gebhart/patrepeval huggingface dataset:
Solid-Phase Separation of Toxic Phosphorothioate Antisense Oligonucleotide-Protein Nucleolar Aggregates Is Cytoprotective (2021)

Phosphorothioate antisense oligonucleotides (PS-ASOs) interact with proteins and can localize to or induce the formation of a variety of subcellular PS-ASO-protein or PS-ASO-ribonucleoprotein aggregates. In this study, we show that these different aggregates that form with varying compositions at various concentrations in the cytosol, nucleus, and nucleolus may undergo phase separations in cells. Some aggregates can form with both nontoxic and toxic PS-ASOs, such as PS bodies, paraspeckles, and nuclear filaments. However, toxic PS-ASOs have been shown to form unique nucleolar aggregates that result in nucleolar dysfunction and apoptosis. These include liquid-like aggregates that we labeled "cloudy nucleoli" and solid-like perinucleolar filaments. Toxic nucleolar aggregates may undergo solid-phase separation and in the solid phase, protein mobility in and out of the aggregates is limited. Other aggregates appear to undergo liquid-phase separation, including paraspeckles and perinucleolar caps, in which protein mobility is negatively correlated with the binding affinity of the proteins to PS-ASOs. However, PS bodies and nuclear filaments are solid-like aggregates. Importantly, in cells that survived treatment with toxic PS-ASOs, solid-like PS-ASO aggregates accumulated, especially Hsc70-containing nucleolus-like structures, in which modest pre-rRNA transcriptional activity was retained and appeared to mitigate the nucleolar toxicity. This is the first demonstration that exogenous drugs, PS-ASOs, can form aggregates that undergo phase separations and that solid-phase separation of toxic PS-ASO-induced nucleolar aggregates is cytoprotective.
Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands (2003)

E-cadherin is involved in the formation of cell-junctions and the maintenance of epithelial integrity. Direct evidence of E-cadherin mutations triggering tumorigenesis has come from the finding of inactivating germline mutations of the gene (CDH1) in hereditary diffuse gastric cancer (HDGC). We screened a series of 66 young gastric cancer probands for germline CDH1 mutations, and two novel missense alterations together with an intronic variant were identified. We then analysed the functional significance of the two exonic missense variants found here as well as a third germline missense variant that we previously identified in a HGDC family. cDNAs encoding either the wild-type protein or mutant forms of E-cadherin were stably transfected into CHO (Chinese hamster ovary) E-cadherin-negative cells. Transfected cell-lines were characterized in terms of aggregation, motility and invasion. We show that a proportion of apparently sporadic early-onset diffuse gastric carcinomas are associated with germline alterations of the E-cadherin gene. We also demonstrate that a proportion of missense variants are associated with significant functional consequences, suggesting that our cell model can be used as an adjunct in deciding on the potential pathogenic role of identified E-cadherin germline alterations.
Fluorescent Ligands Enable Target Engagement Studies for the Intracellular Allosteric Binding Site of the Chemokine Receptor CXCR2 (2023)

Herein, we report the structure-based development of fluorescent ligands targeting the intracellular allosteric binding site (IABS) of CXC chemokine receptor 2 (CXCR2), a G protein-coupled receptor (GPCR) that has been pursued as a drug target in oncology and inflammation. Starting from the cocrystallized intracellular CXCR2 antagonist 00767013 (<b>1</b>), tetramethylrhodamine (TAMRA)-labeled CXCR2 ligands were designed, synthesized, and tested for their suitability as fluorescent reporters to probe binding to the IABS of CXCR2. By means of these studies, we developed Mz438 (<b>9a</b>) as a high-affinity and selective fluorescent CXCR2 ligand, enabling cell-free as well as cellular NanoBRET-based binding studies in a nonisotopic and high-throughput manner. Further, we show that <b>9a</b> can be used as a tool to visualize intracellular target engagement for CXCR2 via fluorescence microscopy. Thus, our small-molecule-based fluorescent CXCR2 ligand <b>9a</b> represents a promising tool for future studies of CXCR2 pharmacology.
Thermal Analysis and Design of Electronics Systems Across Scales Using State-Space Modeling Technique (2021)

Under a given set of boundary conditions (BCs), the thermal performance of an electronic system is generally evaluated based on its steady-state response to constant power loads and thermal BCs that are time-averaged values of the actual transient or cyclic loads and BCs. Such analysis may produce accurate results if the time dependence of the power cycles and thermal BCs is small. Ideally, transient thermal analyses with actual time-dependent BCs and power cycles should be performed to determine the steady-state behavior. While being less overwhelming compared to laboratory experiments, fully time-dependent computational fluid dynamics (CFD) analysis still requires a large amount of CPU time. In order to overcome this large computational cost, several approximate models, such as resistor-capacitor ( R- C) thermal network approaches, have been developed. Although reasonably accurate, these models require rigorous curve-fitting effort followed by an optimization process, which only makes them practical for relatively simple systems. The present study builds a state-space model applicable to heat transfer problems and makes comparisons with the R- C networks. The state-space model is later applied to determine the transient thermal behavior of a complex system, namely, a multidie SOIC chip over a printed circuit board (PCB), with a significant reduction in CPU time and no compromise on the accuracy. Finally, as a demonstration of systemic thermal design, an optimization exercise is performed on the above state-space model, in which the power cycles on individual die elements are controlled to limit the maximum temperature on the package die.
Receiver-coordinated distributed transmit beamforming with kinematic tracking (2012)

A distributed transmit beamforming technique is described for a scenario with two or more transmit nodes and one intended receiver. The protocol includes a measurement epoch, feedback from the intended receiver to the transmit nodes, and a beamforming epoch. The intended receiver tracks the clock and kinematic parameters of the independent transmit nodes and coordinates the transmit nodes by feeding back state predictions which are then used as phase corrections to facilitate passband phase and frequency alignment at the receiver. A three-state dynamic model is developed to describe the stochastic kinematics and clock evolution of each transmit node relative to the frame of the receiver/coordinator. Steady-state analysis techniques are used to analytically predict the tracking performance as well as the beamforming gain as a function of the system parameters. Numerical results show that near-ideal beamforming performance can be achieved if the period between successive observations at the receiver/coordinator is sufficiently small.
Organic vapor jet printing at micrometer resolution using microfluidic nozzle arrays (2011)

Organic vapor jet printing with a print head comprised of a microfluidic Si nozzle array is used to deposit parallel lines of an organic semiconductor thin film with a line width of 16 μm and edge resolution of 4 μm. Line width and feature size are functions of process conditions, depending strongly on nozzle-to-substrate separation distance. Experimental results are accurately characterized by a direct simulation Monte Carlo model. The model suggests that feature sizes of &amp;lt;1.5 μm are attainable by this printing process. The ability of the print head to codeposit doped films is demonstrated by growing the emissive layer of a green phosphorescent organic light emitting diode sandwiched between hole and electron transport layers deposited by vacuum thermal evaporation. This device had an external quantum efficiency of 8.8±1.3%, comparable to a similar device entirely grown by vacuum thermal evaporation.
Experimental Verification of Transmitter Carrier Offset Scheme for ATSC 3.0 System (2020)

The broadcast networks in reality may suffer from unexpected network failures, which attribute to the pilot signal overlap between the desired signal and the co-channel interference (CCI) from untrusted adjacent transmitters. This paper demonstrates the feasibility of a transmitter carrier offset (TCO) technique to resolve the pilot contamination problem in Advanced Television Systems Committee (ATSC) 3.0 systems. Based on professional exciters and commercial receivers that fully comply with ATSC 3.0 standards, laboratory experiments are conducted to verify the TCO gain in several service scenarios. The experiments specifically address a single CCI-source case, and the presented results show that the ATSC 3.0 TCO effectively alleviates the signal-to-interference ratio (SIR) requirement penalty due to the unfortunate signal overlapping.
Neprilysin Regulates Pulmonary Artery Smooth Muscle Cell Phenotype Through a Platelet-Derived Growth Factor Receptor–Dependent Mechanism (2013)

Reduced neprilysin (NEP), a cell surface metallopeptidase, which cleaves and inactivates proinflammatory and vasoactive peptides, predisposes the lung vasculature to exaggerated remodeling in response to hypoxia. We hypothesize that loss of NEP in pulmonary artery smooth muscle cells results in increased migration and proliferation. Pulmonary artery smooth muscle cells isolated from NEP(-/-) mice exhibited enhanced migration and proliferation in response to serum and platelet-derived growth factor, which was attenuated by NEP replacement. Inhibition of NEP by overexpression of a peptidase dead mutant or knockdown by small interfering RNA in NEP(+/+) cells increased migration and proliferation. Loss of NEP led to an increase in Src kinase activity and phosphorylation of PTEN, resulting in activation of the platelet-derived growth factor receptor (PDGFR). Knockdown of Src kinase with small interfering RNA or inhibition with PP2, a src kinase inhibitor, decreased PDGFR(Y751) phosphorylation and attenuated migration and proliferation in NEP(-/-) smooth muscle cells. NEP substrates, endothelin 1 or fibroblast growth factor 2, increased activation of Src and PDGFR in NEP(+/+) cells, which was decreased by an endothelin A receptor antagonist, neutralizing antibody to fibroblast growth factor 2 and Src inhibitor. Similar to the observations in pulmonary artery smooth muscle cells, levels of phosphorylated PDGFR, Src, and PTEN were elevated in NEP(-/-) lungs. Endothelin A receptor antagonist also attenuated the enhanced responses in NEP(-/-) pulmonary artery smooth muscle cells and lungs. Taken together our results suggest a novel mechanism for the regulation of PDGFR signaling by NEP substrates involving Src and PTEN. Strategies that increase lung NEP activity/expression or target key downstream effectors, like Src, PTEN, or PDGFR, may be of therapeutic benefit in pulmonary vascular disease.
Lung lamellar body amphiphilic topography: A morphological evaluation using the continuum theory of liquid crystals: I. Closed surfaces: Closed spheres, Concentric tori, and Dupin cyclides (1988)

The structure and symmetry of the bilayers of in vivo phospholipid lung lamellar bodies is shown to be analogous to thermotropic smectic-A liquid crystals and in vitro lyotropic multilamellar liquid crystalline liposomes. This structural similarity has led us to extend biophysical and geometrical principles that have long been used to predict the layer conformation in these in vitro systems to in vivo lung lamellar bodies. These configurations were demonstrated by electron micrographs of thin sections of rodent, monkey, and human lung lamellar bodies prepared by lipid-retaining embedment procedures. The bilayer configurations in all species were consistent with the two geometries predicted by minimal energy solutions of a continuum theory of liquid crystals subject to the boundary conditions imposed by the amphiphilic nature of lung surfactant lipid: concentric (either closed or partially closed) spheres and Dupin cyclides. These bilayer arrangements in lung lamellar bodies were virtually identical to the bilayer configuration of in vitro multilamellar liposomes. The agreement between the two predicted configurations and our observations shows that multilamellar liquid crystalline bilayer aggregate organization is universal in any aqueous environment.
Epicardial only mapping and ablation of ventricular tachycardia: a case series (2015)

Epicardial only ablation seems feasible and effective and useful in a limited subset of patients with incessant VT. However, endpoints are more difficult to evaluate and long-term follow-up is needed.
Overview of IMS project; next generation environmental friendly soldering technology "EFSOT" (2002)

The 21st century can be called the era of the environment, and various efforts are being made to protect the global environment. For the materials used in the soldering of electronic circuits, there is also concern over the harmful effects of Pb, which is an important component of those materials, and so there is a trend to eliminate the Pb component. Under this background, and founded on the recognized importance of developing an alternative connection technology that has little environmental impact and harm, the IMS Project: Development of the Next Generation Environmental Friendly Soldering Technology began in June, 2000 in cooperation of industry and academia, and supported by the Ministry of Economy, Trade and Industry and the IMS (Intelligent Manufacturing Systems) Promotion Center. The project comprises four areas, which are evaluation of the impact of Pb-free soldering on the environment, evaluation of the safety of the metals with respect to living creatures, recycling technology, and the development of production technology. To achieve a worldwide consensus and application, the project is being internationalized.
Reflection high-energy positron diffraction study on the first surface layer (2014)

Reflection high-energy positron diffraction (RHEPD) is a powerful tool for studying surface structure. In particular, the topmost surface layer can be observed, facilitated by the characteristic of total reflection for positrons. A previous RHEPD study on a Ag surface, using a 22Na-based beam, is revisited and the analysis detailed.
Enrichment of germline DNA-repair gene mutations in patients with colorectal cancer. (2017)

1500 Background: Twin studies showed that 30% of all colorectal cancer (CRC) patients have an inherited genetic susceptibility. Several CRC predisposition genes have been described to date. However, mutations in these genes explain the risk in only 5-10% of CRC cases. In this study, we hypothesized that some of the CRC heritability may be explained by excess disruptive germline mutations in DNA repair genes (DRGs). Methods: Exome sequencing data of 716 in the discovery cohort (CanSeq and NHS/HPFS studies) and 1609 CRC patients in the validation cohort (TCGA and NSCCG studies) were used to evaluate germline variants in a pre-selected group of 42 DRGs and 12 known CRC risk genes. Frequencies of disruptive mutations in our cohorts were examined relative to 27173 non-Finnish European cancer-free adults from the ExAC cohort to evaluate for enrichment. Results: Of 716 patients in the discovery cohort, 27 (3.8%) patients harbored germline mutations in APC (n = 11), MSH6 (n = 2), MUTYH (n = 11), CHEK2 (n = 1) and TP53 (n = 2). Interestingly, germline mutations in ATM and PALB2 were significantly enriched in our CRC discovery cohort (OR = 2.7; P = 0.044; and OR = 4.8; P = 0.026, respectively). Evaluation of germline data from another 1609 CRC patients (validation cohort) also showed significantly higher rates of ATM mutations (5; 0.7%; OR = 2.1; P = 0.044), and a trend for enrichment of PALB2 mutations (3; 0.4%; OR = 2.8; P = 0.056). Secondary analysis of actionable germline mutations in a highly penetrant cancer risk gene set ( ATM, BRCA1, BRCA2, BRIP1 and PALB2) suggest a broader enrichment trend in CRC patients for these genes (Discovery: OR = 1.7; P = 0.06; Validation: OR = 2; P = 1.96e-04). Conclusions: Our analysis of germline variants in 2325 CRC patients showed the first robust evidence for germline ATM mutations to confer a higher risk of developing CRC. We also presented evidence to support PALB2 as a potential novel CRC risk gene. Overall, our study shows that mutations in some DRGs may explain some of the missing CRC heritability. It also indicates that a significant percentage of CRC patients, who carry mutations in highly actionable genes where cancer screening recommendations for patients and families do exist, are not captured with current testing recommendations.
Joint decoding of independently encoded compressive multi-view video streams (2013)

We design a video coding and decoding framework for multi-view video systems based on compressed sensing imaging principles. Specifically, we focus on joint decoding of independently encoded compressively-sampled multi-view video streams. We first propose a novel distributed coding/decoding architecture designed to leverage inter-view correlation through joint decoding of the received compressively-sampled frames. At the encoder side, we select one view (referred to as K-view) as a reference for the other views (referred to as CS-views). The video frames of the CS-view are encoded and transmitted at a lower measurement rate than those of the selected K-view. At the decoder side, we generate side information to decode the CS-views as follows. First, each K-view frame is down-sampled and reconstructed, and then compared with the initially reconstructed CS-view frame to obtain an estimate of the inter-view motion vector. The original CS-view measurements are then fused with the generated side image to reconstruct the CS-view frame through a newly designed algorithm that operates in the measurement domain. We also propose a blind video quality estimation method that can be used within the proposed framework to design channel-adaptive rate control algorithms for quality-assured multi-view video streaming. We extensively evaluate the proposed scheme using real multi-view video traces. Results indicate that up to 1.6 dB improvement in terms of PSNR can be achieved by the proposed scheme compared with traditional independent decoding of CS frames.
Brain Connectivity Exposed by Anisotropic X-ray Dark-field Tomography (2018)

To understand the interaction of different parts of the human brain it is essential to know how they are connected. Such connections are predominantly related to the brain's white matter, which forms the neuronal pathways, the axons. These axons, also referred to as nerve fibers, have a size on the micrometer scale and are therefore too small to be imaged by standard X-ray systems. In this paper, we use a grating interferometer and a method based on Anisotropic X-ray Dark-field Tomography (AXDT) with the goal to generate a three-dimensional tomographic reconstruction of these functional structures. A first preclinical survey shows that we successfully reconstruct the orientations of the brain fibers connectivity with our approach.
Mechanisms With Costly Knowledge (2016)

We propose investigating the design and analysis of game theoretic mechanisms when the players have very unstructured initial knowledge about themselves, but can refine their own knowledge at a cost.
ChemInform Abstract: Formation of Thin Films of Organi—Inorganic Perovskites for High‐Efficiency Solar Cells (2015)

Abstract Review: [emphasis on (MeNH 3 )PbI 3 and (MeNH 3 )PbI 3‐x Cl x perovskites; 49 refs.
Whiskers Area as Extracerebral Reference Tissue for Quantification of Rat Brain Metabolism Using 18F-FDG PET: Application to Focal Cerebral Ischemia (2011)

The method presented here allows for the quantitative noninvasive determination of cerebral glucose consumption in rats, takes into account local variations of the lumped constant, and is suitable for follow-up measurements of individuals.
Identifying effective pedagogical practices for commenting computer source code (abstract only) (2012)

Few, if any, pedagogical practices exist for helping students embrace best practices in writing software documentation, particularly source code comments. Although instructors often stress the importance of good commenting, two problems exist. First, it can be difficult to actually define these best practices, and second, it can be difficult to grade or assess students' application of such methods/practices. This Birds-of-a-Feather session focuses on capturing for dissemination a concrete list of code commenting best practices used by the attendees as they teach their classes.
Development of Adapted Material Testing for Cold Pilgering Process of ODS Tubes (2013)

Development of fast-neutron sodium-cooled Generation IV reactors is resulting in extremely severe environment conditions for cladding tubes [1]. Both temperature and irradiation level will increase compared to the nowadays conditions. Due to their characteristics in irradiated environment, the oxide dispersion strengthened (ODS) ferritic and martensitic steels are natural candidate cladding materials[2]. However, they exhibit low deformation capabilities at room temperature, leading to problematic issues for forming such as pilgering. In order to improve the fabrication route for tubes, both metallurgical and numerical approaches can be conducted [3,4,5]. To reach predictive description of damage location and evolution, an adapated Latham and Cockoft model has been developed. This model is, of course, highly depending on the stress and strain prediction of the numerical model which itself is linked to the behavior law. In this work, we will describe an adapted material test developed in order to reproduce the cyclic, non uniform loading of the material during pilgering. An advanced cyclic beahvior law is introduced in the software. The model of Chaboche using 2 isotropic and 2 kinematic variables is chosen[6]. An inverse analysis procedure is used to identify both isotropic and kinematic hardening parameters. The results obtained using the identified behavior law are compared to both experimental observation and to other models including monotonic or cyclic laws identified on traditional test.
Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression (2000)

During lung injury, fibroblasts migrate into the alveolar spaces where they can be exposed to pulmonary surfactant. We examined the effects of Survanta and surfactant protein A (SP-A) on fibroblast growth and apoptosis and on type I collagen, collagenase-1, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. Lung fibroblasts were treated with 100, 500, and 1,000 microg/ml of Survanta; 10, 50, and 100 microg/ml of SP-A; and 500 microg/ml of Survanta plus 50 microg/ml of SP-A. Growth rate was evaluated by a formazan-based chromogenic assay, apoptosis was evaluated by DNA end labeling and ELISA, and collagen, collagenase-1, and TIMP-1 were evaluated by Northern blotting. Survanta provoked fibroblast apoptosis, induced collagenase-1 expression, and decreased type I collagen affecting mRNA stability approximately 10-fold as assessed with the use of actinomycin D. Collagen synthesis and collagenase activity paralleled the gene expression results. SP-A increased collagen expression approximately 2-fold and had no effect on collagenase-1, TIMP-1, or growth rate. When fibroblasts were exposed to a combination of Survanta plus SP-A, the effects of Survanta were partially reversed. These findings suggest that surfactant lipids may protect against intraluminal fibrogenesis by inducing fibroblast apoptosis and decreasing collagen accumulation.