gebhart/patrepeval huggingface dataset:
Development of carcinoid tumors of the glandular stomach and effects of eradication in Helicobacter pylori-infected Mongolian gerbils. (2009)

The relation between Helicobacter pylori (Hp) eradication and prevention of stomach carcinoid development has hitherto remained unclear. We therefore examined this problem using an Hp-infected and Hp-eradicated Mongolian gerbil (MG) model. Enterochromaffin-like (ECL) lesions (hyperplasia/dysplasia and carcinoid) were histopathologically evaluated in the glandular stomachs of Hp-infected and Hp-eradicated MGs. In addition, serum gastrin levels were analyzed. Hp infection induced significant increase in the development of ECL lesions in the glandular stomach, as well as serum gastrin levels as compared with non-infected MGs, while Hp eradication was associated with significant alleviation. The development of ECL lesions in the glandular stomach strongly correlated with titers of anti-Hp antibodies and serum gastrin levels in MGs. In conclusion, Hp infection induces carcinoid development, and Hp eradication prevents its occurrence in the glandular MG stomach, this being strongly linked with reduction in serum gastrin levels.
Optimized Fmoc solid‐phase synthesis of the cysteine‐rich peptide linaclotide (2010)

Linaclotide, a small 14-mer peptide highly rich in cysteines, is currently in phase III clinical trials for the treatment of gastrointestinal disorders. The challenge in the assembly of linaclotide consists of achieving the correct and clean folding of its three disulfide bridges. For this purpose, a number of regioselective, semiregioselective, and random strategies have been studied. In addition to selecting distinct protecting groups for the thiol function, their position in the sequence, the influence of the neighboring protecting groups, as well as the order in which the disulfides fold were studied. Here we describe an optimized solid-phase synthesis of linaclotide that should allow the production of this peptide in multigram amounts.
Urinary Biomarkers Indicative of Apoptosis and Acute Kidney Injury in the Critically Ill (2016)

Our findings do not support that apoptosis detected with CK-18 M30 level would be useful in assessing the development of AKI in the critically ill. Urine HSP or cell-free DNA levels did not differ between AKI and non-AKI patients.
MAZIDAĞ-DERİK (MARDİN) FOSFAT PELOİDLERİNİN SEDİMANTER PETROGRAFİSİ VE KÖKENİ (1989)

Üst Kretase karbonat istifi içerisinde yataklanan Mazıdağ fosfatlarının büyük bölümü, yükselen derin deniz sularının şelf zonunafosfat sağladığı devirlerde depolanmıştır. Bu periyotta çökelen zoo-fitoplanktonca (diyatome) zengin organik çamur, fosfatınesas kaynağını oluşturmuştur. Balık kemiği, dişi ve benzer diğer iskeletsel parçalar da yer yer bu üretime katılmışlardır. Birincilfosfat depolarının bir kısmı oluşumlarından sonra denizaltı akıntıları ile taşınmışlar ve yeniden depolanmışlardır. Bazıları dadeniz tabanı yükselmesi sonucunda karstlaşmaya uğrayarak, fosfat kabuk oluşumuna yol açmışlardır. Bu karmaşık olaylar sonucundatüreyen çeşitli özellikli fosfat taneler arasında peloidler bol miktarda olup, bunlar içerisinde farklı kaynaktan türeme aşağıdakidört tip ayrılmıştır : Yerinde çökelimle,fosfatlaşmış intraklastların, biyoklastların aşınmasiyle ve balık kemiklerinin fosformikritleşmeşineuğraması sonucunda meydana gelenler. Bu peloid tanelerin mikroiç yapılan da farklı olup, bunlar elektron mikroskopisiyardımıyle; (a) amorf; (b) ınikroyumru; (c) yarı kristalli; (d) mikrokristalli; (e) çimentolayıcı tipte beş değişik oluşumtipine ayrılmışlardır.
Transcriptome sequencing, microarray, and proteomic analyses reveal cellular and metabolic impact of hepatitis C virus infection in vitro†‡§ (2010)

RNA-Seq technology, especially when combined with established methods, demonstrated that HCV infection has potentially wide-ranging effects on cellular gene and protein expression. This in vitro study indicates a substantial metabolic impact of HCV infection and highlights new mechanisms of virus-host interaction which may be highly relevant to pathogenesis in vivo.
Mucosal and Systemic Immune Responses in Humans after Primary and Booster Immunizations with Orally Administered Invasive and Noninvasive Live Attenuated Bacteria (1999)

The mucosal and systemic immune responses after primary and booster immunizations with two attenuated live oral vaccine strains derived from a noninvasive (Vibrio cholerae) and an invasive (Salmonella typhi) enteric pathogen were comparatively evaluated. Vaccination with S. typhi Ty21a elicited antibody-secreting cell (ASC) responses specific for S. typhi O9, 12 lipopolysaccharide (LPS), as well as significant increases in levels of immunoglobulin G (IgG) and IgA antibodies to the same antigen in serum. A strong systemic CD4(+) T-helper type 1 cell-mediated immune (CMI) response was also induced. In contrast to results with Ty21a, no evidence of a CMI response was obtained after primary immunization with V. cholerae CVD 103-HgR in spite of the good immunogenicity of the vaccine. Volunteers who received a single dose of CVD 103-HgR primarily developed an IgM ASC response against whole vaccine cells and purified V. cholerae Inaba LPS, and seroconversion of serum vibriocidal antibodies occurred in four of five subjects. Serum IgG anti-cholera toxin antibody titers were of lower magnitude. For both live vaccines, the volunteers still presented significant local immunity 14 months after primary immunization, as revealed by the elevated baseline antibody titers at the time of the booster immunization and the lower ASC, serum IgG, and vibriocidal antibody responses after the booster immunization. These results suggest that local immunity may interfere with colonization of the gut by both vaccine strains at least up to 14 months after basis immunization. Interestingly, despite a low secondary ASC response, Ty21a was able to boost both humoral (anti-LPS systemic IgG and IgA) and CMI responses. Evidence of a CMI response was also observed for one of three volunteers given a cholera vaccine booster dose. The direct comparison of results with two attenuated live oral vaccine strains in human volunteers clearly showed that the capacity of the vaccine strain to colonize specific body compartments conditions the pattern of vaccine-induced immune responses.
Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome (2003)

These findings indicate that those patients who develop IBS post infection exhibit greater IL-1beta mRNA expression, both during and after the infection, compared with individuals who do not develop PI-IBS. We conclude that such patients may be susceptible to inflammatory stimuli, and that inflammation may play a role in the pathogenesis of PI-IBS.
Acoustic Source Localization in Aircraft Interiors Using Microphone Array Technologies (2006)

Using three microphone array configurations at two aircraft body stations on a Boeing 777-300ER flight test, the acoustic radiation characteristics of the sidewall and outboard floor system are investigated by experimental measurement. Analysis of the experimental data is performed using sound intensity calculations for closely spaced microphones, PATCH Inverse Boundary Element Nearfield Acoustic Holography, and Spherical Nearfield Acoustic Holography. Each method is compared assessing strengths and weaknesses, evaluating source identification capability for both broadband and narrowband sources, evaluating sources during transient and steady-state conditions, and quantifying field reconstruction continuity using multiple array positions.
Characterization of mRNA for a Proline-Rich Protein of Cotton Fiber (1995)

Cotton (Gossypium hirsutum L.) mRNA (H6) is expressed predominantly in fiber cells and is present during early primary cell wall formation. However, H6 protein is found to accumulate during later stages, when active secondary cell wall formation occurs, indicating possible regulation at the translational level and function in the secondary cell wall assembly. The nucleotide-derived amino acid sequence of pCK-H6 is proline rich (35 mol %) with a calculated molecular mass of 21 kD. Cotton protein H6 contains a repetitive pentameric motif (17) of alanine (serine)-threonine (serine)-proline-proline-proline. Its amino acid composition and solubility indicate that it may belong to the group of arabinogalactan proteins. Both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (55 kD) and size-exclusion chromatography (77-83 kD) overestimated the size of in vitro synthesized H6 protein compared to the molecular mass derived from the nucleotide sequence (21 kD). The conformation of the molecule determined by its unusual primary structure may be the cause of its anomalous mobility. The presence of a proline-rich, arabinogalactan-type protein in cotton fiber raises the interesting possibility that it may be an integral part of the plasmalemma taking part in the development and architecture of the secondary wall of cotton fiber.
Simple Host−Guest Chemistry To Modulate the Process of Concentration and Crystallization of Membrane Proteins by Detergent Capture in a Microfluidic Device (2008)

This paper utilizes cyclodextrin-based host-guest chemistry in a microfluidic device to modulate the crystallization of membrane proteins and the process of concentration of membrane protein samples. Methyl-beta-cyclodextrin (MBCD) can efficiently capture a wide variety of detergents commonly used for the stabilization of membrane proteins by sequestering detergent monomers. Reaction Center (RC) from Blastochloris viridis was used here as a model system. In the process of concentrating membrane protein samples, MBCD was shown to break up free detergent micelles and prevent them from being concentrated. The addition of an optimal amount of MBCD to the RC sample captured loosely bound detergent from the protein-detergent complex and improved sample homogeneity, as characterized by dynamic light scattering. Using plug-based microfluidics, RC crystals were grown in the presence of MBCD, giving a different morphology and space group than crystals grown without MBCD. The crystal structure of RC crystallized in the presence of MBCD was consistent with the changes in packing and crystal contacts hypothesized for removal of loosely bound detergent. The incorporation of MBCD into a plug-based microfluidic crystallization method allows efficient use of limited membrane protein sample by reducing the amount of protein required and combining sparse matrix screening and optimization in one experiment. The use of MBCD for detergent capture can be expanded to develop cyclodextrin-derived molecules for fine-tuned detergent capture and thus modulate membrane protein crystallization in an even more controllable way.
Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) (2006)

Endothelial cells synthesize and release various factors that regulate angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and permeability. Endothelial dysfunction has been associated with a number of pathophysiological processes. Oxidative stress appears to be a common denominator underlying endothelial dysfunction in cardiovascular diseases. However, depending on the pathology, the vascular bed studied, the stimulant, and additional factors such as age, sex, salt intake, cholesterolemia, glycemia, and hyperhomocysteinemia, the mechanisms underlying the endothelial dysfunction can be markedly different. A reduced bioavailability of nitric oxide (NO), an alteration in the production of prostanoids, including prostacyclin, thromboxane A2, and/or isoprostanes, an impairment of endothelium-dependent hyperpolarization, as well as an increased release of endothelin-1, can individually or in association contribute to endothelial dysfunction. Therapeutic interventions do not necessarily restore a proper endothelial function and, when they do, may improve only part of these variables.
The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice (2008)

Autophagy is the principal cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Recently, autophagy has been implicated in neurodegeneration, but whether it is detrimental or protective remains unclear. Here we report that beclin 1, a protein with a key role in autophagy, was decreased in affected brain regions of patients with Alzheimer disease (AD) early in the disease process. Heterozygous deletion of beclin 1 (Becn1) in mice decreased neuronal autophagy and resulted in neurodegeneration and disruption of lysosomes. In transgenic mice that express human amyloid precursor protein (APP), a model for AD, genetic reduction of Becn1 expression increased intraneuronal amyloid beta (Abeta) accumulation, extracellular Abeta deposition, and neurodegeneration and caused microglial changes and profound neuronal ultrastructural abnormalities. Administration of a lentiviral vector expressing beclin 1 reduced both intracellular and extracellular amyloid pathology in APP transgenic mice. We conclude that beclin 1 deficiency disrupts neuronal autophagy, modulates APP metabolism, and promotes neurodegeneration in mice and that increasing beclin 1 levels may have therapeutic potential in AD.
Phase I Study of Vorinostat in Combination with Temozolomide in Patients with High-Grade Gliomas: North American Brain Tumor Consortium Study 04-03 (2012)

Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway.
The Carotenoid 7, 8‐Dihydro‐ψ end Group can be Cyclized by the Lycopene Cyclases from the Bacterium Erwinia Uredovora and the Higher Plant Capsicum Annuum (1996)

The genes for geranylgeranyl diphosphate synthase (crtE) and phytoene synthase (crtB) from the epiphytic bacterium Erwinia uredovora and the phytoene desaturase gene from the photosynthetic bacterium Rhodobacter capsulatus (Rc-crtI) were introduced into Escherichia coli, which resulted in the accumulation of the acyclic carotenoid, neurosporene. Further introduction of the lycopene cyclase gene from E. uredovora (crtY) or the higher plant Capsicum annuum (Icy) resulted in the production of a bicyclic carotenoid, 7,8-dihydro-beta-carotene, via monocyclic beta-zeacarotene. zeta-Carotene was also found to be cyclized to bicyclic 7,8,7',8'-tetrahydro-beta-carotene by the Erwinia cyclase. These results indicate that both lycopene cyclases can cyclize a 7,8-dihydro-psi end group to a 7,8-dihydro-beta end group, in addition to the usual cyclization of the psi end group to the beta end group. Furthermore, beta-carotene hydroxylase from Erwinia (CrtZ) was able to add a hydroxyl group to the 7,8-dihydro-beta end group and the beta end group.
Predicting molecular interactions and inducible complementarity: Fragment docking of fab‐peptide complexes (1994)

Antibody-antigen interactions are representative of a broad class of receptor-ligand interactions involving both specificity and potential inducible complementarity. To test possible mechanisms of antigen-antibody recognition and specificity computationally, we have used a Metropolis Monte Carlo algorithm to dock fragments of the epitope Glu-Val-Val-Pro-His-Lys-Lys to the X-ray structures of both the free and the complexed Fab of the antibody B13I2 (raised against the C-helix of myohemerythrin). The fragments Pro-His and Val-Pro-His, which contain residues experimentally identified as important for binding, docked correctly to both structures, but all tetrapeptide and larger fragments docked correctly only to the complexed Fab, even when torsional flexibility was added to the ligand. However, only tetrapeptide and larger fragments showed significantly more favorable energies when docked to the complexed Fab coordinates than when docked to either the free Fab or a non-specific site remote from the combining site. Comparison of the free and complexed B13I2 structures revealed that atoms within 5 A of Val-Pro-His showed little movement upon peptide binding, but atoms within 5 A of the other four epitope residues showed greater movements. These results computationally distinguished recognition and binding processes with practical implications for drug design strategies. Overall, this new fragment docking approach establishes distinct roles for the "lock-and-key" (recognition) and the "handshake" (binding) paradigms in antibody-antigen interaction, suggests an incremental approach to incorporating flexibility in computational docking, and identifies critical regions within receptor binding sites for ligand recognition.
On the Decay Behavior of the CO2Absorption Capacity of CaO-Based Sorbents (2004)

To explore the use of a CaO-based sorbent to capture CO2 from flue gases of combustors in multiple absorption/desorption cycles, formulas for the decay behavior of the absorption capacity have been examined and a new simple equation has been proposed. This equation is shown to describe the reported data better and uses only one parameter. By analogy with the deactivation of catalysts by sintering, it is suggested that sintering of the sorbents is the cause of the capacity decay. With the proposed equation, the activities of different sorbents can be compared using the value of a single parameter, which describes the rate of decay of activity.
A 1/4-inch 330 K square pixel progressive scan CMOS active pixel image sensor (1997)

In this paper, three pixel structures have been studied as candidates to realize high density CMOS active pixel sensors. A novel cell structure, the "I-shaped" cell, in which the active regions are formed along a straight line, has been proposed for high-packing density devices. The "I-shaped" cells can realize minimum cell area of 16F/sup 2/, 14F/sup 2/, and 14F/sup 2/ (F: design rule) for three-transistor-type, two-transistor-type, and one-transistor-type pixels, respectively. A 1/4-inch format progressive scan CMOS active pixel sensor with 640 (H)/spl times/480 (V) pixels has been fabricated using a 0.6-/spl mu/m CMOS process. The sensor operates with 5.0 V single power supply, and power consumption is below 30 mW.
Clinical Adrenal Insufficiency in Patients Receiving Megestrol Therapy (1997)

Megestrol therapy was associated with the development of clinical adrenal insufficiency in our patients, as proved by rapid corticotropin test.
Differences in pH-Dependent Activation Rates of Substituted Benzimidazoles and Biological in vitro Correlates (1998)

Gastric proton pump inhibitors (PPIs) are substituted benzimidazole prodrugs that require an acid-induced activation. Its rate depends on the reactivity of the molecule relative to the environmental pH and determines the drug's tissue selectivity. Factors affecting the exposure of moderately acidic tissues to the activated PPI are the area under the serum concentration-time curve (AUC), serum protein binding, the partition coefficient logP and the serum elimination half-life relative to the chemical activation half-life at a critical tissue pH of about 5. These parameters have therefore been determined in a comparative fashion in the present study. The data shows that pantoprazole is less likely to undergo unwanted activation at moderately acidic targets as opposed to the parietal cell, compared to omeprazole. Actually, although 40 mg pantoprazole (steady state) gave a slightly higher serum AUC of the total parent compound than 40 mg omeprazole (10.5 vs. 7.1 micromol x h x l[-1]), a higher serum protein binding of pantoprazole versus omeprazole (98 vs. 96%) reversed the AUC values for the free drug in favor of a lower value for pantoprazole (0.19 vs. 0.28 micromol x h x l[-1]). It is the free parent compound that equilibrates across cell membranes to be activated in acidic tissue compartments. At pH 5.1, the activation half-life of pantoprazole was 4.7 versus 1.4 h for omeprazole, the latter being in the order of the common serum elimination half-life determined in an intraindividual comparison (1.24 vs. 1.25 h). Thus, pantoprazole is eliminated faster from blood than it is activated at a pH of about 5, while omeprazole is as quickly activated at this pH as it is eliminated from blood. Biological in vitro experiments confirmed that pantoprazole displays a lower liability to interfere with unwanted biological targets. This has been demonstrated in vitro for inhibition of both renal Na+/K+-ATPase, lysosomal acidification and the production of reactive oxygen species by neutrophils.
Effect of Temperature and Draw Ratio on Force- Extension Properties of Twisted Fibers1 (1965)

When single fibers are twisted under constant tension before testing, a decrease in strength is observed. This reduction in strength is generally small with fibers having low orientation (low draw ratio) and increases as the draw ratio increases. The difference in the strength resulting from twist is negatively correlated with temperature.
Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse. (1990)

A new water-soluble derivative of camptothecin, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), did not exhibit potent antitumor activity in vitro against experimental tumor cells. The 50% effective doses of CPT-11 against KB and L1210 cells were 1100 and 5500 ng/ml, respectively. These values were markedly higher than those of camptothecin (CPT, 0.98 and 3.7 ng/ml) or 7-ethyl-10-hydroxycamptothecin (SN-38, 0.37 and 3.6 ng/ml). CPT-11 was found to be converted into SN-38 in mouse serum. In vitro incubation of CPT-11 in mouse serum or tissue homogenate enhanced the growth-inhibitory activity much more than that expected from the concentration of CPT-11. This enhancement of the activity coincided with that expected from the SN-38 concentration in incubated serum or homogenate, though the contribution of CPT-11 could not be refuted. SN-38 is considered to play a major role in the antitumor activity when CPT-11 is incubated in serum or homogenate. The plasma CPT-11 concentration decreased biexponentially after i.v. administration of CPT-11 into mice with a biological half-life of 0.8 to 1.1 h. The area under the plasma CPT-11 concentration-time curve showed dose dependency. The SN-38 concentration decreased for the first 30 min after administration and was then maintained for a few hours at about 0.1 microgram/ml after i.v. administration of 20 and 40 mg/kg of CPT-11 followed by the log-linear terminal phase with a half-life of about 2 h which was independent of the dose. It is suggested that the maintenance of plasma SN-38 concentration might be necessary for it to exhibit antitumor activity in vivo.
Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells (2007)

siRNAs targeted to gene promoters can direct epigenetic modifications that result in transcriptional gene silencing in human cells. It is not clear whether the antisense strand of the siRNAs bind directly to DNA or to a sense-stranded RNA transcript corresponding to the known promoter region. We present evidence that an RNA polymerase II expressed mRNA containing an extended 5' untranslated region that overlaps the gene promoter is required for RNA-directed epigenetic modifications and transcriptional silencing of the RNA-targeted promoter. These promoter-associated RNAs were detected by their hybridization to the antisense strand of the complementary promoter-directed siRNA. Antisense phosphorothioate oligodeoxynucleotides were used to degrade the promoter-associated RNA transcripts, the loss of which abrogated the effect of siRNA-mediated transcriptional gene silencing, as well as the complexing of the siRNA with the silent state histone methyl mark and the promoter-associated RNA. These data demonstrate that low-copy promoter-associated RNAs transcribed through RNAPII promoters are recognized by the antisense strand of the siRNA and function as a recognition motif to direct epigenetic silencing complexes to the corresponding targeted promoters to mediate transcriptional silencing in human cells.