gebhart/patrepeval huggingface dataset:
Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation (2019)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Triacylglycerol accumulation in the liver is a hallmark of NAFLD. Metabolic studies have confirmed that increased hepatic de novo lipogenesis (DNL) in humans contributes to fat accumulation in the liver and to NAFLD progression. Mice deficient in carboxylesterase (Ces)1d expression are protected from high-fat diet-induced hepatic steatosis. To investigate whether loss of Ces1d can also mitigate steatosis induced by over-activated DNL, WT and Ces1d-deficient mice were fed a lipogenic high-sucrose diet (HSD). We found that Ces1d-deficient mice were protected from HSD-induced hepatic lipid accumulation. Mechanistically, Ces1d deficiency leads to activation of AMP-activated protein kinase and inhibitory phosphorylation of acetyl-CoA carboxylase. Together with our previous demonstration that Ces1d deficiency attenuated high-fat diet-induced steatosis, this study suggests that inhibition of CES1 (the human ortholog of Ces1d) might represent a novel pharmacological target for prevention and treatment of NAFLD.
Diffusion Weighted Image Denoising Using Overcomplete Local PCA (2013)

Diffusion Weighted Images (DWI) normally shows a low Signal to Noise Ratio (SNR) due to the presence of noise from the measurement process that complicates and biases the estimation of quantitative diffusion parameters. In this paper, a new denoising methodology is proposed that takes into consideration the multicomponent nature of multi-directional DWI datasets such as those employed in diffusion imaging. This new filter reduces random noise in multicomponent DWI by locally shrinking less significant Principal Components using an overcomplete approach. The proposed method is compared with state-of-the-art methods using synthetic and real clinical MR images, showing improved performance in terms of denoising quality and estimation of diffusion parameters.
Powder metallurgy Rene 95 rotating turbine engine parts, volume 2 (1981)

A Rene 95 alloy as-HIP high pressure turbine aft shaft in the CF6-50 engine and a HIP plus forged Rene 95 compressor disk in the CFM56 engine were tested. The CF6-50 engine test was conducted for 1000 C cycles and the CFM56 test for 2000 C cycles. Post test evaluation and analysis of the CF6-50 shaft and the CFM56 compressor disk included visual, fluorescent penetrant, and dimensional inspections. No defects or otherwise discrepant conditions were found. These parts were judged to have performed satisfactorily.
A novel synthesis of 14‐(hydroxymethylalkyl) derivatives of dibenzoxanthenes and 3,3‐dimethyl‐4‐(2‐hydroxy‐1‐naphthyl)benzo[f]chroman (1998)

Abstract Several reactions of 2‐naphthol with 2‐alkyl‐2‐hydroxymethylaldehydes have been investigated. Novel synthesis of 14‐(hydroxymethyl)alkyldibenzo[ a,j ]xanthenes and 3,3‐dimethyl‐4‐(2‐hydroxy‐1‐naphthyl)benzo[ f ]chroman has been realized.
Folliculin Controls Lung Alveolar Enlargement and Epithelial Cell Survival through E-Cadherin, LKB1, and AMPK (2014)

Spontaneous pneumothoraces due to lung cyst rupture afflict patients with the rare disease Birt-Hogg-Dubé (BHD) syndrome, which is caused by mutations of the tumor suppressor gene folliculin (FLCN). The underlying mechanism of the lung manifestations in BHD is unclear. We show that BHD lungs exhibit increased alveolar epithelial cell apoptosis and that Flcn deletion in mouse lung epithelium leads to cell apoptosis, alveolar enlargement, and an impairment of both epithelial barrier and overall lung function. We find that Flcn-null epithelial cell apoptosis is the result of impaired AMPK activation and increased cleaved caspase-3. AMPK activator LKB1 and E-cadherin are downregulated by Flcn loss and restored by its expression. Correspondingly, Flcn-null cell survival is rescued by the AMPK activator AICAR or constitutively active AMPK. AICAR also improves lung condition of Flcn(f/f):SP-C-Cre mice. Our data suggest that lung cysts in BHD may result from an underlying defect in alveolar epithelial cell survival, attributable to FLCN regulation of the E-cadherin-LKB1-AMPK axis.
Qualitative Methods for Determining Students’ Satisfaction with Teaching Quality (2014)

This research is focused on the possibility to increase the quality of teaching by determining the motivating factors that lead to improved teaching and to learn the factors that lead to a decrease in the level of student involvement in teaching and scientific activities. The results based on observation and logical assumptions provide information about students’ vision on the ideal type of teacher and teaching style. Most of the students appreciate as good personality traits: teachers’ openness to dialogue, human nature, personal experience in the area of study and teachers’ explanatory skills in delivering scientific information.
ClarIDHy: A phase 3 multicenter randomized double-blind study of AG-120 versus placebo in patients with non-resectable or metastatic cholangiocarcinoma with an IDH1 mutation. (2018)

TPS545 Background: Advanced cholangiocarcinoma (CC) is a life-threatening disease with limited effective chemotherapy options. Mutations in isocitrate dehydrogenase 1 (mIDH1) occur in 13–15% of CC cases, and up to 25% of intrahepatic CC cases, leading to epigenetic and genetic changes that promote oncogenesis via production of the oncometabolite 2-hydroxyglutarate (2-HG). AG-120 (ivosidenib), a first-in-class oral mIDH1 inhibitor, displayed a favorable safety profile and clinical activity in a phase 1 study enrolling 73 mIDH1 CC patients who had received ≥1 prior systemic regimen. As of 10 Mar 2017, 4/73 (5%) had a partial response and 41/73 (56%) stable disease. Progression free survival (PFS) rates at 6 months and 12 months were 38.5% and 20.7%, respectively. The 500 mg once daily dose level of AG-120 was selected for further development in mIDH1 CC. Methods: ClarIDHy is a global, phase 3, multicenter, double-blind, randomized (2:1) study of AG-120 (500 mg once daily) vs. matched placebo in 186 mIDH1 CC patients (ClinicalTrials.gov NCT02989857). Key eligibility criteria: non-resectable or metastatic CC, documented mIDH1 by central laboratory testing, ECOG performance status 0–1, measurable disease (RECIST v1.1), documented disease progression after ≤2 prior systemic therapies in the advanced setting including at least 1 gemcitabine- or 5-fluorouracil-containing regimen, and no prior mIDH inhibitor therapy. Crossover from placebo to AG-120 will be allowed at time of radiographic disease progression. Primary endpoint: PFS assessed by independent radiologists. Secondary endpoints: safety, tolerability, overall response rate (RECIST 1.1), overall survival, pharmacokinetic/pharmacodynamic analyses, and quality of life (EORTC QLQ-C30 and QLQ-BIL21 scales). An independent data monitoring committee will monitor the data during study conduct. The ClarIDHy study is currently activated at participating sites in the US, UK, EU, and S. Korea. R eused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2017 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT02989857.
The Dopamine Metabolite 3-Methoxytyramine Is a Neuromodulator (2010)

Dopamine (3-hydroxytyramine) is a well-known catecholamine neurotransmitter involved in multiple physiological functions including movement control. Here we report that the major extracellular metabolite of dopamine, 3methoxytyramine (3-MT), can induce behavioral effects in a dopamine-independent manner and these effects are partially mediated by the trace amine associated receptor 1 (TAAR1). Unbiased in vivo screening of putative trace amine receptor ligands for potential effects on the movement control revealed that 3-MT infused in the brain is able to induce a complex set of abnormal involuntary movements in mice acutely depleted of dopamine. In normal mice, the central administration of 3-MT caused a temporary mild hyperactivity with a concomitant set of abnormal movements. Furthermore, 3-MT induced significant ERK and CREB phosphorylation in the mouse striatum, signaling events generally related to PKA-mediated cAMP accumulation. In mice lacking TAAR1, both behavioral and signaling effects of 3-MT were partially attenuated, consistent with the ability of 3-MT to activate TAAR1 receptors and cause cAMP accumulation as well as ERK and CREB phosphorylation in cellular assays. Thus, 3-MT is not just an inactive metabolite of DA, but a novel neuromodulator that in certain situations may be involved in movement control. Further characterization of the physiological functions mediated by 3-MT may advance understanding of the pathophysiology and pharmacology of brain disorders involving abnormal dopaminergic transmission, such as Parkinson's disease, dyskinesia and schizophrenia.
Structure and Macromolecular Organization of Type VI Collagena (1985)

Collagen VI is a large, disulfide-bonded protein complex which is widely distributed in connective tissue. The constituent polypeptide chains (Mr = 110,000-140,000) consist of collagenous and noncollagenous segments, are degraded to chains of about half the size when collagen VI is solubilized by pepsin, and assemble to a unique pattern of oligomers. As revealed by electron microscopy, the triple-stranded protomer consists of a triple helix 105 nm in length flanked on each side by globular domains of similar size (diameter about 7 nm). Protomers are assembled to dimers by an antiparallel staggered alignment of triple-helical segments. This leads to inner regions, 75 nm in length, of two slightly supercoiled triple helices flanked by globular domains. At both sides 30-nm-long outer triple-helical segments emerge that are terminated by globules. Tetramers are formed from laterally aligned dimers that cross with their outer triple-helical segments in a scissors-like fashion. The same structures, except with much smaller globular domains, are found in pepsin-treated collagen VI. Disulfide-linked collagen VI produced by cultured fibroblasts has a size similar to that of genuine collagen VI found in tissue extracts. Larger forms of collagen VI are assembled from tetramers by end-to-end aggregation which because of an overlap of the outer segments brings all globular domains close together. This arrangement predicts microfibrillar structures in tissues with a periodicity of 100-110 nm and a diameter of 5-10 nm. Structures consistent with this proposal were indeed found by immunoelectron microscopy of placenta and aorta using the ferritin technique. Large, lateral aggregates of collagen VI microfibrils may in addition exist in cell cultures and tissues ("zebra collagen," "Luse bodies") and are presumably maintained by contacts between globular domains.
Implementation of genomic predictors of chemotherapy response for guiding preoperative therapy in a prospective breast cancer trial (2009)

11057 Background: Personalized approaches to breast cancer therapy depend on genomic assays. While assays based on fixed tissues offer greater convenience, the spectrum of biology interrogated is limited. Full-transcriptome assays using microarrays are more challenging, but have the advantage of providing multiple prognostic and predictive signatures in one assay. We have created a clinical infrastructure with the objective of obtaining full genome expression data on breast cancer samples as a clinical assay for use in a prospective trial. Methods: “Performance of Genomic Expression Profiles to Direct the Use of Preoperative Chemotherapy for Early Stage Breast Cancer” is a prospective trial validating genomic signatures for predicting response to doxorubicin (A) or docetaxel (T) treatment in HER2 negative cancers. Fresh-frozen cores are reviewed by the study pathologist for tumor content. RNA is then extracted and probe generated to hybrize to an Affymetrix U133Plus2.0 microarray. Microarray data quality is determined using summary metrics for U133Plus2.0 arrays and principal component analysis (PCA) plots. The data is then used for predicting A or T sensitivity. Results: Thirteen cancers have been analyzed in the context of the above trial. Histologic type was lobular for 1, and predominantly ductal for 12 (10 ER positive, 3 ER negative). Median tumor size was 3.4 cm (range, 1.8–5.7). Microarray analysis was successful on 11 tumors (84%), providing data of sufficient quality to make predictions of A and T sensitivity. One sample hybridization failed QC as detected by PCA analysis, and one sample had insufficient RNA. The median “tissue to array data” time and “study consent to initiation of treatment” time were 5 days (range, 3–8) and 14 days (range, 11–36), respectively. Conclusions: Our initial experience shows that full-genome expression analysis on frozen tumor using an Affymetrix platform is feasible as a clinical assay for breast cancer. The resulting data is being used in a prospective marker validation protocol for predicting chemosensitivity. The data can also be analyzed for a variety of other potential prognostic and predictive signatures for guiding therapy. No significant financial relationships to disclose.
Quantitative Correlation Between Low-Field Mobility and High-Field Carrier Velocity in Quasi-Ballistic-Transport MISFETs with High-k Gate Dielectrics (2010)

Abstract not Available.
In Vitro Development of in Vitro-Matured Porcine Oocytes Following Chemical Activation or in Vitro Fertilization1 (1994)

Porcine cumulus-oocyte complexes were cultured in BSA-free Whitten's medium or modified Medium 199, each supplemented with porcine follicular fluid (PFF) and hormonal supplements (OMWM and OMM199, respectively) for 20 h; they then were cultured without hormonal supplements for an additional 20 (experiments 1 and 3) or 24 h (experiment 2). At the end of culture (experiment 1), the intracellular glutathione concentration was higher (p < 0.05) in oocytes matured in OMWM vs. OMM199. After activation by Ca2+ ionophore (experiment 2), the incidence of activation in the OMWM group was lower (p < 0.01) than in the OMM199 group. However, the incidence of pronuclear formation was higher (p < 0.01) in the OMWM group than in the OMM199 group at 8 h after activation. The percentage of embryos that developed to the morula stage was higher (p < 0.01) in the group matured in OMWM vs. OMM199 after 5 days of culture. After in vitro fertilization (experiment 3), the incidence of male pronuclear formation and the percentage of monospermic oocytes that formed one male and one female pronuclei were higher (p < 0.05) after maturation in OMWM vs. OMM199. The percentage of cleaved embryos that developed to the 8-cell and morula stages was higher (p < 0.05) in the OMWM group as compared to the OMM199 group. These results indicate that culture in modified Whitten's medium as compared with a standard medium (modified Medium 199) improves cytoplasmic maturation of porcine oocytes as evaluated by intracellular glutathione content, pronuclear formation, and development in vitro after artificial activation or fertilization in vitro.
Conjugated Polyelectrolyte‐Based Complex Fluids as Aqueous Exciton Transport Networks (2022)

The ability to assemble artificial systems that mimic aspects of natural light-harvesting functions is fascinating and attractive for materials design. Given the complexity of such a system, a simple design pathway is desirable. Here, we argue that associative phase separation of oppositely charged conjugated polyelectrolytes (CPEs) can provide such a path in an environmentally benign medium: water. We find that complexation between an exciton-donor and acceptor CPE leads to formation of a complex fluid. We interrogate exciton transfer from the donor to the acceptor CPE within the complex fluid and find that transfer is highly efficient. We also find that excess molecular ions can tune the modulus of the inter-CPE complex fluid. Even at high ion concentrations, CPEs remain complexed with significantly delocalized electronic wavefunctions. Our work lays the rational foundation for complex, tunable aqueous light-harvesting systems via the intrinsic thermodynamics of associative phase separation.
A functional preservation strategy for the production of highly photoluminescent emerald carbon dots for lysosome targeting and lysosomal pH imaging (2018)

Lysosomes, which can be easily targeted by molecules with abundant amino groups, play critical roles in endocytosis, autophagy, and phagocytosis; thus, it is important to accurately characterize lysosomes, including lysosomal pH, in living cells to understand their physiological and pathological functions. Herein, a new type of highly photoluminescent (PL) emerald carbon dots (CDs) was easily prepared through a functional preservation strategy (FPS) by simply mixing p-benzoquinone and ethanediamine at room temperature. The as-prepared CDs possessed abundant amino groups preserved from ethanediamine owing to FPS, and they exhibited excellent photostability as compared to the commercial LysoTracker probes. Consequently, they actively targeted lysosomes to sensitively respond to lysosomal pH in vitro owing to their abundant amino groups and good hydrophilicity. Thus, we could successfully monitor lysosomal pH dynamics during apoptosis in live cells.
Oxygen chiral phosphodiesters. 5. Stereochemical course of the hydrolysis of thymidine 3'-[(4-nitrophenyl)[17O,18O]phosphate] in water (oxygen-16) catalyzed by the exonuclease from bovine spleen (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxygen chiral phosphodiesters. 5. Stereochemical course of the hydrolysis of thymidine 3'-[(4-nitrophenyl)[17O,18O]phosphate] in water (oxygen-16) catalyzed by the exonuclease from bovine spleenShujaath Mehdi and John A. GerltCite this: J. Am. Chem. Soc. 1981, 103, 23, 7018–7020Publication Date (Print):November 1, 1981Publication History Published online1 May 2002Published inissue 1 November 1981https://pubs.acs.org/doi/10.1021/ja00413a065https://doi.org/10.1021/ja00413a065research-articleACS PublicationsRequest reuse permissionsArticle Views53Altmetric-Citations27LEARN 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
Effects of inhibitors of N-linked oligosaccharide processing on the biosynthesis and function of insulin and insulin-like growth factor-I receptors. (1988)

We have used specific inhibitors of oligosaccharide processing enzymes as probes to determine the involvement of oligosaccharide residues in the biosynthesis and function of insulin and insulin-like growth factor-I receptors. In a previous study (Duronio, V., Jacobs, S., and Cuatrecasas, P. (1986) J. Biol. Chem. 261, 970-975) swainsonine was used to inhibit mannosidase II, resulting in the production of receptors containing only hybrid-type oligosaccharides. These receptors had a slightly lower molecular weight and were much more sensitive to endoglycosidase H, but otherwise behaved identically to normal receptors. In this study, we used two compounds that inhibit oligosaccharide processing at earlier steps: (i) N-methyl-1-deoxynojirimycin (MedJN), which inhibits glucosidases I and II and yields glucosylated, high mannose oligosaccharides, and (ii) manno-1-deoxynojirimycin (MandJN), which inhibits mannosidase I and yields high mannose oligosaccharides. In the presence of MandJN, HepG2 cells synthesized receptors of lower molecular weight, which were cleaved into alpha and beta subunits and were able to bind hormone and autophosphorylate. These receptors were as sensitive to endoglycosidase H as receptors made in the presence of swainsonine. In the presence of MedJN, receptors of only slightly lower molecular weight than normal were synthesized and were shown to contain some glucosylated high mannose oligosaccharides. These receptors were able to bind hormone and retained hormone-sensitive autophosphorylation activity. In both cases, the incompletely processed receptors could be detected at the cell surface by cross-linking of iodinated hormone and susceptibility to trypsin digestion, although less receptor was present in cells treated with MedJN. Studies of receptor synthesis using pulse-chase labeling showed that the receptor precursors synthesized in the presence of MedJN were cleaved into alpha and beta subunits at a slower rate than normal receptors or those made in the presence of MandJN. Inhibition of oligosaccharide processing had no effect on the association of the receptor subunits into disulfide-linked oligomeric complexes.
Revealing the Timeline of Structural MRI Changes in Premanifest to Manifest Huntington Disease (2021)

Our findings support the use of disease progression modeling to reveal new information from sMRI, which can potentially inform imaging marker selection for clinical trials.
Foveal Fine Structure in Retinopathy of Prematurity: An Adaptive Optics Fourier Domain Optical Coherence Tomography Study (2008)

The foveas of subjects with a history of mild ROP have significant structural abnormalities that are probably a consequence of perturbations of neurovascular development.
Synthesis of long-chain fatty acids by a cell-free system from Mycoplasma laidlawii A (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of long-chain fatty acids by a cell-free system from Mycoplasma laidlawii AShlomo Rottem and Charles PanosCite this: Biochemistry 1970, 9, 1, 57–63Publication Date (Print):January 6, 1970Publication History Published online1 May 2002Published inissue 6 January 1970https://pubs.acs.org/doi/10.1021/bi00803a008https://doi.org/10.1021/bi00803a008research-articleACS PublicationsRequest reuse permissionsArticle Views49Altmetric-Citations23LEARN 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