gebhart/patrepeval huggingface dataset:
Long-lasting Analgesia via Targeted in vivo Epigenetic Repression of Nav1.7 (2019)

ABSTRACT Current treatments for chronic pain rely largely on opioids despite their unwanted side effects and risk of addiction. Genetic studies have identified in humans key targets pivotal to nociceptive processing, with the voltage-gated sodium channel, Na V 1.7 (SCN9A), being perhaps the most promising candidate for analgesic drug development. Specifically, a hereditary loss-of-function mutation in Na V 1.7 leads to insensitivity to pain without other neurodevelopmental alterations. However, the high sequence similarity between Na V subtypes has frustrated efforts to develop selective inhibitors. Here, we investigated targeted epigenetic repression of Na V 1.7 via genome engineering approaches based on clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9 and zinc finger proteins as a potential treatment for chronic pain. Towards this end, we first optimized the efficiency of Na V 1.7 repression in vitro in Neuro2A cells, and then by the lumbar intrathecal route delivered both genome-engineering platforms via adeno-associated viruses (AAVs) to assess their effects in three mouse models of pain: carrageenan-induced inflammatory pain, paclitaxel-induced neuropathic pain and BzATP-induced pain. Our results demonstrate: one, effective repression of Na V 1.7 in lumbar dorsal root ganglia; two, reduced thermal hyperalgesia in the inflammatory state; three, decreased tactile allodynia in the neuropathic state; and four, no changes in normal motor function. We anticipate this genomically scarless and non-addictive pain amelioration approach enabling L ong-lasting A nalgesia via T argeted in vivo E pigenetic R epression of Nav1.7, a methodology we dub pain LATER , will have significant therapeutic potential, such as for preemptive administration in anticipation of a pain stimulus (pre-operatively), or during an established chronic pain state. One sentence summary In situ epigenome engineering approach for genomically scarless, durable, and non-addictive management of pain.
Ka -band waveguide phase shifter using tunable electromagnetic crystal sidewalls (2003)

Tunable electromagnetic crystal (EMXT) structures have been used as sidewalls in special waveguides for frequencies of 30-40 GHz. This has the effect of substituting tunable impedance surfaces in place of the normal conducting metal sidewalls. The resulting EMXT waveguide boundary conditions can then be controlled in situ to achieve desired phase shifting and/or field flattening effects. Proof-of-concept experiments have been done using fix-tuned EMXT sidewalls with various resonant frequencies, and the measurements indicate that the insertion loss is low. An InP quantum barrier varactor approach is used to implement the tunable Ka-band EMXT waveguide phase shifter. The dependence of transmission amplitude and phase on the center frequency of sidewall resonance has been simulated and measured. Measurements and simulation results agree very well. The loss mechanism of the demonstrated phase shifter is well understood. Our results indicate that tunable EMXT waveguide will provide simple and low-loss phase-shifting systems.
Exploration of Mechanical and Electromyographic Responses of Trunk Muscles to High-Intensity Resistive Exercise (1989)

The purposes of this study were to determine the effects of high intensity exercise on fatigue of the trunk muscles within a test session, and on multiple kinetic and electromyographic (EMG) variables over a 6-week training period. Fourty-five normal men and women (20-40 years of age) completed the study. The KIN/COM trunk testing unit (Chattecx Corporation, Chattanooga, Tennessee) was used for both testing and training. The results of the study follow: 1) The KIN/COM trunk testing system was very accurate, and the method used was highly reproducible for the kinetic variables. Reproducibility for the endurance variables was mixed, and isolated EMG variables were poor. 2) Kinetic and EMG decrements associated with fatigue did occur in the trunk muscles with ten continuous cycles of maximal concentric and eccentric contractions. 3) Trunk muscle strength gains were highest for the same mode of exercise used in training (specificity), but significant strength gains also were seen in different modes of muscle contraction (transfer of training). For the trunk extensors, the eccentric form of exercise was superior. 4) The rate of isometric torque development and decay was increased by exercise in men. 5) Trunk muscle endurance was retained when gains in strength occurred. 6) The majority of variables reflecting strength and endurance were retained. The methods and results can serve as guidelines for the evaluation of trunk muscle function and resistive exercise in the clinic.
The effects of prolonged dark exposure on visual thresholds in young and adult rats. (1979)

A comparison of electroretinogram (ERG) thresholds measured on rats reared in continuous darkness and under cyclic lighting conditions shows that by 30 days of age the dark-reared animals have achieved significantly lower thresholds than the animals reared under cyclic illumination. Ten days of continuous dark exposure produces this same increase in sensitivity in adult rats reared in cyclic lighting. These changes in sensitivity appear to reflect structural changes occurring within the rod outer segments.
Mitochondria as a pharmacological target: Magnum overview (2013)

Abstract Mitochondria, responsible for energy metabolism within the cell, act as signaling organelles. Mitochondrial dysfunction may lead to cell death and oxidative stress and may disturb calcium metabolism. Additionally, mitochondria play a pivotal role in cardioprotective phenomena and a variety of neurodegenerative disorders ranging from Parkinson's to Alzheimer's disease. Mitochondrial DNA mutations may lead to impaired respiration. Hence, targeting the mitochondria with drugs offers great potential for new therapeutic approaches. The purpose of this overview is to present the recent state of knowledge concerning the interactions of various substances with mitochondria. © 2013 IUBMB Life, 65(3):273–281, 2013
Drug Delivery to the Human and Mouse Uterus Using Immunoliposome Targeted to the Oxytocin Receptor (2017)

( Am J Obstet Gynecol. 2017;216(3):283.e1–283.e14) There is a need for pharmacotherapy during preterm labor, postpartum hemorrhage and other obstetric complications that is safe, effective and specifically targets uterine myocytes with minimal side effects. One emerging mode to deliver agents to specific tissues is targeted liposomes, which are artificial vesicles composed of ≥1 phospholipid bilayers. This study examined the possibility of developing a method for targeting uterine myometrial tissue with therapeutic agents using an immunoliposome platform.
A new stereo matching algorithm for binocular vision (2009)

The stereo matching algorithms for binocular vision are very popular and widely applied. However, the algorithms may have lower matching quality or higher time complexity. To improve that, a new stereo matching algorithm based on square and gradient for binocular vision is proposed in the paper. It divides an image line into a serious of ranges with comparing the gradients of the points in left and right image lines. The best matching in each range is found based on the summery of squared differences. The algorithm inherits the high quality of gradient algorithm and high performance of SSD algorithm and meanwhile avoids the additive noise.
Conjugates of Ara-AMP with Lactosaminated Albumin: A Study on Their Immunogenicity in Mouse and Rat (1987)

Complexes of albumin with oligosaccharides have been successfully employed in experimental chemotherapy as hepatotropic carriers of antiviral drugs or as vectors of anticancer-agents, but their clinical use is hampered by an immune response they might evoke. In the present experiments we have studied the humoral immunogenicity of conjugates of 9-beta-D-arabinofuranosyl adenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), in mice and rats. These complexes were prepared with the aim of increasing the chemotherapeutic index of ara-AMP in the treatment of chronic hepatitis B virus (HBV) infection. L-SA-ara-AMP conjugates prepared with heterologous albumin produced antibodies in mice and rats when repeatedly injected intraperitoneally. The same conjugates prepared with homologous albumin induced only low amounts of antibodies, when given by repeated intraperitoneal injection, whereas they did not evoke antibodies in mice and were tolerogenic in rats when administered repeatedly by the intravenous route. These results suggest that in a clinical use of drug conjugates prepared with oligosaccharide-albumin complexes the risk of an immune response can be reduced by employing human albumin and by injecting the conjugates by the intravenous route.
PPO15-PEO22-PPO15 block copolymer assisted synthesis of monolithic macro- and microporous carbon aerogels exhibiting high conductivity and remarkable capacitance (2009)

Ultralightweight (specific gravity 5 × 10−2) and highly conductive (2.5 S/cm) monolithic carbon aerogels exhibiting a three-dimensionally continuous micro- and macroporous structure have been prepared through a PPO-PEO-PPO block copolymer assisted route. The resulting carbon aerogels were highly suitable as electrodes of electric double layer capacitors, with remarkable values of capacitance of up to 225 F/g (normalized by mass) and 31 µF/cm2 (normalized by BET surface area).
The release characteristics of a model protein from self-assembled succinimide-terminated poly(lactide-co-glycolide ethylene oxide fumarate) nanoparticles (2008)

Lactide-co-glycolide-based functionalized nanoparticles (NPs), because of their high surface areas for conjugation and biodegradability, are attractive as carriers for stabilization and sustained delivery of therapeutic agents and protein drugs. The objective of this work was to compare the release characteristics of model molecules encapsulated in NPs produced from poly(lactide-co-glycolide fumarate) (PLGF) macromer with those of model molecules conjugated to NPs produced from succinimide (NHS)-terminated PLGF-NHS macromer. Poly(lactide fumarate) (PLAF), PLGF and poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromers were synthesized by condensation polymerization. The hydroxyl end-groups of PLAF and PLGF macromers were reacted with N,N(')-disuccinimidyl carbonate (DSC) to produce succinimide-terminated PLAF-NHS and PLGF-NHS macromers. The macromers were self-assembled by dialysis to form NPs. The amphiphilic PLEOF macromer was used as the surfactant to stabilize the NPs in the process of self-assembly. 1-(2-pyridylazo)-2-naphthol (PAN) was used as a model small molecule for encapsulation in PLAF or PLGF NPs and bovine serum albumin (BSA) was used as a model protein for conjugation to PLAF-NHS and PLGF-NHS NPs. The profile of release of the encapsulated PAN from PLAF and PLGF NPs was non-linear and consisted of a burst release followed by a period of sustained release. The release profile for BSA, conjugated to PLAF-NHS and PLGF-NHS NPs, was linear up to complete degradation of the NPs. PLGF and PLAF NPs degraded in 15 and 28 days, respectively, while PLGF-NHS and PLAF-NHS NPs degraded in 25 and 38 days, which demonstrated that the release was dominated by erosion of the matrix. PLAF-NHS and PLGF-NHS NPs are potentially useful as carriers for sustained in situ release of protein drugs.
Energiebedarf, Energieversorgung und Prognosen für die zukünftige Rolle der Solarenergie (1993)

Sowohl der Weltenergiebedarf als auch der Energiebedarf der Bundesrepublik Deutschland stiegen in der Vergangenheit bis 1973 um etwa 5 % pro Jahr. Abb.1.1 zeigt diese Entwicklung für den Weltprimärenergiebedarf. Zusätzlich ist hier das Anwachsen der Weltbevölkerung eingetragen. Man erkennt deutlich den starken Anstieg des Energiebedarfs in der Nachkriegszeit, der eng mit dem steigenden Lebenskomfort in der westlichen Welt gekoppelt und nur unwesentlich durch das Wachstum der Bevölkerung in der Dritten Welt bedingt ist. Mit steigender Industrialisierung der Entwicklungsländer wäre ein weiterer drastischer Anstieg des Weltenergiebedarfs zu erwarten. Abb. 1.2 gibt die Entwicklung des realen Primärenergieverbrauchs in der Bundesrepublik wieder. Ab 1973, dem Zeitpunkt der ersten Ölkrise, unterlag der Verbrauch der Primärenergieträger starken Schwankungen und blieb im wesentlichen konstant. Hier zeigt sich bereits der enge Zusammenhang zwischen Energiepreis und Energieverbrauch:
72 Offset of ticagrelor prior to coronary artery bypass graft surgery (cabg) surgery (2017)

Introduction Ticagrelor is a more potent platelet inhibitor than clopidogrel but also has a more rapid offset of inhibitory effect. The optimal timing of discontinuation of ticagrelor prior to coronary artery bypass graft (CABG) surgery is unknown. In the ONSET/OFFSET study of patients with stable coronary artery disease, ticagrelor’s effects dissipated within 48–120 hours of discontinuation. However, there is evidence that the pharmacodynamics of antiplatelet therapy are significantly altered during an acute coronary syndrome (ACS) and the ONSET/OFFSET study results should not be extrapolated to ACS patients. Although the PLATO study suggested that it was safe to discontinue ticagrelor 48 hours prior to CABG, regulatory authorities recommended that ticagrelor should be discontinued 5 days prior to CABG. The PLATO study also showed that ticagrelor was associated with fewer deaths following pulmonary adverse events and sepsis compared to clopidogrel. It is unknown whether ticagrelor’s additional property of inhibiting cellular adenosine uptake might underlie this observation. The aim of this study was to characterise the offset of ticagrelor’s activity in inhibiting platelets and also in inhibiting cellular adenosine uptake in ACS patients. Methods Patients admitted with ACS, treated with ticagrelor and referred for CABG were recruited. Venous blood was drawn from patients at the following 6 timepoints: 2 hours (h), 24 hour, 48 hour, 72 hour, 96 hour, and 120 hour after the last dose of ticagrelor prior to CABG. Whole-blood aggregometry was carried out using the Multiplate analyzer with adenosine diphosphate 6.45 µM as agonist and the final value of area under the curve (AUC) (units, U) was recorded. Results were analysed using linear mixed models. A local protocol was referred to, where an AUC of &gt;50U supports safe progression to surgery, while values 50U indicates need for re-testing 24–48 hours later. Inhibition of adenosine uptake was determined by measuring the adenosine plasma concentration using liquid chromatography. Results 13 patients were recruited, all of whom received ticagrelor prior to CABG surgery. At 96 hour post ticagrelor, the mean AUC was 82.8U, (95% confidence interval, 60.4, 105.2). Only at 96 hour was the lower limit of the confidence interval &gt;50U. From the mixed model analysis, the comparison between 72 hour and 120 hour post ticagrelor showed a significant difference (p=0.007) while 96 hour and 120 hour showed no significant difference (p=1.000). Adenosine plasma concentration was measured in 7 patients who received ticagrelor and showed no significant difference in adenosine plasma concentration across all timepoints. Conclusion ACS patients might be safe to undergo CABG surgery 4 days after the cessation of ticagrelor. Ticagrelor might have no measurable effect on adenosine transport in ACS patients. Abstract 72 Figure 1 Abstract 72 Figure 2
Targeted knockdown of canine KIT (stem cell factor receptor) using RNA interference (2011)

Canine mast cell tumours often express KIT mutations that result in constitutive activation of the c-kit receptor and which are associated with more aggressive disease. The aim of the current study was to determine whether small inhibitory RNA (SiRNA) molecules could specifically target canine KIT mRNA for knock-down. Canine beta-2 microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and KIT sequences were cloned into the psiCHECK™-2 vector. SiRNA molecules, designed to target gene-specific sequences, were co-transfected with plasmid DNA into Chinese hamster ovary (CHO) cells. Renilla and firefly luciferase activity was measured using the Dual-GLO(®) Luciferase Assay (Promega). Using this reporter system, canine housekeeping gene-specific SiRNA molecules demonstrated knockdown of their targets (72.0% knockdown for B2M and 94.5% knockdown for GAPDH). An SiRNA molecule targeting exon 2 of canine KIT successfully knocked-down reporter gene expression of a KIT(26-407) construct (90.8% knockdown). An SiRNA molecule targeting a 48 base-pair in-tandem duplication mutation in KIT exon 11 selectively knocked down expression of the KIT(1569-1966mutant) construct (93.1% knockdown) but had no effect on the KIT(1569-1918wild-type) construct. The results show that RNA interference can be used to inhibit canine KIT mRNA expression and has the potential to selectively target the mutant version of KIT that is expressed by some malignant mast cells.
Approximate Nearest Neighbor Search as a Multi-Label Classification Problem (2019)

We formulate approximate nearest neighbor (ANN) search as a multi-label classification task. The implications are twofold. First, tree-based indexes can be searched more efficiently by interpreting them as models to solve this task. Second, in addition to index structures designed specifically for ANN search, any type of classifier can be used as an index.
Large-area high-throughput high-resolution lithography systems for flat-panel displays and microelectronic modules (1998)

We have developed a novel class of projection lithography system that provide both high-throughput resist patterning and dielectric via formation for production of a variety of electronic modules, including flat-panel displays, multichip modules, printed circuit boards, and microelectromechanical systems. The new technology eliminates limitations of current lithography tools, including contact and proximity tools, conventional projection systems, steppers and scanners, and direct-write machines. Further, the new system concept is highly modular, thereby providing equipment upgradability as well as choice of user-specified system configurations. These results are achieved with a novel, hexagonal seamless scanning concept and a single-planar stage system configuration that provide both high optical and scanning efficiencies, and combine high-resolution imaging with very large exposure area capability. We describe the new technology and present experimental results. These lithography systems are highly attractive for cost-effective production of microelectronic products with feature sizes ranging from 15 micrometers to below 1 micrometers and substrate sizes ranging from 150 X 150 mm to larger than 610 X 660 mm.
DNA sequence recognition by the indolocarbazole antitumor antibiotic AT2433-B1 and its diastereoisomer - eScholarship (2002)

The antibiotic AT2433-B1 belongs to a therapeutically important class of antitumor agents. This natural product contains an indolocarbazole aglycone connected to a unique disaccharide consisting of a methoxyglucose and an amino sugar subunit, 2,4-dideoxy-4-methylamino-l-xylose. The configuration of the amino sugar distinguishes AT2433-B1 from its diastereoisomer iso-AT2433-B1. Here we have investigated the interaction of these two disaccharide indolocarbazole derivatives with different DNA sequences by means of DNase I footprinting and surface plasmon resonance (SPR). Accurate binding measurements performed at 4 and 25°C using the BIAcore SPR method revealed that AT2433-B1 binds considerably more tightly to a hairpin oligomer containing a [CG]4 block than to an oligomer with a central [AT]4 tract. The kinetic analysis shows that the antibiotic dissociates much more slowly from the GC sequence compared to the AT one. Preferential binding of AT2433-B1 to GC-rich sequences in DNA was independently confirmed by DNase I footprinting experiments performed with a 117 bp DNA restriction fragment. The specific binding sequence 5′-AACGCCAG identified from the footprints was then converted into a biotin-labeled DNA hairpin duplex and compound interactions with this specific sequence were characterized by high resolution BIAcore SPR experiments. Such a combined approach provided a detailed understanding of the molecular basis of DNA recognition. The discovery that the glycosyl antibiotic AT2433-B1 preferentially recognizes defined sequences offers novel opportunities for the future design of sequence-specific DNA-reading small molecules.
High−precision skimmers for supersonic molecular beams (1975)

High−quality skimmers for supersonic molecular beams may be fabricated in a variety of shapes by a method which involves both electroforming and machining operations.
Life-game, with glass beads and molecules, on the principles of the origin of life (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLife-game, with glass beads and molecules, on the principles of the origin of lifeManfred Eigen and Herman Haglund Cite this: J. Chem. Educ. 1976, 53, 8, 468Publication Date (Print):August 1, 1976Publication History Received3 August 2009Published online1 August 1976Published inissue 1 August 1976https://doi.org/10.1021/ed053p468RIGHTS & PERMISSIONSArticle Views267Altmetric-Citations3LEARN 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 InReddit PDF (2 MB) Get e-Alerts Get e-Alerts
Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage (2018)

Taken together, our findings validated that the strategy of using NB and TMZ could be a highly efficient way to achieve anticancer synergism.
Learning the price response of active distribution networks for TSO-DSO coordination (2021)

The increase in distributed energy resources and flexible electricity consumers has turned TSO-DSO coordination strategies into a challenging problem. Existing decomposition/decentralized methods apply divide-and-conquer strategies to trim down the computational burden of this complex problem, but rely on access to proprietary information or fail-safe real-time communication infrastructures. To overcome these drawbacks, we propose in this paper a TSO-DSO coordination strategy that only needs a series of observations of the nodal price and the power intake at the substations connecting the transmission and distribution networks. Using this information, we learn the price response of active distribution networks (DN) using a decreasing step-wise function that can also adapt to some contextual information. The learning task can be carried out in a computationally efficient manner and the curve it produces can be interpreted as a market bid, thus averting the need to revise the current operational procedures for the transmission network. Inaccuracies derived from the learning task may lead to suboptimal decisions. However, results from a realistic case study show that the proposed methodology yields operating decisions very close to those obtained by a fully centralized coordination of transmission and distribution.