gebhart/patrepeval huggingface dataset:
Abstract 9761: Novel Modulators of Low Density Lipoprotein Receptor Metabolism (2014)

Intervention with drugs to reduce Low Density Lipoprotein-cholesterol (LDL-C) has proven to decrease the risk of subsequent cardiovascular events, including mortality. Our goal is to develop novel, small molecule, LDL-C lowering drugs by targeting the Low Density Lipoprotein Receptor (LDLR) degradation pathway, which is modulated by the protease proprotein convertase subtilisin-like kexin type 9 (PCSK9). PCSK9 has been shown to bind to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR; it enhances the degradation of the LDLR by an unknown. We successfully integrated virtual screening methods and cell based assays into a simple, efficient procedure and identified compounds that interfere with the PCSK9-LDLR interaction. Using the atomic coordinates of the crystal structure of the PCSK9/LDLR-EGF-A complex, about a million drug-like compounds were docked in silico into the region of PCSK9 where LDLR-EGF-A binds. We selected 179 top scoring compounds that showed the best fit in the binding site as well as the greatest number of interactions with PCSK9. These compounds were tested in (a) our PCSK9/LDLR dependent HEK293 cell-based recombinant assay and (b) the endogenously expressed LDLR in HepG2/PCSK9 dependent cell based assay for their ability to upregulate the LDLR. From these screening campaigns, eleven compounds consistently exhibited concentration dependent increase in the LDLR as comparable to control, with IC 50 s in the low micromolar range. Three of the top picks were shown to exhibit a 5 to 10 fold up-regulation at 1.6 μM in two cell lines. In addition, these compounds also exhibited an increase in the fluorescently labeled DiI-LDL uptake in the nanomolar range in situ . Furthermore, in a two week animal study, subcutaneous injection of 4 mg/kg of one of these compounds resulted in a 32% reduction of the total cholesterol level in mice fed a high fat/high cholesterol diet as compared to 27% cholesterol reduction obtained with 40 mg/kg Atorvastatin. To our knowledge, no small molecule antagonist against PCSK9 has been reported, only mAbs. Thus, identifying such an oral small molecule PCSK9 inhibitor represents a tremendous advance and opportunity for drug development.
Phase Variations of the Mycoplasma penetrans Main Surface Lipoprotein Increase Antigenic Diversity (1999)

Mycoplasma penetrans is a recently identified mycoplasma, isolated from urine samples collected from human immunodeficiency virus (HIV)-infected patients. Its presence is significantly associated with HIV infection. The major antigen recognized during natural and experimental infections is an abundant P35 lipoprotein which, upon extraction, segregates in the Triton X-114 detergent phase and is the basis of M. penetrans-specific serological assays. We report here that the P35 antigen undergoes spontaneous and reversible phase variation at high frequency, leading to heterogeneous populations of mycoplasmas, even when derived from a clonal lineage. This variation was found to be determined at the transcription level, and although this property is not unique among the members of the class Mollicutes, the mechanism by which it occurs in M. penetrans differs from those previously described for other Mycoplasma species. Indeed, the P35 phase variation was due neither to a p35 gene rearrangement nor to point mutations within the gene itself or its promoter. The P35 phase variation in the different variants obtained was concomitant with modifications in the pattern of other expressed lipoproteins, probably due to regulated expression of selected members of a gene family which was found to potentially encode similar lipoproteins. M. penetrans variants could be selected on the basis of their lack of colony immunoreactivity with a polyclonal antiserum against a Triton X-114 extract, strongly suggesting that the mechanisms involved in altering surface antigen expression might allow evasion of the humoral immune response of the infected host.
A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling (2022)

Summary Altered myeloid inflammation and lymphopenia are hallmarks of severe infections, including SARS-CoV-2. Here, we identified a gene program, defined by correlation with EN-RAGE ( S100A12 ) gene expression, which was up-regulated in patient airway and blood myeloid cells. The EN-RAGE program was expressed in 7 cohorts and observed in patients with both COVID-19 and acute respiratory distress syndrome (ARDS) from other causes. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE + myeloid cells express features consistent with suppressor cell functionality, with low HLA-DR and high PD-L1 surface expression and higher expression of T cell-suppressive genes. Sustained EN-RAGE signature expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers, such as PD-1. IL-6 upregulated many of the severity-associated genes in the EN-RAGE gene program in vitro , along with potential mediators of T cell suppression, such as IL-10. Blockade of IL-6 signaling by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of ENRAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.
Thiazolidinediones and insulin resistance: Peroxisome proliferatoractivated receptor γ activation stimulates expression of the CAP gene (1998)

c-Cbl-associated protein (CAP) is a signaling protein that interacts with both c-Cbl and the insulin receptor that may be involved in the specific insulin-stimulated tyrosine phosphorylation of c-Cbl. The restricted expression of CAP in cells metabolically sensitive to insulin suggests an important potential role in insulin action. The expression of CAP mRNA and proteins are increased in 3T3-L1 adipocytes by the insulin sensitizing thiazolidinedione drugs, which are activators of the peroxisome proliferator-activated receptor gamma (PPARgamma). The stimulation of CAP expression by PPARgamma activators results from increased transcription. This increased expression of CAP was accompanied by a potentiation of insulin-stimulated c-Cbl tyrosine phosphorylation. Administration of the thiazolidinedione troglitazone to Zucker (fa/fa) rats markedly increased the expression of the major CAP isoform in adipose tissue. This effect was sustained for up to 12 weeks of treatment and accompanied the ability of troglitazone to prevent the onset of diabetes and its complications. Thus, CAP is the first PPARgamma-sensitive gene identified that participates in insulin signaling and may play a role in thiazolidinedione-induced insulin sensitization.
Local resistance measurement across grain boundaries in low-temperature polycrystalline silicon layer of thin film transistor using scanning spreading resistance microscopy (2006)

Local resistance distribution in a low-temperature polycrystalline Si layer of a thin film transistor with a lightly doped drain (LDD) structure was investigated using scanning spreading resistance microscopy. The local resistance around the grain boundaries was found to be lower than that at grain insides in the drain, LDD, and channel regions. At the center of the grain boundaries, however, slightly higher resistance part was sandwiched between low resistance regions. Identifying the drain, the LDD, and the channel regions is succeeded by an analysis in which only the lower local resistances were used.
SU‐FF‐J‐106: FMISO‐PET Hypoxia Imaging: A Novel Method to Plan IMRT‐Based Boost Radiation to Hypoxic Subvolumes (2005)

Purpose: To investigate the use of [F‐18] fluoromisonidazole (FMISO) PET and intensity modulated radiation treatment (IMRT) planning to escalate the dose to hypoxic subvolumes in patients with advanced head and neck tumors. Method and Materials: Seventy‐three patients with head and neck cancer underwent FMISO‐PET scans, with fifty‐three of them also undergoing FDG‐PET scans as part of ongoing research studies. An initial treatment plan used a PTV defined with a 0.5‐cm margin around physician‐defined primary GTVs and affected nodal systems. The prescription dose is 70 Gy to the PTV and 50 Gy to the affected nodes, while sparing the spinal cord, mandible, and parotid glands. Physician‐defined regions of enhanced FMISO signal were used to define boost volumes on coregistered FMISO‐PET/CT images. The boost plan prescription dose to the hypoxic subvolumes is an additional 10 Gy. Results: Initial results from example treatment plans for two head and neck cancer patients are as follows (average over patients): to the PTV V 100 = 87.2%, D min = 6081 cGy, D 10 = 7303 cGy and to the nodal system V 100 = 95.9%, D min = 4764 cGy, D 10 = 5280 cGy. The IMRT boost plan yields V 100 = 95.1%, D min = 979 cGy, D 10 = 1012 cGy to the hypoxic PTV. The critical structures of interest received the following dose distributions from the composite IMRT plans: cord D 1 = 3890 cGy, left (contralateral) parotid gland D 1 = 1965 cGy, right parotid gland D 1 = 4907 cGy (same side as primary tumor), and mandible D 5 = 6220 cGy. Conclusion: We demonstrate the feasibility of directing dose‐escalated IMRT to hypoxic subvolumes in head and neck cancer using coregistered FMISO‐PET and CT images. Ongoing research and patient studies are expected to provide conclusive information on the clinical role of this procedure.
Unexpected Results of a Turnover Number (TON) Study Utilising Ruthenium‐Based Olefin Metathesis Catalysts (2005)

Abstract A turnover number (TON) study of ruthenium‐based metathesis catalysts has been conducted for ring‐closing metathesis (RCM) in dilute solution. Unexpectedly the results indicate that 1 st generation metathesis catalysts can give higher TON in RCM of simple unsubstituted terminal olefins than their second generation counterparts. In particular, the 1 st generation Hoveyda–Grubbs catalyst showed unexpectedly high activity, particularly when compared to the 2 nd generation catalysts.
Compensation of frequency-selective I/Q imbalances in space-time coded multi-antenna OFDM systems (2008)

In multi-antenna transmission systems, multiple parallel radio implementations are needed. To keep the overall transceiver implementation feasible, this poses big restrictions on the size and cost of individual radios, resulting in various imperfections in the analog radio front-ends. One good example is the so-called I/Q imbalance problem related to the amplitude and phase matching of the transceivers I and Q chains. This paper considers this I/Q mismatch problem in space-time coded multi-antenna OFDM system context, taking both transmitter and receiver sides into account and assuming the challenging yet practical case of frequency-dependent I/Q mismatches. Practical pilot-based I/Q imbalance compensation scheme is proposed, stemming from the derived signal and system models and proper pilot allocation. The performance of the compensator is analyzed using extensive computer simulations and shown to virtually reach the perfectly matched reference system performance with low pilot overhead. Also some important practical issues such as pilot interpolation as well as the effects of channel estimation errors in the imbalance compensation context are addressed.
Scission of a coordinated acetylide ligand on the tungsten-triosmium framework. Synthesis, crystal structure, and reactivity studies of CpWOs3(CO)11(C.tplbond.CR) (R = Ph and nBu) (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTScission of a coordinated acetylide ligand on the tungsten-triosmium framework. Synthesis, crystal structure, and reactivity studies of CpWOs3(CO)11(C.tplbond.CR) (R = Ph and nBu)Yun Chi, Gene Hsiang Lee, Shie Ming Peng, and Chang Ho WuCite this: Organometallics 1989, 8, 6, 1574–1576Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/om00108a038https://doi.org/10.1021/om00108a038research-articleACS PublicationsRequest reuse permissionsArticle Views35Altmetric-Citations25LEARN 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
Implementation of collective I/O in the Intel Paragon parallel file system (1997)

Article Free Access Share on Implementation of collective I/O in the Intel Paragon parallel file system: initial experiences Author: Rajesh Bordawekar Center for Advanced Computing Research, California Institute of Technology, 1201 E. California Blvd., Pasadena, CA Center for Advanced Computing Research, California Institute of Technology, 1201 E. California Blvd., Pasadena, CAView Profile Authors Info & Claims ICS '97: Proceedings of the 11th international conference on SupercomputingJuly 1997 Pages 20–27https://doi.org/10.1145/263580.263586Published:11 July 1997Publication History 13citation254DownloadsMetricsTotal Citations13Total Downloads254Last 12 Months12Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Oxygen-regulated mRNAs for light-harvesting and reaction center complexes and for bacteriochlorophyll and carotenoid biosynthesis in Rhodobacter capsulatus during the shift from anaerobic to aerobic growth (1986)

The stability and regulation by oxygen of mRNAs for the photosynthetic apparatus in Rhodobacter capsulatus have been studied by using proflavin to inhibit transcription and by shifting cells from anaerobic to aerobic conditions. The results from the inhibition experiments show that the mRNA for the light-harvesting LH-II polypeptides (beta, alpha) is more stable than that for the light-harvesting LH-I polypeptides (beta, alpha) during anaerobic growth, whereas the mRNAs for the reaction center polypeptides L (RC-L), M (RC-M), and H (RC-H) are less stable than both the LH-I and LH-II mRNAs. When photosynthetic cells are shifted from anaerobic to aerobic conditions, an immediate decrease in the levels of mRNA for the LH-I, LH-II, RC-L, RC-M, and RC-H proteins was observed. The level of mRNA for the LH-II proteins, however, is more sensitive to oxygen and is reduced faster than the level of mRNA for the LH-I proteins. These results suggest that oxygen represses the expression of genes coding for the light-harvesting antenna and reaction center complexes and may selectively accelerate the degradation of mRNA for the LH-II proteins. The mRNAs for several enzymes in the bacteriochlorophyll biosynthetic pathway are regulated by oxygen in a similar manner. The mRNAs for carotenoid biosynthetic enzymes, however, are regulated by oxygen in a different way. We have found that the amounts of mRNAs for carotenoid biosynthetic enzyme, relative to the amounts of mRNAs for LH and RC, increased during the shift from anaerobic to aerobic conditions. We have particularly shown that although the expression of most photosynthetic genes in R. capsulatus is repressed by oxygen, the crtA gene, located in the BamHI H fragment of the R' plasmid pRPS404 and responsible for the oxidation of spheroidene to spheroidenone, responds to oxygen in an opposite fashion. This exzymatic oxidation may protect the photosynthetic apparatus from photooxidative damage.
Constellation Design for Bit-Interleaved Coded Modulation (BICM) Systems in Advanced Broadcast Standards (2017)

This paper presents a generic methodology to optimize constellations based on their geometrical shaping for bit-interleaved coded modulation (BICM) systems. While the method can be applicable to any wireless standard design it has been tailored to two delivery scenarios typical of broadcast systems: 1) robust multimedia delivery and 2) UHDTV quality bitrate services. The design process is based on maximizing the BICM channel capacity for a given power constraint. The major contribution of this paper is a low complexity optimization algorithm for the design of optimal constellation schemes. The proposal consists of a set of initial conditions for a particle swarm optimization algorithm, and afterward, a customized post processing procedure for further improving the constellation alphabet. According to the broadcast application cases, the sizes of the constellations proposed range from 16 to 4096 symbols. The BICM channel capacities and performance of the designed constellations are compared to conventional quadrature amplitude modulation constellations for different application scenarios. The results show a significant improvement in terms of system performance and BICM channel capacities under additive white Gaussian noise and Rayleigh independently and identically distributed channel conditions.
Performance of a spatial error correction technique in SMOS brightness temperature images (2012)

Soil Moisture and Ocean Salinity (SMOS) brightness temperature synthesized images are obtained after a comprehensive calibration and error correction procedure. However, the final images are still contaminated by small but non-negligible spatial errors: the so-called pixel bias. These errors have been found to be very stable in the SMOS Alias-Free Field of View (AF-FoV) and can be mitigated, to a large extent, by applying a multiplicative mask to the measured brightness temperatures at the antenna plane. This paper describes the procedure to upgrade this mask to cover SMOS Extended AF-FoV.
Quality Indicators for the Management of Barrett’s Esophagus, Dysplasia, and Esophageal Adenocarcinoma: International Consensus Recommendations from the American Gastroenterological Association Symposium (2020)

The development of and adherence to quality indicators in gastroenterology, as in all of medicine, is increasing in importance to ensure that patients receive consistent high-quality care. In addition, government-based and private insurers will be expecting documentation of the parameters by which we measure quality, which will likely affect reimbursements. Barrett’s esophagus remains a particularly important disease entity for which we should maintain up-to-date guidelines, given its commonality, potentially lethal outcomes, and controversies regarding screening and surveillance. To achieve this goal, a relatively large group of international experts was assembled and, using the modified Delphi method, evaluated the validity of multiple candidate quality indicators for the diagnosis and management of Barrett’s esophagus. Several candidate quality indicators achieved >80% agreement. These statements are intended to serve as a consensus on candidate quality indicators for those who treat patients with Barrett’s esophagus.
Traffic-aware training and scheduling for the 2-user MISO broadcast channel (2014)

In this paper we study the stability region of the 2-user MISO broadcast channel where the transmitter employs Zero Forcing precoding when both users are scheduled, taking into account the time overheads needed for uplink channel training. We show that, with proper signalling design, combining a decentralized policy with the baseline centralized one for user selection can increase the stability region of the system.
Postoperative Radiotherapy of the Prostate for Patients Undergoing Radical Prostatectomy With Positive Margins, Seminal Vesicle Involvement and/or Penetration through the Capsule (1990)

A group of 159 patients previously reported as having margins positive for disease after radical prostatectomy with or without adjunctive postoperative radiation was reanalyzed to determine whether the reported benefit did indeed exist. Upon re-examination of the 159 patients 15 were identified who did not receive radical prostatectomy but who were analyzed as if they had received this therapy. An updated review of the total pool of 159 patients with analysis as to failure, death of any cause or death of prostatic cancer demonstrated no benefit of postoperative radiation therapy for margin positive disease. Exclusion of patients who did not receive radical prostatectomy and analysis as described also failed to identify any benefit of postoperative adjunctive radiation therapy.
Enhanced Expression of Serum and Glucocorticoid-Inducible Kinase-1 in Kidneys of <i>L-</i>NAME-Treated Rats (2006)

L-NAME treatment leads to hypertension, proteinuria and renal fibrosis. It increases renal transcription and expression of SGK1, which has previously been shown to foster matrix protein deposition and could thus contribute to renal injury.
Supplementary Figure from Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma <i>In Situ</i> (2023)

Supplementary Figure from Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma &lt;i&gt;In Situ&lt;/i&gt;
An efficient twitter data collection and analytics framework for effective disaster management (2022)

The world has faced an exponential increase in disasters and it is very evident that losses incurred due to disasters and the risk of disasters are also increasing. The literature [1] states that India has faced 371 natural hazards resulting in considerable deaths, infrastructural, agricultural, and economic devastation. Social networking development has been expeditious and has been considered beneficial in disaster management. In culture, social media sites such as Twitter and Facebook have reached an irreplaceable stature that demonstrates the prominence of colossal data acquired. Social networking data can be gathered and used for disaster-specific data analysis, which can be used to extract disaster logistics, identify patterns, and provide public preparedness assistance. The proposed work establishes a data collection system that is capable of capturing disaster-related tweets such as landslides, rain and flood in focus, eliminating obsolete and irrelevant data, retaining related data such as media and location without breaching social media ethics privacy policies. Within the period from May 2020 to December 2021, the system was able to collect 9,21,897 tweets. The diversity of culture, language and expressions prevalent in different parts of the globe is reflected in the way knowledge is conveyed, which makes it relevant to collect tweets in Indian languages. So, for easier data analysis, this system gathers tweets that are in Indian languages and translates them into English for efficient data analysis.