring for hypoglycemia events in young people with T1DM.
Potent Inhibitors of Secretory Phospholipase A2:  Synthesis and Inhibitory Activities of Indolizine and Indene Derivatives (1996)

Phospholipase A2 is an enzyme which hydrolyzes the sn-2 position of certain cellular phospholipids. The liberated lysophospholipid and arachidonic acid are precursors in the biosynthesis of various biologically active products. As human nonpancreatic sPLA2 is present in high levels in the blood of patients in several pathological conditions, the potent sPLA2 inhibitors have been suggested to be useful drugs. Here we describe the synthesis, structure-activity relationship, and inhibitory activities of indolizine and indene derivatives. 1-(Carbamoylmethyl)indolizine derivatives and 1-oxamoylindolizine derivatives exhibited very potent inhibitory activity. The former was unstable to air oxidation, but the latter exhibited an improvement both in stability and in potency. Some compounds approached the stoichiometric limit of the chromogenic assay.
Epoxidation of an unsaturated tertiary amine. Application to the synthesis of two pirprofen metabolites (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEpoxidation of an unsaturated tertiary amine. Application to the synthesis of two pirprofen metabolitesNaba K. Chaudhuri and Thomas J. BallCite this: J. Org. Chem. 1982, 47, 26, 5196–5198Publication Date (Print):December 1, 1982Publication History Published online1 May 2002Published inissue 1 December 1982https://pubs.acs.org/doi/10.1021/jo00147a032https://doi.org/10.1021/jo00147a032research-articleACS PublicationsRequest reuse permissionsArticle Views169Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
P450cin Active Site Water: Implications for Substrate Binding and Solvent Accessibility (2013)

In P450cin, Tyr81, Asp241, Asn242, two water molecules, and the substrate participate in a complex H-bonded network. The role of this H-bonded network in substrate binding and catalysis has been probed by crystallography, spectroscopy, kinetics, isothermal titration calorimetry (ITC), and molecular dynamics. For the Y81F mutant, the substrate binds about 20-fold more weakly and Vmax decreases by about 30% in comparison to WT. The enhanced susceptibility of the heme to H₂O₂-mediated destruction in Y81F suggests that this mutant favors the open, low-spin conformational state. Asn242 H-bonds directly with the substrate, and replacing this residue with Ala results in water taking the place of the missing Asn side chain. This mutant exhibits a 70% decrease in activity. Crystal structures and molecular dynamics simulations of substrate-bound complexes show that the solvent has more ready access to the active site, especially for the N242A mutant. This accounts for about a 64% uncoupling of electron transfer from substrate hydroxylation. These data indicate the importance of the interconnected water network on substrate binding and on the open/closed conformational equilibrium, which are both critically important for maintaining high-coupling efficiency.