gebhart/patrepeval huggingface dataset:
Pharmacological Inhibitors of Fatty Acid Synthase (FASN)-Catalyzed Endogenous Fatty Acid Biogenesis: A New Family of Anti-Cancer Agents? (2006)

The expression and activity of Fatty Acid Synthase (FASN; the sole enzyme capable of the reductive de novo synthesis of long-chain fatty acids from acetyl-CoA, malonyl-CoA, and nicotinamide adenine dinucleotide phosphate -NADPH-) is extremely low in nearly all nonmalignant adult tissues, whereas it is significantly up-regulated or activated in many cancer types, thus creating the potential for a large therapeutic index. Since the pioneering observation that inhibition of FASN activity by the mycotoxin cerulenin preferentially kills cancer cells and retards the growth of tumors in xenografts models, numerous in vitro and in vivo studies have confirmed the potential of FASN as a target for antineoplastic intervention. Other FASN inhibitors such as the cerulenin derivative C75, the beta-lactone orlistat, the green tea polyphenol epigallocatechin-3-gallate (EGCG) and other naturally occurring flavonoids (i.e., luteolin, quercetin, and kaempferol), as well as the antibiotic triclosan, have been identified and have been shown to limit cancer cell growth by inducing apoptotic cell death. Though the exact mode of action of these FASN inhibitors is under discussion, it has been revealed that depletion of end-product fatty acids, toxic intracellular accumulation of supra-physiological concentrations of the FASN substrate malonyl-CoA and/or limited membrane synthesis and/or functioning by altered production of phospholipids partitioning into detergent-resistant membrane microdomains (lipid raft-aggregates), can explain, at least in part, the cytostatic, cytotoxic as well as the apoptotic effects occurring upon pharmacological inhibition of FASN activity in cancer cells. Moreover, several cancer-associated molecular features including nonfunctioning p53, overexpression of the Her-2/neu (erbB-2) oncogene, and hyperactivation of the PI-3'K down-stream effector protein kinase B (AKT), appear to determine an exacerbated sensitivity to FASN inhibition-induced cancer cell death. Although few of these inhibitors are expected to be "exclusively" selective for FASN, the potential of FASN as a target for antineoplastic intervention has eventually been confirmed by RNA interference (RNAi)-knockdown of FASN. Certainly, future studies should definitely elucidate the ultimate biochemical link between FASN inhibition and cancer cell death. Although the combination of FASN structural complexity and until recently the lack of X-ray crystallography data of mammalian FASN created a significant challenge in the exploitation of FASN as a valuable target for drug development, it is hoped that the improvement in the selectivity and potency of forthcoming novel FASN-targeted small molecule inhibitors by taking advantage, for instance, of the recent 4.5 A resolution X-ray crystallographic map of mammalian FASN, will direct the foundation of a new family of chemotherapeutic agents in cancer history.
A Novel Approach to Anharmonicity for a Wealth of Applications in Nonlinear Science Technologies (2011)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Patrick Hanusse; A Novel Approach to Anharmonicity for a Wealth of Applications in Nonlinear Science Technologies. AIP Conf. Proc. 19 April 2011; 1339 (1): 303–308. https://doi.org/10.1063/1.3574867 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioAIP Conference Proceedings Search Advanced Search |Citation Search
Molecular design of crown ethers. 4. Syntheses and selective cation binding of 16-crown-5 and 19-crown-6 lariats (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular design of crown ethers. 4. Syntheses and selective cation binding of 16-crown-5 and 19-crown-6 lariatsMikio Ouchi, Yoshihisa Inoue, Kazuhito Wada, Shinichi Iketani, Tadao Hakushi, and Edwin WeberCite this: J. Org. Chem. 1987, 52, 12, 2420–2427Publication Date (Print):June 1, 1987Publication History Published online1 May 2002Published inissue 1 June 1987https://pubs.acs.org/doi/10.1021/jo00388a016https://doi.org/10.1021/jo00388a016research-articleACS PublicationsRequest reuse permissionsArticle Views1468Altmetric-Citations73LEARN 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 Get e-Alerts
A micro-perfusion bioreactor for on line investigation of ECM remodeling under hydrodynamic and biochemical stimulation (2016)

Tissue-on-chip (TOC) systems aim at replicating complex biological dynamics in vitro with the potential either to improve the understanding of human biology or to develop more accurate therapeutic strategies. To replicate faithfully the intricate interrelationships between cells and their surrounding microenvironment, the three-dimensional (3D) tissue model must possess a responsive extracellular matrix (ECM). ECM remodeling plays a pivotal role in guiding cells and tissues functions and such aspect is somewhat denied during in vitro studies. For this purpose, we fabricated a micro-perfusion bioreactor capable to sustain the viability of 3D engineered tissue models recapitulating the process of the native ECM deposition and assembly. Engineered human dermis micro-tissue precursors (HD-μTP) were used as building blocks to generate a final tissue. HD-μTP were loaded in the perfusion space of the micro-perfusion bioreactor and, under the superimposition of different fluid dynamic regimes and biochemical stimulation, they synthesized new collagen proteins that were, then, assembled in the perfusion space forming a continuum of cells embedded in their own ECM. The micro-perfusion bioreactor was fabricated to allow the on-line monitoring of the oxygen consumption and the assembly of the newly formed collagen network via real time acquisition of the second harmonic generation (SHG) signal. The possibility to detect the collagen reorganization due to both fluid dynamic and biochemical stimulation, let us to define the optimal perfusion configuration in order to obtain a TOC system based on an endogenous and responsive ECM.
Predicting clinical outcome through gene expression profiling in stage III melanoma (2007)

8502 Background: Melanoma patients with clinically involved regional lymph nodes (Stage IIIB&amp;C) represent a prognostically heterogeneous population. Current prognostic factors cannot distinguish the 30% of patients who will achieve long term survival from those who will relapse early. We hypothesized that gene expression profiling could identify these different prognostic groups and provide a greater understanding of the genetic mechanisms involved. Methods: Lymph node sections from 29 patients with Stage IIIB &amp; IIIC melanoma and divergent clinical outcome as defined by time to tumor progression (TTP), including 16 poor (TTP&lt;6 months) and 13 good (TTP&gt;28 months) prognosis patients, were subjected to molecular profiling using spotted oligonucleotide arrays containing 30,888 probes as an initial test set. The differentially expressed genes were determined using a Wilcoxon-Mann-Whitney t-test with the false discovery rate controlling method of Benjamini-Hochberg and validated using quantitative real-time RT-PCR. Using logistic regression, a predictive score algorithm was developed based on the 15 genes for which the correlation between the two platforms was the strongest. The score was then applied to two independent validation sets of 10 and 14 patient samples. Results: Supervised analysis using differentially expressed genes was able to distinguish the two prognostic groups in the test set. The score correlated directly with clinical outcome, with higher scores associated with improved TTP. When the score was then applied to two independent sets of Stage III melanoma patient samples, it predicted clinical outcome accurately in 90% of samples. Conclusions: Stage IIIB and IIIC melanoma can be prognostically sub-classified according to the expression of 15 genes. To our knowledge this is the first study focused on Stage III disease using ex vivo patient samples. These results are encouraging and this genetic signature is currently being validated on a larger cohort. This method will allow appropriate stratification of stage III melanoma patients in adjuvant clinical trials, ameliorating the inherent biological heterogeneity that can confound these studies. [Table: see text]
Comparative analysis of charging modes of series resonant converter for a energy storage capacitor (2012)

In this paper, charging mode of series resonant converter for a high voltage energy storage capacitor are compared in terms of charging time, losses of switch, peak resonant current, voltage and switch utilization in each operation mode. Operating principles of the full bridge series resonant converter with capacitor load are explained and charging characteristics are analyzed in discontinuous and continuous operation mode. Based on the analysis and the simulation focused on above five performance indexes, 0.65ω <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> <; ω <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> <; 0.75ω <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> is evaluated to the best range of switching frequency for charging of an energy storage capacitor. 1.8 kJ/s SRC prototype is assembled with TI 28335 DSP controller and 40 kJ, 7 kV capacitor. Design rules based on the comparative analysis are verified by experiment.
Guest Editorial Special Issue on DC Protection (2021)

As the concept of DC power and energy delivery, whether it is applied to microgrids, distribution, facilities, or transportation systems, is increasingly applied, protection is a paramount concern. There is an increasing number of applications where DC distribution is not only a benefit but a necessary means of building up the electrical system. These applications cover the range of voltages, low voltage DC (LVDC), medium voltage DC (MVDC), and high voltage DC (HVdc), and with corresponding increases in power ratings. At the low end of the voltage/power range, applications include electric vehicles, remote households and communities, telecommunication, data centers, and electric vehicle (EV) charging stations. Emerging system applications having a large number of electronically controlled loads, such as electrified ships and aircraft and ultra-fast multi-EV charging stations are moving the demand for resilient DC power distribution into the high end of the LVDC range (1 kV) into the MW power range. Considering the growth of the renewable energy infrastructure and the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dc backbone</i> of source/load interfacing power electronic converters (PECs), the future movement toward MVDC power and energy distribution and delivery is inevitable. Considerable research and developments have been applied to the source and load interfacing PEC hardware, controls, and inter-compatibility in DC systems, with relatively little attention paid to eventualities of failures at points of PEC connection and inter-connection.
Analysis of BCL-6 mutations in classic Hodgkin disease of the B- and T-cell type (2001)

BCL-6 is essential for germinal center formation and thus for affinity maturation of immunoglobulin (Ig) genes by somatic mutations. The 5'-noncoding region of the BCL-6 gene is even a target for the mutation machinery. Translocations of the BCL-6 gene to heterologous promoters and mutations of its 5'-noncoding regulatory region were reported to be potential mechanisms for deregulating BCL-6 expression and for playing a role in the genesis of non-Hodgkin lymphoma. In line with this hypothesis is the observation that B-cell lymphoma with somatic mutations, such as diffuse large B-cell lymphoma and follicular lymphoma, also carry BCL-6 mutations, some of which are recurrently detectable. Classic Hodgkin disease (cHD) is also derived from B cells with high loads of somatic mutations and thus a further candidate for BCL-6 mutations. To determine the presence and potential role of BCL-6 mutations in cHD, the 5'-noncoding BCL-6 proportion of single Hodgkin and Reed-Sternberg (HRS) cells from 6 cases of cHD and 6 cases of HD-derived cell lines was analyzed. All B-cell-derived HD cases and cell lines harbored BCL-6 mutations. In contrast, both T-cell-derived HD cases and cell lines were devoid of BCL-6 mutations. With only one exception, there were no lymphoma-specific recurrent BCL-6 mutations detected, and BCL-6 protein was absent from the HRS cells of most cases. In conclusion, (1) somatic BCL-6 mutations are restricted to cHD cases of B-cell origin, and (2) the BCL-6 mutations represent mostly irrelevant somatic base substitutions without consequences for BCL-6 protein expression and the pathogenesis of cHD.
The Concept of Metabolic Clearance Rate in Endocrinology (1993)

Culture-derived neonatal Fischer-344 (Rtllvl) rat islets have reduced immunogenicity and have been shown to be fully transplantable into Wistar Furth (Rtlu) recipients. In studies designed to test the MHC-restriction of the autoimmune disease process in the BB/Wor rat, MHC-matched (Wistar Furth) and MHC-mismatched (Fischer-344) neonatal islets were isolated by a nonenzymatic tissue culture procedure and transplanted to the renal subcapsular site of BB/Wor rats before the onset of disease. All MHC-mismatched and most MHC-matched grafts survived intact. In this study we report the growth of MHC-matched and mismatched islet tissue at the graft site. Grafts in diabetes resistant animals averaged 60 +/- 26 micrograms, a comparable mass to that which was transplanted. Grafts in diabetic animals were significantly increased in size, averaging 176 +/- 156 micrograms (P = 0.01). Analysis of nuclear to cytoplasmic volume ratios indicates that the increase in mass was primarily due to islet hyperplasia rather than hypertrophy. Factors contributing to the growth of islet tissue in situ are discussed.
Inclusion complexes between amphiphilic molecules and carboxymethylamylose in aqueous solution: ketone type-II photoelimination behavior as a probe of the "guest" microenvironment (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInclusion complexes between amphiphilic molecules and carboxymethylamylose in aqueous solution: ketone type-II photoelimination behavior as a probe of the "guest" microenvironmentY. Hui, J. R. Winkle, and D. G. WhittenCite this: J. Phys. Chem. 1983, 87, 1, 23–25Publication Date (Print):January 1, 1983Publication History Published online1 May 2002Published inissue 1 January 1983https://pubs.acs.org/doi/10.1021/j100224a008https://doi.org/10.1021/j100224a008research-articleACS PublicationsRequest reuse permissionsArticle Views53Altmetric-Citations17LEARN 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 options Get e-Alerts
Efficacy of entecavir treatment for lamivudine‐resistant hepatitis B over 3 years: Histological improvement or entecavir resistance? (2009)

Entecavir in the long term would be useful for histological improvement of breakthrough hepatitis induced by lamivudine-resistant HBV mutants in patients with chronic hepatitis B. However, the relatively high rate of entecavir resistance is a concern, and other strategies need to be considered when available.
EXTERNAL REPRESENTATIONS FOR DATA DISTRIBUTIONS: IN SEARCH OF COGNITIVE FIT (2013)

Data distributions can be represented using different external representations, such as histograms and boxplots. Although the role of external representations has been extensively studied in mathematics, this is less the case in statistics. This study helps to fill this gap by systematically varying the representation that accompanies a task between participants, and assessing how university students use such representations in comparing aspects of data distributions. Following a cognitive fit approach, we searched for matches between items and representations. Depending on the item, some representations led to better achievement than other representations. However, due to the low overall accuracy rates and various difficulties that students displayed in interpreting these representations, we cannot make strong claims regarding matches between items and representations.&#x0D; First published May 2013 at Statistics Education Research Journal Archives
Cumulative Attribute Space for Age and Crowd Density Estimation (2013)

A number of computer vision problems such as human age estimation, crowd density estimation and body/face pose (view angle) estimation can be formulated as a regression problem by learning a mapping function between a high dimensional vector-formed feature input and a scalar-valued output. Such a learning problem is made difficult due to sparse and imbalanced training data and large feature variations caused by both uncertain viewing conditions and intrinsic ambiguities between observable visual features and the scalar values to be estimated. Encouraged by the recent success in using attributes for solving classification problems with sparse training data, this paper introduces a novel cumulative attribute concept for learning a regression model when only sparse and imbalanced data are available. More precisely, low-level visual features extracted from sparse and imbalanced image samples are mapped onto a cumulative attribute space where each dimension has clearly defined semantic interpretation (a label) that captures how the scalar output value (e.g. age, people count) changes continuously and cumulatively. Extensive experiments show that our cumulative attribute framework gains notable advantage on accuracy for both age estimation and crowd counting when compared against conventional regression models, especially when the labelled training data is sparse with imbalanced sampling.
Clinical trial of neuroEPO in mild‐to‐moderate Alzheimer’s disease (2021)

Abstract Background NeuroEPO, a nasal pharmaceutical solution of recombinant human erythropoietin with low sialic acid, was in clinical development for the treatment of mild‐moderate Alzheimer’s disease. Method A double‐blind, randomized, placebo‐controlled, multicenter, prospective, with adaptive design, phase II/III clinical trial involving 174 patients with mild‐to‐moderate Alzheimer’s, was conducted. NeuroEPO or placebo, with different doses, was administered by nasal route 3 times a weeks for 48 weeks. The primary outcome measure was score on the 11‐item cognitive subscale of the Alzheimer’s disease Assessment Scale (ADAS‐cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment). Secondary outcome measures included Clinician’s Interview‐Based Impression of Change Plus Caregiver Input (CIBIC‐plus), Global Dementia Scale (GDS), activities of daily living (ADL), hippocampal volume change over time (measured with MRI), neuropsychological scales, e lectroencephalography ( EEG ) and adverse events. Result There were statistically significant differences between neuroEPO and placebo in median change from baseline in the primary outcome at week 48. The change in ADAS‐cog11 scores final‐initial (PP population) for patients in the neuroEPO 0.5 mg (n= 50, median change: ‐ 4.0), neuroEPO 1.0 mg (n=49, median change: ‐ 5.0) and placebo (n=49, median change: 4.0) groups. A difference of 8.0 points CI 95% (6.0; 10.0) neuroEPO 0.5 mg vs. placebo and 9.0 points CI 95% (6.8; 11.2) neuroEPO 1.0 mg vs. placebo at week 48, (p=0.000), was observed. Patients receiving both doses of neuroEPO also showed a significant difference in global improvement (CIBIC‐Plus, p=0.000) and e lectroencephalography (EEG, p=0.003) compared with placebo group. About hippocampal volume change, 105 patients were analyzed. From them, 58% remained stable and 42% decline hippocampus volume. No serious adverse events related with neuroEPO were reported. Conclusion NeuroEPO improved clinical outcomes in patients with Alzheimer’s disease with good security profile. Therefore, it could be useful in the treatment of these kind of patients.
Supramolecular and Hybrid Bonding Polymers (2020)

Abstract Staudinger established a century ago the existence of covalent macromolecules, work that led to the development of transformative materials of great benefit to society and a “quantum leap” in our understanding of biological systems. Over the past few decades the concept of supramolecular polymers has emerged–chemical systems in which structural units bond strongly to each other non‐covalently. These dynamic systems actually exist in the natural world and can create soft materials with structures, properties, and functions beyond the ones we know in Staudinger polymers. We reflect here on the potential of novel systems in which covalent and supramolecular polymers are chemically integrated and describe them as hybrid bonding polymers . This paper describes the concept with recent examples from the Stupp laboratory, and discusses their potential functions as robotic materials that mimic living matter and structures that offer new ideas on how to recycle and reuse soft materials.