gebhart/patrepeval huggingface dataset:
( R )-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells (2014)

SET domain containing (lysine methyltransferase) 7 (SETD7) is implicated in multiple signaling and disease related pathways with a broad diversity of reported substrates. Here, we report the discovery of (R)-PFI-2-a first-in-class, potent (Ki (app) = 0.33 nM), selective, and cell-active inhibitor of the methyltransferase activity of human SETD7-and its 500-fold less active enantiomer, (S)-PFI-2. (R)-PFI-2 exhibits an unusual cofactor-dependent and substrate-competitive inhibitory mechanism by occupying the substrate peptide binding groove of SETD7, including the catalytic lysine-binding channel, and by making direct contact with the donor methyl group of the cofactor, S-adenosylmethionine. Chemoproteomics experiments using a biotinylated derivative of (R)-PFI-2 demonstrated dose-dependent competition for binding to endogenous SETD7 in MCF7 cells pretreated with (R)-PFI-2. In murine embryonic fibroblasts, (R)-PFI-2 treatment phenocopied the effects of Setd7 deficiency on Hippo pathway signaling, via modulation of the transcriptional coactivator Yes-associated protein (YAP) and regulation of YAP target genes. In confluent MCF7 cells, (R)-PFI-2 rapidly altered YAP localization, suggesting continuous and dynamic regulation of YAP by the methyltransferase activity of SETD7. These data establish (R)-PFI-2 and related compounds as a valuable tool-kit for the study of the diverse roles of SETD7 in cells and further validate protein methyltransferases as a druggable target class.
Autoencoder-Based Detection of Dynamic Allostery Triggered by Ligand Binding Based on Molecular Dynamics (2019)

Dynamic allostery on proteins, triggered by regulator binding or chemical modifications, transmits information from the binding site to distant regions, dramatically altering protein function. It is accompanied by subtle changes in side-chain conformations of the protein, indicating that the changes in dynamics, and not rigid or large conformational changes, are essential to understand regulation of protein function. Although a lot of experimental and theoretical studies have been dedicated to investigate this issue, the regulation mechanism of protein function is still being debated. Here, we propose an autoencoder-based method that can detect dynamic allostery. The method is based on the comparison of time fluctuations of protein structures, in the form of distance matrices, obtained from molecular dynamics simulations in ligand-bound and -unbound forms. Our method detected that the changes in dynamics by ligand binding in the PDZ2 domain led to the reorganization of correlative fluctuation motions among residue pairs, which revealed a different view of the correlated motions from the PCA and DCCM. In addition, other correlative motions were also found as a result of the dynamic perturbation from the ligand binding, which may lead to dynamic allostery. This autoencoder-based method would be usefully applied to the signal transduction and mutagenesis systems involved in protein functions and severe diseases.
Activation of NRF2 by topical apocarotenoid treatment mitigates radiation-induced dermatitis (2020)

Radiation therapy is a frontline treatment option for cancer patients; however, the effects of radiotherapy on non-tumor tissue (e.g. radiation-induced dermatitis) often worsen patient quality of life. Previous studies have implicated the importance of redox balance in preventing dermatitis, specifically in reference to modulation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) signaling pathway. Due to the cytoprotective functions of transcriptional target genes of NRF2, we investigated how modulation of NRF2 expression could affect DNA damage, oxidative stress, and cell viability in response to radiotherapy. Specifically, it was noted that NRF2 knockdown sensitized human skin keratinocytes to ionizing radiation; likewise, genetic ablation of NRF2 in vivo increased radiosensitivity of murine epidermis. Oppositely, pharmacological induction of NRF2 via the apocarotenoid bixin lowered markers of DNA damage and oxidative stress, while preserving viability in irradiated keratinocytes. Mechanistic studies indicated that topical pretreatment using bixin as an NRF2 activator antagonized initial DNA damage by raising cellular glutathione levels. Additionally, topical application of bixin prevented radiation-induced dermatitis, epidermal thickening, and oxidative stress in the skin of SKH1 mice. Overall, these data indicate that NRF2 is critical for mitigating the harmful skin toxicities associated with ionizing radiation, and that topical upregulation of NRF2 via bixin could prevent radiation-induced dermatitis.
Recent Trends in Collaborative, Open Source Drug Discovery (2011)

The pharmaceutical sector has traditionally played a predominant role in screening compounds against a molecular target and optimizing chemistry to develop drugs. The basic research studies in the academic sector have provided the pharmaceutical companies with many biological targets with potential impact on therapeutics. These welldefined contributions of the pharmaceutical and academic sectors in drug discovery field are being redefined to meet the fiscal and innovation challenges in the current drug discovery landscape. There is an increased capital and personnel investment in academia in the areas of highthroughput screening and technology transfer. The pharma has adopted an open innovation paradigm which seeks to complement internal intellect with external global talent and expertise, with the overall goal of expediting complex data interpretation and introduction of more effective and safe drugs. The pharmaacademia sectors are collaborating on several mutually beneficial alliances and the changing landscape at pharmaacademiainterface necessitates an urgent need for a better understanding of the role of academia in translational research and suitable technology transfer terms to sustain collaborative opportunities.The collaborative partnership between pharma and academia is expected to provide the required boost to identify novel targets and develop new and effective drugs.
Investigation of High Temperature Silica Based Fiber Optic Materials (Final Report) (2018)

This report summarizes technical progress during the program “Investigation of High Temperature Silica Based Fiber Optic Materials”, performed by the Center for Photonics Technology of the Bradley Department of Electrical and Computer Engineering at Virginia Tech. The objective of this program was to investigate and characterize the performance of commercially available optical fibers at elevated temperatures in replicated fuel gas streams. It also includes performing a comprehensive study of the interactions with the chemical constituents with respect to structural, optical, and mechanical stability and developing design strategies to assure reliable performance of deployed optical fibers and sensors. In the eight quarters of the project, work was done to complete the database of test results and findings for the creation of an optical fiber selection guide for high temperature applications. It is anticipated that this design tool will provide the scientific community with the information necessary to deploy sensing systems with the most robust and reliable fused silica optical fibers. Standard telecommunications grade germanium doped single and multimode fibers have been shown to perform reliably up to temperatures of 1100°C in non-hydrogen environments and/or properly designed sensor applications. Pure silica core single mode and low OH, large core step index multimode fibers, which have also shown to perform reliability up to temperatures of 1000ºC, are recommended for hydrogen and moist environments.
Alternating repetition time balanced steady state free precession (2006)

A novel balanced SSFP technique for the separation or suppression of different resonance frequencies (e.g., fat suppression) is presented. The method is based on applying two alternating and different repetition times, TR(1) and TR(2). This RF scheme manipulates the sensitivity of balanced SSFP to off-resonance effects by a modification of the frequency response profile. Starting from a general approach, an optimally broadened stopband within the frequency response function is designed. This is achieved with a TR(2) being one third of TR(1) and an RF-pulse phase increment of 90 degrees . With this approach TR(2) is too short ( approximately 1 ms) to switch imaging gradients and is only used to change the frequency sensitivity. Without a significant change of the spectral position of the stopband, TR(1) can be varied over a range of values ( approximately 2.5-4.5 ms) while TR(2) and phase cycling is kept constant. On-resonance spins show a magnetization behavior similar to balanced SSFP, but with maximal magnetization at flip angles about 10 degrees lower than in balanced SSFP. The total scan time is increased by about 30% compared to conventional balanced SSFP. The new technique was applied on phantoms and volunteers to produce rapid, fat suppressed images.
Direct observation of hymenes in diatoms by low-voltage SEM (1995)

From the early days of Kolkwitz and Marsson (1908) diatoms have proved to be valuable in pollution studies, especially of river systems. Economic applications have developed because the remains of sedimentary diatoms were found to be useful for many industrial processes owing to the fine structure and inert nature of the siliceous materials. Their ecological significance arises from observing that diatoms that grew in oceanic and freshwater sediments contain indications of past environmental conditions; more recently, diatoms have been used to detect pH changes attributed to 'acid rain.' The first record of a diatom can be traced back to the early 1700s when an English gentleman looked at roots of the pond-weed Lemna using his simple microscope. Today, extensive studies using TEM and SEM techniques have provided much new information about the fixed and variable details of the diatom, yet research focusing on the morphology of the shell structure remains very active.
OSCAR: An Optimized Scheduling Cell Allocation Algorithm for Convergecast in IEEE 802.15.4e TSCH Networks (2021)

Today's wireless sensor networks expect to receive increasingly more data from different sources. The Time Slotted Channel Hopping (TSCH) protocol defined in the IEEE 802.15.4-2015 version of the IEEE 802.15.4 standard plays a crucial role in reducing latency and minimizing energy consumption. In the case of convergecast traffic, nodes close to the root have consistently heavy traffic and suffer from severe network congestion problems. In this paper, we propose OSCAR, an novel autonomous scheduling TSCH cell allocation algorithm based on Orchestra. This new design differs from Orchestra by allocating slots according to the location of the node relative to the root. The goal of this algorithm is to allocate slots to nodes according to their needs. This algorithm manages the number of timeslots allocated to each node using the value of the rank described by the RPL routing protocol. The goal is that the closer the node is to the root, the more slots it gets in order to maximize the transmission opportunities. To avoid overconsumption, OSCAR sets up a mechanism to adjust the radio duty cycle of each node by reducing the slots allocated to inactive nodes regardless of their position in the network. We implement OSCAR on Contiki-ng and evaluate its performance by both simulations and experimentation. The performance assessment of OSCAR shows that it outperforms Orchestra on the average latency and reliability, without significantly increasing the average duty cycle, especially when the traffic load is high.
Breast cancer : origins, detection, and treatment : proceedings of the International Breast Cancer Research Conference, London, United Kingdom, March 24-28, 1985 (1986)

The control of breast cancer, a leading cause of cancer death in women, will depend ultimately on our understanding of the disease--its origin, and progression which in turn will permit the effective management of its treatment, its detection, and perhaps even its prevention. It is for a better understanding of this spectrum of biological processes crossing back and forth across scientific and clinical disciplines that this volume strives. Several broad topics have been addressed in organizing a large mass of work representing state of the art updates from many of the major breast cancer research groups around the world. The chapters in the first section speak to the factors affecting the growth and development of normal and malignant mammary epithelium. Special emphasis is placed on insights drawn from developmental biology, the cellular interactions that occur in the mammary gland during growth and differentiation; and the study of hormones and growth factors in the regulation of growth and differentiation of normal and malignant breast tissues. In the section on the biology of breast cancer, there is a characterization of relevant model systems for the study of breast cancer and their contribution to our understanding of preneoplasia and progression in mammary cancer. Included as well is the current status of major studies on the immunological aspects of breast cancer and the latest efforts in the development of markers for metastasis in breast cancer.
Stem‐cell therapy for dilated cardiomyopathy: a pilot study evaluating retrograde coronary venous delivery (2013)

Retrograde venous delivery of tyrosine mutant adeno-associated virus 2-stromal-derived factor-1 adipose-derived mesenchymal stem cells appears safe. Stem-cell therapy in dogs with occult-dilated cardiomyopathy does not appear to offer advantage compared to recently published survival data in similarly affected Dobermanns.
miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma (2012)

Our data show that miR-21 and SOX2 are tightly regulated already during embryogenesis and define a distinct population with putative tumor cell of origin characteristics. Furthermore, we believe that miR-21 is a mediator of PDGF-driven brain tumors, which suggests miR-21 as a promising target for treatment of glioma.
COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors (2021)

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.
Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice (2022)

Periodontitis (periodontal disease) is a highly prevalent disease, affecting over 65 million adults in the United States alone. Characterized by an overburden of invasive bacteria, gum inflammation and plaque buildup, over time, these symptoms can result in severe loss of gingival tissue attachment, bone resorption and even tooth loss. Although current treatments (local antibiotics and scaling and root planing procedures) target the bacterial dysbiosis, they do not address the underlying inflammatory imbalance in the periodontium. In the healthy steady state, the body naturally combats destructive, imbalanced inflammatory responses through regulatory pathways mediated by cells such as regulatory T cells (Tregs). Consequently, we hypothesized that local enrichment of regulatory lymphocytes (Tregs) could restore local, immunological homeostasis and prevent the main outcome of bone loss. Accordingly, we locally delivered a combination of TGFβ, Rapamycin, and IL2 microspheres in a ligature-induced murine periodontitis model. Herein, we have demonstrated this preventative treatment decreases alveolar bone loss, increases the local ratio of Tregs to T effector cells and changes the local microenvironment's expression of inflammatory and regenerative markers. Ultimately, these Treg-inducing microspheres appear promising as a method to improve periodontitis outcomes and may be able to serve as a platform delivery system to treat other inflammatory diseases.
Epitaxial growth and strain relaxation studies of BaTiO3 and BaTiO3/SrTiO3 superlattices grown by MBE on SrTiO3-buffered Si(001) substrate (2019)

In this work, the epitaxy of SrTiO3 and BaTiO3 perovskites on the (001)-oriented silicon substrate by molecular beam epitaxy is investigated. The heterostructures are studied by means of various structural and electrical characterization techniques. In this study especially, the authors reveal experimentally by nanobeam electron diffraction analysis the critical thickness prior relaxation of BaTiO3 grown on an SrTiO3/Si pseudosubstrate. They also propose to use a strain mediated superlattice composed of stacked [BaTiO3/SrTiO3] bilayers to prevent misfit dislocation formation. Using this approach, they could demonstrate high quality and dislocation free BaTiO3 ferroelectric layers integrated on silicon as confirmed by piezo-force microscopy techniques.
Suppression of cortical representation through backward conditioning (2003)

Temporal stimulus reinforcement sequences have been shown to determine the directions of synaptic plasticity and behavioral learning. Here, we examined whether they also control the direction of cortical reorganization. Pairing ventral tegmental area stimulation with a sound in a backward conditioning paradigm specifically reduced representations of the paired sound in the primary auditory cortex (AI). This temporal sequence-dependent bidirectional cortical plasticity modulated by dopamine release hypothetically serves to prevent the over-representation of frequently occurring stimuli resulting from their random pairing with unrelated rewards.
Effectiveness of a Binocular Video Game vs Placebo Video Game for Improving Visual Functions in Older Children, Teenagers, and Adults With Amblyopia (2018)

anzctr.org.au Identifier: ACTRN12613001004752.
EnforSDN: Network policies enforcement with SDN (2015)

Network services, such as security, load-balancing, and monitoring, are an indisputable part of modern networking infrastructure and are traditionally realized as specialized appliances or middleboxes. Middleboxes complicate the management, the deployment, and the operations of the entire network. Moreover, they induce network performance issues and scalability limitations by requiring huge amounts of traffic to be, often sub-optimally redirected, and sometimes redundantly processed. Recent trends of server virtualization and Network Function Vir-tualization (NFV) exacerbate these scalability and performance issues. In this paper, we present EnforSDN — a new management approach that exploits SDN principles to decouple the policy resolution layer from the policy enforcement layer in network service appliances. Our approach improves the enforcement management, network utilization and communication latency, without compromising the policy and the functionality of the network. Using emulated SDN-based data center environment, we demonstrate higher throughput and lower latency achieved with EnforSDN, as compared to a baseline SDN network. In addition, we show that EnforSDN reduces the overall network appliances load, as well as the forwarding tables size.
Selective Inhibition of Monoamine Oxidase B by Aminoethyl Substituted Benzyl Ethers (1999)

Aminoethyl 3-chlorobenzyl ether was shown previously (Ding, C.Z. and Silverman, R.B. (1993). Bioorg. Med. Chem. Lett., 3, 2077-2078) to be a potent and selective time-dependent, but reversible inhibitor of monoamine oxidase B (MAO B). Based on this result, a series of novel aminoethyl substituted benzyl ethers was synthesized and the compounds were examined as potential inhibitors of both isozymic forms of MAO. Each compound in the series inhibits both MAO A and MAO B competitively, and IC(50) values for each compound were determined. In general, the B isozyme is much more sensitive to these inhibitors than the A isozyme (except for the o- and p-substituted nitro analogues), in some cases by more than two orders of magnitude. The selectivity in favor of MAO B inhibition is relatively high for all of the meta-substituted analogues and quite low for all of the ortho-substituted analogues. Having the substituent at the ortho-position is most favorable for MAO A inhibition. With MAO B the meta-analogues were, in general, more potent than the corresponding ortho- and para-analogues with respect to their reversible binding constants. The meta-iodo analogue is the most potent analogue.
636: Hematogenous Versus Lymphatic Dissemination: The Role of the Vascular Endothelial Growth Factor (VEGF) Family in the Metastatic Process of Clear Cell Renal Cell Carcinoma (2005)

You have accessJournal of UrologyDiscussed Poster, Monday, May 23, 2005, 8:00 am - 12:00 pm1 Apr 2005636: Hematogenous Versus Lymphatic Dissemination: The Role of the Vascular Endothelial Growth Factor (VEGF) Family in the Metastatic Process of Clear Cell Renal Cell Carcinoma John T. Leppert, John S. Lam, Hong Yu, David B. Seligson, Jun Dong, Steven Horvath, Allan J. Pantuck, Robert A. Figlin, and Arie S. Belldegrun John T. LeppertJohn T. Leppert More articles by this author , John S. LamJohn S. Lam More articles by this author , Hong YuHong Yu More articles by this author , David B. SeligsonDavid B. Seligson More articles by this author , Jun DongJun Dong More articles by this author , Steven HorvathSteven Horvath More articles by this author , Allan J. PantuckAllan J. Pantuck More articles by this author , Robert A. FiglinRobert A. Figlin More articles by this author , and Arie S. BelldegrunArie S. Belldegrun More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34876-6AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "636: Hematogenous Versus Lymphatic Dissemination: The Role of the Vascular Endothelial Growth Factor (VEGF) Family in the Metastatic Process of Clear Cell Renal Cell Carcinoma." The Journal of Urology, 173(4S), p. 173 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 173 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information John T. Leppert More articles by this author John S. Lam More articles by this author Hong Yu More articles by this author David B. Seligson More articles by this author Jun Dong More articles by this author Steven Horvath More articles by this author Allan J. Pantuck More articles by this author Robert A. Figlin More articles by this author Arie S. Belldegrun More articles by this author Expand All Advertisement Loading ...