gebhart/patrepeval huggingface dataset:
Highly diastereoselective alkylations of chiral amide enolates: new routes to hydroxyethylene dipeptide isostere inhibitors of HIV-1 protease (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHighly diastereoselective alkylations of chiral amide enolates: new routes to hydroxyethylene dipeptide isostere inhibitors of HIV-1 proteaseD. Askin, M. A. Wallace, J. P. Vacca, R. A. Reamer, R. P. Volante, and I. ShinkaiCite this: J. Org. Chem. 1992, 57, 10, 2771–2773Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://pubs.acs.org/doi/10.1021/jo00036a004https://doi.org/10.1021/jo00036a004research-articleACS PublicationsRequest reuse permissionsArticle Views623Altmetric-Citations120LEARN 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
Therapeutic peptides and peptidomimetics (1997)

Peptidomimetics are one set of probes used in the transition pathway of small molecule drug design. Cyclization of the peptide backbone and its modification with aromatic residues constitutes an effective approach to mimetic drug design and circumvents obstacles associated with delivery and formulation of peptides and peptidomimetics. In the past year, examples of mimicking beta-turn structures has led to combining design strategies with molecular libraries, demonstrating that peptidomimetics can provide valuable clues about receptor similarities not revealed by their endogenous ligands. This information can lead to the development of dual inhibitors. In addition, this work suggests that the use of libraries and rational design need not be mutually exclusive approaches to lead discovery.
Design, simulation and evaluation of kinematic alternatives for Insertable Robotic Effectors Platforms in Single Port Access Surgery (2010)

This paper presents the task specifications for designing a novel Insertable Robotic Effectors Platform (IREP) with integrated stereo vision and surgical intervention tools for Single Port Access Surgery (SPAS). This design provides a compact deployable mechanical architecture that may be inserted through a single Ø15 mm access port. Dexterous surgical intervention and stereo vision are achieved via the use of two snake-like continuum robots and two controllable CCD cameras. Simulations and dexterity evaluation of our proposed design are compared to several design alternatives with different kinematic arrangements. Results of these simulations show that dexterity is improved by using an independent revolute joint at the tip of a continuum robot instead of achieving distal rotation by transmission of rotation about the backbone of the continuum robot. Further, it is shown that designs with two robotic continuum robots as surgical arms have diminished dexterity if the bases of these arms are close to each other. This result justifies our design and points to ways of improving the performance of existing designs that use continuum robots as surgical arms.
Alignment of Carbon Nanotubes by Acoustic Manipulation in a Fluidic Medium (2007)

We describe a novel solution-based acoustic manipulation technique for the parallel alignment of carbon nanotubes on solid substrates. The acoustic radiation force and acoustic streaming, which are generated from the transmission of ultrasound through a fluid, facilitate the mobility of the nanotubes and result in their alignment on the substrate surface. A theoretical model considering various forces and resultant torques exerted on the nanotubes is first proposed for analyzing the alignment through a fluid medium.
Constant Potential Pretreatment of Carbon Fiber Electrodes forin VivoElectrochemistry (1991)

Abstract A constant potential procedure to pretreat carbon fiber electrodes is described. This essentially consists of two steps: +3.0 V for 30 s and -2.0 V for 10 s. The anodic potential treatment enhances sensitivity for catechols, and cathodic potential treatment improves selectivity, which results in a potential shift of AA from catechols. The optimum parameters and experimental conditions for electrochemical treatment were explored. Treated carbon fiber electrode used in rat brain showed well-defined and separated peaks of AA and catechols.
Cloning regions of the Drosophila genome by microdissection of polytene chromosome DNA and PCR with nonspecific primer (1990)

A simple and rapid procedure to isolate clones carrying sequences from a specific region of the polytene chromosome of Drosophila is demonstrated. The procedure involves microdissection of the region of interest, amplification of the DNA by PCR using a primer designed to prime the synthesis nonspecifically, labeling of the amplified DNA using the random primer method, and screening of a standard library with the probe to identify and isolate clones carrying sequences homologous to the dissected region. This procedure has the potential to replace the difficult procedure of microcloning, as well as facilitate chromosome walking.
Handling individual mammalian embryos using microfluidics (2001)

We have designed, built, and tested microfluidic systems capable of transporting individual, preimplantation mouse embryos (100-microm to 150-microm diameter) through a network of channels. Typical channels are 160 to 200 microm deep, 250 to 400 microm wide at the top, and narrower at the bottom (0 to 250 microm wide) due to the fabrication process. In these channels, a pressure gradient of 1 Pa/mm causes the medium to flow on the order of 10(-10) m3/s (100 nl/s), with an average speed of 1 to 2 mm/s. Under these flow conditions the embryos roll along the bottoms of the channels, traveling at 1/2 the speed of the fluid. By manipulating the pressure at the wells connected to the ends of the channels, the embryos can be transported to (and retained at) specific locations including culture compartments and retrieval wells.
Functionality of Endothelial Cells and Pericytes From Human Pluripotent Stem Cells Demonstrated in Cultured Vascular Plexus and Zebrafish Xenografts (2013)

We demonstrate that vascular derivatives of hiPSC, such as ECs and pericytes, are fully functional and can be used to study defective endothelia-pericyte interactions in vitro for disease modeling and studies on tumor angiogenesis.
Filamentous Bacterial Viruses VIII. Liquid Crystals of fd (1973)

Abstract Concentrated suspensions of filamentous bacterial viruses form cholesteric liquid crystals. Under appropriate conditions, spherulites are observed. The twisted nematic phase shows form optical rotation. In dry gels, where the pitch of the twisted layer is comparable to the wavelength of light, Bragg reflection from the sheets is observed.
Biosynthesis and metabolism in vivo of intervertebral-disc proteoglycans in the mouse (1983)

The synthesis and turnover in vivo of 35S-labelled proteoglycans in mouse cervical, thoracic and lumbar intervertebral discs, and in costal cartilage, was investigated after intraperitoneal injection of [35S]sulphate. Intervertebral discs and costal cartilage synthesize similar amounts of 35S-labelled proteoglycans per microgram of DNA. Discs and cartilage all synthesize a major proteoglycan species (approx. 85%) of large hydrodynamic size and a minor species (approx. 15%) of small size. Both proteoglycans carry chondroitin sulphate chains. Keratan sulphate was not found associated with either species. The total 35S-labelled proteoglycan pool had a metabolic half-life (t1/2) of 10-12 days in discs, and 17 days in cartilage. The extractable major and minor species turned over at similar rates. Those proteoglycans left in the tissue after 29 days turn over very slowly. Approx. 50% of the major 35S-labelled proteoglycan species formed mixed aggregates with hyaluronic acid and rat chondrosarcoma proteoglycan. The ability to form aggregates did not decrease up to 45 days after synthesis. Of the heterogeneous population of proteoglycans comprising the major species, those remaining in the tissue 9 days after synthesis were of smaller average hydrodynamic size and had shorter chondroitin sulphate side chains than the average size at the time of synthesis. With increasing time after synthesis, proteoglycans were less readily extracted from the tissue by 4.0 M-guanidinium chloride than at the time of synthesis.
Elevated Levels of Circulating Cell Adhesion Molecules in Uncomplicated Essential Hypertension (1997)

Elevated levels of circulating soluble cell adhesion molecules are associated with the development of cardiovascular disease. We tested the hypothesis that circulating levels of soluble cell adhesion molecules are elevated in older men with uncomplicated essential hypertension, which may contribute to the increased risk of atherosclerosis in this population. Circulating levels of soluble intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin were measured in 11 hypertensive (69+/-1 years) and ten normotensive (65+/-1 years) older men who were free of overt atherosclerotic disease, diabetes, and dyslipidemia. The hypertensive subjects had higher (P < .05) circulating levels of soluble intercellular adhesion molecule-1 (232.4+/-16.5 v 189.8+/-11.1 ng/mL) and vascular adhesion molecule-1 (737.3+/-65.6 v 565.7+/-46.8 ng/mL) compared with their normotensive peers. However, there was no difference in the levels of soluble E-selectin between the hypertensive (51.1+/-3.9 ng/ mL) and normotensive (48.8+/-6.6 ng/mL) subjects. Univariate analysis revealed a positive correlation between soluble intercellular adhesion molecule-1 and both systolic (r = 0.50, P = .02) and diastolic (r = 0.49, P = .03) blood pressure. In addition, soluble vascular adhesion molecule-1 was positively correlated with age (r = 0.60, P = .004) and systolic blood pressure (r = 0.43, P = .05). The results of this study support the hypothesis that circulating levels of soluble cell adhesion molecules are elevated in older men with uncomplicated essential hypertension.
Functional evaluation of flail hip joint after periacetabular resection of the pelvis. (1997)

Five patients subjected to flail hip joint after resection of primary bone tumor of the pelvis involving acetabular region were examined with respect to function. When a thick portion of the supraacetabular pelvic neck was left in place, the operated legs functioned well regardless of whether the head of the femur was placed anterior or posterior to the iliac wing. In a patient who had only a thin portion of the iliac wing left in place and in those who underwent total excision of the ilium or hemiresection of the pelvis, the function of operated legs was poorer than with a thick portion of the supraacetabular pelvic neck left in place, but still more than 50% of leg function remained. Although flail hip joint results in a larger leg-length discrepancy than do other techniques, it enables favorable healing of the operative wound. Therefore, this method should be considered for women or sedentary patients with primary bone tumor of the pelvis involving acetabular region.
The Quantitatively Important Relationship between Homocysteine Metabolism and Glutathione Synthesis by the Transsulfuration Pathway and Its Regulation by Redox Changes (2000)

Homocysteine is a key junction metabolite in methionine metabolism. It suffers two major metabolic fates: transmethylation catalyzed by methionine synthase or betaine homocysteine methyl transferase and transsulfuration catalyzed by cystathionine beta-synthase leading to cystathionine. The latter is subsequently converted to cysteine, a precursor of glutathione. Studies with purified mammalian methionine synthase and cystathionine beta-synthase have revealed the oxidative sensitivity of both junction enzymes, suggesting the hypothesis that redox regulation of this pathway may be physiologically significant. This hypothesis has been tested in a human hepatoma cell line in culture in which the flux of homocysteine through transsulfuration under normoxic and oxidative conditions has been examined. Addition of 100 microM H(2)O(2) or tertiary butyl hydroperoxide increased cystathionine production 1.6- and 2.1-fold from 82 +/- 7 micromol h(-)(1) (L of cells)(-)(1) to 136 +/- 15 and 172 +/- 23 micromol h(-)(1) (L of cells)(-)(1), respectively. The increase in homocysteine flux through the transsulfuration pathway exhibited a linear dose dependence on the concentrations of both oxidants (50-200 microM H(2)O(2) and 10-200 microM tertiary butyl hydroperoxide). Furthermore, our results reveal that approximately half of the intracellular glutathione pool in human liver cells is derived from homocysteine via the transsulfuration pathway. The redox sensitivity of the transsulfuration pathway can be rationalized as an autocorrective response that leads to an increased level of glutathione synthesis in cells challenged by oxidative stress. In summary, this study demonstrates the importance of the homocysteine-dependent transsulfuration pathway in the maintenance of the intracellular glutathione pool, and the regulation of this pathway under oxidative stress conditions. Aberrations in this pathway could compromise the redox buffering capacity of cells, which may in turn be related to the pathophysiology of the different homocysteine-related diseases.
Boceprevir, Calpain Inhibitors II and XII, and GC-376 Have Broad-Spectrum Antiviral Activity against Coronaviruses (2021)

As the COVID-19 pandemic continues to unfold, the morbidity and mortality are increasing daily. Effective treatment for SARS-CoV-2 is urgently needed. We recently discovered four SARS-CoV-2 main protease (M<sup>pro</sup>) inhibitors including boceprevir, calpain inhibitors II and XII, and GC-376 with potent antiviral activity against infectious SARS-CoV-2 in cell culture. In this study, we further characterized the mechanism of action of these four compounds using the SARS-CoV-2 pseudovirus neutralization assay. It was found that GC-376 and calpain inhibitors II and XII have a dual mechanism of action by inhibiting both viral M<sup>pro</sup> and host cathepsin L in Vero cells. To rule out the cell-type dependent effect, the antiviral activity of these four compounds against SARS-CoV-2 was also confirmed in type 2 transmembrane serine protease-expressing Caco-2 cells using the viral yield reduction assay. In addition, we found that these four compounds have broad-spectrum antiviral activity in inhibiting not only SARS-CoV-2 but also SARS-CoV, and MERS-CoV, as well as human coronaviruses (CoVs) 229E, OC43, and NL63. The mechanism of action is through targeting the viral M<sup>pro</sup>, which was supported by the thermal shift-binding assay and enzymatic fluorescence resonance energy transfer assay. We further showed that these four compounds have additive antiviral effect when combined with remdesivir. Altogether, these results suggest that boceprevir, calpain inhibitors II and XII, and GC-376 might be promising starting points for further development against existing human coronaviruses as well as future emerging CoVs.
Component Based Development With Visual C (2002)

An interaction of different human alleles and endemic bacterial strains may be clinically manifested as different outcome of the disease in different hosts infected with the same genotype. The primary objective of this study was to investigate this issue in the model of Mycobacterium tuberculosis and human DC-SIGN encoding CD209 promoter SNP (rs4804803) in Russian Siberian population. We sought to find a possible combination of M. tuberculosis lineage and human host allele/genotype correlating with unfavorable outcome of the disease. The 101 paired DNA samples from patients with pulmonary TB (human and M. tuberculosis DNA) were studied by 12-loci MIRU-VNTR typing (M. tuberculosis strains) and CD209 -336 A/G typing (human DNA). Ninety autopsy DNA samples as a source of human and mycobacterial nucleic acids from persons who died from TB were also subjected to the same genotyping procedures. A human control group consisted of 177 healthy individuals. The Beijing genotype was more frequently identified in autopsy versus patient samples, in 70.0% and 51.5%, respectively (χ(2)=6.06, P=0.01). Regarding other M. tuberculosis genetic families, no significant difference in LAM family distribution among patient strains and autopsy samples has been found. In contrast, Ural genotype was significantly less frequently detected in the autopsy samples (χ(2)=6.12, P=0.01). Allelic and genotypic frequencies of the CD209 -336A/G did not differ significantly under global comparison when contrasting controls versus patients versus autopsy samples. However intriguing and contrasting significant associations were found in the male subgroup under M. tuberculosis genotype-stratified comparisons. Firstly, male carriers of -336AA genotype were more frequently infected with Beijing genotype (χ(2)=5.2, P=0.02). Secondly and remarkably, this association was inverted in the autopsy sample: male carriers of -336AA genotype died less frequently due to TB caused by a Beijing rather than a non-Beijing strain (χ(2)=5.37, P=0.02). In conclusion, we hypothesize that although carriers of CD209 -336A allele are more sensitive to infection with a Beijing strain, a combination of human CD209 -336G allele and M. tuberculosis Beijing genotype leads more frequently to the lethal outcome in pulmonary TB male patients in Russian (Caucasian) population.
Similarity of Chlamydia pneumoniae strains in the variable domain IV region of the major outer membrane protein gene (1992)

DNA was amplified by polymerase chain reaction from the gene encoding the major outer membrane protein (MOMP) of Chlamydia pneumoniae in order to examine the relatedness of strains isolated from diverse geographical regions. Primers for this reaction were chosen to span a 207-bp region comparable to that of the fourth variable segment of the MOMP gene of Chlamydia trachomatis. Among C. trachomatis, sequence heterogeneity is characteristic within variable sequence domain IV (VDIV) and correlates with serovar type. In contrast, sequence analysis of polymerase chain reaction products from 13 C. pneumoniae isolates indicated that all tested strains were identical in this segment of the MOMP gene. The predicted amino acid sequences from the C. pneumoniae VDIV gene products shared only 13.3 to 30% homology with published VDIV regions from serovars of C. trachomatis. Homology of these VDIV amino acid sequences with sequences from strains of C. psittaci ranged from 45.7 to 60%. The sequence conservation of the VDIV region of the MOMP gene indicates that C. pneumoniae strains may be more genetically homogeneous than C. trachomatis or Chlamydia psittaci strains. Future investigations of antigenic diversity among C. pneumoniae strains should be aimed at the evaluation of variation in other regions of the C. pneumoniae genome.
Myocardin is differentially required for the development of smooth muscle cells and cardiomyocytes (2011)

Myocardin is a serum response factor (SRF) coactivator exclusively expressed in cardiomyocytes and smooth muscle cells (SMCs). However, there is highly controversial evidence as to whether myocardin is essential for normal differentiation of these cell types, and there are no data showing whether cardiac or SMC subtypes exhibit differential myocardin requirements during development. Results of the present studies showed the virtual absence of myocardin(-/-) visceral SMCs or ventricular myocytes in chimeric myocardin knockout (KO) mice generated by injection of myocardin(-/-) embryonic stem cells (ESCs) into wild-type (WT; i.e., myocardin(+/+) ESC) blastocysts. In contrast, myocardin(-/-) ESCs readily formed vascular SMC, albeit at a reduced frequency compared with WT ESCs. In addition, myocardin(-/-) ESCs competed equally with WT ESCs in forming atrial myocytes. The ultrastructural features of myocardin(-/-) vascular SMCs and cardiomyocytes were unchanged from their WT counterparts as determined using a unique X-ray microprobe transmission electron microscopic method developed by our laboratory. Myocardin(-/-) ESC-derived SMCs also showed normal contractile properties in an in vitro embryoid body SMC differentiation model, other than impaired thromboxane A2 responsiveness. Together, these results provide novel evidence that myocardin is essential for development of visceral SMCs and ventricular myocytes but is dispensable for development of atrial myocytes and vascular SMCs in the setting of chimeric KO mice. In addition, results suggest that as yet undefined defects in development and/or maturation of ventricular cardiomyocytes may have contributed to early embryonic lethality observed in conventional myocardin KO mice and that observed deficiencies in development of vascular SMC may have been secondary to these defects.
Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a β-linked self-glycolipid (2010)

TCR-mediated recognition of beta-linked self-glycolipids bound to CD1d is poorly understood. Here, we have characterized the TCR repertoire of a CD1d-restricted type II NKT cell subset reactive to sulfatide involved in the regulation of autoimmunity and antitumor immunity. The sulfatide/CD1d-tetramer(+) cells isolated from naïve mice show an oligoclonal TCR repertoire with predominant usage of the Valpha3/Valpha1-Jalpha7/Jalpha9 and Vbeta8.1/Vbeta3.1-Jbeta2.7 gene segments. The CDR3 regions of both the alpha- and beta-chains are encoded by either germline or nongermline gene segments of limited lengths containing several conserved residues. Presence of dominant clonotypes with limited TCR gene usage for both TCR alpha- and beta-chains in type II NKT cells reflects specific antigen recognition not found in the type I NKT cells but similar to the MHC-restricted T cells. Although potential CD1d-binding tyrosine residues in the CDR2beta region are conserved between most type I and type II NKT TCRs, CDR 1alpha and 3alpha regions differ significantly between the two subsets. Collectively, the TCR repertoire of sulfatide-reactive type II NKT cells exhibits features of both antigen-specific conventional T cells and innate-like cells, and these findings provide important clues to the recognition of beta-linked glycolipids by CD1d-restricted T cells in general.