gebhart/patrepeval huggingface dataset:
Chiral enamines derived from 2‐(2′‐pyrido)acetophenone and 2‐(2′‐quinolino)acetophenone as ligands in copper(I) catalyzed enantioselective cyclopropanations (1995)

Abstract Optically active enamines of 2‐(2′‐pyrido)acetophenone or 2‐(2′‐quinolino)acetophenone with (R)‐1‐phenylethylamine, (R)‐1‐(1‐naphthyl)ethylamine, (R)‐cyclohexylethylamine, and (R)‐phenylglycinol were prepared and their copper(I) complexes used in the enantioselective cyclopropanation of styrene with ethyl‐ and menthyldiazoacetate. Enantioselectivities of up to 42% enantiomeric excess were obtained for cis / trans 2‐phenylcyclopropan‐1‐carboxylic acid ethyl esters, as determined by gas‐liquid chromatography (GLC) on chiral chromatographic columns. © 1995 Wiley‐Liss, Inc.
Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100 (2016)

We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV)16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFN)γ production, tumor necrosis factor (TNF)α production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR) sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth "booster" dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.
HAEMODYNAMIC EFFECT OF ENDOTHELIN, A NOVEL POTENT VASOCONSTRICTOR IN DOGS (1990)

1. The effects of endothelin (40 and 400 pmol/kg, intravenous (i.v.), a novel vasoconstrictor, on haemodynamics were evaluated in normal dogs and dogs treated with hexamethonium. 2. The lower dose of endothelin caused no significant changes in mean blood pressure (MBP), heart rate (HR), cardiac output (CO), or total peripheral resistance (TPR) in normal dogs. In dogs treated with hexamethonium MBP decreased transiently associated with decrease in TPR. 3. In both dogs, the higher dose of endothelin caused MBP increase with CO increase in an early phase, and with TPR increase in a later phase. In normal dogs, the CO decreased 60 min after endothelin, but in dogs treated with hexamethonium the decrease in CO was not significant. 4. Electrocardiograms showed ST changes and arrhythmias. 5. Thus, endothelin has dual effects on both the vasculature and the heart, its effect depending on its dose and the time after its administration: initial vasodilation followed by prolonged vasoconstriction, and cardiostimulation followed by cardiosuppression. The cardiosuppression appears to be mediated in part by a neural mechanism.
Circulating tumor cells (CTC) and prostate specific antigen (PSA) as response indicator biomarkers in chemotherapy-naïve patients with progressive castration-resistant prostate cancer (CRPC) treated with MDV3100. (2010)

4546 Background: The availability of reliable indicators of treatment efficacy is a critical unmet need in drug development for CRPC. MDV3100 is a second-generation oral androgen receptor antagonist that induces a prolonged apoptotic response in xenograft models and is active in men with progressive CRPC. We explored outcomes based on PSA and CTC number in relation to radiographic progression. Methods: 65 chemotherapy-naive patients with progressive CRPC were treated at doses of 30 to 360 mg/day. PSA levels were measured monthly, and CTC number at baseline, wks 4 and 12 using the CellSearch assay. A “PSA response” was defined as 3 consecutive declines within 12 wks of the start of treatment. Time to radiographic progression free survival (RPFS) was assessed by Prostate Cancer Working Group 2 criteria. The likelihood ratio test from the Cox proportional hazards model was used to determine the factors associated with RPFS, defined as being alive without progression. Results: The RPFS probability at 12 months was 0.56 (95% CI: 0.43, 0.73) with a median follow up of 13 months (2.4 to 26). 48 (74%) of the 65 pts were evaluable at the 12 wk landmark. CTC number, PSA, and PSA response, all assessed at 12 weeks, were all significant predictors of RPFS (p < 0.001). The joint model most predictive of RPFS time was CTC at 12 weeks and PSA response (3 consecutive declines). The concordance probability estimate (CPE) was used to measure the predictive accuracy of the model. The CPE for this joint model was 0.78, significantly higher than a model with each factor alone (CTC at 12 weeks – CPE= 0.63; PSA response- CPE=0.72). Conclusions: CTC at 12 weeks and PSA response provide independent predictive information for radiographic progression free survival time in chemotherapy-naive CRPC. Sustained PSA declines are consistent with the observed preclinical apoptotic response. Each biomarker may provide unique information. The results will be studied prospectively in an ongoing phase III randomized trial of MDV3100 with a survival endpoint. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medivation Medivation Medivation Medivation Medivation, Veridex Medivation
Abstract 4764: The therapeutic potential of lnc-HLX-2-7 in group 3 medulloblastomas in children (2023)

Abstract Medulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the non-coding RNA genome, in particular long non-coding RNAs (lncRNAs), contributes to MB formation and tumor progression. Here we report the identification of a novel lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 MBs. In this study, we report that lnc-HLX-2-7 RNA specifically accumulates in the HLX (host gene of lnc-HLX-2-7) promoter region and activates HLX expression by recruiting multiple factors including enhancer elements. RNA sequencing and chromatin immunoprecipitation revealed that HLX directly binds to the promoters of several tumor-promoting genes, including MYC, and activates their expression. Furthermore, intravenous treatment with antisense oligonucleotides targeting lnc-HLX-2-7 coated with cerium-oxide nanoparticle (CNP-lnc-HLX-2-7) reduced tumor growth (40-50%) in intracranial MB xenograft mouse model (n=10, p&amp;lt;0.01, t-test). We found that the combinatorial therapy of CNP-lnc-HLX-2-7 and cisplatin further inhibits tumor growth and significantly prolongs mouse survival compared to CNP-lnc-HLX-2-7 monotherapy (n=10, p&amp;lt;0.01, t-test) only. We report here the importance of the lnc-HLX-2-7-HLX-MYC axis in regulating group 3 MB progression and provide a strong rationale for using lnc-HLX-2-7 as a specific and potent therapeutic target for the group 3 MBs in children. Citation Format: Keisuke Katsushima, Bongyong Lee, Menglang Yuan, Stacie Stapleton, George Jallo, Sudipta Seal, Charles G. Eberhart, Ranjan J. Perera. The therapeutic potential of lnc-HLX-2-7 in group 3 medulloblastomas in children. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4764.
Sub-Lexical and Contextual Modeling of Out-of-Vocabulary Words in Speech Recognition (2013)

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In Vivo Collagen Turnover Following Experimental Balloon Angioplasty Injury and the Role of Matrix Metalloproteinases (1996)

Extracellular matrix formation is the major component of the restenosis lesion that develops after balloon angioplasty. Although ex vivo studies have shown that the synthesis of collagen is stimulated early after balloon angioplasty, there is a delay in accumulation in the vessel wall. The objectives of this study were to assess collagen turnover and its possible regulation by matrix metalloproteinases (MMPs) in a double-injury iliac artery rabbit model of restenosis. Rabbits were killed at four time points (immediately and at 1, 4, and 12 weeks) after balloon angioplasty. In vivo collagen synthesis and collagen degradation were measured after a 24-hour incubation with [14C]proline. Arterial extracts were also run on gelatin zymograms to determine MMP (gelatinase) activity. Collagen turnover studies were repeated in a group of 1-week postangioplasty rabbits that were treated with daily subcutaneous injections of either a nonspecific MMP inhibitor, GM6001 (100 mg/kg per day), or placebo. Collagen synthesis and degradation showed similar temporal profiles, with significant increases in the balloon-injured iliac arteries compared with control nondilated contralateral iliac arteries immediately after angioplasty and at 1 and 4 weeks. Peak collagen synthesis and degradation occurred at 1 week and were increased (approximately four and three times control values, respectively). Gelatin zymography was consistent with the biochemical data by showing an increase of a 72-kD gelatinase (MMP-2) in the balloon-injured side immediately after the second injury, peaking at 1 week, and still detectable at 4 and 12 weeks (although at lower levels). In balloon-injured arteries, the MMP inhibitor reduced both collagen synthesis and degradation. Overall, at 1 week after balloon angioplasty, GM6001 resulted in a 33% reduction in collagen content in balloon-injured arteries compared with placebo (750 +/- 143 to 500 +/- 78 micrograms hydroxyproline per segment, P < .004), which was associated with a nonsignificant 25% reduction in intimal area. Our data suggest that degradation of newly synthesized collagen is an important mechanism regulating collagen accumulation and that MMPs have an integral role in collagen turnover after balloon angioplasty.
Progress Towards the Development of Anti-Inflammatory Inhibitors of IKK&#946; (2009)

The IkappaB kinases (IKKs) are essential components of the signaling pathway by which the NF-kappaB p50/RelA transcription factor is activated in response to pro-inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor (TNFalpha). NF-kappaB signaling results in the expression of numerous genes involved in innate and adaptive immune responses. The pathway is also implicated in chronic inflammatory disorders including rheumatoid arthritis (RA), chronic obstructive pulmonary disorder (COPD), and asthma. Inhibition of the kinase activity of the IKKs is therefore a promising mechanism for intervention in these diseases. Here, we will review the literature describing small molecule inhibitors of IKKbeta (IKK2), the most widely studied of the IKKs.
Observation of the decay Λ b 0  → pK − μ + μ − and a search for CP violation (2017)

A search for CP violation in the decay 0 b pK - + -is presented. This decay is mediated by flavour-changing neutral-current transitions in the Standard Model and is potentially sensitive to new sources of CP violation. The study is based on a data sample of proton-proton collisions recorded with the LHCb experiment, corresponding to an integrated luminosity of 3 fb -1 . The 0 b pK - + -decay is observed for the first time, and two observables that are sensitive to different manifestations of CP violation are measured, A
Reduced18F-Folate Conjugates as a New Class of PET Tracers for Folate Receptor Imaging (2018)

5-Methyltetrahydrofolate (5-MTHF), a reduced folate form, is the biologically active folate involved in many different metabolic processes. To date, there are no studies available in the literature on <sup>18</sup>F-labeled 6 S- and 6 R-5-MTHF radiotracers for imaging folate receptor (FR)-α-positive tissues. Therefore, the goal of this study was to synthesize four <sup>18</sup>F-labeled 5-MTHF derivatives conjugated at either the α- or γ-carboxylic functionality of glutamate and to assess their suitability for FR-targeting. Organic syntheses of the precursors and the four reference compounds, namely, 6 S-α, 6 S-γ, 6 R-α, and 6 R-γ-click-fluoroethyl-5-MTHF, were carried out in low to moderate overall chemical yields. The radiosyntheses of the α- and γ-conjugated <sup>18</sup>F-labeled folate derivatives were accomplished in approximately 100 min, low radiochemical yields (1-7% d.c.) and high molar activities (139-245 GBq/μmol). Radiochemically pure tracers were obtained after the addition of a mixture of antioxidants consisting of sodium ascorbate and l-cysteine. In vitro, all four 5-MTHF conjugates showed similar binding affinities to FR-α (IC<sub>50</sub> = 17.7-24.0 nM), whereas folic acid showed a significantly higher binding affinity to the FR-α. Cell uptake and internalization experiments with KB cells demonstrated specific uptake and internalization of the radiofolate conjugates. Metabolite studies in mice revealed high in vivo stability of the radiotracers in mice. Biodistribution and positron emission tomography (PET) imaging studies in FR-positive KB tumor-bearing mice demonstrated that the 6 S- and 6 R-5-MTHF conjugates exhibited a different accumulation pattern in various organs including the kidneys and the liver, whereas no significant differences in radioactivity accumulation in the kidneys and the liver were found for both the α- and γ-conjugated diastereoisomers. Despite the considerably lower binding affinities of the 5-MTHF derivatives compared to the corresponding folic acid conjugates similar high KB tumor uptake was observed for all the folate conjugates investigated (8-11% IA/g). Based on these results, we conclude that <sup>18</sup>F-labeled 5-MTHF conjugates are a promising new class of radiotracers for targeting FR-positive tumor tissues.
Use of Legumes and Yeast as Novel Dietary Protein Sources in Extruded Canine Diets (2021)

The popularity of plant-based protein sources has increased as consumer demand for grain-free and novel protein sources increase. Minimal research has been conducted as regards to use of legumes and yeast and their effects on acceptability and digestibility in canine diets. The objective of this study was to evaluate macronutrient apparent total tract digestibility (ATTD), gastrointestinal tolerance, and fermentative end-products in extruded, canine diets. Five diets were formulated to be isocaloric and isonitrogenous with either garbanzo beans (GBD), green lentils (GLD), peanut flour (PFD), dried yeast (DYD), or poultry by-product meal (CON) as the primary protein sources. Ten adult, intact, female beagles (mean age: 4.2 ± 1.1 yr, mean weight: 11.9 ± 1.3 kg) were used in a replicated, 5 × 5 Latin square design with 14 d periods. Each experimental period consisted of 10 d of diet adaptation, followed by 4 d of total fecal and urine collection. A fasted, 5 ml blood sample was collected at the end of each period and analyzed for serum metabolites and complete blood count. Serum metabolites were within normal ranges and all dogs remained healthy throughout the study. Fecal quality, evaluated on a 5-point scale, was considered ideal. Macronutrient ATTD was similar among dietary treatments, with diets highly digestible (>80%). Total fecal branched-chain fatty acid concentrations were highest (<i>P</i> < 0.05) for DYD (23.4 μmol/g) than GLD (16.1 μmol/g) and PFD (16.0 μmol/g) but not different (<i>P</i> > 0.05) than other treatments. The plant-based protein treatments had greater (<i>P</i> < 0.05) total fecal short chain fatty acid (SCFA) concentrations (average 627.6 μmol/g) compared with CON (381.1 μmol/g). Fecal butyrate concentration was highest (<i>P</i> < 0.05) for DYD than all other dietary treatments (103.9 μmol/g vs. average 46.2 μmol/g). Fecal microbial communities showed <i>Firmicutes, Bacteroidetes, Fusobacteria</i>, and <i>Proteobacteria</i> as abundant phyla. There was greater β-diversity for dogs fed DYD which differed from all other diets in both weighted and unweighted UNIFRAC analyses. Inclusion of these novel, plant-based, protein sources showed no detrimental effects on nutrient digestibility or fecal characteristics and represent viable protein sources in canine diets that can produce beneficial shifts in fecal metabolites.
A-112 DNA and Protein Co-immunization Improves the Magnitude, Longevity, and mucosal dissemination of Immune Responses (2014)

Background: To increase effectiveness of DNA vaccines, we developed a method of simultaneous vaccination of DNA and protein. DNA & protein (inactivated viral particles) co-immunization induced both systemic and mucosal Ab responses, which correlated with slower virus acquisition; and potent T cell responses, which correlated with protection from chronic viremia. Different regimens of DNA & protein vaccines using purified SIV/HIV-1 Env were evaluated to further improve mucosal dissemination. Methods: Macaques were vaccinated with SIV/HIV DNAs via the IM route using in vivo electroporation followed by protein administered into the same muscle. Immune responses were monitored in blood and mucosal sites including vaginal and rectal secretions. Results: DNA & protein co-immunization induced rapid and high humoral responses while maintaining robust cellular responses typically obtained with DNA. We found high systemic and mucosal antibody binding titers against gp120 as well as scaffolded V1/V2 env region; high levels of Env-specific IgG in saliva; Env-specific IgG and IgA in rectal mucosa; robust humoral responses in vaginal and rectal secretions. Importantly, while IM administered DNA vaccine induced cellular responses disseminated to mucosal sites, we noted poor dissemination of the humoral responses. In contrast, co-immunization with Env led to the significant increases in mucosal Ab dissemination. Co-immunization also resulted in improved longevity of immune responses detectable for several years. Conclusions: Intramuscular DNA & protein co-delivery increases the magnitude and longevity of systemic and mucosal humoral immune responses in immunized macaques and is proposed as a practical and efficient method for human vaccination.
Comprehensive analysis of epigenetic modification under a persistent postoperative pain-like state (2021)

The most common complaint after surgery is postsurgical pain. Generally, this was considered to resolve after a recovery period. However, persistent pain after surgery, so-called chronic postsurgical pain (CPSP), is now recognized as a critical problem. To elucidate the factors that contribute to CPSP, we developed a new mouse model of persistent postoperative pain induced by electrocautery and investigated the molecular mechanism of the development of CPSP. Acute hyperalgesia was observed with both incision and electrocautery, whereas persistent hyperalgesia was only observed after electrocautery. Consistent with behavioral data, electrocautery treatment induced long-lasting neuronal activation related to synaptic plasticity and potently increased mRNA levels of the key modulators of neuropathic pain in the spinal cord, compared to incision. Furthermore, we found that the overexpression of these genes was observed almost exclusively in CPSP-activated neurons associated with epigenetic modifications. These findings suggest that electrocautery-associated invasion contributes to CPSP along with epigenetic modification. We are currently investigating the possible changes in brain function caused by electrocautery.
Dynamic resource allocation for interference management in orthogonal frequency division multiple access cellular communications (2010)

Next generation wireless communications rely on large bandwidths and orthogonal frequency division multiple access (OFDMA) techniques to achieve high data rates. In an OFDMA-based cellular network, interference management is key to system performance characteristics, such as capacity, coverage and stability. Conventional cellular systems typically employ frequency reuse, such as 1/3, or 1/7 frequency reuse, to reduce inter-cell interference, resulting in low bandwidth efficiency. This study introduces a frequency resource and interference management scheme for use in an OFDMA cellular communication system, referred to as dynamic frequency resource allocation, in which the network divides frequency band into multiple partitions with various inter-sector interference blocking capabilities. In addition, an interference identification scheme that allows the network to acquire a terminal&apos;s interference properties is also proposed. Therefore the terminals under different inter-sector interference can be dynamically assigned with the most efficient frequency resources depending on the interference sources, enabling the network to optimise both bandwidth usage and cell edge performance with increased flexibility and accuracy.
Open source barriers to entry, revisited (2018)

Research has revealed that significant barriers exist when entering Open-Source Software (OSS) communities and that women disproportionately experience such barriers. However, this research has focused mainly on social/cultural factors, ignoring the environment itself --- the tools and infrastructure. To shed some light onto how tools and infrastructure might somehow factor into OSS barriers to entry, we conducted a field study with five teams of software professionals, who worked through five use-cases to analyze the tools and infrastructure used in their OSS projects. These software professionals found tool/infrastructure barriers in 7% to 71% of the use-case steps that they analyzed, most of which are tied to newcomer barriers that have been established in the literature. Further, over 80% of the barrier types they found include attributes that are biased against women.
Fluoride-free synthesis of high-silica CHA-type aluminosilicates by seed-assisted aging treatment for starting gel (2022)

High-silica CHA-type aluminosilicates (Si/Al molar ratio >100) were synthesized hydrothermally in the absence of fluoride media, where the seed-assisted aging treatment played an important role on the crystallization. These aluminosilicates showed a long catalytic lifetime with high selectivity toward lower olefins in the methanol-to-olefins reaction.
Convergence in neural memories (1989)

One of the simplest optimization problems solved by Ising spin models of neural memory is associative memory retrieval. The authors study deterministic convergence properties of the Hopfield synchronous retrieval algorithm for such models. In this case a memory, stored in the network by an appropriate choice of connections, is retrieved by setting the neural outputs to the binary pattern of the recall key (probe) and allowing the network to converge to a stable state. Precise conditions are developed that ensure that all stored memories are fixed points of the retrieval algorithm. An orthogonality-nearness criterion is then obtained for a memory probe itself to be a stationary point and thus outside the error-correcting capability of the memory. A local stability result quantifies the spatial relationship required for fast convergence.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>