gebhart/patrepeval huggingface dataset:
A Cdk4/6-dependent phosphorylation gradient regulates the early to late G1 phase transition (2021)

During early G1 phase, Rb is exclusively mono-phosphorylated by cyclin D:Cdk4/6, generating 14 different isoforms with specific binding patterns to E2Fs and other cellular protein targets. While mono-phosphorylated Rb is dispensable for early G1 phase progression, interfering with cyclin D:Cdk4/6 kinase activity prevents G1 phase progression, questioning the role of cyclin D:Cdk4/6 in Rb inactivation. To dissect the molecular functions of cyclin D:Cdk4/6 during cell cycle entry, we generated a single cell reporter for Cdk2 activation, RB inactivation and cell cycle entry by CRISPR/Cas9 tagging endogenous p27 with mCherry. Through single cell tracing of Cdk4i cells, we identified a time-sensitive early G1 phase specific Cdk4/6-dependent phosphorylation gradient that regulates cell cycle entry timing and resides between serum-sensing and cyclin E:Cdk2 activation. To reveal the substrate identity of the Cdk4/6 phosphorylation gradient, we performed whole proteomic and phospho-proteomic mass spectrometry, and identified 147 proteins and 82 phospho-peptides that significantly changed due to Cdk4 inhibition in early G1 phase. In summary, we identified novel (non-Rb) cyclin D:Cdk4/6 substrates that connects early G1 phase functions with cyclin E:Cdk2 activation and Rb inactivation by hyper-phosphorylation.
Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma (2014)

Epithelial-to-mesenchymal transition (EMT), in which epithelial cells loose their polarity and become motile mesenchymal cells, is a determinant of melanoma metastasis. We compared gene expression signatures of mesenchymal-like melanoma cells with those of epithelial-like melanoma cells, and identified Thrombospondin 1 (THBS1) as highly up-regulated in the mesenchymal phenotype. This study investigated whether THBS1, a major physiological activator of transforming growth factor (TGF)-beta, is involved in melanoma EMT-like process. We sought to examine expression patterns in distinct melanoma phenotypes including invasive, de-differentiated, label-retaining and drug resistant populations that are putatively associated with an EMT-like process. Here we show that THBS1 expression and secretion was elevated in melanoma cells exhibiting invasive, drug resistant, label retaining and mesenchymal phenotypes and correlated with reduced expression of genes involved in pigmentation. Elevated THBS1 levels were detected in Vemurafenib resistant melanoma cells and inhibition of THBS1 led to significantly reduced chemoresistance in melanoma cells. Notably, siRNA-mediated silencing of THBS1 and neutralizing antibody to THBS1 reduced invasion in mesenchymal-like melanoma cells, while ectopic THBS1 expression in epithelial-like melanoma cells enhanced invasion. Furthermore, the loss of THBS1 inhibited in vivo motility of melanoma cells within the embryonic chicken neural tube. In addition, we found aberrant THBS1 protein expression in metastatic melanoma tumor biopsies. These results implicate a role for THBS1 in EMT, and hence THBS1 may serve as a novel target for strategies aimed at the treatment of melanoma invasion and drug resistance.
Collective Die Bonding: An Enabling Toolkit for Heterogeneous Integration (2020)

The increasing demand for high performance devices with increased functionality onto a single device/package and with reduced form factor were the main factors driving the development of heterogeneous integration technology. Heterogeneous integration (HI) refers to the assembly and packaging of multiple separately manufactured components onto a single chip in order to increase functionality. Components with different functionality, substrate materials, and process technologies are joined in a single package in a System in Package (SIP) approach. The functionality of the components could vary throughout the entire device supply chain starting from signal processors to memory, micro-electro-mechanical systems (MEMS), and silicon photonics. The possibility to join multiple functionalities onto a die enables new packaging architectures and design concepts. One such concept is based on the not new concept of die-to-wafer bonding but allows for bonding multiple dies to a wafer in a single process. Packaging is the final manufacturing process transforming devices into functional products for the end user. Packaging must provide electrical and photonic connections for signal input and output, power input, and voltage control. It also provides for thermal dissipation and the physical protection required for increased product reliability. In this work, we report results using a method and process flow enabling local die bonding compatible with the highest alignment accuracy and cleaning requirements to support a very high yield. A customized temporary carrier with alignment features was utilized to place known good dies (KGD) on the carrier and enable die processing prior to the final bonding process.
An Improved Route to 3,4-Thiophenedithiolate (1996)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTAn Improved Route to 3,4-ThiophenedithiolateJerry L. Reddinger and John R. ReynoldsView Author Information Department of Chemistry, Center for Macromolecular Science and Engineering, University of Florida, Gainesville, Florida 32611 Cite this: J. Org. Chem. 1996, 61, 14, 4833–4834Publication Date (Web):July 12, 1996Publication History Received20 February 1996Published online12 July 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jo960336khttps://doi.org/10.1021/jo960336kbrief-reportACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views415Altmetric-Citations19LEARN 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-Alertsclose SUBJECTS:Coordination compounds,Materials,Molecules,Reaction products,Solvents Get e-Alerts
P‐91: Parametric Evaluation of Computer Displays for Optimized Display Data Transmission (2011)

Abstract Display sub‐system is among the highest power consuming entity on a computer platform and the energy efficiency of the display pipeline has a significant impact on the battery life, especially in mobile devices. Traditional display sub‐systems expend a lot of energy to maintain the stable images on the screen by transmitting the entire screen contents to display even if there is little or no change in the screen. This paper characterizes the computer generated screen updates for different type of workloads by two independent techniques: HW &amp; SW and presents an analysis of the screen updates. Our data shows that typically only less than 20% of the screen content changes and there is 20–200ms idle time period between active frames. Future display technologies can take advantage of this redundancy in screen contents to save power on the display sub‐system.
Treatment of metastatic uveal melanoma (mUM) directed by a comprehensive molecular tumour analysis program (CMTA). (2018)

9566 Background: There is a lack of active treatment against mUM. Such “hard-to-treat” tumour might benefit from treatment decisions driven by a complete genomic and transcriptomic analysis program. Methods: From 1.3.2016 to 1.12.2017, mUM were included in the prospective TREAT20Plus study and were subjected to a CMTA including WGS, WES, RNAseq, cell culture and systems biological/pharmacodynamic modelling. Treatment recommendations were made by a molecular tumour board. Results: Twenty six patients (12 F, 14M). Age: 61 (32-80). PS: 0 (0-2). Metastases: 4 (1-10). Abnormal LDH: 19. Pre-treatment: 1 (0-5) and type: iv chemotherapy: 11, checkpoint-inhibitors (-i): 7, intra-hepatic: 13, vaccine: 1. Insufficient material in 3 patients. The mutation burden was low: 32 (15-449). The treatment recommendations (TRec) were based on the different mutations or activation profiles: A) MEK-i. for mutations of GNAQ: 11, GNA11: 13. B) a MET-i. for MET overexpression: 17. ALK-i. for the oncogenic ALK ATI isoform: 3. C) CDK4/6-i. for CDKN2A loss: 1. D) checkpoint-i. for mutation burden > 100: 3. E) For the other alterations no off-label treatment was available: mutation of BAP1: 8 or SF3B1: 10, overexpression of MYC: 14, BCL2: 24, CCND2: 16, ERBB3: 5 , biallelic loss of TNFAIP3: 1. Among novel non-recurring gene-fusions: inactivating gene fusion affecting MITF: 1. In 1 patient repeated biopsies at time of recurrence after MEK-i disclosed biallelic loss of CDKN2A. The pharmacodynamic modeling confirmed TREc in 10 and helped with the decision in 8 patients. A treatment was initiated in 15 patients: Trametinib: 6, Cabozantinib: 3, Crizotinib: 6, Palbociclib: 1. A treatment was not initiated for 8 patients: 4 too early, 4 rapid progression. Among the 12 evaluable patients the antitumor response was: minor response: 2, stable disease: 4, progressive disease: 5, too early: 1. Median PFS of the treated patients: 5,5 months. Conclusions: Precision medicine in mUM is clinically feasible. It leads to a better understanding of the biology of the tumour and of the potential therapeutic targets. Its clinical efficacy is limited by the non-availability of drugs as single agent or in combination. Clinical trial information: EA4/063/13.
A phase 2 study on efficacy, safety and intratumoral pharmacokinetics of oral selinexor (KPT-330) in patients with recurrent glioblastoma (GBM). (2015)

2044 Background: Patients (pts) with recurrent GBM have few treatment options and a poor prognosis. Selinexor is an oral inhibitor of XPO1 mediated nuclear export resulting in nuclear retention of multiple tumor suppressor proteins (TSPs) including p53, pRB, CDKN2A, p21 and FOXO. Mean IC50 of selinexor in pt derived GBM neurosphere cultures was 133 nM. In a pt derived orthotopic murine xenograft model, selinexor demonstrated marked inhibition of tumor growth in vivo and prolonged survival (P= .001). Methods: This study (NCT01986348) is an open label, multicenter, two-arm phase II trial enrolling pts with recurrent GBM after radiation therapy with concurrent and adjuvant temozolomide. Pts in Arm A received 3 doses (50 mg/m2) of selinexor prior to surgery, and resumed selinexor after surgery. Pts in Arm B received selinexor alone (50 mg/m2 BIW) until disease progression. Results: (Jan 22, 2015) 7 pts (6/1 M/F, median age 57, 1–2 prior treatment regimens) were treated on Arm A and 15 pts (11/4, M/F, median age 62; 1–3 prior treatment regimens) were treated on Arm B. Mean plasma PK concentration was 999 nM (311-2071 nM) and mean tumor concentration was 136 nM (40-291 nM) in 6 pts. Grade 1/2 AE’s (Arm B) included thrombocytopenia (27%/27%), anorexia (13%/33%), fatigue (7%/40%), and hyponatremia (47%/0%). One Grade 3 AE was reported in ≥ 2 pts (fatigue) and no Grade 4 AEs were reported. Investigator reported best responses for 12 evaluable pts (Arm B) were: 2 partial responses (17%), 4 stable disease (33%) and 6 progressive disease (50%). Analysis of XPO1 and TSP expression in tumor tissue is ongoing. Conclusions: Oral selinexor at 50 mg/m2 BIW achieves concentrations in GBM tissue exceeding the IC50 in pre-clinical models. Main toxicities are fatigue and anorexia. Partial responses and stable disease were observed. Clinical trial information: NCT01986348.
In-Orbit validation of SMOS full polarimetric equations (2013)

This paper analyzes the consistency of SMOS fully polarimetric measurement mode by comparing measured data over the ocean with the expected results. These last are based on an accurate ocean model provided by LOCEAN and simulated taking into account both the co- and cross-polar field antenna patterns. The successful image reconstruction by means of the so-called model full-pol G matrix (M-FPG) method validates SMOS main full-pol features: the full-pol switching scheme, the accuracy of the full-pol antenna pattern measurements and the full-polarimetric visibility equations.
Neuraminidase Inhibitors for Influenza: Oseltamivir Phosphate (Tamiflu ® ) and Zanamivir (Relenza ® ) (2006)

This chapter contains sections titled: Introduction Synthesis of Oseltamivir Phosphate (Tamiflu®) Synthesis of Zanamivir (Relenza®) References
FDM-FSK star network with a tunable optical filter demultiplexer (1987)

An optical frequency-division-multiplexed star network is analysed and demonstrated experimentally using two 45Mbit/s frequency-shift-keyed laser channels at 1.5 μm. A tunable fibre Fabry–Perot filter is used as demultiplexer. The analysis predicts and experiment supports a minimum channel spacing of about six times bit rate B for a single FFP and 3B for a tandem FFP.
Wireless Passive Autonomous Sensors with Electromagnetic Transduction (2011)

International audience
Homarine, a Common Metabolite in Edible Mediterranean Molluscs: Occurrence, Spectral Data and Revision of a Related Structure (2001)

Homarine was isolated from nine edible species of marine molluscs belonging to classes Gastropoda, Bivalvia, and Cephalopoda. A thorough chromatographic, NMR and MS study provided evidence that homarine is a common and abundant metabolite of all these species. This study casts doubt on a previous assertion that 1,1'-dimethyl-[2,2']-bipyridinium is a metabolite of the Bivalve Callista chione.
Disease modification and symptom relief in osteoarthritis using a mutated GCP ‐2/ CXCL6 chemokine (2022)

We showed that the chemokine receptor C-X-C Motif Chemokine Receptor 2 (CXCR2) is essential for cartilage homeostasis. Here, we reveal that the CXCR2 ligand granulocyte chemotactic protein 2 (GCP-2) was expressed, during embryonic development, within the prospective permanent articular cartilage, but not in the epiphyseal cartilage destined to be replaced by bone. GCP-2 expression was retained in adult articular cartilage. GCP-2 loss-of-function inhibited extracellular matrix production. GCP-2 treatment promoted chondrogenesis in vitro and in human cartilage organoids implanted in nude mice in vivo. To exploit the chondrogenic activity of GCP-2, we disrupted its chemotactic activity, by mutagenizing a glycosaminoglycan binding sequence, which we hypothesized to be required for the formation of a GCP-2 haptotactic gradient on endothelia. This mutated version (GCP-2-T) had reduced capacity to induce transendothelial migration in vitro and in vivo, without affecting downstream receptor signaling through AKT, and chondrogenic activity. Intra-articular adenoviral overexpression of GCP-2-T, but not wild-type GCP-2, reduced pain and cartilage loss in instability-induced osteoarthritis in mice. We suggest that GCP-2-T may be used for disease modification in osteoarthritis.
FM screen design using DBS algorithm (2002)

We describe an algorithm to design a frequency modulated screen using the direct binary search algorithm. Compared with the direct binary search algorithm itself, we show that we can maintain halftone image quality while significantly reducing the required computation.
Table S2 from Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas (2023)

&lt;p&gt;Evidence-based variant categorization&lt;/p&gt;
Direct optimization of F-measure for retrieval-based personal question\n answering (2018)

Recent advances in spoken language technologies and the introduction of many\ncustomer facing products, have given rise to a wide customer reliance on smart\npersonal assistants for many of their daily tasks. In this paper, we present a\nsystem to reduce users' cognitive load by extending personal assistants with\nlong-term personal memory where users can store and retrieve by voice,\narbitrary pieces of information. The problem is framed as a neural retrieval\nbased question answering system where answers are selected from previously\nstored user memories. We propose to directly optimize the end-to-end retrieval\nperformance, measured by the F1-score, using reinforcement learning, leading to\nbetter performance on our experimental test set(s).\n
Abstract 659: A novel manganese MRI contrast agent (PyC3A) for the evaluation of hepatic neoplasms (2018)

Abstract Introduction: Magnetic resonance imaging (MRI) is routinely used to diagnosis hepatic neoplasms. However, Gadolinium (Gd) is contraindicated in patients with severe renal impairment, and recent evidence also suggests Gd accumulates in brain tissue after repeated contrast injections. Manganese (Mn2+) is a paramagnetic ion that is cleared via biliary excretion, and provides an ideal alternative to Gd-based MR contrast agents. We present a novel Mn-based contrast agent, [Mn(PyC3A)(H2O)]- (referred to as PyC3A), and compare its efficacy to gadoxetic acid (Eovist) by imaging orthotopically implanted colorectal cancer hepatic metastases in mice. Methods: Male BALB/c mice (n = 8) were injected in the left lobe of the liver with 5x104 MC26/MCA-26 murine colon carcinoma cells, and were imaged on postoperative day 10 using a 4.7T MR scanner with PyC3A and gadoxetic acid (Eovist) 24 hrs apart. Signal contrast-to-noise ratio (CNR) was calculated for normal liver relative to tumor for each probe and compared. Results: Relaxivity of PyC3A in blood plasma was shown to be comparable to commercial Gd contrast agents. Biodistribution analysis confirmed that PyC3A clears via a mixed renal/hepatobiliary pathway with greater than 99% clearance within 24 hours. For imaging hepatic metastases, all mice survived to the study endpoint and developed radiographically discernible tumors (5 ± 2 mm diameter) without evidence of carcinomatosis. Calculated CNRs for liver relative to tumor for all recorded times are shown in Table 1. There was no difference in CNR between gadoxetic acid and PyC3A for all time points, suggesting near-equivalent enhancement of normal liver and tumor by both probes. Conclusions: PyC3A provides resolution of metastatic liver metastases that is comparable to gadoxetic acid. PyC3A may provide a safe and effective alternative to Gd constrast agents for imaging hepatic neoplasms in patients with renal impairment. Table 1. Contrast-to-Noise Ratio (CNR) of Normal Liver Relative to TumorTime (minutes post injection)Gadoxetic AcidPyC3Ap-value02.61 ± 1.082.60 ± 1.640.9237.72 ± 4.677.53 ± 3.020.9387.85 ± 3.898.85 ± 4.430.66138.02 ± 3.987.62 ± 5.490.88189.79 ± 4.175.60 ± 3.080.06238.72 ± 4.167.03 ± 2.060.36 Citation Format: Derek J. Erstad, Ian Ramsay, Mozhdeh Sojoodi, Christian Farrar, NIcholas J. Rotile, Shen Li, Sarani Ghoshal, Lanuti Michael, Peter Caravan, Kenneth K. Tanabe, Bryan C. Fuchs, Eric Gale. A novel manganese MRI contrast agent (PyC3A) for the evaluation of hepatic neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 659.
An Investigation of the Limit Equilibrium Method and Numerical Modeling for Rock Slope Stability Analysis (2014)

The following paper presents a review of the methods used to model large scale rocks in practice. The objective of the work is to create a resource available to geotechnical engineers pertaining to recent results, common programs used in practice, method limitations and recommendations for future use, and research of modeling programs. The following methods are included: (1) the distinct element method (discontinuum) using Itasca's universal discrete element code (UDEC); (2) the finite difference method (continuum) using Itasca's fast LaGrangian analysis of continua (FLAC); and (3) the limit equilibrium method using Geostudios: SlopeW. From the investigations and literature performed within this paper, the intention was to present studies within the past decade and increase confidence within engineers when utilizing numerical models.
Transfer dehydrogenative coupling of triethylsilane catalysed by ruthenium and rhodium complexes. A new Si–C bond forming process (1994)

Four-legged piano stool complexes (η6-arene)Ru(H)2(SiEt3)2 and (η5-C5Me5)Rh(H)2(SiEt3)2 catalyse the transfer dehydrogenative coupling of Et3SiH in the presence of a hydrogen acceptor such as tert-butylethylene to yield the carbosilane dimer, HSiEt2CHMeSiEt3, and 2,2-dimethylbutane by a mechanism involving an intermediate η2-silene complex, LnM(Et2SiCHMe), generated by β-hydrogen elimination from a silyl group.
Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss In Spike (2022)

Abstract To provide a unique global view of the relative potential for evasion of CD8+ and CD4+ T cells by SARS-CoV-2 lineages as they evolve over time, we performed a comprehensive analysis of predicted HLA-I and HLA-II binding peptides in spike (S) and nucleocapsid (N) protein sequences of all available SARS-CoV-2 genomes as provided by NIH NCBI at a bi-monthly interval between March and December of 2021. A data supplement of all B.1.1.529 (Omicron) genomes from GISAID in early December was also used to capture the rapidly spreading variant. A key finding is that throughout continued viral evolution and increasing rates of mutations occurring at T-cell epitope hotspots, protein instances with worst case binding loss did not become the most frequent for any Variant of Concern (VOC) or Variant of Interest (VOI) lineage; suggesting T-cell evasion is not likely to be a dominant evolutionary pressure on SARS-CoV-2. We also determined that throughout the course of the pandemic in 2021, there remained a relatively steady ratio of viral variants that exhibit conservation of epitopes in the N protein, despite significant potential for epitope loss in S relative to other lineages. We further localized conserved regions in N with high epitope yield potential, and illustrated HLA-I binding heterogeneity across the S protein consistent with empirical observations. Although Omicron’s high volume of mutations caused it to exhibit more epitope loss potential than most frequently observed versions of proteins in almost all other VOCs, epitope candidates across its most frequent N proteins were still largely conserved. This analysis adds to the body of evidence suggesting that N may have merit as an additional antigen to elicit immune responses to vaccination with increased potential to provide sustained protection against COVID-19 disease in the face of emerging variants.
Expanded-Beam Through-Substrate Coupling Interface for Alignment Tolerant Packaging of Silicon Photonics (2018)

We demonstrate an alignment tolerant through-substrate coupling interface by combining an optimized downward-directionality grating on a silicon photonic chip with a hybrid integrated polymer lens, generating a collimated beam at lambda = 1310nm for more than 600 mu m.