gebhart/patrepeval huggingface dataset:
Abstract 2060: microRNA-dependent modulation of histone acetylation in Waldenstrom's Macroglobulinemia (2010)

Abstract Introduction. Epigenetic regulation of gene-expression, including histone acetylation, is commonly deregulated in many malignancies leading to aberrant transcription, but microRNA (miRNA)-dependent modulation of histone acetylation in Waldenstrom's Macroglobulinemia (WM) has not been evaluated yet. Methods. miRNA and gene-expression profiling have been performed on bone-marrow-derived CD19+ WM cells, compared to their normal cellular counterparts. Purified cRNA was hybridized to HG-U133Plus2.0 GeneChip (Affimetrix). A liquid phase Luminex microbead miRNA profiling (Luminex, Austin, TX) has been used for miRNA studies. To further define those miRNAs differentially expressed between groups (patients vs normal), the data were filtered on significance of differences using ANOVA test, (P &amp;lt; 0.01). Microbead-miRNA profiling data were validated data by stem-loop qRT-PCR. To identify specific predicted miRNA-targeted mRNAs, TargetScan, PicTar, and miRanda algorithms were used. Functional studies were performed on precursor-miRNA-9* and anti-miRNA-206-transfected WM cells, as compared to either scramble probe-transfected or non-transfected cells. HDAC activity was determined by using Colorimetric HDAC Activity Assay Kit. Effect on signaling cascades have been evaluated by western blot and immunofluorescence. DNA proliferation, cytotoxicity, cell cycle, and apoptosis were assessed by thymidine incorporation, MTT, PI, and Apo2.7 staining, respectively. Results. WM cells present with a specific miRNA signature characterized by increased expression of miRNA-206 and decreased expression of miRNA-9* (ANOVA;P&amp;lt; 0.01). Predicted targets for miRNA-206 and −9* include histone-deacetylases (HDAC4; HDAC5) and -acetyltransferases (Myst3). We first demonstrated that primary WM cells are characterized by unbalanced expression of HDACs and HATs at gene level with higher level of HDACs and lower level of HATs, responsible for decreased acetylated-histone-H3 and -H4, at protein level and increased HDAC activity. miRNA-206 and −9* played a functional role in regulating histone-acetylation and HDAC activity in WM cells, based on their ability to target HDACs and HATs; leading to induction of toxicity in precursor-miRNA-9* or anti-miRNA-206-transfected cells, as shown by reduced proliferation rate, cell cycle arrest, induction of apoptosis, supported by PARP-, caspase-8- and −9-cleavage. In addition, miRNA-9*-induced autophagy in WM cells by modulating Rab7 and LC3B. Conclusion. These findings confirm that histone-modifying genes and HDAC activity are de-regulated in WM cells; this may be partially driven by the aberrant expression of miRNA-206 and −9* in the tumor clone; and provide the basis for the development of miRNA-based targeted therapies in WM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2060.
PPARγ-K107 SUMOylation regulates insulin sensitivity but not adiposity in mice (2018)

The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and is the target for the insulin-sensitizing thiazolidinedione (TZD) drugs used to treat type 2 diabetes. In cell-based in vitro studies, the transcriptional activity of PPARγ is inhibited by covalent attachment of small ubiquitin-related modifier (SUMOylation) at K107 in its N terminus. However, whether this posttranslational modification is relevant in vivo remains unclear. Here, using mice homozygous for a mutation (K107R) that prevents SUMOylation at this position, we demonstrate that PPARγ is SUMOylated at K107 in white adipose tissue. We further show that in the context of diet-induced obesity PPARγ-K107R-mutant mice have enhanced insulin sensitivity without the corresponding increase in adiposity that typically accompanies PPARγ activation by TZDs. Accordingly, the PPARγ-K107R mutation was weaker than TZD treatment in stimulating adipocyte differentiation in vitro. Moreover, we found that both the basal and TZD-dependent transcriptomes of inguinal and epididymal white adipose tissue depots were markedly altered in the K107R-mutant mice. We conclude that PPARγ SUMOylation at K107 is physiologically relevant and may serve as a pharmacologic target for uncoupling PPARγ's beneficial insulin-sensitizing effect from its adverse effect of weight gain.
Glial activation in prion diseases is strictly nonautonomous and requires neuronal PrP Sc (2021)

Although prion infections cause cognitive impairment and neuronal death, transcriptional and translational profiling shows progressive derangement within glia but surprisingly little changes within neurons. Here we expressed PrP C selectively in neurons, astrocytes or oligodendrocytes of mice. After prion infection, both astrocyte and neuron-restricted PrP C expression led to copious brain accumulation of PrP Sc . As expected, neuron-restricted expression was associated with typical prion disease. However, mice with astrocyte-restricted PrP C expression experienced a normal life span, did not develop clinical disease, and did not show astro- or microgliosis. Besides confirming that PrP Sc is innocuous to PrP C -deficient neurons, these results show that astrocyte-born PrP Sc does not activate the extreme neuroinflammation that accompanies the onset of prion disease and precedes any molecular changes of neurons. This points to a nonautonomous mechanism by which prion-infected neurons instruct astrocytes and microglia to acquire a specific cellular state that, in turn, drives neural dysfunction.
IFITM-2 and IFITM-3 but Not IFITM-1 Restrict Rift Valley Fever Virus (2013)

We show that interferon-induced transmembrane protein 1 (IFITM-1), IFITM-2, and IFITM-3 exhibit a broad spectrum of antiviral activity against several members of the Bunyaviridae family, including Rift Valley fever virus (RVFV), La Crosse virus, Andes virus, and Hantaan virus, all of which can cause severe disease in humans and animals. We found that RVFV was restricted by IFITM-2 and -3 but not by IFITM-1, whereas the remaining viruses were equally restricted by all IFITMs. Indeed, at low doses of alpha interferon (IFN-α), IFITM-2 and -3 mediated more than half of the antiviral activity of IFN-α against RVFV. IFITM-2 and -3 restricted RVFV infection mostly by preventing virus membrane fusion with endosomes, while they had no effect on virion attachment to cells, endocytosis, or viral replication kinetics. We found that large fractions of IFITM-2 and IFITM-3 occupy vesicular compartments that are distinct from the vesicles coated by IFITM-1. In addition, although overexpression of all IFITMs expanded vesicular and acidified compartments within cells, there were marked phenotypic differences among the vesicular compartments occupied by IFITMs. Collectively, our data provide new insights into the possible mechanisms by which the IFITM family members restrict distinct viruses.
Acoustic wave electroless deposition monitor (1987)

A new type of electroless deposition monitor has been constructed from a monolithic acoustic wave device utilizing plate modes with shear displacement components. This device, which operates at 158 MHz, provides a highly accurate means of measuring mass changes (1 ng/cm/sup 2/) accompanying electrochemical reactions. The acoustic wave, in the form of a plate mode, is launched by applying a radio frequency signal to an interdigital transducer on one face of a piezoelectric substrate. Electroless deposition is carried out on the opposite face of the quartz in the path of the wave. The acoustic plate mode, which propagates along the quartz plate to the receiving transducer, has components of displacement at the surface/electrolyte interface. Changes in mass at the quartz/electrolyte interface affect the acoustic wave velocity, which is monitored with high accuracy by utilizing the device as the feedback element of an oscillator circuit. The electroless deposition of Cu at a rate of 2 to 3 A/sec from aqueous Cu/sup 2 +//formaldehyde was monitored with sub-angstrom resolution. 18 refs., 6 figs.
A Glucose Biosensor Based on Surface-Enhanced Raman Scattering:  Improved Partition Layer, Temporal Stability, Reversibility, and Resistance to Serum Protein Interference (2003)

This work updates the recent progress made toward fabricating a real-time, quantitative, and biocompatible glucose sensor based on surface-enhanced Raman scattering (SERS). The sensor design relies on an alkanethiolate tri(ethylene glycol) monolayer that acts as a partition layer, preconcentrating glucose near a SERS-active surface. Chemometric analysis of the captured SERS spectra demonstrates that glucose is quantitatively detected in the physiological concentration range (0−450 mg/dL, 0−25 mM). In fact, 94% of the predicted glucose concentrations fall within regions A and B of the Clarke error grid, making acceptable predictions in a clinically relevant range. The data presented herein also demonstrate that the glucose sensor provides stable SERS spectra for at least 3 days, making the SERS substrate a candidate for implantable sensing. Glucose sensor reversibility and reusability is evaluated as the sensor is alternately exposed to glucose and saline solutions; after each cycle, difference spectra reveal that the partitioning process is largely reversible. Finally, the SERS glucose sensor successfully partitions glucose even when challenged with bovine serum albumin, a serum protein mimic.
Organic Nanoparticles: Adapting Emerging Techniques from the Electronics Industry for the Generation of Shape‐Specific, Functionalized Carriers for Applications in Nanomedicine (2007)

This chapter contains sections titled: Overview Methods Bottom-Up Approaches for the Synthesis of Organic Nanoparticles Top-Down Approaches for the Fabrication of Polymeric Nanoparticles Microfluidics Photolithography Imprint Lithography IRINT Outlook References
P-126 PTG-100, An Oral Peptide Antagonist of Integrin α4β7 that Alters Trafficking of Gut Homing T Cells in Preclinical Animal Models (2016)

The α4β7 integrin is a clinically validated target in inflammatory bowel disease (IBD). Vedolizumab (Entyvio®), a humanized monoclonal antibody that specifically binds to the α4β7 integrin, is FDA-approved for the treatment of moderate-to-severe ulcerative colitis and Crohn's disease. Vedolizumab binds to α4β7 on circulating memory/effector T cells in the blood and blocks their homing to intestinal tissues expressing the ligand MAdCAM-1. The aim of this study is to characterize PTG-100, a novel oral α4β7 antagonist peptide that is largely restricted to the gut tissues, and is pharmacologically active in murine colitis models and in normal cynomolgus monkeys. Pharmacokinetic (PK) studies of PTG-100 were conducted in mice, rats, and cynomolgus monkeys, with peptide concentrations measured by mass spectrometry. Pharmacodynamic (PD) studies were conducted in murine colitis models and in healthy cynomolgus monkeys. Cell trafficking in blood and gut lymphoid tissues was measured by FACS or immunohistochemistry (IHC). PTG-100 is a potent antagonist of α4β7 (IC50 = 1 nM), but inactive against α4β1, αLβ2 or αEβ7 as measured in a variety of biochemical and cellular assays. Oral dosing of PTG-100 in normal or dextran sodium sulfate (DSS)-treated mice and rats showed dose-dependent exposure in the small intestine, colon, mesenteric lymph nodes (MLN) and Peyer's Patches (PP), but much lower exposure if any in blood and urine. Oral dosing of a fluorescent dye conjugate of PTG-100 and imaging by fluorescence microscopy or IHC showed the peptide accumulates in the lamina propria of tissues from the small intestine. Daily dosing with PTG-100 in murine DSS colitis models showed a dose-dependent reduction of CD4+CD44high CD45RBlow β7+ T cells in the MLN and PP, and a concomitant increase in the spleen and blood as measured by FACS. There was also a strong reduction of β7+ cell infiltration into lamina propria lesions of the distal colon as measured by IHC. PTG-100 also caused a dose-dependent reduction in body weight loss and mucosal injury as assessed by endoscopy. Daily oral dosing of PTG-100 in normal cynomolgus monkeys resulted in high blood receptor occupancy of memory T cells, and a dose-dependent increase in the percentage of α4β7 memory CD4+ T cells in the blood. There were no adverse clinical or microscopic changes with PTG-100 administration in 6-week GLP toxicology studies in rat and monkey up to 90 and 75 mg·kg−1·d−1, respectively. Safety pharmacology and mutagenesis studies demonstrated no adverse findings. PTG-100 is a first-in-class oral α4β7-selective antagonist being developed for the treatment of patients with IBD. PTG-100 reaches high concentrations in gut tissues and alters the trafficking of gut-homing T cells in mice and cynomolgus monkeys. The lack of toxicity in the full battery of safety and toxicology studies to date coupled with low exposure in blood suggest that PTG-100 will be suitable for human trials.
Recent Advances in the Treatment of Achalasia (1997)

Achalasia is a disorder of the esophagus characterized by aperistalsis and failure of the lower esophageal sphincter to relax. This article discusses traditional and new therapies directed against the sphincter muscle. Because limitations of these treatments do exist, alternatives to sphincter destruction are presented.
Routing and Addressing with Length Variable IP Address (2019)

IP addressing has become the core of Internet since the Internet was invented and its significance has never changed. However, with the dramatic development of Internet in recent years, the conventional IP address is facing with more and more problems, such as address exhaustion, low packet efficiency in Internet of Things, etc. The reason is that the conventional IP address is designed with fixed length, lacking of extensibility, while the demands for address varies greatly in different cases. To solve these problems, we propose a new address system called Flexible Address System (FAS). The FAS is designed with an infinite address space and can provide variable-length addresses on demand. Accordingly, multiple Routing Information Bases (RIBs) are used on routers to store FAS routing entries according to their different length. Further, a new data structure called Multi-Entrance-Trie (METrie) is proposed as the realization of multiple RIBs. The METrie is designed with multiple entrance nodes, enabling fast lookup. Experiments show that the METrie can achieve a high efficiency lookup on routers with less storage costs, implying that the FAS is friendly to the scale of routing table.
EP074/#619 Single molecule array (SIMOA) for the detection of cervical dysplasia and cancer (2022)

<h3>Objectives</h3> The appropriate triage of abnormal cervical cancer screening results can limit colposcopy to those at highest risk. The objective of this study was to incorporate antibodies associated with cervical dysplasia and carcinoma onto the Single Molecule Array (Simoa) platform and to identify the optimal combination of biomarkers. <h3>Methods</h3> Patient samples were collected from colposcopy, gynecologic oncology or gynecology and radiation oncology. Antibody-coated capture beads with biomarkers of interest were added to the cervical sample, incubated with a biotinylated detection antibody to form an enzyme-labeled immunocomplex, then loaded onto an array of microwells. A fluorogenic substrate was added and single molecule quantitation was performed by counting active wells with the Simoa HD-X Analyzer. <h3>Results</h3> 138 patient samples were collected (normal=77, low-grade=14, high-grade=24, ACIS/CIS=8, Cancer=15). Eight Simoa assays were developed and calibrated for the biomarkers CA125, CEACAM1, CDKN2A, CEA, HPV16E7, Ki67, ORF1, and VEGF. AUC-ROC curves for the detection of high-grade cervical dysplasia or carcinoma were obtained: Ki67 0.80, CEACAM1 0.78, CDKN2A 0.72, ORF1 0.71, VEGF 0.71, CA125 0.52, and HPV16E7 0.51. A logistic regression model combining multiple markers demonstrated that the addition of CDKN2A and CEACAM1 to Ki67 resulted in a modest improvement of AUC to 0.83 with an accuracy of 80%. <h3>Conclusions</h3> Detection of cervical biomarkers using Simoa is feasible with Ki67, CDKN2A, and CEACAM1 demonstrating good test performance. This assay has the potential to triage patients with abnormal cytology and/or positive human papillomavirus test results. Future work will validate this biomarker panel and platform with an external cohort.
Modeling and experimental results for condensing supercritical CO2 power cycles. (2011)

This Sandia supported research project evaluated the potential improvement that 'condensing' supercritical carbon dioxide (S-CO{sub 2}) power cycles can have on the efficiency of Light Water Reactors (LWR). The analytical portion of research project identified that a S-CO{sub 2} 'condensing' re-compression power cycle with multiple stages of reheat can increase LWR power conversion efficiency from 33-34% to 37-39%. The experimental portion of the project used Sandia's S-CO{sub 2} research loop to show that the as designed radial compressor could 'pump' liquid CO{sub 2} and that the gas-cooler's could 'condense' CO{sub 2} even though both of these S-CO{sub 2} components were designed to operate on vapor phase S-CO{sub 2} near the critical point. There is potentially very high value to this research as it opens the possibility of increasing LWR power cycle efficiency, above the 33-34% range, while lowering the capital cost of the power plant because of the small size of the S-CO{sub 2} power system. In addition it provides a way to incrementally build advanced LWRs that are optimally designed to couple to S-CO{sub 2} power conversion systems to increase the power cycle efficiency to near 40%.
Quantitative analysis of the intrinsic muscles of the hand (1991)

Abstract As part of a study involving three‐dimensional modeling of the hand, the intrinsic muscles of the hand were evaluated quantitatively to estimate the range of muscular forces crossing the fingers. The Brand method of dissection allowed determination of muscle volume, fiber length, and physiologic cross section to estimate the maximal force. The intrinsic muscles were grouped by components on the basis of their origins in the trilaminar scheme of Cunningham as (1) dorsal abductors from the central ray, exemplified by the bipennate dorsal interossei; (2) the intermediate layer consisting of inter‐phalangeal joint extensors, exemplified by the unipennate palmar interossei with insertions into the extensor expansion; and (3) a superficial layer of adductors arising from the third metacarpal ridge, referred to as contrahentes. The fiber lengths of either component of the dorsal interossei averaged 1.3 cm. The intermediate layer of muscle, numbered as flexores breves (FB), included the palmar interossei FB 4,7,9 ; the superficial components of the dorsal interossei FB 3,5,6,8 ; and the accessory adductor pollicis FB 2 . Fiber lengths averaged 1.7 cm. The superficial heads of the flexor pollicis brevis and abductor digiti quinti are possibly the border representations of the intermediate layer as FB 1 and FB 10 . The thenar muscles made up 37%, dorsal interossei 24%, palmar interossei (flexores breves) of the fingers 16%, lumbricals 7%, and hypothenar muscles 16% of the total intrinsic muscle mass. The ratio of muscle mass to fiber length, the physiologic cross‐sectional area, is useful in estimating available force. This quantitative analysis of the intrinsic musculature may find application in the understanding of hand function and biomechanics.
Evaluation of a multi‐atlas based method for segmentation of cardiac CTA data: a large‐scale, multicenter, and multivendor study (2010)

A fully automatic method for whole heart and cardiac chamber segmentation was presented and evaluated using multicenter/multivendor CTA data. The accuracy and robustness of the method were demonstrated by successfully applying the method to 1420 multicenter/ multivendor data sets.
“BASOLATERAL” AND MITOCHONDRIAL MEMBRANE TRANSPORT DEFECT IN THE HEPATOCYTES IN LYSINURIC PROTEIN INTOLERANCE (1983)

In lysinuric protein intolerance, diamino acid transport is defective at the basolateral membrane of the jejunal and renotubular epithelia. The plasma has depressed concentrations of ornithine and arginine but, in contrast, supranormal levels of another urea cycle intermediate, citrulline. The patients have "ornithinopenic" postprandial hyperammonemia. The concentrations of the diamino acids and citrulline in the patients' liver were normal or elevated rather than depressed. Their extrarenal plasma clearance of citrulline and its conversion to arginine and ornithine were retarded. A hypothesis reconciles these apparently conflicting findings: in the hepatocytes the transport defect is located in the "basolateral" cell membrane and in the mitochondrial membranes. The diamino acids accumulate in the cytoplasm, because exit from the cells and transport into the mitochondria are impaired, but these acids are depleted in the mitochondria, where ornithine is needed in the urea cycle. As a result, the urea cycle is reversed at this point, producing citrulline.
A Robust Adaptive Beamforming Framework With Beampattern Shaping Constraints (2009)

We propose a framework based on the use of a set of beampattern shaping constraints. The proposed beamformer possesses not only adaptive interference-rejection ability and robustness against large steering direction errors, but also direct sidelobe control. It contains a new weighing ratio that can automatically control the relative proportions of interference-rejection and sidelobe suppression in different scenarios, without ambiguity. Unlike other beamformers, the proposed beamformer is robust against strong moving interferences, requiring only a coarse estimation of their directions-of-arrival. The generic framework encompasses different optimization strategies for specific application problems.
A fully intraocular 0.0169mm<sup>2</sup>/pixel 512-channel self-calibrating epiretinal prosthesis in 65nm CMOS (2013)

Since their conception and success in human trials, the flexibility and spatial resolution of retinal prostheses have been of major interest. Clinical studies have revealed that hundreds of channels are needed to restore functional visual perception, and more sophisticated waveforms present advantages over biphasic pulses. Initial designs targeted stimulation current levels up to 1mA to ensure functionality. For such designs, an output compliance of >10V was required, and HV technologies were used at the expense of area and power consumption. Human clinical trials have recently shown that implanted electrodes present a stimulus threshold as low as 50μA. In addition, advances in implant technology promise close placement of electrode array and retinal tissue, which can further decrease the required current. Thus, highly scaled LV technologies can provide alternative means to reduce area and power, and to support hundreds of flexible independent channels for fully intraocular implants. In this paper, a self-calibrating 512-channel epiretinal prosthesis in 65nm CMOS is presented. It features dual-band telemetry for power and data, clock recovery, a 2-step calibration technique to match biphasic stimulation currents, and an independent arbitrary output waveform per channel. The implant integrates coils (power and data), IC, external capacitors and electrode array using a biocompatible parylene substrate, providing a fully intraocular solution.