gebhart/patrepeval huggingface dataset:
P4‐073: A PHARMACOGENETICS‐SUPPORTED CLINICAL TRIAL TO DELAY ONSET OF MILD COGNITIVE IMPAIRMENT DUE TO ALZHEIMER'S DISEASE USING LOW‐DOSE PIOGLITAZONE: AN UPDATE ON THE TOMORROW STUDY (2014)

The increasing number of individuals at risk for developing late onset Alzheimer's disease (LOAD) has shifted attention from treatment to delaying symptom onset. Research is focusing on early intervention in the AD cognitive decline continuum. Length variation of a polyT tract (rs10524523) in the TOMM40 gene has been associated with LOAD age of onset. TOMM40 is adjacent to, and in linkage disequilibrium with, the APOE gene. A biomarker risk assignment algorithm (BRAA) will identify individuals at high risk for developing mild cognitive impairment (MCI) due to AD in the next 5 years. The BRAA incorporates an individual's age and TOMM40 and APOE genotypes. TOMMORROW will simultaneously qualify a BRAA for assigning 5-year risk for developing MCI due to AD and evaluate the efficacy of low-dose pioglitazone to delay onset of MCI due to AD in cognitively normal, high-risk individuals.Low - risk subjects will be assigned to placebo; high-risk subjects will be evenly randomized to either low-dose pioglitazone or placebo. The study will enroll approximately 5800 subjects (ages 65- 83) and will apply operationalized criteria for MCI due to AD, a primary endpoint event. The anticipated treatment period is 4 years, ending when a target number (410 in the high - risk group) of primary endpoint diagnoses have been reached. Along with the Clinical Dementia Rating scale, key assessments that enable the diagnosis are 12 neuropsychological measures representing 5 key cognitive domains affected in early AD. A separate neuropsychological instrument validation strategy will ensure that the test measures perform consistently across cultures and languages.Approximately 50 sites in 7 countries will participate. The study was initiated in summer 2013 in the US and in the EU and Australia in late 2013/early 2014. To date, over 1,000 subjects have been screened and over 160 subjects randomized. The study was designed with input from international experts and finalized following discussions with US and EU regulatory authorities. It represents a unique opportunity to qualify the BRAA to stratify risk of developing MCI due to AD in the next 5 years and to explore therapeutic intervention in the earliest phase of the AD continuum.
Automated Color Classification of Single Wheat Kernels Using Visible and Near‐Infrared Reflectance (1998)

ABSTRACT Modification of an existing single kernel wheat characterization system allowed collection of visible and near‐infrared (NIR) reflectance spectra (450–1,688 nm) at a rate of 1 kernel/4 sec. The spectral information was used to classify red and white wheats in an attempt to remove subjectivity from class determinations. Calibration, validation, and prediction results showed that calibrations using partial least squares regression and derived from the full wavelength profile correctly classed more kernels than either the visible region (450–700 nm) or the NIR region (700–1,688 nm). Most results showed &gt;99% correct classification for single kernels when using the visible and NIR regions. Averaging of single kernel classifications resulted in 100% correct classification of bulk samples.
Compensation of nonlinear phase shifts with third-order dispersion in short-pulse fiber amplifiers (2005)

We show that nonlinear phase shifts and third-order dispersion can compensate each other in short-pulse fiber amplifiers. This compen-sation can be exploited in any implementation of chirped-pulse amplification, with stretching and compression accomplished with diffraction gratings, single-mode fiber, microstructure fiber, fiber Bragg gratings, etc. In particular, we consider chirped-pulse fiber amplifiers at wavelengths for which the fiber dispersion is normal. The nonlinear phase shift accumulated in the amplifier can be compensated by the third-order dispersion of the combination of a fiber stretcher and grating compressor. A numerical model is used to predict the compensation, and experimental results that exhibit the main features of the calculations are presented. In the presence of third-order dispersion, an optimal nonlinear phase shift reduces the pulse duration, and enhances the peak power and pulse contrast compared to the pulse produced in linear propagation. Contrary to common belief, fiber stretchers can perform as well or better than grating stretchers in fiber amplifiers, while offering the major practical advantages of a waveguide medium.
Genetic polymorphism of the α2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans (1995)

It is likely that a number of independent heritable traits, each encoded by a singular gene, contribute to pathologic elevations in blood pressure in humans. Genetic polymorphisms of individual genes may result in intermediate phenotypes which, by themselves, do not raise blood pressure, but, coupled with environmental or epistatic forces, contribute to the prevalence of human hypertension. The gene for the alpha 2-adrenergic receptor encoded by chromosome 10 (C10 A2AR) is polymorphic, and Southern blotting with a cDNA probe following restriction enzyme digest of this gene results in fragments of either 6.3 kb or 6.7 kb in size. We reported an association between homozygosity for the 6.3 kb allele and hypertension in blacks. Blacks with hypertension also have an increased risk for thrombotic stroke, increased baroreceptor sensitivity, and decreased sodium excretion. We noted that the C10 A2AR, which modulates norepinephrine release in blood-pressure-regulating regions of the brain, is also expressed on platelets and in the kidney. We postulated that functional changes associated with the C10 A2AR gene polymorphism could be responsible for increased baroreceptor sensitivity, epinephrine-mediated platelet aggregation, and decreased sodium excretion in some individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of Gastric Secretion by Omeprazole and Efficiency of Calcium Carbonate on the Control of Hyperphosphatemia in Patients on Chronic Hemodialysis (1998)

Contradictions exist in the literature regarding the effect of gastric secretion inhibition on phosphate absorption. In healthy controls, omeprazole would decrease the hyperphosphatemia or the hyperphosphaturia induced by an acute phosphate load, suggesting an inhibition of phosphate absorption. In chronic hemodialysis patients, gastric hypersecretion is associated with hyperphosphatemia, but inhibition of gastric hypersecretion by ranitidine in those receiving calcium carbonate (CaCO3) as a phosphate binder would paradoxically exacerbate their hyperphosphatemia. Because of these conflicting observations, we performed an open crossover study on 16 chronic stable hemodialyzed patients with a daily mean intake of 9.4+/-4 g of CaCO3, and we compared the plasmatic predialysis levels of phosphate, calcium, protides, bicarbonates, intact parathyroid hormone (PTH), urea, and creatininemia during 2 successive periods of 2 months, the first one without omeprazole and the second one with 20 mg omeprazole intake in the morning. Phosphatemia increased with omeprazole but not significantly from 1.80+/-0.38 to 1.89+/-0.42 mM whereas corrected calcemia decreased significantly (p = 0.04) from 2.41+/-0.18 to 2.36+/-0.16 mM as did bicarbonatemia from 26.7+/-3.5 to 25.7+/-3.1 mM (p < 0.05). No change in creatininemia or in blood urea was observed, suggesting the stable efficiency of dialysis as well as the stable intakes of protein and therefore of phosphate during the two study periods. In conclusion, inhibition of gastric secretion by omeprazole increases the plasmatic phosphate predialytic level but in a nonsignificant way. This increase may be explained by a slight but significant concomitant decrease of calcemia and bicarbonatemia. These results do not support the phosphate binding efficiency of CaCO3 being decreased by the inhibition of gastric acid secretion.
Intramolecular ene reactions. 7. Asymmetric induction in intramolecular ene reactions of chiral 1,7-dienes: a diastereo- and enantioselective synthesis of substituted cyclohexanes (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular ene reactions. 7. Asymmetric induction in intramolecular ene reactions of chiral 1,7-dienes: a diastereo- and enantioselective synthesis of substituted cyclohexanesLutz F. Tietze, Uwe Beifuss, and Michael RutherCite this: J. Org. Chem. 1989, 54, 13, 3120–3129Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/jo00274a031https://doi.org/10.1021/jo00274a031research-articleACS PublicationsRequest reuse permissionsArticle Views1082Altmetric-Citations47LEARN 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
The relationship between gastric acid secretion and gastric H+,K+-ATPase activity. (1985)

The H+,K+-ATPase has been postulated to be the enzyme responsible for H+ secretion by the parietal cell. Omeprazole has been shown to be an inhibitor of acid secretion in vivo, but also in in vitro test models for acid secretion, including partly purified H+,K+-ATPase, the inhibitory action of omeprazole has been demonstrated (Wallmark, B., Jaresten, B. M., Larsson, H., Ryberg, B., Brändström, A., and Fellenius, E. (1983) Am. J. Physiol. 245, G64-G71). It was thus possible to use this compound to demonstrate a correlation between H+,K+-ATPase activity in rat oxyntic mucosa and in vivo H+ secretion. Two results were found. (a) Increasing oral doses of omeprazole progressively inhibited acid secretion, H+,K+-ATPase activity, and phosphoenzyme formation of a microsomal fraction isolated from the inhibited rat mucosa. Furthermore, a Mg2+-stimulated ATPase activity, associated with the H+,K+-ATPase membrane fraction, was not affected by the omeprazole treatment. (b) Recovery of H+,K+-ATPase activity following complete omeprazole inhibition was correlated with the appearance of acid secretion. The results indicate a strict relationship between the activity of the gastric H+,K+-ATPase in the microsomal fraction and gastric acid secretion.
Personality Changes in Alzheimer's Disease (1992)

We profiled personality changes that were measured cross-sectionally on the Blessed Dementia Scale in 80 patients with Alzheimer's disease who were examined at a dementia clinic. The most common personality changes were diminished initiative/growing apathy (61.3%), relinquishment of hobbies (55.0%), and increased rigidity (41.3%). The least frequent personality change was sexual misdemeanor (3.8%). Discriminant function analysis showed that the Global Deterioration Scale, the Clinical Rating Scale for Symptoms of Psychosis in Alzheimer's Disease, and the duration of dementia symptoms were the best predictors to classify personality change in an overall score of personality. However, cognitive impairment, as measured by the Blessed Memory-Information-Concentration Test and Mini-Mental State Examination, was not a good predictor of overall personality change. Personality and behavioral changes are common in Alzheimer's disease and may not be attributed entirely to intellectual impairment.
A Comparison of Current Graph Database Models (2012)

The limitations of traditional databases, in particular the relational model, to cover the requirements of current applications has lead the development of new database technologies. Among them, the Graph Databases are calling the attention of the database community because in trendy projects where a database is needed, the extraction of worthy information relies on processing the graph-like structure of the data. In this paper we present a systematic comparison of current graph database models. Our review includes general features (for data storing and querying), data modeling features (i.e., data structures, query languages, and integrity constraints), and the support for essential graph queries.
Cramming More Components Onto Integrated Circuits (1998)

The future of integrated electronics is the future of electronics itself. The advantages of integration will bring about a proliferation of electronics, pushing this science into many new areas. Integrated circuits will lead to such wonders as home computers—or at least terminals connected to a central computer—automatic controls for automobiles, and personal portable communications equipment. The electronic wristwatch needs only a display to be feasible today. But the biggest potential lies in the production of large systems. In telephone communications, integrated circuits in digital filters will separate channels on multiplex equipment. Integrated circuits will also switch telephone circuits and perform data processing. Computers will be more powerful, and will be organized in completely different ways. For example, memories built of integrated electronics may be distributed throughout the machine instead of being concentrated in a central unit. In addition, the improved reliability made possible by integrated circuits will allow the construction of larger processing units. Machines similar to those in existence today will be built at lower costs and with faster turnaround.
Constitutive Insulin-like Growth Factor-II Expression Interferes with the Enterocyte-like Differentiation of CaCo-2 Cells (1996)

In this study we have examined the role of insulin-like growth factor-II (IGF-II) in the differentiation of the CaCo-2 human colon carcinoma cell line. We have shown previously that IGF-II is an autocrine growth factor for CaCo-2 cells. IGF-II expression is high in proliferating, undifferentiated CaCo-2 cells and markedly decreases when cells become confluent and start to differentiate. To evaluate whether differentiation of CaCo-2 cells depends on an IGF-II related pathway, we treated cells with a blocking antibody to the IGF-I receptor that mediates most IGF-II biological effects. Treatment of preconfluent CaCo-2 cells with this antibody decreased by 40% autonomous cell proliferation and induced differentiation as shown by an increase in sucrase isomaltase activity and apolipoprotein A-I (apoA-I) mRNA levels. To examine the significance of autocrine IGF-II production in CaCo-2 cell differentiation, we generated stable CaCo-2 cell lines that constitutively express rat IGF-II under the control of a Rous sarcoma virus promoter. Sustained expression of IGF-II resulted in: (a) increased proliferative rate; (b) high IGF-I receptor number, even after reaching confluence; (c) increased capability of anchorage-independent growth; (d) inhibition of the expression of apoA-I and SI mRNAs. Analysis of several independent IGF-II-transfected clones showed an inverse correlation between IGF-II mRNA levels and expression of the differentiation markers, the cells expressing the higher levels of the transfected IGF-II being the less differentiated ones. Our data suggest that perturbation of IGF-II-mediated cell proliferation interferes with the enterocyte-like differentiation pathway of CaCo-2 cells.
Chlamydomonas IFT88 and Its Mouse Homologue, Polycystic Kidney Disease Gene Tg737, Are Required for Assembly of Cilia and Flagella (2000)

Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. We cloned and sequenced a Chlamydomonas cDNA encoding the IFT88 subunit of the IFT particle and identified a Chlamydomonas insertional mutant that is missing this gene. The phenotype of this mutant is normal except for the complete absence of flagella. IFT88 is homologous to mouse and human genes called Tg737. Mice with defects in Tg737 die shortly after birth from polycystic kidney disease. We show that the primary cilia in the kidney of Tg737 mutant mice are shorter than normal. This indicates that IFT is important for primary cilia assembly in mammals. It is likely that primary cilia have an important function in the kidney and that defects in their assembly can lead to polycystic kidney disease.
Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib) (1997)

A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3-(trifluoromethyl)- H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.
A packed bed Ammonia Fiber Expansion reactor system for pretreatment of agricultural residues at regional depots (2012)

Background: Pretreatment of biomass at regional depots could simplify supply logistics for the emerging biofuels industry. Ammonia Fiber Expansion (AFEX™) could be an appropriate pretreatment method for use at depots, if the process can be simplified. Here we investigate pretreatment of corn stover and wheat straw using a simple packed bed AFEX system that exploits the high porosity of biomass to facilitate ammonia transport. Results & discussion: Steam stripping vertical packed beds allowed recovery of more than 90% residual ammonia as substantially dry vapor. AFEX-treated biomass gave enzyme hydrolysis yields equal to biomass treated in stirred batch reactors, and formed durable pellets. Conclusion: Packed bed AFEX shows significant promise as a biomass pretreatment for use at distributed depots.
Attenuation of sn-1,2-diacylglycerol second messengers by diacylglycerol kinase. Inhibition by diacylglycerol analogs in vitro and in human platelets. (1986)

Diacylglycerol kinase is though to play a central role in the metabolism of diacylglycerol second messengers in agonist-stimulated cells. A series of diacylglycerol analogs were tested for their ability to act as substrates or inhibitors of diacylglycerol kinase with the goal of determining the substrate specificity of the enzyme, and of discovering inhibitors. Screening of these compounds was performed using a partially purified diacylglycerol kinase from pig brain. Modified assays for this enzyme using co-sonicated mixtures of diacylglycerol and anionic phospholipids were developed. This enzyme was found to be quite specific for sn-1,2-diacylglycerol (KM 24 microM for dioctanoyl-glycerol). Among the analogs investigated, only 1,2-dioctanoyl-2-amino-1,3-propanediol was utilized at a significant rate. Two analogs, dioctanoylethylene glycol (KI 58 microM) and 1-monooleoylglycerol (KI 91 microM), were potent inhibitors in vitro. These compounds were tested for effects on diacylglycerol formation and metabolism in thrombin-stimulated human platelets. Dioctanoylethylene glycol inhibited diacylglycerol phosphorylation in platelets (70-100% at 100 microM) leading to a longer-lived diacylglycerol signal. This compound may be a useful tool for studies of diacylglycerol kinase in other cell types. 1-Monooleoylglycerol treatment elevated diacylglycerol levels up to 4-fold in unstimulated platelets and up to 10-fold in thrombin-stimulated platelets. The implications with regard to the pathways of diacylglycerol metabolism in human platelets are discussed.
5-Aza-2'-deoxycytidine is chemopreventive in a 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone-induced primary mouse lung tumor model (1999)

Carcinogenesis is a multistep process in which many alterations in both genetic and epigenetic controls lead to a growth advantage for neoplastic cells. Hypermethylation has been established as the basis of genomic imprinting, but recent studies have also shown that alterations in genomic methylation patterns may contribute to tumorigenesis. The chemical 5-aza-2'-deoxycytidine (5-aza-dC) has been used both in vitro and in vivo to inhibit DNA methylation. In this study, we investigated the chemopreventive efficacy of 5-aza-dC in a well-established primary mouse lung tumor model. Five-week-old male (C3H/HeJ x A/J) F1 hybrid mice were treated for 24 consecutive weeks with 5-aza-dC, three times per week i.p. Lung tumors were induced with two consecutive weekly doses of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone starting 1 week after initial treatment with 5-aza-dC. We demonstrated that 5-aza-dC exhibits a chemopreventive effect in this primary mouse lung tumor model which, like human lung adenocarcinomas, harbors an activating K-ras mutation. Treatment with 5-aza-dC resulted in a 23% reduction in tumor incidence, as well as a 42% reduction in tumor multiplicity. This work supports further investigation of methylation inhibitors likes 5-aza-dC for early intervention, prevention and treatment of lung cancer.
Interleukin 4 down-regulates expression of c-kit and autocrine stem cell factor in human colorectal carcinoma cells. (1995)

Stem cell factor (SCF) is a cytokine which plays an important role in the development of precursor cells. We have investigated the expression of SCF and its receptor, the c-kit proto-oncogene, in human colorectal carcinoma cell lines. Using reverse transcription-PCR, we confirmed the expression of c-kit in two lines (LS174T and LS1034) and of SCF in 9 of 11 cell lines tested. In a Northern blot, a single transcript of 6.6 kb was detected for SCF mRNA. In addition, two lines (LS174T and HT29) synthesized SCF protein, as detected by Western blot analysis. SCF stimulated proliferation and colony formation of LS174T in a dose-dependent manner up to 160%. A half-maximal effect was obtained with about 5.5 ng/ml of SCF under both growth conditions. LS174T cells expressed the M(r) 145,000 c-kit protein on the cell surface and a neutralizing anti-c-kit mAb inhibited colony formation of LS174T by 40%. Interleukin 4 (IL-4) completely inhibited SCF-induced proliferation of LS174T cells. Interestingly, IL-4 induced an almost complete down-regulation of both c-kit and SCF expression in LS174T. Our findings suggest that in LS174T cells, an SCF-mediated autocrine loop is functional and that IL-4 down-regulates the expression of both the receptor and the ligand of this circuit.