gebhart/patrepeval huggingface dataset:
Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI (2007)

Treatment of atherosclerotic disease often focuses on reducing plasma LDL-cholesterol or increasing plasma HDL-cholesterol. We examined in vitro the effects on HDL receptor [scavenger receptor class B type I (SR-BI)] activity of three classes of clinical and experimental plasma HDL-cholesterol-elevating compounds: niacin, fibrates, and HDL376. Fenofibrate (FF) and HDL376 were potent (IC(50) approximately 1 microM), direct inhibitors of SR-BI-mediated lipid transport in cells and in liposomes reconstituted with purified SR-BI. FF, a prodrug, was a more potent inhibitor of SR-BI than an activator of peroxisome proliferator-activated receptor alpha, a target of its active fenofibric acid (FFA) derivative. Nevertheless, FFA, four other fibrates (clofibrate, gemfibrozil, ciprofibrate, and bezafibrate), and niacin had little, if any, effect on SR-BI, suggesting that they do not directly target SR-BI in vivo. However, similarities of HDL376 treatment and SR-BI gene knockout on HDL metabolism in vivo (increased HDL-cholesterol and HDL particle sizes) and structure-activity relationship analysis suggest that SR-BI may be a target of HDL376 in vivo. HDL376 and other inhibitors may help elucidate SR-BI function in diverse mammalian models and determine the therapeutic potential of SR-BI-directed pharmaceuticals.
Brugada Syndrome and Early Repolarisation: Distinct Clinical Entities or Different Phenotypes of the Same Genetic Disease? (2016)

Brugada and early repolarisation (ER) syndromes are currently considered two distinct inherited electrical disorders with overlapping clinical and electrocardiographic features. A considerable number of patients diagnosed with ER syndrome have a genetic mutation related to Brugada syndrome (BrS). Due to the high variable phenotypic manifestation, patients with BrS may present with inferolateral repolarisation abnormalities only, resembling the ER pattern. Moreover, the complex genotype-phenotype interaction in BrS can lead to the occurrence of mixed phenotypes with ER syndrome. The first part of this review focuses on specific clinical and electrocardiographic features of BrS and ER syndrome, highlighting the similarity shared by the two primary electrical disorders. The genetic background, with emphasis on the complexity of genotype-phenotype interaction, is explored in the second part of this review.
Frequency Band Energy Statistics Method and the Applications in Monitoring the Work Conditions for Mechanical Equipments (2010)

A new manner, named frequency band energy statistics method, has been proposed for the analysis of the spectra from the vibration signals. The recorded vibration signals were first divided into multi-segments. Then each segment was calculated via the FFT transformation and 1/3 octave spectrum to obtained the characteristics of energy distribution, by making the histogram maps of the obtained features of the frequency energies. Consequently, we can monitor the work conditions and fault diagnosis for the mechanical equipments by the compared analysis of the corresponding histogram maps of equipments with normal and abnormal work conditions. The results show that present method exhibits a very strong sensitivity to the changes of vibration signal, leading to the fine detection of the minor changes form the equipment work conditions. Current work might provide a novel and facile method for definitely monitoring the work conditions and fault diagnosis of the mechanical equipments.
Effect of Initial Resist Thickness on Residual Layer Thickness of Nanoimprinted Structures (2005)

Quantification and control of the residual layer thickness is a critical challenge facing nanoimprint lithography. This thickness must be known to within a few nanometers, yet there are very few nondestructive measurement techniques capable of extracting such information. Here we describe a specular x-ray reflectivity technique that can be used to not only quantify the thickness of the residual layer with sub-nm resolution, but also to extract the pattern height, the line-to-space ratio, and relative linewidth variations as a function of the pattern height. This is illustrated through a series of imprints where the initial film thickness is varied. For films with sufficient resist material to fill the mold, complete pattern filling is observed and the residual layer thickness is directly proportional to the initial film thickness. When there is insufficient resist material in the film to completely fill the patterns in the mold, a finite residual layer thickness of approximately 50–100A is still observed.
Nucleotides and nucleic acids: A source of inspiration for the development of new, phosphorus-centered functional groups (2006)

Synthetic methodologies aiming at the creation of new phosphorus-centered functional groups are reported, as well as applications to the field of nucleotide chemistry. Thus, difluorophosphonothioate-based, ionic reagents 3b and 3d are shown to allow the stereocontrolled and efficient synthesis of phosphonodifluoromethyl analogues of nucleoside-3'-phosphates. An alternate, radical approach describes the use of hypophosphorous acid to stereoselectively link two furanosyl units in positions 3 and 5, and to provide an access to alpha,alpha-difluoro-H-phosphinates. These intermediates are shown to be precursors to the corresponding fluorinated phosphonic acids, phosphonothioic acids and variously substituted phosphinates.
3D Anisotropic Thermal Conductivity of Exfoliated Rhenium Disulfide (2017)

ReS<sub>2</sub> represents a different class of 2D materials, which is characterized by low symmetry having 1D metallic chains within the planes and extremely weak interlayer bonding. Here, the thermal conductivity of single-crystalline ReS<sub>2</sub> in a distorted 1T phase is determined at room temperature for the in-plane directions parallel and perpendicular to the Re-chains, and the through-plane direction using time-domain thermoreflectance. ReS<sub>2</sub> is prepared in the form of flakes having thicknesses of 60-450 nm by micromechanical exfoliation, and their crystalline orientations are identified by polarized Raman spectroscopy. The in-plane thermal conductivity is higher along the Re-chains, (70 ± 18) W m<sup>-1</sup> K<sup>-1</sup> , as compared to transverse to the chains, (50 ± 13) W m<sup>-1</sup> K<sup>-1</sup> . As expected from the weak interlayer bonding, the through-plane thermal conductivity is the lowest observed to date for 2D materials, (0.55 ± 0.07) W m<sup>-1</sup> K<sup>-1</sup> , resulting in a remarkably high anisotropy of (130 ± 40) and (90 ± 30) for the two in-plane directions. The thermal conductivity and interface thermal conductance of ReS<sub>2</sub> are discussed relative to the other 2D materials.
Abstract 3381: TERT promoter mutation in granulosa cell tumours of the ovary: Prevalence and prognostic significance (2017)

Abstract Granulosa cell tumours (GCTs) of the ovary account for 90% of sex cord-stromal tumours and have a high recurrence rate up to 50%. A missense mutation in the FOXL2 gene (c.402C&amp;gt;G; pC134W) is a defining feature of GCT and is used as a robust marker for diagnosis. However, other than the FOXL2 mutation the pathogenesis and the driving pathways remain unknown. Determining secondary genetic events in GCTs is essential to understanding and improving prognosis. In a pilot study, we completed an analysis of whole genome sequencing of ten GCTs and matched normal cases to generate a comprehensive catalogue of coding and non-coding events. We identified a TERT promoter mutation (c.228C&amp;gt;T) in 50% of these cases. TERT is normally inactivated in somatic tissues; however, this promoter mutation has been shown to re-activate transcription of TERT. We validated this TERT mutation in an international cohort of 300 GCTs and found it was present in approximately 25% of cases overall. These TERT promoter mutations have been used to revise the molecular classification of other cancer types such as gliomas. In GCT, we found that this TERT mutation was correlated with a significantly worse survival outcome in patients with primary GCT (p&amp;lt;0.005). Further, we found that this TERT mutation was present in a larger proportion of recurrent cases. Thus, this mutation may denote a novel subtype of GCT with a worse prognosis. Previous research has shown that TERT activation is evident in over 90% of cancers and is a fundamental step in tumourigenesis that enables unlimited proliferation. This TERT promoter mutation in GCT provides an explanation of how granulosa cells escape atresia and attain immortality. Thus, we hypothesize a mechanism in which the FOXL2 mutation prevents apoptosis and the TERT mutation allows limitless proliferation for oncogenes to transform granulosa cells. However, the current cell models of GCT lack relevant functional pathways and do not recapitulate the biology of these tumours. Therefore, we are developing more suitable cell models to test our hypothesis. We believe that understanding the interaction between these TERT and FOXL2 mutations may lead to novel cancer cell-specific targeted therapies. Citation Format: Jessica A. Pilsworth, Dawn R. Cochrane, Zhouchunyang Xia, Hugo M. Horlings, Winnie Yang, Melissa K. McConechy, Satoshi Yanagida, Anniina E. Färkkilä, Adele P. Wong, Genny Trigo-Gonzalez, S.W. Grace Cheng, Yikan Wang, Ali Bashashati, Gregg B. Morin, Esther Oliva, Sohrab P. Shah, David G. Huntsman. TERT promoter mutation in granulosa cell tumours of the ovary: Prevalence and prognostic significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3381. doi:10.1158/1538-7445.AM2017-3381
Bim and Bcl-2 Mutually Affect the Expression of the Other in T Cells (2007)

The life and death of T cells is controlled to a large extent by the relative amounts of Bcl-2-related proteins they contain. The antiapoptotic protein Bcl-2 and the proapoptotic protein Bim are particularly important in this process with the amount of Bcl-2 per cell dropping by about one-half when T cells prepare to die. In this study we show that Bcl-2 and Bim each control the expression of the other. Absence of Bim leads to a drop in the amount of intracellular Bcl-2 protein, while having no effect on the amounts of mRNA for Bcl-2. Conversely, high amounts of Bcl-2 per cell allow high amounts of Bim, although in this case the effect involves increases in Bim mRNA. These mutual effects occur even if Bcl-2 is induced acutely. Thus these two proteins control the expression of the other, at either the protein or mRNA level.
P1‐183: Use of CSF AB1‐42 and AB1‐40 in the Clinical Typing of Alzheimer’s Disease (2016)

Over recent years, the use of cerebrospinal fluid (CSF) β-amyloid1-40 (Aβ1-40) levels for diagnosing Alzheimer’s disease (AD) and distinguishing AD from other dementias has increased. Especially the ratio of Aβ1-42/Aβ1-40 is currently gaining interest. In this study we evaluated the diagnostic impact of adding Aβ1-40 to the measurements of INNOTEST β-AMYLOID(1-42) obtained according to the classical (precision-based) and modified (accuracy-based) test procedure. A set of 145 CSF samples of individuals characterized according to the NIA-AA criteria (58 AD and 87 non-AD) was analyzed at Fujirebio Europe with the INNOTEST β-AMYLOID(1-42) (cat # 81576) and the INNOTEST β-AMYLOID(1-40) (cat # 80462). For both assays, tests were performed both according to the procedure described in the product’s package insert, and to a modified procedure for Aβ1-42 (e.g. longer sample incubation time, 10 μL sample volume). The clinical performance of the Aβ1-42 measurements alone and in a ratio with Aβ1-40 was compared with empirical ROC analysis. The AUC for the classical INNOTEST β-AMYLOID(1-42) measurements was 0.89 (95% CI: [0.84 – 0.95]), whereas the use of modified INNOTEST β-AMYLOID(1-42) resulted in an AUC of 0.81 (95% CI: [0.75 – 0.88]). The clinical performance of Aβ1-42 with the accuracy-based assay was significantly reduced compared to the classical INNOTEST β-AMYLOID(1-42) (p < 0.0001). When calculating the ratio with Aβ1-40 for both Aβ1-42 measurements, the AUC for the classical procedure increases slightly but not significantly to 0.93 (95% CI: [0.88 – 0.97], p = 0.2533), whereas for the modified procedure the ratio increased significantly (p = 0.0005) to 0.93 (95% CI: [0.89 – 0.97]). The AUCs of the Aβ1-42 / Aβ1-40 ratios calculated with the modified and classical Aβ1-42 are not significantly different (p = 0.4466). Improving the analytical performance of the INNOTEST β-AMYLOID(1-42) by use of a modified test procedure decreased its clinical performance. Using these accuracy-based Aβ1-42 measurements in a ratio with Aβ1-40 resolved this issue. The parallel quantification of Aβ1-40can be a significant aid and will become more important in the diagnosis of AD and distinguishing AD from other dementias, especially in cases where the classical CSF biomarker profile is inconclusive.
Metal- and Ligand-Accelerated Catalysis of the Baylis−Hillman Reaction (1998)

The Baylis-Hillman reaction, the coupling of an unsaturated carbonyl compound/nitrile with aldehydes, is a valuable reaction but is limited in its practicality by poor reaction rates. We have endeavored to accelerate the reaction using Lewis acids and found that while conventional Lewis acids gave reduced rates group III, and lanthanide triflates (5 mol %) gave increased rates. The optimum metal salts were La(OTf)(3) and Sm(OTf)(3), which gave rate accelerations (k(rel)) of approximately 4.7 and 4.9, respectively, in reactions between tert-butyl acrylate and benzaldehyde when using stoichiometric amounts of DABCO. At low loadings of DABCO (up to 10 mol %), no reaction occurred due to association of DABCO with the metal. Use of additional ligands to displace the DABCO from the metal was studied, and the rate of reaction was found to increase further in most cases. Of the ligands tested, at 5 mol %, (+)-binol gave one of the largest rate accelerations (3.4-fold) and was studied in more detail. It was found that reactions occurred even at low DABCO concentration so that here the Lewis base and Lewis acid were able to promote the reaction without interference from each other. While the (+)-binol (and other chiral ligands) failed to provide any significant asymmetric induction, a substantial nonlinear effect was observed with binol. Thus, use of racemic binol gave no effect on the rate. In seeking to maximize the rate attainable, more soluble (liquid) ligands were studied. Diethyl tartrate and triethanolamine gave rate enhancements of 5.2x and 3.5x at 50 mol %, respectively, versus 1.5x and 2.3x at 5 mol %. The best protocol was to use 100 mol % DABCO, 50 mol % triethanolamine, and 5 mol % La(OTf)(3). This gave overall rate accelerations of between 23-fold and 40-fold depending on the acrylate and approximately 5-fold for acrylonitrile. A simple acid wash removed the reagents, leaving the product in the organic phase. While triethanolamine accelerated the reaction without the lanthanum triflate (18-22-fold at 80 mol %), the reaction in the presence of the metal salt was faster. The system was tested synthetically on various substrates and found to give good rate accelerations with both activated (benzaldehyde and p-nitrobenzaldehyde) and less activated aldehydes (anisaldehyde and cyclohexanecarboxaldehyde) with acrylates. The limited amount of dimerized acrylate in the latter reactions is noteworthy and should extend the range of substrates that can be made by the Baylis-Hillman reaction using our optimum conditions.
Additional file 1: of Evaluation of myocardial involvement in patients with connective tissue disorders: a multi-parametric cardiovascular magnetic resonance study (2016)

Details of the used T1 mapping and T2 mapping sequences. (DOC 25 kb)
Abstract LB-257: Ganitumab (AMG 479), an anti IGF-1R antibody, inhibits the proliferation of melanoma cells (2012)

Abstract It has been shown that the Insulin-like growth factor receptor type I (IGF-1R) signaling pathway is highly active in metastatic melanoma. IGF-1 binding induces autophosphorylation of IGF-1R and initiation of MAPK and Akt pathways signaling which control cellular proliferation and survival. IGF-1 is a critical factor for growth of many types of cancer, including melanomas, and inhibition of its activity can trigger apoptosis by suppressing the PI3K-AKT and MAPK pathways. Our main objective in this study was to evaluate the therapeutic potential of a novel antibody to the IGF-1R (ganitumab) in a large panel of melanoma cancer cells. We have evaluated 41 human melanoma lines with well established genotypes. Among the 41 cell lines, 22 harbored the BRAF mutation, 10 were NRAS mutant and 9 were wild type for BRAF and NRAS mutations. Treatment with ganitumab (100µg/ml) resulted in inhibition of cell proliferation at 120 hrs in 20 out of 41 cell lines. We found that the response to ganitumab was independent of genotype. We chose 6 cell lines, 3 from the responder population and 3 non-responders (2 BRAF, 2 NRAS and 2 wild types) to further investigate the mechanism of action of ganitumab. Results from flow cytometry suggest that treatment of melanoma cells with 100 µg/ml ganitumab caused a 10% increase in apoptosis 72 hrs after treatment in sensitive cell lines compared with the resistant cell lines where we could not detect an increase in apoptotic cells. The effect of ganitumab was also investigated in a 3D colony soft agar formation assay. Melanoma cell lines sensitive to ganitumab showed a significant reduction in the ability to form colonies in soft agar compared with the cells that did not respond to the antibody. Ganitumab treatment led to a decrease in pAKT, pERK and pS6 in sensitive cell lines regardless of their driver oncogenic mutations when compared with non responder cell lines that showed no inhibition of these markers. In conclusion, inhibition of oncogenic MAPK and PI3K signaling by ganitumab resulted in activity in vitro against a large subset of melanoma cell lines. Our findings provide the rationale for further preclinical evaluation of ganitumab as a melanoma therapeutic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-257. doi:1538-7445.AM2012-LB-257
A 1.6-GB/s data-rate 1-Gb synchronous DRAM with hierarchical square-shaped memory block and distributed bank architecture (1996)

This paper describes key techniques for a 1.6-GB/s high data-rate 1-Gb synchronous DRAM (SDRAM). Its high data transfer rate and large memory capacity are targeted to the advanced unified memory system in which a single DRAM (array) is used as both the main memory and the three-dimensional (3-D) graphics frame memory in a time sharing fashion. The 200-MHz high-speed operation is achieved by the unique hierarchical square-shaped memory block (SSMB) layout and the novel distributed bank (D-BANK) architecture. A 0.29 /spl mu/m/sup 2/ cell and 581.8 mm/sup 2/ small die area are achieved using 0.15-/spl mu/m CMOS technology. The /spl times/61 chip uses 196-pin BGA type chip-scale-package (CSP). Implementation of a built-in self-test (BIST) circuit with a margin test capability is also described.
Improvement of the ohmic characteristics of Pd contacts to p-type GaN using an Ag interlayer (2005)

We have investigated the addition effect of an Ag interlayer (2 nm) at the Pd and GaN interface on the ohmic behaviour of a single Pd contact (110 nm). The Ag layer is broken up into nano-dots (11–22 nm in size) when annealed at temperatures of 330–530 °C. It is shown that the use of the Ag interlayer is effective in widening the temperature range for the ohmic formation of the Pd contact and improving the adhesion of the Pd contact to GaN. The improved ohmic behaviours are attributed to the reduction of Schottky barrier heights due to the shift of the surface Fermi level towards the valence-band edge and the formation of Ag nano-dots at the Pd/GaN interfaces.
Radiation-induced apoptosis of endothelial cells in the murine central nervous system: protection by fibroblast growth factor and sphingomyelinase deficiency. (2000)

Injury to the central nervous system (CNS) by ionizing radiation may be a consequence of damage to the vascular endothelium. Recent studies showed that radiation-induced apoptosis of endothelial cells in vitro and in the lung in vivo is mediated by the lipid second messenger ceramide via activation of acid sphingomyelinase (ASM). This apoptotic response to radiation can be inhibited by basic fibroblast growth factor or by genetic mutation of ASM. In the CNS, single-dose radiation has been shown to result in a 15% loss of endothelial cells within 24 h, but whether or not this loss is associated with apoptosis remains unknown. In the present studies, dose- and time-dependent induction of apoptosis was observed in the C57BL/6 mouse CNS. Apoptosis was quantified by terminal deoxynucleotidyl transferase-mediated nick end labeling, and specific endothelial apoptosis was determined by histochemical double labeling with terminal deoxynucleotidyl transferase-mediated nick end labeling and Lycopersicon esculentum lectin. Beginning at 4 h after single-dose radiation, apoptosis was ongoing for 24 h and peaked at 12 h at an incidence of 0.7-1.4% of the total cells in spinal cord sections. Up to 20% of the apoptotic cells were endothelial. This effect was also seen in multiple regions of the brain (medulla, pons, and hippocampus). A significant reduction of radiation-induced apoptosis was observed after i.v. basic fibroblast growth factor treatment (0.45-4.5 microg/mouse). Identical results were noted in C3H/HeJ mice. Furthermore, irradiated ASM knockout mice displayed as much as a 70% reduction in endothelial apoptosis. This study demonstrates that ionizing radiation induces early endothelial cell apoptosis throughout the CNS. These data are consistent with recent evidence linking radiation-induced stress with ceramide and suggest approaches to modify the apoptotic response in control of radiation toxicity in the CNS.