gebhart/patrepeval huggingface dataset:
Activation of peroxisome proliferator-activated receptor α stimulates ADAM10-mediated proteolysis of APP (2015)

Amyloid precursor protein (APP) derivative β-amyloid (Aβ) plays an important role in the pathogenesis of Alzheimer's disease (AD). Sequential proteolysis of APP by β-secretase and γ-secretase generates Aβ. Conversely, the α-secretase "a disintegrin and metalloproteinase" 10 (ADAM10) cleaves APP within the eventual Aβ sequence and precludes Aβ generation. Therefore, up-regulation of ADAM10 represents a plausible therapeutic strategy to combat overproduction of neurotoxic Aβ. Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor that regulates genes involved in fatty acid metabolism. Here, we determined that the Adam10 promoter harbors PPAR response elements; that knockdown of PPARα, but not PPARβ or PPARγ, decreases the expression of Adam10; and that lentiviral overexpression of PPARα restored ADAM10 expression in Ppara(-/-) neurons. Gemfibrozil, an agonist of PPARα, induced the recruitment of PPARα:retinoid x receptor α, but not PPARγ coactivator 1α (PGC1α), to the Adam10 promoter in wild-type mouse hippocampal neurons and shifted APP processing toward the α-secretase, as determined by augmented soluble APPα and decreased Aβ production. Accordingly, Ppara(-/-) mice displayed elevated SDS-stable, endogenous Aβ and Aβ1-42 relative to wild-type littermates, whereas 5XFAD mice null for PPARα (5X/α(-/-)) exhibited greater cerebral Aβ load relative to 5XFAD littermates. These results identify PPARα as an important factor regulating neuronal ADAM10 expression and, thus, α-secretase proteolysis of APP.
Combined Irinotecan and Oxaliplatin in Patients with Advanced Pre-Treated Pancreatic Cancer (2004)

Chemotherapy with irinotecan and oxaliplatin is an active and well-tolerated combination in patients with advanced pre-treated pancreatic cancer.
Stability of Ketamine and Its Metabolites Norketamine and Dehydronorketamine in Human Biological Samples (2001)

Ketamine is a NMDA receptor antagonist used since 1970 for the induction of anesthesia. It has a rapid onset and short duration of action, so it is a preferred agent for short-term surgical procedures. Ketamine possesses sedative and analgesic properties and maintains hemodynamic stability; it therefore is used in patients during the neuro-reanimation period (1). Ketamine produces posthypnotic emergence reactions, such as prolonged hallucination and delirium. The frequency of ketamine abuse is increasing (2), and fatal ketamine poisoning cases have been reported (3)(4).

Ketamine is metabolized by the hepatic microsomal cytochrome P450 enzymes to two major metabolites, norketamine (NK) and dehydronorketamine (DHNK), which are further biotransformed to glucuronide conjugates and then excreted in the urine (5). The activities of these metabolites have not been well studied in humans, but in animals, it was reported that they possess an anesthetic effect and that they might be responsible for the emergent reactions to ketamine anesthesia (5). In view of the growing importance of ketamine, both as a therapeutic agent and more recently as a drug of abuse, we studied the stability of ketamine and its two major metabolites, NK and DHNK, in biological samples under various conditions to optimize the conditions for transport and storage of these biological samples. Little has been reported about the stability of ketamine and its metabolites in human blood samples. In a recent study, ketamine was found to be stable in plasma samples stored at −20 °C for up to 3 months (6). In this study, the stability of ketamine metabolites …
LONG-TERM STUDY OF REACTIONS TO VARIOUS SILICONE BREAST IMPLANTS IN RABBITS (1976)

A long-term study of the fixation and the encapsulation of soft alloplastic implants in rabbits was done-with examination of the capsules at one, 6, 12, and 18 months. No evidence of hematoma, infection, or carcinogenesis was observed. The type of filling in the prosthesis had no demonstrable effect on the encapsulation. The mobility of the prostheses correlated directly with the capsules evoked by plain silicone, perforated silicone-backed, Dacron-backed, and polyurethane-covered prostheses (in order of decreasing mobility). A patch on the base of a given prosthesis did not influence the amount or character of the capsule formed around the remainder of that prosthesis. The results of this study are discussed in the light of past information, to point out the need for further basic research on these problems.
Female Voiding Dysfunction (2008)

Female voiding dysfunction unrelated to childbirth is common but poorly understood, and most often occurs as a result of detrusor hypotonia and less frequently in association with bladder outlet obstruction. Specific causes include anti-incontinence surgery, bladder over-distension, painful infective, allergic or chemical reactions of the urogenital tissues, bladder outlet obstruction, dyssynergia of the bladder-urethral sphincter mechanism, neurogenic, pharmacological, and psychogenic causes. A thorough history and examination is essential in the clinical assessment. It should be followed by investigations including urine microbiology, frequency volume diaries, ultrasound scan, uroflowmetry, and, when indicated, subtracted voiding cystometry, electromyography, and cystourethroscopy. The main treatment modalities are catheterization (self-intermittent, suprapubic, urethral, in order of preference), bladder retraining, biofeedback, and, rarely, surgery or sacral neuromodulation.
Phylogenetic relationships within the family Halobacteriaceae inferred from rpoB′ gene and protein sequences (2007)

In order to clarify the current phylogeny of the haloarchaea, particularly the closely related genera that have been difficult to sort out using 16S rRNA gene sequences, the DNA-dependent RNA polymerase subunit B' gene (rpoB') was used as a complementary molecular marker. Partial sequences of the gene were determined from 16 strains of the family Halobacteriaceae. Comparisons of phylogenetic trees inferred from the gene and protein sequences as well as from corresponding 16S rRNA gene sequences suggested that species of the genera Natrialba, Natronococcus, Halobiforma, Natronobacterium, Natronorubrum, Natrinema/Haloterrigena and Natronolimnobius formed a monophyletic group in all trees. In the RpoB' protein tree, the alkaliphilic species Natrialba chahannaoensis, Natrialba hulunbeirensis and Natrialba magadii formed a tight group, while the neutrophilic species Natrialba asiatica formed a separate group with species of the genera Natronorubrum and Natronolimnobius. Species of the genus Natronorubrum were split into two groups in both the rpoB' gene and protein trees. The most important advantage of the use of the rpoB' gene over the 16S rRNA gene is that sequences of the former are highly conserved amongst species of the family Halobacteriaceae. All sequences determined so far can be aligned unambiguously without any gaps. On the other hand, gaps are necessary at 49 positions in the inner part of the alignment of 16S rRNA gene sequences. The rpoB' gene and protein sequences can be used as an excellent alternative molecular marker in phylogenetic analysis of the Halobacteriaceae.
Atmospheric Dielectric-Barrier Discharges Scalable From 1 mm to 1 m (2008)

Three types of atmospheric dielectric-barrier discharges are presented to illustrate their potential for uniform surface treatment with a length scale spanning from 1 mm to 1 m. As these atmospheric discharges are scaled up in size, it is increasingly difficult to sustain their plasma stability. By using nanosecond images, it is shown that the use of high excitation frequencies is beneficial in achieving excellent uniformity and robust plasma stability, which are both desirable for uniform and reproducible surface treatment.
Supramolecular H-Bonded Assemblies of Redox-Active Metallodendrimers and Positive and Unusual Dendritic Effects on the Recognition of H2PO4- (2003)

The DSM polyamine dendrimers dend-DAB-(NH2)x of generations 1 (x = 4) to 4 (x = 32) form H-bonded dendritic assemblies with the phenol AB3 units p-HOC6H4C(CH2CHCH2)3 and p-HOC6H4C{(CH2)3SiCH2NHCOFc}3 (Fc = ferrocenyl), as shown by the shifts of the NH2 and OH signals giving a concentration-dependent common signal between 2.4 and 4.1 ppm in CDCl3. The supramolecular dendrimers efficiently recognize H2PO4- anions with positive and unusual dendritic effects upon electrochemical titration involving half-stoichiometry for G1, a sudden cyclovoltammetry wave change at the equivalent point, and a dramatic intensity decrease of the new wave.
Changes in Texture and Catalytic Activity of Nanocrystalline MgO during Its Transformation to MgCl2 in the Reaction with 1-Chlorobutane (2001)

The interaction of 1-chlorobutane with nanocrystalline MgO at 200−350 °C has been found to result in both stoichiometric and catalytic dehydrochlorination of 1-chlorobutane to isomers of butene and simultaneous topochemical conversion of MgO to MgCl2. The obtained magnesium chloride appeared to be an active catalyst for the dehydrochlorination reaction, so the rate of 1-chlorobutane conversion grows significantly with time. Changes in the MgO texture during the topochemical reaction are discussed and their effect on the catalytic activity is estimated.
Molecular cloning of the large subunit of transforming growth factor type beta masking protein and expression of the mRNA in various rat tissues. (1990)

Masking protein (MP), which neutralizes the activity of transforming growth factor type beta 1 (TGF-beta 1), is composed of a dimeric N-terminal part of a TGF-beta 1 precursor of Mr 39,000 and an unknown large subunit of Mr 105,000-120,000. The deduced primary structure of the MP large subunit was elucidated by determining the nucleotide sequence of its cDNA. The cDNA encodes a prepro-precursor of 1712 amino acid residues with a calculated Mr of 186,596. The mature large subunit seems to be derived proteolytically from a prepro-precursor and the calculated Mr is 91,606. The precursor has seven N-linked glycosylation sites and an unusual structure containing 18 epidermal growth factor-like domains and four cysteine-rich internal repeats. The large subunit mRNA is synthesized in parallel with the expression of TGF-beta 1 mRNA in various rat tissues.
Construction of Cell-Resistant Surfaces by Immobilization of Poly(ethylene glycol) on Gold (2004)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTConstruction of Cell-Resistant Surfaces by Immobilization of Poly(ethylene glycol) on GoldK. Mougin, M. B. Lawrence, E. J. Fernandez, and A. C. HillierView Author Information Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904, Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, and Department of Chemical Engineering and Department of Chemistry, Iowa State University, Ames, Iowa 50011 Cite this: Langmuir 2004, 20, 10, 4302–4305Publication Date (Web):April 17, 2004Publication History Received19 January 2004Revised7 March 2004Published online17 April 2004Published inissue 1 May 2004https://pubs.acs.org/doi/10.1021/la049824ahttps://doi.org/10.1021/la049824abrief-reportACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views455Altmetric-Citations30LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Adsorption,Alcohols,Cell physiology,Gold,Layers Get e-Alerts
Structural characterization of human interferon gamma Heterogeneity of the carboxyl terminus (1987)

Natural human interferon γ (IFN-γ) was purified from the conditioned medium of peripheral blood leukocytes using selective silica gel adsorption and antibody-affinity chromatography. SDS-PAGE and Western blot analysis demonstrated three major species with molecular masses of 25 kDa, 20 kDa and 17 kDa. Structural analysis of this natural IFN-γ preparation demonstrated a pyroglutamate residue at the amino terminus and a heterogeneous carboxyl terminus. The longest and most predominant polypeptide was 138 amino acids in length, which is five residues shorter than the sequence predicted from the cDNA. The presence of multiple-carboxyl-terminal forms indicated possible proteolytic processing during induction or protein purification. Limited proteolytic digestion of full-length recombinant IFN-γ with endoproteinase Lys-C and trypsin revealed that the carboxyl-terminal 15 residues could be released under conditions in which the core portion of the polypeptide chain remained intact. Thus, the heterogeneity of natural IFN-γ may be explained by partial proteolytic degradation of the molecule and differences in the degree of glycosylation as previously reported [Rinderknecht, E., O'Conner, B. H. & Rodriguez, H. (1984) J. Biol. Chem. 259, 6790–6797].
Inhibition of angiogenesis, tumour growth and metastasis by the NO‐releasing vasodilators, isosorbide mononitrate and dinitrate (1995)

1. The effect of the nitric oxide (NO)-producing nitrovasodilators isosorbide mononitrate (ISMN) and isosorbide dinitrate (ISDN) were assessed on (a) the in vivo model of angiogenesis of the chick chorioallantoic membrane (CAM) and (b) on the growth and metastatic properties of the Lewis Lung carcinoma (LLC) in mice. 2. Isosorbide 5-mononitrate (ISMN) and isosorbide dinitrate (ISDN), inhibited angiogenesis in the CAM dose-dependently. ISMN was more potent in inhibiting this process. Both compounds were capable of completely reversing the angiogenic effect of alpha-thrombin. These effects of ISMN and ISDN on angiogenesis were comparable to those previously observed with sodium nitroprusside which generates NO non-enzymatically. 3. Mice, implanted intramuscularly with LLC, received daily i.p. injections of ISMN for 14 days resulting in a significant decrease in the size of the primary tumour and a reduction in the number and size of metastatic foci in the lungs. ISDN had a similar but less pronounced effect than that observed with ISMN. 4. Addition of ISMN or ISDN to cultures of bovine, rabbit and human endothelial cells and to cultures of LLC cells had no effect on their growth characteristics. 5. These results indicate that ISMN and ISDN inhibit angiogenesis and tumor growth and metastasis in an animal tumour model. The possibility should therefore be considered that these nitrovasodilators which are widely used therapeutically and have well characterized pharmacological profiles, may also possess antitumour properties in the clinic.
The mismatched nucleotides in the 5'-terminal hairpin of minute virus of mice are required for efficient viral DNA replication (1995)

The 5'-terminal sequence in the DNA of the parvovirus minute virus of mice (MVM) is a palindrome. It can form a hairpin, the stem of which is entirely base-paired except for three consecutive unpaired nucleotides which form a bubble. Since this structure is well conserved among different parvoviruses, we examined its importance for viral replication by generating MVM mutants with alterations in this region. A clone of MVMp DNA which contained the entire 3' end and more than half of the 5' palindrome was made. Although it lacked the sequence information to form a wild-type bubble, this DNA was infectious. On transfection into A9 fibroblasts, it gave rise to a virus (MVMs) which had a bubble in its 5' palindrome. The bubble consisted of four mismatched nucleotides in the same location as the unpaired nucleotides of the wild-type palindrome. Apparently, neighboring plasmid sequences were incorporated into the viral DNA, enabling formation of the mismatch. This observation suggested that a bubble is critical for growth of MVM but that its sequence is not. To find out whether MVM lacking a bubble in the 5' palindrome is viable, we made a second clone in which the plasmid sequences incorporated in MVMs were removed. Transfection of this DNA gave rise to a virus (MVMx) in which the nucleotides unpaired in the wild-type hairpin are now fully base-paired. Although MVMx can be propagated, it is defective in comparison with wild-type MVMp; it exhibited about a 50-fold-lower ratio of plaque-forming units to DNA content. In mixed infections, MVMp consistently outgrew the bubbleless MVMx. The rate of accumulation of DNA replication intermediates was lower for MVMx than for the wild-type virus. Quantitative analysis of the 5' termini of replicative form DNA suggested that the ability of MVMx to convert hairpin 5' termini to extended termini is impaired. In contrast, the virus with the altered bubble, MVMs, behaved like the wild-type MVMp in all the assays. We conclude that MVM lacking a bubble in its 5'-terminal DNA hairpin is less infectious than and has a selective disadvantage compared with wild-type MVM. The nucleotide sequence of the bubble is not critical. We provide evidence that the presence of a bubble is necessary for efficient viral DNA replication.
Culture of human epidermal Langerhans cells in a skin equivalent (1998)

Langerhans cells (LCs) have been cultured in a skin equivalent (SE). Seventy-two SEs were produced by inserting skin biopsies from nine subjects into dermal equivalents consisting of fibroblasts in a collagen matrix. The SEs were cultured in a serum-free medium containing 2-mercaptoethanol with or without 5 ng/mL granulocyte-monocyte colony-stimulating factor (GM-CSF). The SEs were cultured for 12 or 15 days. In the latter case, 0, 1 or 10 microg/mL cyclosporin A (CyA) was added for the last 3 days. The SEs were then snap frozen for immunohistochemistry. The migration of LCs was evaluated by measuring the distances from the inserted skin biopsy in the SEs to the HLA-DR + and CD1a+ dendritic cells localized at the longest distance from the biopsy in the epidermal outgrowth on both sides of the biopsy. The density of these cells was estimated in 15-day-old SEs by counting them on both sides of the inserted skin biopsy and dividing the number of positive cells by the migrated distances. All epidermal outgrowths (range 0.6-3.7 mm) were well differentiated and displayed HLA-DR+, CD1a+ and Lag+ dendritic cells. Only occasionally were CD83+ cells observed. In the 15-day-old SEs cultured with GM-CSF, a few CD86+ cells were seen in the epidermal outgrowths and occasionally CD80+ cells. The median (n = 4) density of CD1a+ and HLA-DR+ cells in the epidermal outgrowths at day 15 was 5.2 and 9.1 cells/mm, respectively. GM-CSF did not influence migration in 12-day-old SEs, but there was a tendency to increased migration of HLA-DR+ dendritic cells in 15-day-old SEs. CyA did not affect migration or density. We conclude that LCs can be cultured with an in vivo-like density in a SE. They express the phenotype of immature antigen-presenting cells efficient in capturing and processing antigen. This model may be suitable for studies of the initial phase of contact allergic reactions.
Cyclic AMP promotes the survival of dopaminergic neurons in vitro and protects them from the toxic effects of MPP+. (1995)

We have studied how stimulation of protein kinase C and cAMP-dependent protein kinases affect the development of mesencephalic dopaminergic neurons in vitro. IGF-I and bFGF did not activate either second messenger system nor affect the survival of dopaminergic neurons but stimulated dopamine uptake per neuron. Phorbol esters, which stimulate protein kinase C, had no effect on dopamine uptake. Dibutyryl-cAMP caused an increase in dopamine uptake, which was blocked with (Rp)-cAMPS, a specific inhibitor of cAMP-dependent protein kinases. Treating cells with specific phosphodiesterase type IV inhibitors elevated the forskolin-induced increase in dopamine uptake. Furthermore, cAMP, but neither bFGF nor activation dependent astrocyte factor (ADAF), was able to prevent the degeneration of dopaminergic neurons induced by MPP+. These results suggest that increased intracellular cAMP protects dopaminergic neurons in situations of stress and therefore reveal novel possibilities for the treatment of Parkinson's disease.
Incorporating Network RAM and Flash into Fast Backing Store for Clusters (2011)

We present Nswap2L, a fast backing storage system for general purpose clusters. Nswap2L implements a single device interface on top of multiple heterogeneous physical storage devices, particularly targeting fast random access devices such as Network RAM and flash SSDs. A key design feature of Nswap2L is the separation of the interface from the underlying physical storage, data that are read and written to our ``device" are managed by our underlying system and may be stored in local RAM, remote RAM, flash, local disk or any other cluster-wide storage. Nswap2L chooses which physical device will store data based on cluster resource usage and the characteristics of various storage media. In addition, it migrates data from one physical device to another in response to changes in capacity and to take advantage of the strengths of different types of physical media, such as fast writes over the network and fast reads from flash. Performance results of our prototype implementation of Nswap2L added as a swap device on a 12 node Linux cluster show speed-ups of over 30 times versus swapping to disk and over 1.7 times versus swapping to flash. In addition, we show that for parallel benchmarks, Nswap2L using Network RAM and a flash device that is slower than Network RAM can perform better than Network RAM alone.
Effect of oral glutathione on hepatic glutathione levels in rats and mice (1989)

Administration of oral glutathione (GSH) increases hepatic GSH levels in fasted rats, in mice treated with GSH depletors such as diethyl maleate and in mice treated with high doses of paracetamol. An increase in hepatic GSH levels after administration of oral GSH does not occur in animals treated with buthionine sulphoximine, an inhibitor of GSH synthesis. Administration of oral GSH leads to an increase in the concentration of L-cysteine, a precursor of GSH, in portal blood plasma. Oral administration of L-methionine produced a significant decrease of hepatic ATP in fasted rats, but not in fed rats. Administration of N-acetylcysteine or GSH did not affect the hepatic ATP levels. The results show that the oral intake of GSH is a safe and efficient form of administration of its constituent amino acids in cases when GSH synthesis is required to replete hepatic GSH levels.