gebhart/patrepeval huggingface dataset:
Abstract B01: Alternative splicing as a therapeutic vulnerability in pediatric rhabdomyosarcoma (2020)

Abstract Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma, and children who present with metastatic disease at the time of diagnosis have a poor prognosis and survival rate. The molecular events distinguishing these tumors are poorly understood. Comprehensive genetic analysis of pediatric RMS samples has revealed that these tumors are “quiet” at the genomic level and have a relatively low mutation rate. Thus, we have turned our attention to the RMS spliceome, the alternatively or aberrantly spliced transcripts, to identify new therapeutic targets. Indeed, recent advances in high-throughput sequencing technologies have uncovered a surprising number of alternatively spliced variants associated with tumorigenesis, implicating regulated splicing in the tumor phenotype. We hypothesize that differentially spliced isoforms provide a novel opportunity to modulate splicing as a therapeutic intervention in these cancers. We have identified two major splicing networks that are altered in response to tumor specific physiologic changes in RMS. We have identified RNA binding protein and their specific cis-regulatory sequence binding sites that control the splicing changes. In collaboration with Ionis Pharmaceuticals, we have designed splice-switching oligonucleotides that target the specific sequences in the pre-mRNA transcript to occlude protein binding and engineer splicing away from the tumorigenic isoforms. The splice switching oligonucleotides (SSOs) have been successful in targeting the desired transcripts to change the splice isoform, repressing RMS cell growth, and preventing migration, invasion, and angiogenesis. We are currently testing the SSOs in RMS xenograft models as well as in genetically engineered mice to assess their efficacy in vivo. Our long-term goal is to understand the role of alternative splicing in cancer and to target pre-mRNA splicing pathway as a therapeutic intervention point. From these studies, we expect to better understand the cellular events that activate alternative splicing in the pathway to tumorigenesis and how to target transcripts for therapeutic benefit in the future. Furthermore, our findings implement a new splice-modulating paradigm for cancer treatment and pioneer a strategy that may be applied throughout the spliceome to treat cancer and provide a new avenue of rational therapy design. Citation Format: Safiya Khurshid, Matias Montes, Ryan Roberts, Frank Rigo, Dawn S. Chandler. Alternative splicing as a therapeutic vulnerability in pediatric rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B01.
Relationship Between Molecular Structure and Electrical Performance of Oligothiophene Organic Thin Film Transistors (2003)

Organic thin film transistors (TFTs) based on alkyl‐substituted oligothiophenes with varying chromophore and alkyl side‐chain length have been fabricated. The TFT performance is shown to depend on side‐chain length and contact configuration, but is found to be relatively insensitive to chromophore length. Mobilities as large as 1.1 cm 2 /V s were obtained. TFTs with ultra‐thin self‐assembled monolayer gate dielectrics have also been prepared and investigated.
Understanding the feasibility of scaled III&#x2013;V TFET for logic by bridging atomistic simulations and experimental results (2012)

A detailed comparison between III-V TFET's experimental characteristics and atomistic quantum mechanical predictions is reported to study the validity of the performance improvement predictions of a scaled TFET. Simulations did not employ any fitting parameters to match the experimental data, but instead used material and geometry parameters as the only inputs. The results show that the experimental and simulation characteristics are in reasonable agreement, suggesting that the experimental devices are without significant unknown effects or defects, and the atomistic simulations have good predictability. The differences between scaled TFET predictions and large experimental TFET devices are shown to be due to the geometry, meaning that improved electrostatics with thin body and double-gate (DG) is required for TFET scaling. Results demonstrate that the III-V TFET is a realistic candidate for future low-voltage logic applications.
Intramolecular hydride shift polymerization by cationic mechanism. II. Spectroscopic analysis of poly‐3‐methylbutene‐1 (1964)

Abstract The structures of cationically obtained poly‐3‐methylbutene‐1, isotactic poly‐3‐methylbutene‐, and hydrogenated 3,4‐polyisoprene have been investigated by nuclear magnetic resonance and infrared spectroscopy. These studies corroborate the previously proposed structure of an α,α′‐dimethylpropane repeating unit for the cationic polymer and they confirm the conventional 1,2 head‐to‐tail enchainment for the isotactic polymer and for the hydrogenated 3,4‐polyisoprene. The NMR spectra of cationic poly‐3‐methylbutene‐1 and polyisoprene are very similar and show only two peaks. They are quite different from the spectra of isotactic poly‐3‐methylbutene‐1 and hydrogenated 3,4‐polyisoprene. The isotactic product was solubilized by careful pyrolysis to render it amenable to spectroscopic studies. Unfortunately, present‐day NMR spectroscopy does not possess high enough resolution to be useful in the quantitative investigation of mixtures of 1,3 and 1,2 enchainments. The NMR spectrum of polyisobutylene oxide can be used to distinguish cationic poly‐3‐methylbutene‐1 from the isotactic modification and from the hydrogenated 3,4‐polyisoprene. The more important bands have been analyzed and assigned. Isotactic poly‐3‐methylbutene‐1 and hydrogenated 3,4‐polyisoprene both have a conventional 1,2 structure, and their infrared spectra are essentially identical.
A 4.1Tb/s bisection-bandwidth 560Gb/s/W streaming circuit-switched 8&#x00D7;8 mesh network-on-chip in 45nm CMOS (2010)

An on-die multi-core circuit-switched network achieves 2.64Tb/s throughput for an 8×8 2D mesh, consuming 4.73W in 45nm CMOS at 1.1V and 50°C. Pipelined circuit-switched transmission, circuit channel queue circuits and dual supplies enable up to 1.51Tb/s/W energy efficiency, with scalable streaming performance of 6.43Tb/s.
SARS-CoV-2 Neutralizing Antibodies for COVID-19 Prevention and Treatment (2021)

Prophylactic and therapeutic drugs are urgently needed to combat coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over the past year, SARS-CoV-2 neutralizing antibodies have been developed for preventive or therapeutic uses. While neutralizing antibodies target the spike protein, their neutralization potency and breadth vary according to recognition epitopes. Several potent SARS-CoV-2 antibodies have shown degrees of success in preclinical or clinical trials, and the US Food and Drug Administration has issued emergency use authorization for two neutralizing antibody cocktails.Nevertheless, antibody therapy for SARS-CoV-2 still faces potential challenges, including emerging viral variants of concern that have antibody-escape mutations and the potential for antibody-mediated enhancement of infection or inflammation. This review summarizes representative SARS-CoV-2 neutralizing antibodies that have been reported and discusses prospects and challenges for the development of the next generation of COVID-19 preventive or therapeutic antibodies.
Deposition of Microcrystalline Si1-xGex by RF Magnetron Sputtering on SiO2 Substrates (2009)

Microcrystalline Si1-xGex (x∼0.8) films have been deposited by magnetron sputtering on SiO2 substrates. Crystallinity was evaluated by spectroscopic ellipsometry, Raman scattering, X-ray diffraction (XRD), transmission electron microscopy (TEM), and electron backscatter diffraction (EBSD). Detailed investigation of the deposition behavior revealed that crystalline phase begins to form at 300 °C, which roughly corresponds to half of the melting temperature of the material. At 300 °C, crystallinity changes with thickness, i.e., crystallinity improves as thickness increases. It was found out that this change in the crystallinity is not due to the heat up of the substrate, but is an essential phenomenon. At 350 °C, on the other hand, crystalline phase is formed almost from the beginning of the deposition. However, surface (<100 nm) crystallinity of the 300 °C sample is higher compared with 350 °C sample when the film thickness is more than 500 nm. Substrate bias effect was also investigated. Crystallinity of 300 °C sample improves while that of 350 °C sample degrades when RF bias power is applied to the substrate.
Splenectomy in Hodgkinʼs disease (1982)

One hundred twenty-four patients with advanced Hodgkin's disease were treated uniformly with combination chemotherapy and radiotherapy. Splenectomy was not performed in 32 patients due to obvious stage IV disease, a medical contraindication, or patient refusal. Comparison of the splenectomy and nonsplenectomy patients revealed no differences in nadir white blood cell counts, platelet counts, or the total dosages of drugs that were administered. Survival and disease free survival curves with a 5-year median follow up also failed to show any difference in the two groups. Splenectomy does not offer a therapeutic advantage in those patients whose treatment would not be altered by splenic histology.
An F0contour control model using an F0contour codebook (2006)

Abstract In this paper the authors propose a fundamental frequency (F 0 ) control model using a representative vector and then propose a method to train the control rules for the model parameters using a speech database. The representative vector is a vector which represents the typical F 0 contour for accent phrases, and a set of representative vectors is referred to as a representative vector codebook. The authors generated F 0 contour for sentences by performing linear expansion or contraction by mora in line with the length of the phoneme duration and the parallel shift (offset) on the logarithmic frequency axis and then concatenating them for representative vectors selected for each accent phrase. Training the control rules corresponds to extracting from the speech database the representative vector codebook, the representative vector selection rules, and the offset prediction rules. Based on the criterion that the error between the F 0 contour for the speech database and the contour generated by the model (the approximation error) be minimized, the control rules were trained. The results of training experiments for the control rules using a speech database consisting of four female speakers showed that an F 0 contour close to the original speaker can be generated even for sentences not included in the training data. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 38(1): 62–72, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/scj.10386
Abstract 563: A biparatopic agonist antibody for OX40 that exhibits superior activity without secondary crosslinking (2019)

The development of agonistic antibodies that activate T-cell co-stimulatory pathways represents a therapeutic strategy with significant clinical potential. However, challenges remain for the translation from in vitro efficacy to clinical success. OX40 and other tumor necrosis factor receptor (TNFR) superfamily members are notorious for requiring high-order receptor clustering in order to achieve full activity. For monoclonal antibodies, this high-order clustering is generally achieved through secondary cross-linking strategies. In vivo, this secondary cross-linking is often supplied through internal immune effector cells via Fc engagement. Bispecific and biparatopic antibodies represent an emerging class of drug molecules that enable unique mechanisms of action relative to their monoclonal counterparts. Here, we describe the use of our bispecific platform for the generation of large panels of biparatopic antibodies which enabled high-throughput screening for the discovery of an array of OX40 agonistic molecules. We have optimized these multivalent antibodies that exceed the potency of the OX40 ligand in NFkB activation without the need for secondary cross-linking. These agonist antibodies have additionally been characterized using primary T cell assays to monitor the kinetics of growth proliferation and cytokine secretion, outperforming cross-linked antibodies currently being tested in clinical trials. In co-culture systems, these agonist antibodies were effective in inhibiting immuno-suppressive properties of Tregs. Our lead OX40 agonist antibody has been optimized for activity and developability and has entered stable cell line development to further support pre-clinical activities.Citation Format: Bonnie Hammer, Mandar Bawadekar, Matthew Bissen, John Painter, Lauren Lehmann, Francis Qufei Li, Lucas Bailey, Bryan Glaser, Roland Green. A biparatopic agonist antibody for OX40 that exhibits superior activity without secondary crosslinking [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 563.
Janus kinase inhibition prevents cancer- and myocardial infarction-mediated diaphragm muscle weakness in mice (2016)

Respiratory dysfunction is prevalent in critically ill patients and can lead to adverse clinical outcomes, including respiratory failure and increased mortality. Respiratory muscles, which normally sustain respiration through inspiratory muscle contractions, become weakened during critical illness, and recent studies suggest that respiratory muscle weakness is related to systemic inflammation. Here, we investigate the pathophysiological role of the inflammatory JAK1/3 signaling pathway in diaphragm weakness in two distinct experimental models of critical illness. In the first experiment, mice received subcutaneous injections of PBS or C26 cancer cells and were fed chow formulated with or without the JAK1/3 inhibitor R548 for 26 days. Diaphragm specific force was significantly reduced in tumor-bearing mice receiving standard chow; however, treatment with the JAK1/3 inhibitor completely prevented diaphragm weakness. Diaphragm cross-sectional area was diminished by ∼25% in tumor-bearing mice but was similar to healthy mice in tumor-bearing animals treated with R548. In the second study, mice received sham surgery or coronary artery ligation, leading to myocardial infarction (MI), and were treated with R548 or vehicle 1 h postsurgery, and once daily for 3 days. Diaphragm specific force was comparable between sham surgery/vehicle, sham surgery/R548 and MI/R548 groups, but significantly decreased in the MI/vehicle group. Markers of oxidative damage and activated caspase-3, mechanisms previously identified to reduce muscle contractility, were not elevated in diaphragm extracts. These experiments implicate JAK1/3 signaling in cancer- and MI-mediated diaphragm weakness in mice, and provide a compelling case for further investigation.
Thermal Analysis and Optimization of Substrates With Directionally Enhanced Conductivities (1997)

Abstract An approximate analytical solution for the thermal resistance of the axisymmetric chip-on-substrate problem is presented for a substrate with a direction dependent (orthotropic) thermal conductivity. The substrate may be convectively cooled on either, or both, of its planar surfaces. The solution reveals substrate geometries with low maximum substrate temperatures. These optimal substrate sizes are mapped for Biot numbers typical of microelectronic applications. The effects of varying the radial and axial substrate conductivities are investigated. In general, radial conductivity enhancement is beneficial for bottom-side and both-side convective cooling of thin substrates, and for top-side cooling of all substrates. For thin substrates, radial conductivity enhancement provides comparable thermal performance to an equivalent isotropic conductivity enhancement. For electronic packaging applications thin substrates are desirable and radial conductivity enhancement is more beneficial than axial conductivity enhancement.
Damage Cluster Analysis of Patterned Wafers during Solvent Spray Cleaning (2009)

As device structures become smaller they also become more fragile. With the incorporation of metal-high-k layers and shallower implants galvanic corrosion and substrate loss requirements are becoming an important issue. Aqueous chemistries are ceasing to be an option and new solvent cleans are continuously being experimented with. Physical force assisted solvent cleans are increasingly being considered for the removal of particles and resist residues. Whenever a physical force assisted clean is used damage becomes a major concern. In this work the effect of different solvents spray cleans on defect densities over the wafer will be discussed. The damage sites were further analyzed for clusters. The number of defects per cluster for the different solvents was also analyzed. Finally, the cluster size distribution was evaluated for the different solvents.
Engineering functional materials by halogen bonding (2006)

Abstract Engineering functional materials endowed with unprecedented properties require the exploitation of new intermolecular interactions, which can determine the characteristics of the bulk materials. The great potential of Halogen Bonding (XB), namely any noncovalent interaction involving halogens as electron acceptors, in the design of new and high‐value functional materials is now emerging clearly. This Highlight will give a detailed overview on the energetic and geometric features of XB, showing how some of them are quite constant in most of the formed supramolecular complexes ( e.g. , the angle formed by the covalent and the noncovalent bonds around the halogen atom), while some others depend strictly on the nature of the interacting partners. Then, several specific examples of halogen‐bonded supramolecular architectures, whose structural aspects as well as applications in fields as diverse as enantiomers' separation, crystal engineering, liquid crystals, natural, and synthetic receptors, will be fully described. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: PolymChem 45: 1–15, 2007
Supplementary Figure S1 from A 10-Gene Classifier for Distinguishing Head and Neck Squamous Cell Carcinoma and Lung Squamous Cell Carcinoma (2023)

Supplementary Figure S1 from A 10-Gene Classifier for Distinguishing Head and Neck Squamous Cell Carcinoma and Lung Squamous Cell Carcinoma
THE CONFIGURATION PROBLEM OF MICROWAVE CONNECTIONS IN UTRAN (2004)

The spectral efficiency of microwave networks can be greatly improved by properly selecting and configuring themicrowave equipment. Configuration trade-offsand network optimizationtechniques influencing the spectral demand have been investigated in the presented simulation experiments.
Simulation validation using direct execution of wireless Ad-Hoc routing protocols (2004)

Computer simulation is the most common approach to studying wireless ad-hoc routing algorithms. The results, however, are only as good as the models the simulation uses. One should not underestimate the importance of validation, as inaccurate models can lead to wrong conclusions. In this paper, we use direct-execution simulation to validate radio models used by ad-hoc routing protocols, against real-world experiments. This paper documents a common testbed that supports direct execution of a set of ad-hoc routing protocol implementations in a wireless network simulator. The testbed reads traces generated from real experiments, and uses them to drive direct-execution implementations of the routing protocols. Doing so we reproduce the same network conditions as in real experiments. By comparing routing behavior measured in real experiments with behavior computed by the simulation, we are able to validate the models of radio behavior upon which protocol behavior depends. We conclude that it is possible to have fairly accurate results using a simple radio model, but the routing behavior is quite sensitive to one of this model's parameters. The implication is that one should i) use a more complex radio model that explicitly models point-to-point path loss, or ii) use measurements from an environment typical of the one of interest, or iii) study behavior over a range of environments to identify sensitivities.
Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure (2005)

The opioid analgesics, commonly exemplified by morphine, represent the best option for the treatment of severe pain and for the management of chronic pain states, of both malignant and nonmalignant origin. It is well recognized that the prolonged use of opioids is associated with a requirement for ever-increasing doses in order to maintain pain relief at an acceptable and consistent level. This phenomenon is termed analgesic tolerance. While the concept that tolerance can develop as a result of cellular adaptations to the presence of the opioid has been proposed, it is now becoming abundantly clear that tolerance may also be related to a state of hyperalgesia that results from exposure to the opioid itself. Patients who receive long-term opioid therapy sometimes develop unexpected, abnormal pain. Similar paradoxical opioid-induced pain has been confirmed in a number of animal studies, even during the period of continuous opioid delivery. A number of recent studies have demonstrated that such pain may be secondary to neuroplastic changes that occur in the brain and spinal cord. One such change may be the activation of descending pain facilitation mechanisms arising from the rostral ventromedial medulla (RVM) elicited in part by increased activity of cholecystokinin (CCK) in the RVM. A cascade of pronociceptive events may follow, such as opioid-induced upregulation of spinal dynorphin levels that promotes enhanced input from primary afferent nociceptors. This mechanism appears to depend on intact descending pathways from the RVM, since interrupting this pathway abolishes enhanced abnormal pain. Furthermore, extended opioid exposure also can elicit increased calcitonin gene related peptide (CGRP) and substance P expression in the dorsal root ganglia. It is probable that increased pain elicited by opioids is a critical factor in the behavioral manifestation of opioid tolerance because the same manipulations that block abnormal pain also block antinociceptive tolerance. Taken together, such studies show that opioids elicit systems-level adaptations resulting in pain due to descending facilitation, upregulation of spinal dynorphin, and enhanced, evoked release of excitatory transmitters from primary afferents. These adaptive changes in response to sustained exposure to opioids indicate the need for the evaluation of the clinical consequences of long-term opioid administration. Additionally, these findings suggest a need for novel chemistry involving design of agents that may counteract opiate-induced neuroplastic adaptations resulting in pain relief without analgesic tolerance.