gebhart/patrepeval huggingface dataset:
Abstract LB-018: Loss of function mutations of an ETS repressor expand the ETS positive subset of prostate cancer (2016)

Abstract Recent genomic profiling of both primary and metastatic prostate cancers has revealed novel loss-of-function point mutations and copy number deletions of the gene ERF, an ETS transcriptional repressor with a nearly identical DNA-binding domain to the TMPRSS2-ERG oncogene product. Furthermore, ERF homozygous loss or point mutations occur exclusive of the ERG upregulation that occurs in 50% of prostate cancers following fusion of androgen-regulated upstream genomic elements of TMPRSS2 to the ERG gene. We characterized the function of ERF, as well as its relationship to ERG using CRISPR and shRNA technology to investigate both normal prostate- and patient tumor-derived organoid cultures, as well as existing TMPRSS2-ERG positive models. In both normal prostate and tumor models lacking upregulated ERG, inhibition of the ERF repressor leads to an expansion of the androgen transcriptome, and recapitulates phenotypic features seen with ERG upregulation. Cistromic analysis reveals that ERF occupies androgen-receptor (AR) associated chromatin, overlapping with potential ERG sites. Accordingly, in the presence of the upregulated ERG oncogene, ERF is now unable to bind any AR associated chromatin, and the AR transcriptome is expanded. CRISPR-mediated loss of ERG in TMPRSS2-ERG positive models leads to a halt of tumor cell growth, but concomitant loss of the ERF repressor partially restores cellular proliferation. We conclude that ERF is an endogenous repressor of androgen signaling in normal prostatic tissue and a potential tumor suppressor in prostate cancer. It occupies chromatin associated with AR-regulated genes and inhibits their transcriptional regulation. Loss of ERF function, either by mutation or more frequently by competition with the TMPRSS2-ERG gene product, leads to an expansion of the androgen transcriptome. Thereby, the ETS positive subtype of prostate cancer, currently defined by an activating ETS fusion event (e.g. TMPRSS2-ERG) should be expanded to encompass genomic loss of a repressive ETS factor. Citation Format: Rohit Bose, Wassim Abida, Wouter Karthaus, Joshua Armenia, Phillip Iaquinta, John Wongvipat, Michael Doran, Haley Hieronymus, Philip Watson, Patrick Sullivan, Yupu Liang, Nikolaus Schultz, Charles Sawyers. Loss of function mutations of an ETS repressor expand the ETS positive subset of prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-018.
Saxony (2011)

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The influence of soccer cleat design on joint moments (2009)

A few epidemiological studies have linked lower extremity injuries to high rotational resistance between shoe and surface. Torg et al. (1971, 1974) found that injuries in American football were mor...
Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease (2017)

Adenosine A<sub>2A</sub> receptor (A<sub>2A</sub>R) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A<sub>2A</sub>R agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A<sub>2A</sub>R agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A<sub>2A</sub>R agonist regadenoson (1.44 μg/kg per hour) to patients with SCD during VO crises to produce a plasma concentration of ∼5 nM, a concentration known from prior studies to suppress iNKT cell activation in SCD. The primary outcome measure was a >30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to receive a 48-hour infusion of regadenoson or placebo, in addition to standard-of-care treatment, during hospital admission for a VO crisis and had analyzable iNKT cell samples. The proportion of subjects who demonstrated a reduction of >30% in activated iNKT cells was not significantly different between the regadenoson and placebo arms (43% vs 23%; <i>P</i> = .07). There were also no differences between regadenoson and placebo groups in length of hospital stay, mean total opioid use, or pain scores. These data demonstrate that a low-dose infusion of regadenoson intended to reduce the activity of iNKT cells is not sufficient to produce a statistically significant reduction in such activation or in measures of clinical efficacy. This trial was registered at www.clinicaltrials.gov as #NCT01788631.
Active beam steering based on reconfigurable phase-change metasurface (2017)

We present the tunable optical response of phase change material Ge2Sb2Te5, which can be used to metasurfaces with varied functionalities. The concept of reconfigurable metasurface, which have different combination of unit cells with various geometries and phase states are proposed. The research is promising to apply to the area of the metadevice.
p53-Reactive T Cells Are Associated with Clinical Benefit in Patients with Platinum-Resistant Epithelial Ovarian Cancer After Treatment with a p53 Vaccine and Gemcitabine Chemotherapy (2018)

there were no DLTs, but 3 of 11 patients came off study early due to gemcitabine-attributed adverse events (AE). Minimal AEs were attributed to p53MVA vaccination. Immunologic and clinical response: enhanced <i>in vitro</i> recognition of p53 peptides was detectable after immunization in both the CD4<sup>+</sup> and CD8<sup>+</sup> T-cell compartments in 5 of 11 and 6 of 11 patients, respectively. Changes in peripheral T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSC) did not correlate significantly with vaccine response or progression-free survival (PFS). Patients with the greatest expansion of p53-reactive T cells had significantly longer PFS than patients with lower p53-reactivity after therapy. Tumor shrinkage or disease stabilization occurred in 4 patients.<b>Conclusions:</b> p53MVA was well tolerated, but gemcitabine without steroid pretreatment was intolerable in some patients. However, elevated p53-reactive CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses after therapy correlated with longer PFS. Therefore, if responses to p53MVA can be enhanced with alternative agents, superior clinical responses may be achievable. <i>Clin Cancer Res; 24(6); 1315-25. ©2018 AACR</i>.
Blocking p62-dependent SMN degradation ameliorates spinal muscular atrophy disease phenotypes (2018)

Spinal muscular atrophy (SMA), a degenerative motor neuron (MN) disease, caused by loss of functional survival of motor neuron (SMN) protein due to SMN1 gene mutations, is a leading cause of infant mortality. Increasing SMN levels ameliorates the disease phenotype and is unanimously accepted as a therapeutic approach for patients with SMA. The ubiquitin/proteasome system is known to regulate SMN protein levels; however, whether autophagy controls SMN levels remains poorly explored. Here, we show that SMN protein is degraded by autophagy. Pharmacological and genetic inhibition of autophagy increases SMN levels, while induction of autophagy decreases these levels. SMN degradation occurs via its interaction with the autophagy adapter p62 (also known as SQSTM1). We also show that SMA neurons display reduced autophagosome clearance, increased p62 and ubiquitinated proteins levels, and hyperactivated mTORC1 signaling. Importantly, reducing p62 levels markedly increases SMN and its binding partner gemin2, promotes MN survival, and extends lifespan in fly and mouse SMA models, revealing p62 as a potential new therapeutic target for the treatment of SMA.
A regioselective synthesis of 2,3-disubstituted-1-naphthols. The coupling of alkynes with 1,2-aryldialdehydes promoted by NbCl3(DME) (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA regioselective synthesis of 2,3-disubstituted-1-naphthols. The coupling of alkynes with 1,2-aryldialdehydes promoted by NbCl3(DME)Jack B. Hartung Jr. and Steven F. PedersenCite this: J. Am. Chem. Soc. 1989, 111, 14, 5468–5469Publication Date (Print):July 1, 1989Publication History Published online1 May 2002Published inissue 1 July 1989https://pubs.acs.org/doi/10.1021/ja00196a064https://doi.org/10.1021/ja00196a064research-articleACS PublicationsRequest reuse permissionsArticle Views392Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Data from Amplification of MDS1/EVI1 and EVI1, Located in the 3q26.2 Amplicon, Is Associated with Favorable Patient Prognosis in Ovarian Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;Increased copy number involving chromosome 3q26 is a frequent and early event in cancers of the ovary, lung, head and neck, cervix, and BRCA1 positive and basal breast cancers. The p110α catalytic subunit of phosphoinositide-3-kinase (PI3KCA) and protein kinase Cι (PKCι) have previously been shown as functionally deregulated by 3q copy number increase. High-resolution array comparative genomic hybridization of 235 high-grade serous epithelial ovarian cancers using contiguous bacterial artificial chromosomes across 3q26 delineated an ∼2 Mb–wide region at 3q26.2 encompassing PDCD10 to MYNN (chr3:168722613-170908630). Ecotropic viral integration site-1 (EVI1) and myelodysplastic syndrome 1 (MDS1) are located at the center of this region, and their DNA copy number increases are associated with at least 5-fold increased RNA transcript levels in 83% and 98% of advanced ovarian cancers, respectively. Moreover, MDS1/EVI1 and EVI1 protein levels are increased in ovarian cancers and cancer cell lines. EVI1 and MDS1/EVI1 gene products increased cell proliferation, migration, and decreased transforming growth factor-β–mediated plasminogen activator inhibitor-1 promoter activity in ovarian epithelial cells. Intriguingly, the increases in EVI1 DNA copy number and MDS1/EVI1 transcripts are associated with improved patient outcomes, whereas EVI1 transcript levels are associated with a poor patient survival. Thus, the favorable patient prognosis associated with increased DNA copy number seems to be as a result of high-level expression of the fusion transcript MDS1/EVI1. Collectively, these studies suggest that MDS1/EVI1 and EVI1, previously implicated in acute myelogenous leukemia, contribute to the pathophysiology of epithelial ovarian cancer. [Cancer Res 2007;67(7):3074–84]&lt;/p&gt;&lt;/div&gt;
Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function (2016)

Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.
The T-cell receptor delta chain locus is disrupted in the T-ALL associated t(11;14)(p13;q11) translocation (1989)

Two T-ALL patients carrying a t(11;14)(p13;q11) translocation were analyzed. Southern blotting experiments demonstrated that both patients had rearranged their J delta genes and that the translocation involved the delta locus in both cases. In one patient, cloning, restriction mapping, and sequencing showed that the translocation occurred on a D delta 1-D delta 2-J delta 2 rearranged gene. In addition, the rearrangement on chromosome 11 occurred in both patients within a segment of less than or equal to 2 kb showing the presence in this region of a point of recurrent recombination.
Genomics approach using calcineurin/NFAT inhibitors to identify novel effectors of vascular smooth muscle phenotypic modulation (2010)

Calcineurin (Cn) and the NFAT family of transcription factors are critical in vascular smooth muscle cell (SMC) development and pathology. We used a genomics approach to identify novel transcriptional targets of NFAT in SMC phenotypic modulation. SMC phenotypic modulation was induced by treatment with platelet‐derived growth factor‐BB (PDGF). PDGF‐induced proliferation was blocked by either the Cn inhibitor, cyclosporin A (CsA), or the NFAT inhibitor, A285222. Genome‐wide expression arrays were used to identify genes in rat aortic SMCs both 1) differentially expressed in response to PDGF at 3 hours and 2) whose differential expression was reduced by both CsA and A285222; genes theoretically positively regulated by Cn/NFAT. The top 20 PDGF‐upregulated probe sets sensitive to both drugs corresponded to 17 genes. 15 of these genes were expressed at higher levels in intact rat arteries compared to visceral smooth muscle tissues. For validation, SMCs were treated at 10 time‐points across 24 hours. Real‐time RTPCR showed that CsA and A285222 reduced the early upregulation of DSCR1 (Cn regulator), DUSP1 (MAPK inactivator), and PROCR (protein C receptor) more than 50% compared to vehicle controls. Intriguingly, the PROCR promoter contains a highly conserved NFAT site at the ‐8 position. We report PROCR and DUSP1 as novel NFAT‐dependent early genes in VSMC phenotypic modulation. AHA predoc APS postdoc NIH HL81682 AHA SDG
Discovering access-control misconfigurations (2012)

Accesses that are not permitted by implemented policy but that share similarities with accesses that have been allowed, may be indicative of access-control policy misconfigurations. Identifying such misconfigurations allows administrators to resolve them before they interfere with the use of the system. We improve upon prior work in identifying such misconfigurations in two main ways. First, we develop a new methodology for evaluating misconfiguration prediction algorithms and applying them to real systems. We show that previous evaluations can substantially overestimate the benefits of using such algorithms in practice, owing to their tendency to reward predictions that can be deduced to be redundant. We also show, however, that these and other deductions can be harnessed to substantially recover the benefits of prediction. Second, we propose an approach that significantly simplifies the use of misconfiguration prediction algorithms. We remove the need to hand-tune (and empirically determine the effects of) various parameters, and instead replace them with a single, intuitive tuning parameter. We show empirically that this approach is generally competitive in terms of benefit and accuracy with algorithms that require hand-tuned parameters.
Figure S5 from Targeting APLN/APLNR Improves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma (2023)

&lt;p&gt;APLNR is expressed in glioblastoma cells and receptor internalization is activated by apelin peptides specifically.&lt;/p&gt;
Immunodetection and quantification of vascular endothelial growth factor receptor‐3 in human malignant tumor tissues (2004)

Vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligands, vascular endothelial growth factor-C (VEGF-C) and -D (VEGF-D), are the major molecules involved in developmental and pathological lymphangiogenesis. Here we describe for the first time the development of a specific indirect enzyme-linked immunosorbent assay (ELISA) for the quantification of VEGFR-3 in different human cell and tissue lysates. A combination of the goat polyclonal anti-VEGFR-3 antibody and the mouse monoclonal anti-human VEGFR-3 antibody was used. The assay was highly sensitive and reproducible with a detection range of 0.2-25 ng/ml. The assay was specific for VEGFR-3, with no cross-reactivity to VEGFR-1 or VEGFR-2. Complex formation with VEGF-C and VEGF-D had no effect on the sensitivity of the assay. The VEGFR-3 concentration in the lysates of cultured human dermal microvascular endothelial cells was 14-fold higher than in the lysates from human umbilical vein endothelial cells. In human kidney, breast, colon, gastric and lung cancer tissues the protein levels of VEGFR-3 were in the range of 0.6-16.7 ng/mg protein. Importantly, the level of VEGFR-3 protein detected in the ELISA correlated significantly with the number of VEGFR-3 positive vessels observed in histochemical sections, suggesting that the ELISA assay may be a reliable surrogate of measuring VEGFR-3-positive vessel density. The protein levels of VEGFR-3 in 27 renal cell carcinoma samples had a significant correlation with the levels of VEGF-C (p<0.001), or biological active, free VEGF-A (p<0.0001), but not with VEGFR-1 or total VEGF-A. This assay provides a useful tool for the investigations of the expression levels of VEGFR-3 in physiological and pathological processes, particular in cancer and in lymphangiogenesis-related disease.
A Reservation-Based Enhancement of IEEE 802.11 DCF Protocol (2007)

IEEE 802.11 DCF is an asynchronous and distributed MAC protocol which does not require the existence of a central controller for medium access coordination. This flexibility, which is due to DCF's contention-based nature, comes at the expense of the overhead associated with contention resolution. The overhead consists of frame collision time and channel idle time, which is particularly severe when channel is saturated. In this paper, we present an enhancement of DCF which aims at reducing its contention resolution overhead by equipping it with a distributed reservation mechanism. The proposed reservation mechanism enhances collision avoidance mechanism of DCF by enforcing a partially ordered medium access through an implicit agreement between neighboring nodes. Simulation results, using ns-2 network simulator, show that the added reservation scheme 1) effectively reduces DCF's overhead and improves channel utilization particularly when node density and traffic load is high, 2) significantly enhance DCF's fairness.
Super-Resolved Imaging of Early-Stage Dynamics in the Immune Response (2021)

The use of photo-activated fluorescent molecules to create long sequences of low-density, diffraction-limited images gives us the ability to achieve highly-precise molecule localizations. However, this methodology requires lengthy imaging times, resulting in poor temporal resolution. This is particularly problematic when dynamic interactions of live cells on short time scales are of interest. We consider the problem of shortening dramatically the acquisition times in super-resolution microscopy down to seconds, in order to image the cellular dynamics during T-cell activation. For this purpose, we apply our newly developed method for super-resolution microscopy, SPARCOM, to real-time imaging of the immune response initiation. Despite the small number of frames used for reconstruction, we are able to achieve high-quality imaging that shows how T-cell receptors re-organize during the activation events, with respect to the cell’s surface. Thus, our work demonstrates the use of SPARCOM for imaging dynamic cellular processes well below the diffraction limit.
Genetically targeted reporter imaging of deep neuronal network in the mammalian brain (2020)

Abstract Positron Emission Tomography (PET) allows biomolecular tracking, while PET monitoring of brain networks has been hampered by the lack of a suitable reporter. Here, we describe in vivo brain imaging that takes advantage of bacterial dihydrofolate reductase, ecDHFR, and its unique antagonist, TMP. In mice, peripheral administration of radiofluorinated and fluorescent TMP analogs enabled PET and intravital microscopy, respectively, of neuronal ecDHFR expressions. This technique is applicable to the visualization of neuronal ensemble activities elicited by chemogenetic manipulation in the mouse hippocampus. Notably, ecDHFR-PET offers mapping of neuronal projections in non-human primate brains, indicating the availability of ecDHFR-based tracking technologies for network monitoring. Finally, we demonstrate the utility of TMP analogs for PET assays of turnover and self-assembly of proteins tagged with ecDHFR mutants. Our findings may facilitate a broad spectrum of PET analyses of a mammalian brain circuit at molecular levels that were not previously applicable for technical reasons.
Performance Comparison of Duobinary Modulation Formats for 40 Gb/s Long-Haul WDM Transmissions (2006)

With their compact spectrum and high tolerance to residual chromatic dispersion, duobinary formats are attractive for the deployment of 40 Gb/s technology on 10 Gb/s WDM Long-Haul transmission infrastructures. Here, we compare the robustness of various duobinary formats when facing 40 Gb/s transmission impairments.