gebhart/patrepeval huggingface dataset:
Relation of Retinopathy to Coronary Artery Calcification: The Multi-Ethnic Study of Atherosclerosis (2007)

Microvascular disease, reflected by retinal vascular changes, has been shown to predict clinical coronary heart disease. Whether retinal vascular changes are associated with subclinical coronary artery disease is unclear and was examined in this study. The authors conducted a multiethnic, population-based study of 6,147 persons aged 45-84 years, sampled from six US communities in 2002-2004, who were free of clinical cardiovascular disease. Coronary artery calcification (CAC), a noninvasive measure of subclinical coronary artery disease, was assessed by cardiac computed tomography scanning and categorized into three groups of increasing severity: none (average CAC score = 0), mild (1-100), and moderate-to-severe (>100). Retinopathy signs and retinal vascular caliber were graded from retinal photographs following standardized protocols. After adjustment for age, gender, race/ethnicity, blood pressure, diabetes, lipid profile, smoking, and other risk factors, retinopathy was associated with having a moderate-to-severe CAC score (odds ratio = 1.43, 95% confidence interval: 1.18, 1.75). This association remained significant in both men and women and in persons with and without diabetes or hypertension. Variations in retinal vascular caliber were not significantly associated with CAC score. This study shows that retinopathy signs are independently associated with CAC, supporting the concept that common pathophysiologic processes may underlie both micro- and macrovascular disease.
State-dependent bioelectronic interface to control bladder function (2021)

Electrical stimulation therapies to promote bladder filling and prevent incontinence deliver continuous inhibitory stimulation, even during bladder emptying. However, continuous inhibitory stimulation that increases bladder capacity (BC) can reduce the efficiency of subsequent voiding (VE). Here we demonstrate that state-dependent stimulation, with different electrical stimulation parameters delivered during filling and emptying can increase both BC and VE relative to continuous stimulation in rats and cats of both sexes. We show that continuous 10 Hz pudendal nerve stimulation increased BC (120-180% of control) but decreased VE (12-71%, relative to control). In addition to increasing BC, state-dependent stimulation in both rats and cats increased VE (280-759% relative to continuous stimulation); motor bursting in cats increased VE beyond the control (no stimulation) condition (males: 323%; females: 161%). These results suggest that a bioelectronic bladder pacemaker can treat complex voiding disorders, including both incontinence and retention, which paradoxically are often present in the same individual.
Reinforcement Learning-based Automatic Diagnosis of Acute Appendicitis\n in Abdominal CT (2019)

Acute appendicitis characterized by a painful inflammation of the vermiform\nappendix is one of the most common surgical emergencies. Localizing the\nappendix is challenging due to its unclear anatomy amidst the complex\ncolon-structure as observed in the conventional CT views, resulting in a\ntime-consuming diagnosis. End-to-end learning of a convolutional neural network\n(CNN) is also not likely to be useful because of the negligible size of the\nappendix compared with the abdominal CT volume. With no prior computational\napproaches to the best of our knowledge, we propose the first computerized\nautomation for acute appendicitis diagnosis. In our approach, we utilize a\nreinforcement learning agent deployed in the lower abdominal region to obtain\nthe appendix location first to reduce the search space for diagnosis. Then, we\nobtain the classification scores (i.e., the likelihood of acute appendicitis)\nfor the local neighborhood around the localized position, using a CNN trained\nonly on a small appendix patch per volume. From the spatial representation of\nthe resultant scores, we finally define a region of low-entropy (RLE) to choose\nthe optimal diagnosis score, which helps improve the classification accuracy\nshowing robustness even under high appendix localization error cases. In our\nexperiment with 319 abdominal CT volumes, the proposed RLE-based decision with\nprior localization showed significant improvement over the standard CNN-based\ndiagnosis approaches.\n
Abstract A10: A distinct gene module for T cell dysfunction uncoupled from T cell activation and controlled by metallothioneins (2017)

Abstract Reversing the dysfunctional (also known as “exhausted”) T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and for only some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we leveraged mouse models to analyze RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) at various functional states. In a comparative study we identified metallothioneins, regulators of zinc metabolism, as drivers of T cell dysfunction and used genetic perturbation to identify, for the first time, a distinct gene module for T cell dysfunction that is uncoupled from T cell activation and associated with a CD8+ Treg signature. An analysis of TILs at single-cell resolution revealed that our dysfunction module negatively correlates with activation signatures also at the single-cell level, indicating that our uncoupled signatures for T cell dysfunction and activation can represent cell-intrinsic states. Clustering of the single-cells revealed a previously uncharacterized subpopulation of CD8+ TILs that was strongly enriched for our novel dysfunction signature, but not for activation signatures. This subpopulation was depleted of cells from a metallothionein KO mouse model in which T cell dysfunction was not observed, implying that we have indeed identified a phenotypically dysfunctional subpopulation. Using CRISPR/Cas9 genome editing we validate that Gata-3, a transcription factor expressed specifically in our identified subpopulation, is a driver of the dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for specifically targeting the dysfunctional T cell state while leaving T cell activation programs intact. Citation Format: Meromit Singer, Chao Wang, Le Cong, Nemanja D. Marjanovic, Monika S. Kowalczyk, Huiyuan Zhang, Jackson Nyman, Kaori Sakuishi, Sema Kurtulus, David Gennert, Junrong Xia, John YH Kwon, James Nevin, Rebecca H. Herbst, Itai Yanai, Orit Rozenblatt-Rosen, Vijay K. Kuchroo, Aviv Regev, Ana C. Anderson. A distinct gene module for T cell dysfunction uncoupled from T cell activation and controlled by metallothioneins. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A10.
Acceleration of an Aromatic Claisen Rearrangement via a Designed Spiroligozyme Catalyst that Mimics the Ketosteroid Isomerase Catalytic Dyad (2014)

A series of hydrogen-bonding catalysts have been designed for the aromatic Claisen rearrangement of a 1,1-dimethylallyl coumarin. These catalysts were designed as mimics of the two-point hydrogen-bonding interaction present in ketosteroid isomerase that has been proposed to stabilize a developing negative charge on the ether oxygen in the migration of the double bond.1 Two hydrogen bond donating groups, a phenol alcohol and a carboxylic acid, were grafted onto a conformationally restrained spirocyclic scaffold, and together they enhance the rate of the Claisen rearrangement by a factor of 58 over the background reaction. Theoretical calculations correctly predict the most active catalyst and suggest that both preorganization and favorable interactions with the transition state of the reaction are responsible for the observed rate enhancement.
Ultrasensitive fluorescence detection of DNA sequencing gels (1991)

During the three years of this grant we have: (1) Developed and applied a new theory for optimizing high-sensitivity fluorescence detection. (2) Developed and patented a new high-sensitivity confocal-fluorescence laser-excited gel-scanner. (3) Applied this scanner to the development of a new class of versatile and sensitive fluorescent dyes for DNA detection. (4) Developed methods for the detection of single fluorescent molecules by fluorescence burst detection. 11 refs., 10 figs.
HSD3B1 Genotypes Conferring Adrenal-Restrictive and Adrenal-Permissive Phenotypes in Prostate Cancer and Beyond (2019)

Castration-resistant prostate cancer (PCa) almost invariably occurs after androgen deprivation therapy for metastatic disease and is driven in part by androgen synthesis within the tumor. 3β-hydroxysteroid dehydrogenase isoenzyme-1 catalyzes the conversion of adrenal precursor steroids into potent androgens essential for PCa progression. A common 1245 A→C missense-encoding single nucleotide polymorphism in HSD3B1 (rs1047303), the gene that encodes this enzyme, leads to a more stable protein that is resistant to degradation and thus increased production of potent androgens from adrenal precursors, facilitating castration-resistant PCa development. Consistent with this mechanism, this adrenal-permissive HSD3B1(1245C) genotype is associated with inferior outcomes after androgen deprivation therapy for advanced PCa, and increased sensitivity to pharmacologic blockade of adrenal precursors in metastatic disease. Herein, we review current knowledge of the mechanisms conferred by HSD3B1 genotype to alter androgen physiology and accelerate development of castration-resistant disease and its associations with clinical PCa outcomes. In light of its effect on steroid physiology, we also discuss its potential associations with non-PCa phenotypes.
Separation of Human Breast Cancer and Epithelial Cells by Adhesion Difference in a Microfluidic Channel (2007)

A simple, label-free microfluidic cell purification method is presented for separation of cancer cells by exploiting difference in cell adhesion. To maximize the adhesion difference, three types of polymeric nanostructures (50nm pillars, 50nm perpendicular and 50nm parallel lines with respect to the direction of flow) were fabricated using UVassisted capillary moulding and included inside a polydimethylsiloxane (PDMS) microfluidic channel bonded onto glass substrate. The adhesion force of human breast epithelial cells (MCF10A) and human breast carcinoma (MCF7) was measured independently by injecting each cell line into the microfluidic device followed by culture for a period of time (e.g., one, two, and three hours). Then, the cells bound to the floor of a microfluidic channel were detached by increasing the flow rate of medium in a stepwise fashion. It was found that the adhesion force of MCF10A was always higher than that of MCF cells regardless of culture time and surface nanotopography at all flow rates, resulting in a label-free detection and separation of cancer cells. For the cell types used in our study, the optimum separation was found for 2 hours culture on 50nm parallel line pattern followed by flow-induced detachment at a flow rate of 300 ㎕/min.
Inhibition of calcium‐dependent phospholipase A2 improves blood‐brain barrier integrity in ApoE4 carrying mice (2022)

Abstract Background Blood‐brain barrier (BBB) is essential for neural health and function. Degradation of BBB is observed in Alzheimer’s disease (AD) and is more pronounced in individuals carrying the apolipoprotein E4 ( ApoE4 ) allele, which is a major genetic risk factor for AD. ApoE4 increases the activation of calcium‐dependent phospholipase A2 (cPLA2), which is linked to BBB function. Here, we asked if cPLA2 inhibition in ApoE4 carrying mice could repair BBB integrity and if the changes could be observed in vivo by dynamic contrast‐enhanced MRI (DCE‐MRI). Method 16‐month‐old ApoE4 targeted replacement (ApoE4‐TR) mice were divided into a control group treated with vehicle (n=4) and an experimental group treated with a cPLA2 inhibitor ASB‐14780 (n=4). All imaging was performed using a 7T MRI scanner. DCE‐MRI protocol involved acquisition of baseline images (5min), mice receiving a bolus of gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA, 0.3mmol/kg, i.v.)) and followed by post‐bolus scans for 20min. Regions of interest (ROIs), such as the hippocampus and isocortex, were manually defined using T2‐weighted (FSE) anatomical scans in ImageJ. Volume transfer constants (K Trans ) of the contrast agent uptake were calculated for each subject from the dynamic DCE‐MRI scan using the Patlak model on the Rocketship software (MATLAB). Result K Trans values for the isocortex and the hippocampus were calculated for two animals from the control group and three animals from the experimental group. The mean K Trans value in the hippocampus region was 60% lower for the mice treated with cPLA2 inhibitor than controls (p=0.056), 0.0459 ± 0.0168 min ‐1 and 0.117 ± 0.030 min ‐1 respectively. Similarly, the mean K Trans value in the isocortex for the treated mice was 50% lower than the controls (p=0.89), 0.0554 ± 0.018 min ‐1 and 0.110 ± 0.028 min ‐1 respectively. Conclusion We observed that cPLA2 inhibition decreased K Trans values implying increased BBB function. Thus, cPLA2 inhibition can be a possible therapeutic path towards reversing some of the damage to the brain due to AD. Currently, we are validating this observation with larger sample sizes and by analyzing the brains of these mice for changes in molecular signatures of BBB.
Coupling of nitrogen-vacancy centers in diamond to a GaP waveguide (2008)

The optical coupling of guided modes in a GaP waveguide to nitrogen-vacancy (NV) centers in diamond is demonstrated. The electric field penetration into diamond and the loss of the guided mode are measured. The results indicate that the GaP-diamond system could be useful in realizing coupled microcavity-NV devices for quantum information processing in diamond.
Up-regulation of the metabotropic glutamate receptor mGluR4 in hippocampal neurons with reduced seizure vulnerability (2000)

Selective hippocampal cell loss and altered neurotransmitter receptor expression have been proposed as pathogenic mechanisms in the development of chronic mesial temporal lobe epilepsy (TLE). Studies in animal models point to metabotropic glutamate receptors (mGluRs) as modulators of hippocampal epileptogenesis. In addition, mGluRs may constitute specific targets for the development of novel anticonvulsive drugs. As mGluR4 represents an inhibitory class III mGluR associated with the reduction of intracellular cyclic AMP levels and calcium influx, we have analyzed the regional and cellular expression of mGluR4 in surgical hippocampal specimens obtained from patients with TLE by using immunohistochemistry and in situ hybridization. Although the hippocampi of control specimens (n = 11) were almost devoid of mGluR4 immunolabeling, all TLE specimens (n = 35) showed a striking up-regulation of mGluR4 immunoreactivity, in particular within the dentate gyrus. Immunoelectron microscopy localized the receptor protein to the periphery of presynaptic and postsynaptic membranes. In situ hybridization revealed increased transcript levels of mGluR4 in dentate granule cells and residual CA4 neurons of TLE specimens compared with controls. Our results suggest a potential role of mGluR4 in counteracting excitatory hippocampal activity and in modulating seizure-associated vulnerability of hippocampal neurons. These data may also provide a basis for pharmacological studies of mGluR4 agonists as potential novel drugs in the treatment of TLE.
Gap 1 phase length and mouse embryonic stem cell self-renewal (2012)

In somatic cells, the length of the G1 phase of the cell cycle is tightly linked to differentiation, and its elongation can drive differentiation in many cases. Although it has been suggested that the situation is very similar in embryonic stem cells (ESCs), where a rapid cell cycle and a short G1 phase maintain the pluripotent state, evidence has been contradictory. Here we show that, in murine ESCs, elongation of the cell cycle and elongation of G1 are compatible with their pluripotent state. Multiple methods that lengthen the cell cycle and that target cyclin-dependent kinase, retinoblastoma protein, and E2F activity all fail to induce differentiation on their own or even to facilitate differentiation. The resistance of murine ESCs to differentiation induced by lengthening G1 and/or the cell cycle could allow for separate control of these events and provide new opportunities for investigation and application.
Expression of CFTR and a cAMP-stimulated Chloride Secretory Current in Cultured Human Fetal Alveolar Epithelial Cells (1993)

During development the fetal lung secretes fluid that is osmotically linked to chloride (Cl-) transport. One possible pathway for Cl- secretion across the fetal pulmonary epithelium is through the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is expressed in epithelia and functions as a Cl- channel regulated by cyclic adenosine monophosphate (cAMP)-dependent protein kinase and intracellular ATP. Previous studies have shown that CFTR mRNA is expressed throughout the human fetal pulmonary epithelium and CFTR protein can be immunoprecipitated from human fetal lung homogenates. In cultured fetal lung tissue explants, CFTR mRNA was localized to alveolar epithelial cells. To test the hypothesis that fetal alveolar epithelial cells express functional CFTR, we immunolocalized CFTR in human fetal lung and looked for evidence of Cl- secretion in cultured alveolar epithelial cell monolayers. Monoclonal anti-CFTR antibodies localized CFTR in cultured lung explants to the epithelial cells, predominantly at the apical surface. Bioelectric properties of cultured monolayers of midgestation fetal alveolar epithelial cells were measured in modified Ussing chambers. In unstimulated monolayers, transepithelial electrical potential difference (psi t) = -1.1 +/- 0.1 mV, transepithelial resistance (Rt) = 768 +/- 58 omega.cm2, and short-circuit current (Isc) = 1.9 +/- 0.2 microA/cm2 (mean +/- SE, n = 17). Addition of amiloride to the apical surface significantly decreased basal Isc. Apical diphenylamine-2-carboxylate (DPC), a Cl- channel inhibitor, caused no significant change in basal Isc. In the presence of apical amiloride, isoproterenol significantly increased Isc, a response that was inhibited by apical DPC and submucosal bumetanide. The cAMP agonists forskolin and IBMX also stimulated Isc.(ABSTRACT TRUNCATED AT 250 WORDS)
Spatial Correlation of PAN UWB-MIMO Channel Including User Dynamics (2007)

In this paper we present and analyze spatial correlation properties of indoor 4x2 MIMO UWB channels in personal area network (PAN) scenarios. The presented results are based on measurement of radio links between an access point like device and a hand held or belt mounted device with dynamic user. It is found the channel shows spatial correlated wideband power, and spatial uncorrelated complex channel coefficients at different frequencies and delays with respect to a correlation coefficient threshold of 0.7. The Kronecker model is proved not suitable for<br/>the investigated scenarios. The MIMO UWB channel achieves an ergodic capacity close to i.i.d. Rayleigh channel capacity. However the outage capacity degrades due to the wideband power fluctuation / shadowing introduced by user’s body.
Fire Hazards of Small Hydrogen Leaks (2007)

This study examines the types of hydrogen leaks that can support combustion and the effects on stainless steel of long term hydrogen flame exposure. Experimental and analytical work is presented. Hydrogen diffusion flames on round burners were observed. Measurements included limits of quenching, blowoff, and piloted ignition for burners with diameters of 0.36 - 1.78 mm. Results are compared to measurements for methane and propane. A dimensionless crack parameter was identified to correlate the quenching limit measurements. Flow rates were 0.019 - 40 mg/s for hydrogen, 0.12 - 64 mg/s for methane, and 0.03 - 220 mg/s for propane. Hydrogen flames were found to be corrosive to 316 stainless steel tubing.
Intravascular polarization sensitive optical coherence tomography in human patients (2016)

Polarization sensitive optical coherence tomography (PS-OCT) provides measures of tissue birefringence and depolarization. Here, we demonstrate catheter-based PS-OCT in the coronary arteries of human patients to obtain valuable insight into the morphology of atherosclerotic plaques.
Excitation orthogonale d'antennes a resonateur dielectrique par une ligne microfente (2005)

National audience
ChemInform Abstract: Luminescence Properties of a Blue‐Emitting Phosphor: (Sr1‐xEux)Si9Al19ON31 (0 < x ≤ 1). (2013)

Abstract The blue‐emitting title phosphors are synthesized from mixtures of AlN, α‐Si 3 N 4 , SrCO 3 , and Eu 2 O 3 (1 MPa N 2 , 1800 °C, 2 h).
Pedestrian detection with a Large-Field-Of-View deep network (2015)

Pedestrian detection is of crucial importance to autonomous driving applications. Methods based on deep learning have shown significant improvements in accuracy, which makes them particularly suitable for applications, such as pedestrian detection, where reducing the miss rate is very important. Although they are accurate, their runtime has been at best in seconds per image, which makes them not practical for onboard applications. We present a Large-Field-Of-View (LFOV) deep network for pedestrian detection, that can achieve high accuracy and is designed to make deep networks work faster for detection problems. The idea of the proposed Large-Field-of-View deep network is to learn to make classification decisions simultaneously and accurately at multiple locations. The LFOV network processes larger image areas at much faster speeds than typical deep networks have been able to, and can intrinsically reuse computations. Our pedestrian detection solution, which is a combination of a LFOV network and a standard deep network, works at 280 ms per image on GPU and achieves 35.85 average miss rate on the Caltech Pedestrian Detection Benchmark.
Src homology 2 domains of protein tyrosine phosphatase are associated in vitro with both the insulin receptor and insulin receptor substrate‐1 via different phosphotyrosine motifs (1994)

To clarify the role of protein tyrosine phosphatase containing Src homology 2 (SH2) regions on insulin signaling, we investigated the interactions among the insulin receptor, a pair of SH2 domains of SH-PTP2 coupled to glutathione-S-transferase (GST) and insulin receptor substrate-1 (IRS-1)-GST fusion protein (amino-portion, IRS-IN; carboxyl portion, IRS-1C). GST-SH2 protein of SH-PTP2 bound to the wild type insulin receptor, but not to that with a carboxyl-terminal mutation (Y/F2). Furthermore, even though Y/F2 receptors were used, the SH2 protein was also co-immunoprecipitated with IRS-IC, but not with IRS-IN. These results indicate that SH2 domains of SH-PTP2 can directly associate with the Y1322TXM motif on the carboxyl terminus of insulin receptors and also may bind to the carboxyl portion of IRS-1, possibly via the Y1172IDL motif in vitro.