gebhart/patrepeval huggingface dataset:
Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas (2021)

Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and bear dismal prognoses compared to group B ependymomas (PFBs). PFAs overexpress the oncohistone-like protein EZHIP (enhancer of Zeste homologs inhibitory protein), causing global reduction of repressive histone H3 lysine 27 trimethylation (H3K27me3), similar to the oncohistone H3K27M. Integrated metabolic analyses in patient-derived cells and tumors, single-cell RNA sequencing of tumors, and noninvasive metabolic imaging in patients demonstrated enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism in PFAs. Furthermore, high glycolytic gene expression in PFAs was associated with a poor outcome. PFAs demonstrated high EZHIP expression associated with poor prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Genomic H3K27ac was enriched in PFAs at key glycolytic and TCA cycle–related genes including <i>hexokinase-2</i> and <i>pyruvate dehydrogenase</i>. Similarly, mouse neuronal stem cells (NSCs) expressing wild-type EZHIP (EZHIP-WT) versus catalytically attenuated EZHIP-M406K demonstrated H3K27ac enrichment at <i>hexokinase-2</i> and <i>pyruvate dehydrogenase</i>, accompanied by enhanced glycolysis and TCA cycle metabolism. <i>AMPK</i>α<i>-2</i>, a key component of the metabolic regulator AMP-activated protein kinase (AMPK), also showed H3K27ac enrichment in PFAs and EZHIP-WT NSCs. The AMPK activator metformin lowered EZHIP protein concentrations, increased H3K27me3, suppressed TCA cycle metabolism, and showed therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts in mice. Our data indicate that PFAs and EZHIP-WT–expressing NSCs are characterized by enhanced glycolysis and TCA cycle metabolism. Repurposing the antidiabetic drug metformin lowered pathogenic EZHIP, increased H3K27me3, and suppressed tumor growth, suggesting that targeting integrated metabolic/epigenetic pathways is a potential therapeutic strategy for treating childhood ependymomas.
A discrete-time method of demodulating large deviation FM signals (1999)

A method of enhancing the performance of a numerical FM discriminator in specific receive signal conditions, using frequency feedback techniques, is developed and evaluated. The receive signal conditions of interest are: (1) frequency deviations that are large relative to the bandwidth of the message signal; (2) a low-uniform (complex) sample rate commensurate with the bandwidth; and (3) noise strengths that yield values of input carrier-to-noise ratio of the order of 10 dB or more. Through computer simulation, observed phase cycle-slip counts and phase noise variance estimation are used to compare the enhanced demodulator to the performance of a numerical FM discriminator baseline. Based upon the theoretical analyses and simulation results, the presented method of numerical FM demodulation is shown to be a viable technique for enhancing the performance of numerical FM discriminators under the given modulation conditions.
Privacy Protection by Anonymizing Based on Status of Provider and Community (2012)

When a user receives personal services from a service provider, the service can be of a higher quality if the user pro-vides more personal information. However, the risk of privacy violation could increase. Therefore, this paper proposes a privacy protection method that realizes avoidance of unwanted informa-tion disclosure by controlling disclosable attributes according to the results from monitoring two elements: user background in-formation of the provider and user community status. This is done before disclosing individual attributes corresponding to the privacy policy (i.e., the required anonymity level) by each user. The system architecture based on the aforementioned is also pro-posed. The validity of the proposed methods was confirmed by a desk model.
MMR (1999)

We present a system for rendering very complex 3D models at interactive rates. We select a subset of the model as preferred viewpoints and partition the space into virtual cells. Each cell contains near geometry, rendered using levels of detail and visibility culling, and far geometry, rendered as a textured depth mesh. Our system automatically balances the screen-space errors resulting from geometric simplification with those from textureddepth-mesh distortion. We describe our prefetching and data management schemes, both crucial for models significantly larger than available system memory. We have successfully used our system to accelerate walkthroughs of a 13 million triangle model of a large coal-fired power plant and of a 1.7 million triangle architectural model. We demonstrate the walkthrough of a 1.3 GB power plant model with a 140 MB cache footprint.
<i>PLA2G6</i> Mutations Related to Distinct Phenotypes: A New Case with Early-onset Parkinsonism (2016)

<strong>Background:</strong> <em>PLA2G6</em>-associated neurodegeneration (PLAN) is a recessive neurodegenerative disorder characterized by three distinct phenotypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and <em>PLA2G6</em>-related dystonia–parkinsonism. <strong>Methods:</strong> A consanguineous index case from Turkey was diagnosed with early-onset Parkinsonism at the Istanbul Faculty of Medicine. She and her unaffected brother were subjected to whole-genome sequencing. <strong>Results:</strong> In this report, we describe a 33-year-old index case with parental consanguinity and early-onset Parkinsonism. Whole-genome sequencing of this individual revealed that a homozygous p.R747W mutation in <em>PLA2G6</em> segregates with the disease in this family <strong>Discussion:</strong> This result supports the importance of prioritizing this gene in mutational analysis of autosomal recessive Parkinsonism, and confirms the clinical heterogeneity of PLAN.
Artificial Intelligence With Deep Learning Technology Looks Into Diabetic Retinopathy Screening (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
MULTIPLE CRAFT HARVESTING FROM DEEP PARTIAL THICKNESS SCALD WOUNDS HEALED UNDER THE INFLUENCE OF WEAK DIRECT CURRENT (1988)

s of Papers to be Presented at the 48th Annual Session: American Association for the Surgery of Trauma Westin South Coast Plaza Newport Beach, California October 6–8, 1988: PDF Only
The Voltage Dependence of Degradation in n-MOS Transistors (1987)

Hot carrier stressing has been carried out on silicon n-MOS devices as a function of gate voltage, at fixed drain voltages. It is found that a maximum of degradation occurs not only at V q =Vd/2, but also at V q =Vd. It is further found that the time power law for threshold voltage shift changes according to the voltage ratio. It is suggested that while the first peak is due to interface state degradation, the second is due to another process, possibly electron trapping in the oxide.
Self-fit generation of the wide range compression parameters in hearing aids (2019)

OpenMHA is an open source software executing the real time signal processing algorithms with reduced latency between the input and the output signals. In this abstract, we elaborate on a hearing aid fitting algorithm, which tunes the Wide Dynamic Range Compression (WDRC) algorithm parameters through a A-B comparison test. The following approach is adopted-The left and the right audiogram values are clustered using the Gaussian Mixture model. A value is assigned to more than one cluster with a probability. The cluster labels are assigned according to the model yielding the maximum log likelihood-The best fit for the audiogram values of user is used to calculate the WDRC parameters. Recording the audiogram values of individual user and tuning the parameters by the audiologists can be a cumbersome task. Web-app is implemented to present A-B comparison to the users to determine the best fit audiogram values. The Open Speech Platform (OSP) comprises of Embedded Web Server (EWS) presenting the web-app. It guides the user to determine the best fit through a AVL tree based binary search algorithm. The device aims to determine the best fit in reduced number of steps, post which the WDRC parameters are determined through the NAL-NL2 libraries. This search algorithm for each user, and listener’s feedback on the success of the fit using the ecological monetary assessment (EMA) app, with the environmental sound data logging can be leveraged further to create auto fit algorithms in dynamic environments using MCTS in reinforcement learning.
Supplemental Figure 1 from First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors (2023)

&lt;p&gt;Trop-2 expression in archived tissue specimens from 6 patients enrolled in the clinical trial with sacituzumab govitecan.&lt;/p&gt;
Pharmacokinetics and Pharmacodynamics of CNTO 528, a Novel Erythropoietin Receptor Agonist in Normal and Anemic Rats. (2005)

Abstract CNTO 528 is a member of a group of novel stimulants of erythropoiesis that has recently entered clinical trials. Although CNTO 528 bears no sequence homology to erythropoietin (EPO), it is an EPO receptor agonist, capable of rescuing EPO-dependent cells from apoptosis in vitro and stimulating erythropoiesis in vivo. The purpose of these experiments was to explore the pharmacodynamics and pharmacokinetics of CNTO 528 in normal rats and to evaluate its efficacy in rat models of anemia. In vitro, CNTO 528 was approximately 10-fold less potent on a molar basis than recombinant human EPO (rhEPO) in stimulating the growth of UT-7EPO cells. Despite the lower in vitro potency, when compared to rhEPO and darbepoetin in normal rats, a single subcutaneous dose of CNTO 528 caused a longer-lived reticulocytosis and a longer-lived increase in hemoglobin. Also, CNTO 528 caused only minor changes in red cell distribution width (RDW) or mean cell volume (MCV) led to the release of mature reticulocytes and had no effect on mean platelet volume (MPV). We have also shown that CNTO 528 was efficacious in rat models of anemia and in a rat model of pure red cell aplasia. Taken together, our data show that CNTO 528 is a novel stimulant of erythropoiesis in rats.
<title>Research and development of Ce-doped GSO scintillation crystals</title> (1994)

We review the status quo and the history of development of Ce doped GSO (Gd<SUB>2</SUB>SiO<SUB>5</SUB>:Ce) single crystals, a typical heavy and fast scintillator of large light output. GSO:Ce has 6.7 g/cm<SUP>3</SUP> in density, 1.38 cm in radiation length and 30-60 ns in decay constant. The light output is two times as large as BGO. It shows, overall, the best performance among all the scintillators developed until now. The radiation damage caused by gamma ray from Co, proton in GeV order and thermal neutrons were studied on GSO:Ce crystals with various Ce concentrations. A description is given on the luminescence mechanism by Ce in GSO and growth technology for crack-free large GSO crystals. We believe that GSO crystals are scintillators having all the excellent characteristics required for gamma ray detectors.
Chiral catalytic activities in magnetoelectrochemical etching (2015)

Chiral catalytic activities of electrode surfaces fabricated by magnetoelectrochemical etching without oxygen adsorption in a vertical magnetohydrodynamic (MHD) flow have been theoretically examined. Then, the following points were clarified: under anionic specific adsorption, such activities arise from the screw dislocations of 2D pits. Their chirality is donated by microscopic vortexes termed micro-MHD flows, which are formed on the free surfaces covered with ionic vacancies. As a result, under upward (+) and downward (-) magnetic fields, D (dextrorotatory)- and L (levorotatory)-activities appear, respectively.
Greater than 100W diode-pumped Tm:YAG laser and its thermal issues (2001)

We discuss in this paper the serious thermal issues faced by a high average power (&gt;100W) diode-side-pumped 2-micron Tm:YAG laser. An approach to quantify the thermal lensing with subsequent cavity designing to alleviate such thermal issues is presented. The simple approach outlined allows one to come up with appropriate cavity configurations quickly to overcome the thermal rollover and to power scale the laser. Such a technique is applicable to all high average power solid- state rod lasers which inevitably suffers from severe thermal aberrations.
Histone Deacetylase 3 Down-regulates Cholesterol Synthesis through Repression of Lanosterol Synthase Gene Expression (2007)

In vertebrates, a key step in the biosynthesis of cholesterol and steroid hormones is the conversion of (S)-2,3-oxidosqualene to lanosterol. The enzyme that catalyzes this complex cyclization/rearrangement step via the protosteryl cation intermediate is lanosterol synthase ((S)-2,3-epoxysqualene mutase (cyclizing, lanosterol forming), EC 5.4.99.7). Because of the crucial role that lanosterol synthase plays in cholesterol biosynthesis, there is great interest in the identification of drugs that target this enzyme for anticholesteremic purposes. Although most studies on lanosterol synthase in the past have focused on the structural and biochemical functions of this enzyme, almost nothing is known concerning how the synthesis of lanosterol synthase is regulated. Here, we report that histone deacetylase 3 (HDAC3) represses transcription from the lanosterol synthase promoter. Overexpression of HDAC3 decreases, whereas knockdown of HDAC3 by small interfering RNA increases, endogenous lanosterol synthase mRNA in cells. Similarly, in transient transfection assays, overexpression of HDAC3 decreases, whereas depletion of HDAC3 increases, expression of a reporter gene under the control of the lanosterol synthase promoter. Stable cell lines that overexpress HDAC3 show a decrease in lanosterol synthase mRNA and have lower cholesterol concentrations compared with parental cells. Extensive promoter analyses coupled with chromatin immunoprecipitation assays reveal that the transcription factor YY1 binds to and recruits HDAC3 to the lanosterol synthase promoter. Together, our results demonstrate that HDAC3 represses the synthesis of a key regulatory enzyme and reveal a novel mechanism by which the cholesterol biosynthetic pathway can be regulated.
Tea Flavanols Block Advanced Glycation of Lens Crystallins Induced by Dehydroascorbic Acid (2014)

Growing evidence has shown that ascorbic acid (ASA) can contribute to protein glycation and the formation of advanced glycation end products (AGEs), especially in the lens. The mechanism by which ascorbic acid can cause protein glycation probably originates from its oxidized form, dehydroascorbic acid (DASA), which is a reactive dicarbonyl species. In the present study, we demonstrated for the first time that four tea flavanols, (-)-epigallocatechin 3-O-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin 3-O-gallate (ECG), and (-)-epicatechin (EC), could significantly trap DASA and consequently form 6C- or 8C-ascorbyl conjugates. Among these four flavanols, EGCG exerted the strongest trapping efficacy by capturing approximate 80% of DASA within 60 min. We successfully purified and identified seven 6C- or 8C-ascorbyl conjugates of flavanols from the chemical reaction between tea flavanols and DASA under slightly basic conditions. Of which, five ascorbyl conjugates, EGCGDASA-2, EGCDASA-2, ECGDASA-1, ECGDASA-2 and ECDASA-1, were recognized as novel compounds. The NMR data showed that positions 6 and 8 of the ring A of flavanols were the major active sites for trapping DASA. We further demonstrated that tea flavanols could effectively inhibit the formation of DASA-induced AGEs via trapping DASA in the bovine lens crystallin-DASA assay. In this assay, 8C-ascorbyl conjugates of flavanols were detected as the major adducts using LC-MS. This study suggests that daily consumption of beverages containing tea flavanols may prevent protein glycation in the lens induced by ascorbic acid and its oxidized products.
Silicon nitride waveguides with intrinsic single-photon emitters for integrated quantum photonics (2022)

The recent discovery of room temperature intrinsic single-photon emitters in silicon nitride (SiN) provides the unique opportunity for seamless monolithic integration of quantum light sources with the well-established SiN photonic platform. In this work, we develop a novel approach to realize planar waveguides made of low-autofluorescing SiN with intrinsic quantum emitters and demonstrate the single-photon emission coupling into the waveguide mode. The observed emission coupling from these emitters is found to be in line with numerical simulations. The coupling of the single-photon emission to a waveguide mode is confirmed by second-order autocorrelation measurements of light outcoupled off the photonic chip by grating couplers. Fitting the second-order autocorrelation histogram yields $g^{(2)}(0)=0.35\pm0.12$ without spectral filtering or background correction with an outcoupled photon rate of $10^4$ counts per second. This demonstrates the first successful coupling of photons from intrinsic single-photon emitters in SiN to monolithically integrated waveguides made of the same material. The results of our work pave the way toward the realization of scalable, technology-ready quantum photonic integrated circuitry efficiently interfaced with solid-state quantum emitters.
Inhibiting the Recruitment of PLCγ1 to Kaposi’s Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells (2015)

Kaposi's sarcoma (KS), caused by Kaposi's sarcoma herpesvirus (KSHV), is a highly vascularised tumour of endothelial origin. KSHV infected endothelial cells show increased invasiveness and angiogenesis. Here, we report that the KSHV K15 protein, which we showed previously to contribute to KSHV-induced angiogenesis, is also involved in KSHV-mediated invasiveness in a PLCγ1-dependent manner. We identified βPIX, GIT1 and cdc42, downstream effectors of PLCγ1 in cell migration, as K15 interacting partners and as contributors to KSHV-triggered invasiveness. We mapped the interaction between PLCγ1, PLCγ2 and their individual domains with two K15 alleles, P and M. We found that the PLCγ2 cSH2 domain, by binding to K15P, can be used as dominant negative inhibitor of the K15P-PLCγ1 interaction, K15P-dependent PLCγ1 phosphorylation, NFAT-dependent promoter activation and the increased invasiveness and angiogenic properties of KSHV infected endothelial cells. We increased the binding of the PLCγ2 cSH2 domain for K15P by substituting two amino acids, thereby creating an improved dominant negative inhibitor of the K15P-dependent PLCγ1 activation. Taken together, these results demonstrate a necessary role of K15 in the increased invasiveness and angiogenesis of KSHV infected endothelial cells and suggest the K15-PLCγ1 interaction as a possible new target for inhibiting the angiogenic and invasive properties of KSHV.
Glycogen Storage Disease Diagnosed in Adults (1992)

Glycogen storage diseases are usually identified in childhood. We present the clinical, biochemical and histological features of 10 patients first diagnosed in adult life. Five had glycogen storage disease type 1a, one type 1c, two type IX, and in two patients there were previously unreported abnormalities of hepatic glucose-6-phosphatase system activity. Of the latter, one patient had an inhibitor of liver glucose-6-phosphatase (pseudo-1b glycogen storage disease) the other having abnormal glucose-6-phosphatase activity and microsomal pyrophosphate transport. A glucagon test is suggested as a useful screening procedure. Glycogen storage disease should be considered in adults with symptoms suggesting hypoglycaemia.
Scaling analog circuits into deep nanoscale CMOS: Obstacles and ways to overcome them (2015)

Analog circuits provide the critical interfaces between the digital world inside today's integrated circuits and the physical world. Semiconductor technology scaling driven by `Moore's Law' has resulted in a phenomenal scaling of the performance of digital processors and memory. Continuing design innovations have enabled the scaling of analog interfaces onto scaled CMOS technologies, even though device scaling is a mixed blessing for the analog designer. This paper reviews the scaling challenges for analog circuits ranging from fundamental to practical challenges. Design strategies are outlined that in principle can overcome the challenges and can help guide the search for new circuit paradigms. Several examples of innovative analog design paradigms are reviewed and the opportunities in highly scaled CMOS technologies are outlined.