gebhart/patrepeval huggingface dataset:
N‐Alkylation of imides using phase transfer catalysts under solvent‐free conditions (2008)

Abstract magnified image N ‐Alkylation of imides in the reaction of imides and alkylhalides, catalyzed by PT catalysts under solvent‐free conditions, has been developed. The reaction occurs in the presence of K 2 CO 3 , and in many cases it takes place spontaneously. In the N ‐benzylation reaction, it has been recognized that TBAB (tetrabutylammonium bromide) and TBATFB (tetrabutylammonium tetrafluoroborate) show highest catalytic effect. Versatility and synthetic capacity of the solvent‐free alkylation has been confirmed by N ‐benzylation and N ‐ethylation of various imides. The developed procedure gives easy access to N ‐(ω‐bromoalkyl)imides.
The melanoma revolution: From UV carcinogenesis to a new era in therapeutics (2014)

Melanoma, the deadliest form of skin cancer, is an aggressive disease that is rising in incidence. Although melanoma is a historically treatment-resistant malignancy, in recent years unprecedented breakthroughs in targeted therapies and immunotherapies have revolutionized the standard of care for patients with advanced disease. Here, we provide an overview of recent developments in our understanding of melanoma risk factors, genomics, and molecular pathogenesis and how these insights have driven advances in melanoma treatment. In addition, we review benefits and limitations of current therapies and look ahead to continued progress in melanoma prevention and therapy. Remarkable achievements in the field have already produced a paradigm shift in melanoma treatment: Metastatic melanoma, once considered incurable, can now be treated with potentially curative rather than palliative intent.
Stochastic exploration of molecular mechanics energy surfaces. Hunting for the global minimum (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStochastic exploration of molecular mechanics energy surfaces. Hunting for the global minimumMartin SaundersCite this: J. Am. Chem. Soc. 1987, 109, 10, 3150–3152Publication Date (Print):May 1, 1987Publication History Published online1 May 2002Published inissue 1 May 1987https://pubs.acs.org/doi/10.1021/ja00244a051https://doi.org/10.1021/ja00244a051research-articleACS PublicationsRequest reuse permissionsArticle Views354Altmetric-Citations278LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Comprehensive, rapid and sensitive detection of sequence variants of human mitochondrial tRNA genes (1997)

In the present study, a comprehensive, rapid and sensitive method for screening sequence variation of the human mitochondrial tRNA genes has been developed. For this purpose, the denaturing gradient gel electrophoresis (DGGE) technique has been appropriately modified for simultaneous mutation analysis of a large number of samples and adapted so as to circumvent the problems caused by the anomalous electrophoretic behavior of DNA fragments encoding tRNA genes. Eighteen segments of mitochondrial DNA (mtDNA), each containing a single uniform melting domain, were selected to cover all tRNA-encoding regions using the computer program MELT94. All 18 segments were simultaneously analyzed by electrophoresis through a single broad range denaturing gradient gel under rigorously defined conditions, which prevent band broadening and other migration abnormalities from interfering with detection of sequence variants. All base substitutions tested, which include six natural mutations and 14 artificially introduced ones, have been detected successfully in the present study. Several types of evidence strongly suggest that the anomalous behavior in DGGE of tRNA gene-containing mtDNA fragments reflects their tendency to form temporary or stable alternative secondary structures under semi-denaturing conditions. The high sensitivity of the method, which can detect as low as 10% of mutant mtDNA visually, makes it valuable for the analysis of heteroplasmic mutations.
Catalytic Signature of a Heat-Stable, Chimeric Human Alkaline Phosphatase with Therapeutic Potential (2014)

Recombinant alkaline phosphatases are becoming promising protein therapeutics to prevent skeletal mineralization defects, inflammatory bowel diseases, and treat acute kidney injury. By substituting the flexible crown domain of human intestinal alkaline phosphatase (IAP) with that of the human placental isozyme (PLAP) we generated a chimeric enzyme (ChimAP) that retains the structural folding of IAP, but displays greatly increased stability, active site Zn²⁺ binding, increased transphosphorylation, a higher turnover number and narrower substrate specificity, with comparable selectivity for bacterial lipopolysaccharide (LPS), than the parent IAP isozyme. ChimAP shows promise as a protein therapeutic for indications such as inflammatory bowel diseases, gut dysbioses and acute kidney injury.
160-Gbps Nyquist PAM4 transmitter using a digital-preprocessed analog-multiplexed DAC (2015)

We proposed an ultra-wide-band DAC configuration consisting of a digital preprocessor, two sub-DACs, and an analog multiplexer. The output bandwidth is nearly doubled from that of the sub-DACs. The idea was verified by a 160-Gbps Nyquist PAM4 transmission.
Fast Scene Change Detection Based Histogram (2007)

This work presents a new approach to detecting the scene change in the successive capture of photographs of a place within equal time interval. This method is based on a gray level histogram of every image. In this method the histogram of an image is processed to modify it for matching with the processed histogram of a reference image. The coefficient of correlation is taken as the measure of matching. As the method does not do any heavy signal processing, and the images are taken successively with a multi-shot digital still camera, it can be applied for real-time processing of such pictures for detection of a scene change. A multi-camera in multi-position approach is also shown to evaluate the change in scene simultaneously from different angles. Both multi-camera and single-camera approaches are compared in detecting a scene change.
Total antioxidant status and 8-hydroxy-2′-deoxyguanosine levels in gingival and peripheral blood of periodontitis patients (2007)

The oxidative burst in periodontitis may lead to significant local damage to nucleic acids. The significantly decreased TAS level in the gingival blood of CP patients compared with the healthy subjects suggests the possibility of a significant decrease in local antioxidant system capacity during the course of periodontitis. The decreased TAS level in the peripheral blood in the group of all patients with periodontitis may be one of the pathogenic mechanisms underlying the links between periodontal disease and several systemic diseases for which periodontitis is regarded as a independent risk factor.
Antigenic Characterization of the HCMV gH/gL/gO and Pentamer Cell Entry Complexes Reveals Binding Sites for Potently Neutralizing Human Antibodies (2015)

Human Cytomegalovirus (HCMV) is a major cause of morbidity and mortality in transplant patients and in fetuses following congenital infection. The glycoprotein complexes gH/gL/gO and gH/gL/UL128/UL130/UL131A (Pentamer) are required for HCMV entry in fibroblasts and endothelial/epithelial cells, respectively, and are targeted by potently neutralizing antibodies in the infected host. Using purified soluble forms of gH/gL/gO and Pentamer as well as a panel of naturally elicited human monoclonal antibodies, we determined the location of key neutralizing epitopes on the gH/gL/gO and Pentamer surfaces. Mass Spectrometry (MS) coupled to Chemical Crosslinking or to Hydrogen Deuterium Exchange was used to define residues that are either in proximity or part of neutralizing epitopes on the glycoprotein complexes. We also determined the molecular architecture of the gH/gL/gO- and Pentamer-antibody complexes by Electron Microscopy (EM) and 3D reconstructions. The EM analysis revealed that the Pentamer specific neutralizing antibodies bind to two opposite surfaces of the complex, suggesting that they may neutralize infection by different mechanisms. Together, our data identify the location of neutralizing antibodies binding sites on the gH/gL/gO and Pentamer complexes and provide a framework for the development of antibodies and vaccines against HCMV.
Novel route to oligo(deoxyribonucleoside phosphorothioates). Stereocontrolled synthesis of P-chiral oligo(deoxyribonucleoside phosphorothioates) (1991)

The synthesis and separation of diastereoisomerically pure 5'-O-DMT-nucleoside 3'-O-(2-thio-1,3,2-oxathiaphospholane) allows their use as synthons in DBU-catalyzed reaction with the 5'-hydroxyl function of solid-support-bound nucleoside moiety. Since this reaction is stereospecific (greater than 99%), this novel method allows preparation of oligo(nucleoside phosphorothioates) with predetermined chirality at each P-chiral internucleotide phosphorothioate centre.
Hyperpolarized 129Xe Nuclear Magnetic Resonance Studies of Isoreticular Metal-Organic Frameworks (2007)

The pore environments of a series of isoreticular metal-organic frameworks (IRMOF) have been studied using hyperpolarized (HP) 129Xe nuclear magnetic resonance (NMR) spectroscopy. Xenon gas behaved as an efficient probe molecule for interrogating the variability of adsorption sites in functionalized IRMOF materials through variations in the NMR chemical shift of the adsorbed xenon. The xenon adsorption enthalpies extracted from variable-temperature HP 129Xe NMR were found to be lower than published values for the physisorption of xenon. The low heats of adsorption were corroborated by xenon adsorption measurements that revealed two atoms per pore under one atmosphere of pressure at 19 °C. Average pore diameters estimated from the empirical chemical shift and pore size correlations based on a geometrical model were compared with X-ray crystallography data. The exchange processes of xenon in IRMOFs also were explored using 2D exchange spectroscopy (EXSY) 129Xe NMR. It was found the exchange of xenon from adsorption sites within the IRMOF to the free gas space is much slower than that between the adsorption sites within the lattice. Cross-polarization experiments showed that the preferred adsorption sites were spatially removed from the phenylene rings of the network. This agrees with previous spectroscopic, structural, and computational studies of gas adsorption (H2, N2, Ar) in IRMOFs that indicate the preferred binding sites reside near the carboxylate groups of the inorganic clusters.
Dorsal Neck Muscle Vibration Induces Upward Shifts in the Endpoints of Memory-Guided Saccades in Monkeys (2004)

Producing a movement in response to a sensory stimulus requires knowledge of the body's current configuration, and spindle organs embedded within muscles are a primary source of such kinesthetic information. Here, we sought to develop an animal model of kinesthetic illusions induced by mechanically vibrating muscles as a first step toward a mechanistic understanding of how kinesthesia is integrated into neural plans for action. We elected to examine the effects of mechanical vibration of dorsal neck muscles in head-restrained monkeys performing memory-guided saccades requiring them to look to the remembered location of a flashed target only after an imposed delay. During the delay on one-half of all trials, mechanical vibration (usually 1,500 ms in duration, 200 microm in amplitude, 100 Hz in frequency) was applied to the dorsal aspect on one side of the monkey's neck. We compared the metrics of such vibration saccades to control saccades without vibration during the delay interval. Relative to control saccades, the endpoints of vibration saccades were shifted consistently upward, even though the variability in saccadic endpoints was unaltered. Although the stability of the eye was compromised during the delay interval of vibration trials, as evidenced by an increased incidence of upward drifts and downward microsaccades, vibration saccades displayed different metrics than control saccades, including an upwardly deviated radial direction and increased vertical amplitude. The influence of variations in the duration (500-2,500 ms), amplitude (100-300 microm), or frequency (75-125 Hz) of vibration scaled well with the presumed change in spindle activity entrained by vibration. Comparisons of the profile of these results are made to the human literature. We conclude that neck muscle vibration induces alterations in oculomotor performance in monkeys consistent with a central interpretation of illusory neck flexion and downward gaze deviation due to increased activation in the spindles of neck extensor muscles.
Neural decoding of spoken vowels from human sensory-motor cortex with high-density electrocorticography (2014)

We present the first demonstration of single-trial neural decoding of vowel acoustic features during speech production with high performance. The ability to predict trial-by-trial fluctuations in speech production was facilitated by using high-density, large-area electrocorticography (ECoG) combined with an adaptive principal components regression. In experiments from two human neurosurgical patients with a high-density 256-channel ECoG grid implanted over speech cortices, we demonstrate that as much as 81% of the acoustic variability across vowels could be accurately predicted from the spatial patterns of neural activity during speech production. These results demonstrate continuous, single-trial decoding of vowel acoustics.
Traffic of JC Virus from Sites of Initial Infection to the Brain: The Path to Progressive Multifocal Leukoencephalopathy (2002)

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the human brain caused by infection with the human polyomavirus, JC. Up to 80% of humans express serum antibodies to JC virus (JCV), yet considerably fewer people develop PML-predominantly those under immunosuppressive conditions. Recent research showed JCV infection in multiple tissues throughout the body, suggesting sites for viral latency. These observations allow the proposal of pathways that JCV may use from sites of initial infection to the brain. Results from investigations into cell-surface receptors, intracellular DNA-binding proteins, and variant viral regulatory regions also suggest mechanisms that may regulate cellular susceptibility to JCV infection. Together, these data elucidate how JCV may establish infection in various cell types, persist latently or become reactivated, and ultimately reach the brain to cause PML.
Nucleosides. 120. Syntheses of 2'-deoxy-.psi.-isocytidine and 2'-deoxy-1-methyl-.psi.-uridine from .psi.-uridine (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleosides. 120. Syntheses of 2'-deoxy-.psi.-isocytidine and 2'-deoxy-1-methyl-.psi.-uridine from .psi.-uridineAkira Matsuda, Chung K. Chu, U. Reichman, Krzysztof Pankiewicz, Kyoichi A. Watanabe, and Jack J. FoxCite this: J. Org. Chem. 1981, 46, 18, 3603–3609Publication Date (Print):August 1, 1981Publication History Published online1 May 2002Published inissue 1 August 1981https://pubs.acs.org/doi/10.1021/jo00331a005https://doi.org/10.1021/jo00331a005research-articleACS PublicationsRequest reuse permissionsArticle Views397Altmetric-Citations38LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Effective priming of neonates born to immune dams against the immunogenic pseudorabies virus glycoprotein gD by replication-incompetent adenovirus-mediated gene transfer at birth. (1997)

One of the main limitations of the vaccination of neonates from vaccinated or infected mothers is the interference by inherited maternal antibodies, which are known to inhibit the immune response against both live and inactivated vaccines. The efficiency of bypassing this inhibition by the transfer of an immunogenic glycoprotein gene, the gD gene of pseudorabies virus (PRV), into neonates was explored. The experiments were conducted in 1-day-old piglets, which are immunocompetent at birth. The same transcription unit (gD of PRV under the control of the adenovirus major late promoter) was delivered intramuscularly at birth either in the form of naked DNA or cloned in the genome of a replication-defective adenovirus. A booster injection of a conventional live PRV vaccine strain was given at 10 weeks of age, the replication of which was greatly restricted by the residual amounts of colostral antibodies in control animals. Piglets were challenged at the age of 16 weeks with a virulent PRV strain. The replication-defective adenovirus was able to efficiently prime piglets born to immune dams against gD in such a way that inoculation with the Bartha strain protected them against a subsequent challenge with the same level of efficacy in piglets born to naive or immune dams. In contrast, piglets born to immune dams into which the gD gene was not transferred, or transferred as naked DNA at birth, were not protected. These results open the way for early immunization of neonates born to vaccinated or infected mothers.
Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. (1965)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages (2008)

Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in differentiated macrophages. In macrophages, heparan sulphate glycosaminoglycans mediate the initial PRRSV attachment and the receptor sialoadhesin mediates both PRRSV attachment and internalization into endosomes. Upon a pH drop, PRRSV is uncoated and its genome is released from the endosomes into the cytoplasm, which allows virus replication. However, expression of heparan sulphate and sialoadhesin in non-susceptible cells only allows virus internalization, but no virus uncoating and infection, indicating that other factors are involved. In the present study, it is shown that treatment of macrophages with serum (mainly the alpha-globulin fraction) inhibited PRRSV infection without affecting attachment and internalization. Because alpha-globulins contain several protease inhibitors, macrophages were treated with different protease inhibitors to investigate the involvement of proteases in PRRSV uncoating. Treatment of macrophages with broadly active inhibitors of serine or aspartic proteases, but not cysteine- or metallo-proteases, inhibited PRRSV uncoating and infection. Further investigation using specific inhibitors indicated that the aspartic protease cathepsin E is involved during PRRSV uncoating, but did not allow identification of the serine protease involved. The involvement of cathepsin E during PRRSV uncoating was confirmed by partial co-localization of internalized PRRSV with cathepsin E. Furthermore, cathepsin E expression increased with macrophage cultivation, which was positively correlated with an increased susceptibility to PRRSV infection. Together, these data show that, in macrophages, both the aspartic protease cathepsin E and an unidentified trypsin-like serine protease are involved in uncoating of internalized PRRSV and subsequent infection.
Human tumour cathepsin B. Comparison with normal liver cathepsin B (1992)

Cathepsin B was purified from normal human liver and several human tumour tissues and partially characterized. Three forms of cathepsin B, with molecular masses of 25 kDa, 26 kDa (the two appearing as a doublet) and 30 kDa, were detected in SDS/polyacrylamide gels. The 25-26 kDa doublet was associated with the fractions from tumours and normal liver containing the highest cathepsin B activity. Cathepsin B from both sources showed similar pH optima. Both normal liver and tumour cathepsin B exhibited similar kinetics against selected synthetic substrates. At neutral pH and 24 degrees C, cathepsin B from both normal liver and tumour exhibited a lower Km and a higher kcat./Km than at pH 6.0. Their inhibitory profiles against synthetic inhibitors were also similar. Immunological studies with a monospecific antibody against the mature double-chain form of human liver cathepsin B and an antibody against a cathepsin B-derived synthetic peptide established the immunological similarity of liver and tumour enzymes. The N-terminal sequences of the 25 kDa and 26 kDa forms were identical with that of the heavy chain of the mature double-chain form of human cathepsin B, whereas the N-terminal sequence of the 30 kDa species was identical with that of the single-chain form of human cathepsin B. Treatment of the double-chain form of cathepsin B from normal liver and tumours with the endoglycosidase peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase converted the 26 kDa form into 25 kDa in SDS/polyacrylamide gels, suggesting that cathepsin B may exist as both glycosylated and unglycosylated forms. Our results, in contrast with those reported earlier for mouse cathepsin B, indicate that human liver and tumour cathepsin B are similar.
Genetic control of the innate immune response (2003)

Macrophages from each strain responded to LPS with unique gene expression profiles. The variation apparent between genetic backgrounds provides insights into the breadth of possible inflammatory responses, and paradoxically, this divergence was used to identify a common transcriptional program that responds to TLR4 signalling, irrespective of genetic background. Our data indicates that many additional genetic loci control the nature and the extent of transcriptional responses promoted by a single pathogen-associated molecular pattern (PAMP), such as LPS.