gebhart/patrepeval huggingface dataset:
First Total Synthesis and Stereochemical Revision of Laxaphycin B and Its Extension to Lyngbyacyclamide A (2013)

The first total synthesis of laxaphycin B was accomplished through stepwise automated Solid Phase Peptide Synthesis (SPPS), leading to the structural revision of its stereochemistry especially with regard to the configuration of one of the two 3-hydroxyleucines of this cyclic dodecapeptide of marine origin. The analogous Lyngbyacyclamide A was obtained by an extension of this synthesis.
Review of NMDA antagonist-induced neurotoxicity and implications for clinical development (2004)

NMDA receptor antagonists have been investigated for many years as therapeutic agents for the treatment of neurological disorders such as stroke, epilepsy, pain and Parkinson's disease. It has been discovered, however, that many of these compounds cause adverse behavioral (psychotomimetic) effects and can produce neurotoxicity characterized by neuronal vacuolization, induction of heat-shock protein, neuronal/axonal degeneration and regional brain cell death in several animal species. It is unknown whether NMDA antagonists induce neurotoxicity in humans. The mechanism of NMDA antagonist-induced neurotoxicity is not completely known, but some evidence suggests disinhibition of GABAergic inputs to the affected neurons. Several classes of compounds have been shown to prevent NMDA antagonist-induced neurotoxicity. The extent of neurotoxicity produced by NMDA antagonists is affected by many factors, including type of antagonist, dose, length of exposure, age, sex and species. While there are no published regulatory guidelines regarding how NMDA antagonist compounds should be evaluated, sponsors and investigators of these compounds should make every effort to assess the potential for neurotoxicity. NMDA receptor antagonists, as well as other CNS-active compounds need to be analyzed for neurotoxicity through careful experimental design, adequate tissue sampling and through the use of a sensitive method of detection.
Non-Coherent Multiple-Symbol Detection for Diffusive Molecular Communications (2016)

Most of the available works on molecular communication (MC) assume that the channel state information (CSI) is perfectly known at the receiver for data detection. In contrast, in this paper, we study non-coherent multiple-symbol detection schemes which do not require knowledge of the CSI. In particular, we derive the optimal maximum likelihood (ML) multiple-symbol (MLMS) detector. Moreover, we propose an approximated detection metric and a sub-optimal detector to cope with the high complexity of the optimal MLMS detector. Numerical results reveal the effectiveness of the proposed optimal and suboptimal detection schemes with respect to a baseline scheme which assumes perfect CSI knowledge, particularly when the number of observations used for detection is sufficiently large.
Enantioselective Palladium‐Catalyzed Decarboxylative Allylation of Carbazolones: Total Synthesis of (−)‐Aspidospermidine and (+)‐Kopsihainanine A (2013)

Functionalized chiral carbazolones with α-quaternary carbon centers are formed through the ligand-controlled Pd-catalyzed enantioselective decarboxylative allylic alkylation of carbazolones (see scheme). This catalytic asymmetric reaction was employed as the key step in the total synthesis of aspidospermidine and (+)-kopsihainanine A.
Motility and biofilm formation of the emerging gastrointestinal pathogenCampylobacter concisusdiffers under microaerophilic and anaerobic environments (2018)

Campylobacter concisus has been isolated from patients with gastroenteritis and inflammatory bowel disease (IBD), as well as healthy subjects. While strain differences may plausibly explain virulence differentials, an alternative hypothesis posits that the pathogenic potential of this species may depend on altered ecosystem conditions in the inflamed gut. One potential difference is oxygen availability, which is frequently increased under conditions of inflammation and is known to regulate bacterial virulence. Hence, we hypothesized that oxygen influences C. concisus physiology. We therefore characterized the effect of microaerophilic or anaerobic environments on C. concisus motility and biofilm formation, two important determinants of host colonization and dissemination. C. concisus isolates (n = 46) sourced from saliva, gut mucosal biopsies and feces of patients with IBD (n = 23), gastroenteritis (n = 8) and healthy subjects (n = 13), were used for this study. Capacity to form biofilms was determined using crystal violet assay, while assessment of dispersion through soft agar permitted motility to be assessed. No association existed between GI disease and either motility or biofilm forming capacity. Oral isolates exhibited significantly greater capacity for biofilm formation compared to fecal isolates (p<0.03), and showed a strong negative correlation between motility and biofilm formation (r = -0.7; p = 0.01). Motility significantly increased when strains were cultured under microaerophilic compared to anaerobic conditions (p<0.001). Increased biofilm formation under microaerophillic conditions was also observed for a subset of isolates. Hence, differences in oxygen availability appear to influence key physiological aspects of the opportunistic gastrointestinal pathogen C. concisus.
Abstract 395: Effect of pantoprazole to enhance activity of docetaxel against human tumor xenografts by inhibiting autophagy (2015)

Abstract Background: Autophagy allows recycling of cellular components and may facilitate cell survival after chemotherapy. Pantoprazole inhibits proton pumps, including that maintaining low pH in endosomes, and is reported to inhibit autophagy (1). Here we evaluate effects of pantoprazole to modify cytotoxicity of the anticancer drug docetaxel, and underlying mechanisms. Methods: Effects of docetaxel+/-pantoprazole were studied against wild-type and autophagy-deficient cultured PC3 cells derived by shRNA, and against four human xenografts. Effects of pantoprazole on autophagy in cultured cells were evaluated by quantifying LC3-I, LC3-II and p62 proteins in Western blots, and by fluorescent microscopy of cells transfected with the tandem sensor RFP-GFP-LC3. Since autophagy is known to be up-regulated in poorly-nourished tumor regions (2), the distribution of drug effects and of autophagy was quantified in tumor sections in relation to blood vessels and hypoxia by immunohistochemistry (IHC) using γH2AX, a marker of DNA damage, cleaved caspase-3, a marker of apoptosis, Ki67, a marker of proliferation and LC3 and p62 to quantify autophagy. Results: Pantoprazole increased toxicity of docetaxel for cultured cells, increased docetaxel-induced expression of γH2AX and cleaved caspase-3 and decreased Ki67 in tumor sections. Pantoprazole increased growth-delay of four human xenografts of low, moderate and high sensitivity to docetaxel, with minimal increase in toxicity. Docetaxel led to increased autophagy throughout tumor sections. Pantoprazole inhibited autophagy, and effects of pantoprazole were reduced against genetically-modified cells with decreased ability to undergo autophagy. Conclusions: Autophagy is a mechanism of resistance to docetaxel chemotherapy that may be modified by pantoprazole to improve therapeutic index. High-dose pantoprazole increases the therapeutic effectiveness of docetaxel in vitro and in vivo, and its main mechanism of action is via inhibition of autophagy. With this rationale, we are undertaking a phase II study of pantoprazole + docetaxel in men with castrate-resistant prostate cancer. References: 1. Udelnow A, Kreyes A, Ellinger S, Landfester K, Walther P, Klapperstueck T, et al. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One;6(5):e20143. 2. Yang ZJ, Chee CE, Huang S, Sinicrope FA. The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther;10(9):1533-41. Citation Format: Qian Tan, Anthony M. Joshua, Jasdeep K. Saggar, Man Yu, Marina Wang, Bradly Wouters, Ian F. Tannock. Effect of pantoprazole to enhance activity of docetaxel against human tumor xenografts by inhibiting autophagy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 395. doi:10.1158/1538-7445.AM2015-395
Monitoring-based spectrum management for expanding opportunities of white space utilization (2011)

Spectrum management is one of the key functions needed for opportunistic spectrum access (OSA) to utilize white space without causing harmful interference to incumbent receivers. Geo-location database approaches using radio propagation estimation have been regarded as practical spectrum management methods. However, propagation models inevitably include an estimation error of path loss in actual radio environments, resulting in estimation error of carrier to interference ratio (CIR) of the incumbent receivers. Consequently, an allowable transmit power of the opportunistic system has to be limited to keep the CIR at a required level. This could prevent white space from being efficiently utilized. To improve the accuracy of CIR estimation, we propose monitoring-based spectrum management. In the proposed technology, referred to as Interference Monitoring, a monitoring node located near the incumbent receivers actually measures both the interference signals and the incumbent signals. Using the measurement results, the CIR estimates are compensated based on minimum mean square error (MMSE) criterion. The proposed Interference Monitoring can be extended cooperatively to utilize spatial diversity. Analytical evaluations assuming a simple cellular system model show that the Interference Monitoring can more accurately estimate CIR, and thus it can significantly increase the allowable transmit power. For an urban macro cell, the Interference Monitoring with a single node achieved more than a 4 dB increase of the transmit power; the Cooperative Interference Monitoring with 4 nodes achieved more than a 7 dB increase. Thus, the Interference Monitoring can expand opportunities for white space utilization without increasing the interference to the incumbent system.
High-dose intravenous glucocorticoids cause ventricular tachycardia: Case report and review of the literature (2002)

There is widespread recognition of the effect of drugs on prolongation of the QT interval and subsequent development of ventricular tachycardia. Although there are literature reports of adverse cardiac events of high-dose intravenous corticosteroids, the mechanism of these changes is unrecognized. The authors report a case of markedly prolonged QT and resultant ventricular tachycardia characteristic of torsade de pointes in a patient treated with high-dose intravenous steroids and ketoconazole. Based on animal studies, these changes are likely due to a decrease in outward potassium currents. Awareness of the arrhythmogenic effects of high-dose intravenous steroids should prompt electrocardiographic monitoring of these patients.
SIMS Imaging and 3D Microanalysis of Organic Structures (2010)

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.
Stable Binary Complementary White Light-Emitting Diodes Based on Quantum-Dot/Polymer-Bilayer Structures (2008)

A binary complementary white light-emitting diode (LED) was designed and fabricated by employing a colloidal quantum-dot (QD)/polymer-bilayer configuration in the device active region. Stable white electroluminescence is observed from the cumulative emission of the yellow-emitting CdSe-ZnS core-shell QDs and blue-emitting poly(N,N'-bis (4-butylphenyl)-N,N'-bis(phenyl)benzidine) (Poly-TPD) molecules. The white chromaticity of the LED output can be tailored by varying the respective thicknesses of the constituent emissive layers; whereas the emission color exhibits little dependence on the applied bias over a wide voltage range. The maximum luminance of the device reaches 2600 cd/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> under a bias of 9.4 V.
Arylation of 2-Furyl 4-Fluorophenyl Ketone: An Extension of Heck Chemistry towards Novel Integrase Inhibitors (2010)

An optimized procedure for the direct and regioselective arylation of 2-acylfurans has been developed. The versatility of this protocol has been evaluated on a series of aryl and heteroaryl halides, thus obtaining a small collection of 2,5-disubstituted furans in moderate to good yields. Finally, the optimized protocol has been successfully applied to the synthesis of the HIV-1 integrase inhibitor 3 and could be further exploited for the generation of novel substituted furans as potential integrase inhibitors.
NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-α (2004)

We tested the hypothesis that the NAD(P)H oxidase-dependent generation of superoxide anion (O2-*) mediates tumor necrosis factor-alpha (TNF)-induced alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin. The NAD(P)H oxidase subcomponents p47phox and p22phox were assessed by immunofluorescent microscopy and Western blot. The reactive oxygen species O2-* was measured by the fluorescence of 6-carboxy-2',7'-dichlorodihydrofluorescein diacetatedi(acetoxymethyl ester), 5 (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate-acetyl ester, and dihydroethidium. TNF treatment (50 ng/ml for 4.0 h) induced 1) p47phox translocation, 2) an increase in p22phox protein, 3) increased localization of p47phox with p22phox, 4) O2-* generation, and 5) increased permeability to albumin. p22phox antisense oligonucleotide prevented the TNF-induced effect on p22phox, p47phox, O2-*, and permeability. The scrambled nonsense oligonucleotide had no effect. The TNF-induced increase in O2-* and permeability to albumin was also prevented by the O2-* scavenger Cu-Zn superoxide dismutase (100 U/ml). The results indicate that the activation of NAD(P)H oxidase, via the generation of O2-*, mediates TNF-induced barrier dysfunction in PMEM.
Combined Treatment With Dendritic Cells and 5-fluorouracil Elicits Augmented NK Cell-mediated Antitumor Activity Through the Tumor Necrosis Factor-α Pathway (2010)

Antitumor effects and mechanism of combined therapy with a dendritic cell (DC) vaccine and fluorouracil (5-FU) were investigated. Cytotoxic activity against MC38 cells, untreated or pretreated with 5-FU, was examined in splenocytes from mice inoculated with DCs: DCs pulsed with MC38 lysate or treated with LPS or both and untreated DCs. Inoculation with all types of DCs induced the significant cytotoxic activity of splenocytes, and pretreatment of MC38 cells with 5-FU significantly enhanced the cytotoxic activity of splenocytes. Depletion of natural killer (NK) cells, but not of CD8 or CD4 T cells, in the splenocytes from DC (without MC38 lysate-pulse or LPS treatment thereafter)-inoculated mice decreased the cytotoxic activity. The cytotoxic effect was eliminated by treatment with a monoclonal antibody (mAb) against tumor necrosis factor (TNF)-alpha and was partially inhibited by concanamycin A. Inoculation of mice with DCs upregulated TNFalpha expression on NK cells. MC38 cells pretreated with 5-FU exhibited enhanced expression of procaspase 8 and efficiently underwent apoptosis by TNF-alpha with activation of caspase 8. Although treatment with 5-FU upregulated Rae-1 expression on MC38 cells, the NK-cell-mediated cytotoxic activity was not suppressed by treatment with an anti-Rae-1 mAb or an antinatural killer group 2D mAb or both. These results indicate that combined therapy with a DC vaccine and 5-FU is a promising strategy for cancer treatment mediated by the tumoricidal activity of NK cells through the TNF-alpha pathway.
The Draft Genome Dataset of the Asian Cricket Teleogryllus occipitalis for Molecular Research Toward Entomophagy (2020)

DATA REPORT article Front. Genet., 08 May 2020Sec. Livestock Genomics Volume 11 - 2020 | https://doi.org/10.3389/fgene.2020.00470
Picosecond diffuse reflectance laser flash photolysis (1986)

Picosecond pumping and probing of an opaque sample of xanthone adsorbed on to silica gel demonstrates the growth of a transient absorption at 590 nm which levels to a plateau within 800 ps; on the basis of spectral evidence from nanosecond diffuse reflectance laser flash photolysis, this transient is assigned as the triplet state of xanthone.
A comparison of theory and experiment for coupled rotor body stability of a bearingless rotor model in hover and forward flight (1988)

Seven cases were selected for correlation from a 1/5.86 Froude-scale experiment that examined several rotor designs which were being considered for full-scale flight testing as part of the Bearingless Main Rotor (BMR) program. The model rotor hub used in these tests consisted of back-to-back C-beams as flexbeam elements with a torque tube for pitch control. The first four cases selected from the experiment were hover tests which examined the effects on rotor stability of variations in hub-to-flexbeam coning, hub-to-flexbeam pitch, flexbeam-to-blade coning, and flexbeam-to-blade pitch. The final three cases were selected from the forward flight tests of optimum rotor configuration as defined during the hover test. The selected cases examined the effects of variations in forward speed, rotor speed, and shaft angle. Analytical results from Bell Helicopter Textron, Boeing Vertol, Sikorsky Aircraft, and the U.S. Army Aeromechanics Laboratory were compared with the data and the correlations ranged from poor-to-fair to fair-to-good.
Comparison of Lifetime Improvements in Electromigration between Ti Barrier Metal and Chemical Vapor Deposition Co Capping (2010)

As promising technologies for fabrication of highly reliable Cu interconnects, using Ti barrier metal (Cu/Ti) and chemical vapor deposition (CVD) Co capping (Co/Cu/Ta/TaN) were compared. Both Cu interconnects similarly showed longer electromigration (EM) lifetime and larger activation energy of lifetime than conventional Cu interconnects fabricated using Ta/TaN barrier metal without capping metal (Cu/Ta/TaN). The residual resistance of Cu lines was measured cryogenically. Cu/Ti showed a higher residual resistance than Co/Cu/Ta/TaN and Cu/Ta/TaN, which indicates the presence of more impurities and a higher density of grain boundaries in Cu/Ti. Energy dispersive X-ray spectroscopy (EDX) analysis showed that a large amount of Ti doped into the Cu line segregated mostly at the grain boundaries on the Cu surface. It is suggested that Ti doped into a Cu line suppresses Cu diffusion through only the grain boundaries on the Cu surface. On the other hand, Co capping suppresses Cu diffusion through the entire Cu surface. As Cu/Ti improved EM lifetime significantly, the grain boundaries on the Cu surface are proposed to be a predominant diffusion path in EM. Since the density of grain boundaries probably increases on the Cu surface as interconnects shrink, suppressing the grain boundary diffusion on the Cu surface is highly effective to strengthen EM reliability.
Radiotherapy to Bone Has Utility in Multifocal Metastatic Renal Carcinoma (2007)

Renal cell carcinoma metastases to bone are classically considered radioresistant. We reviewed 28 patients who underwent irradiation for metastatic renal cell carcinomas to bone to test the hypothesis that irradiation of renal metastases to bone provides adequate palliation in carefully selected patients. Metastases were multifocal in all patients. All patients were followed until death. Overall, 36 index radiotherapy treatments were given as palliative initial treatment for 36 osseous metastatic sites. Twenty-five of 36 sites (69.5%) had no subsequent radiotherapy. Eight sites (22.2%) underwent repeat radiotherapy at a mean 28.9 weeks after treatment. Two (5.6%) additional sites underwent surgery at the site at an average 74 weeks later, and a pathologic fracture occurred at one (2.8%) site 3 weeks after irradiation. Overall, 33 of 36 (91.7%) sites had only radiotherapy as their source of palliation. Median times to return to pretreatment pain and functional levels, however, were 2 months and 1 month, respectively. Radiotherapy to osseous sites appears to control pain for the short term and generally prevents fractures and avoids the need for surgery in renal cell carcinoma patients with multiple bone metastases.
Tissue Penetration and Half-Life of Cefonicid (1984)

The pharmacokinetics of cefonicid in the serum and tissues of patients undergoing open heart surgery, vaginal hysterectomy, and hip replacement was studied and compared with that of cefazolin and cefoxitin. Cefonicid achieved serum and tissue concentrations that were higher and more prolonged than those of cefazolin and cefoxitin. For cefonicid parallelism was observed between the serum and tissue concentration-time curves. Correlations of these properties to clinical efficacy were not attempted.
Allele-Specific KRT1 Expression Is a Complex Trait (2006)

The differential expression of alleles occurs commonly in humans and is likely an important genetic factor underlying heritable differences in phenotypic traits. Understanding the molecular basis of allelic expression differences is thus an important challenge. Although many genes have been shown to display differential allelic expression, this is the first study to examine in detail the cumulative effects of multiple cis-regulatory polymorphisms responsible for allele-specific expression differences. We have used a variety of experimental approaches to identify and characterize cis-regulatory polymorphisms responsible for the extreme allele-specific expression differences of keratin-1 (KRT1) in human white blood cells. The combined data from our analyses provide strong evidence that the KRT1 allelic expression differences result from the haplotypic combinations and interactions of five cis-regulatory single nucleotide polymorphisms (SNPs) whose alleles differ in their affinity to bind transcription factors and modulate KRT1 promoter activity. Two of these cis-regulatory SNPs bind transcriptional activators with the alleles on the high-expressing KRT1 haplotype pattern having a higher affinity than the alleles on the low-expressing haplotype pattern. In contrast, the other three cis-regulatory SNPs bind transcriptional inhibitors with the alleles on the low-expressing haplotype pattern having a higher affinity than the alleles on the high-expressing haplotype pattern. Our study provides important new insights into the degree of complexity that the cis-regulatory sequences responsible for allele-specific transcriptional regulation have. These data suggest that allelic expression differences result from the cumulative contribution of multiple DNA sequence polymorphisms, with each having a small effect, and that allele-specific expression can thus be viewed as a complex trait.
Transformation of stimulus value signals into motor commands during simple choice (2011)

Decision-making can be broken down into several component processes: assigning values to stimuli under consideration, selecting an option by comparing those values, and initiating motor responses to obtain the reward. Although much is known about the neural encoding of stimulus values and motor commands, little is known about the mechanisms through which stimulus values are compared, and the resulting decision is transmitted to motor systems. We investigated this process using human fMRI in a task where choices were indicated using the left or right hand. We found evidence consistent with the hypothesis that value signals are computed in the ventral medial prefrontal cortex, they are passed to regions of dorsomedial prefrontal cortex and intraparietal sulcus, implementing a comparison process, and the output of the comparator regions modulates activity in motor cortex to implement the choice. These results describe the network through which stimulus values are transformed into actions during a simple choice task.