gebhart/patrepeval huggingface dataset:
Introduction of an azide group into some uridine derivatives via 2',3'-benzoxonium and 2'-3'-azidonium intermediates (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntroduction of an azide group into some uridine derivatives via 2',3'-benzoxonium and 2'-3'-azidonium intermediatesTadashi Sasaki, Katsumaro Minamoto, Toyoyuki Sugiura, and Masanao NiwaCite this: J. Org. Chem. 1976, 41, 19, 3138–3143Publication Date (Print):September 1, 1976Publication History Published online1 May 2002Published inissue 1 September 1976https://doi.org/10.1021/jo00881a015RIGHTS & PERMISSIONSArticle Views217Altmetric-Citations20LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (863 KB) Get e-Alerts Get e-Alerts
Variation in theCOMTGene: Implications for Pain Perception and Pain Treatment (2009)

Catechol-O-methyltransferase (COMT) is an enzyme that inactivates biologically-active catechols, including the important neurotransmitters dopamine, noradrenaline and adrenaline. These neurotransmitters are involved in numerous physiological processes, including modulation of pain. Genetic variation in the COMT gene has been implicated in variable response to various experimental painful stimuli, variable susceptibility to develop common pain conditions, as well as the variable need for opioids in the treatment of cancer pain. Increased insight into how genetic variants within the COMT locus affect pain perception will contribute to improved understanding of the mechanisms involved in the development of common human pain disorders and may lead to improved strategies for pain treatment. So far, a remarkable complex relationship between COMT genotypes or haplotypes and pain phenotypes has been revealed.
PHOSPHORUS METABOLISM AND MANAGEMENT IN CHRONIC KIDNEY DISEASE: Expanding Role for Vitamin D in Chronic Kidney Disease: Importance of Blood 25‐OH‐D Levels and Extra‐Renal 1α‐Hydroxylase in the Classical and Nonclassical Actions of 1α,25‐Dihydroxyvitamin D3 (2007)

Recent advances in the understanding of vitamin D have revolutionized our view of this old nutritional factor and suggested that it has much wider effects on the body than ever believed before. In addition to its well-known effects on calcium/phosphate homeostasis, vitamin D, through its hormonal form, 1alpha,25-dihydroxyvitamin D(3) or calcitriol, is a cell differentiating factor and anti-proliferative agent with actions on a variety of tissues around the body (e.g., skin, muscle, immune system). By influencing gene expression in multiple tissues, calcitriol influences many physiological processes besides calcium/phosphate homeostasis including muscle and keratinocyte differentiation, insulin secretion, blood pressure regulation, and the immune response. The incidence of various diseases including epithelial cancers, multiple sclerosis, muscle weakness as well as bone-related disorders has been correlated with vitamin D deficiency/insufficiency and has led to a re-evaluation of recommended daily intakes both in the normal subject and CKD patient. Critical developments have been the emergence of the value of blood 25-OH-D measurement as a tool in predicting vitamin D-related problems and this has in turn emphasized the importance of the extra-renal version of the 1alpha-hydroxylase, the enzyme responsible for the final step in vitamin D activation. The widespread expression of this extra-renal enzyme supports the view that it exists to boost intracellular concentrations of calcitriol within some target tissues in order to modulate a unique set of genes specifically in those tissues, a process which is therefore dependent upon circulating 25-OH-D. For CKD patients with their tendency to vitamin D substrate insufficiency coupled with their documented loss of the renal 1alpha-hydroxylase in late stages, this new information has profound implications. Physicians must start to manage the vitamin D insufficiency by vitamin D supplements throughout stages 1-5 whilst continuing to provide calcitriol replacement therapy, in the form of calcitriol or its analogs, in stages 3-5.
Event-Specific Plasmid Standards and Real-Time PCR Methods for Transgenic Bt11, Bt176, and GA21 Maize and Transgenic GT73 Canola (2005)

Since the 18th of April 2004, two new regulations, EC/1829/2003 on genetically modified food and feed products and EC/1830/2003 on traceability and labeling of GMOs, are in force in the EU. This new, comprehensive regulatory framework emphasizes the need of an adequate tracing system. Unique identifiers, such as the transgene genome junction region or a specific rearrangement within the transgene DNA, should form the basis of such a tracing system. In this study, we describe the development of event-specific tracing systems for transgenic maize lines Bt11, Bt176, and GA21 and for canola event GT73. Molecular characterization of the transgene loci enabled us to clone an event-specific sequence into a plasmid vector, to be used as a marker, and to develop line-specific primers. Primer specificity was tested through qualitative PCRs and dissociation curve analysis in SYBR Green I real-time PCRs. The primers were then combined with event-specific TaqMan probes in quantitative real-time PCRs. Calibration curves were set up both with genomic DNA samples and the newly synthesized plasmid DNA markers. It is shown that cloned plasmid GMO target sequences are perfectly suitable as unique identifiers and quantitative calibrators. Together with an event-specific primer pair and a highly specific TaqMan probe, the plasmid markers form crucial components of a unique and straighforward tracing system for Bt11, Bt176, and GA21 maize and GT73 canola events.
EFFECTS OF FREEZE–THAW EVENTS ON THE VIABILITY OF CRYPTOSPORIDIUM PARVUM OOCYSTS IN SOIL (2002)

The effects of freeze-thaw events on the inactivation of Cryptosporidium parvum oocysts in soil were examined. Oocysts were inoculated into distilled water in microcentrifuge tubes or into chambers containing soil the water content of which was maintained at 3%, 43%, or 78% of the container capacity. The chambers and tubes were then embedded in 3 soil samples from different aspects of a hillside landscape (Experiments 1 and 2) and in 3 distinct soil types (Experiment 3) and frozen at -10 C. Containers were thawed every 3 days for a period of 24 hr in 1-9 freeze-thaw cycles over 27 days (Experiments 1 and 2) and 2-5 freeze-thaw cycles over 15 days (Experiment 3). Oocyst viability was measured using the fluorescent dyes 4'6-diaminidino-2-phenylindole and propidium iodide. Inactivation rates were greater in soils than in water and greater in dry soil than in moist and wet soils. Soil type showed no effect on inactivation. Oocysts subjected to freeze-thaw cycles had inactivation rates not significantly different from those of oocysts subjected to -10 C under static conditions. The results indicated that 99% of oocysts exposed to soils that are frozen at -10 C will become inactivated within 50 days whether or not freeze-thaw cycles occur.
Structural Biology of the Tumor Suppressor p53 (2008)

The tumor suppressor protein p53 induces or represses the expression of a variety of target genes involved in cell cycle control, senescence, and apoptosis in response to oncogenic or other cellular stress signals. It exerts its function as guardian of the genome through an intricate interplay of independently folded and intrinsically disordered functional domains. In this review, we provide insights into the structural complexity of p53, the molecular mechanisms of its inactivation in cancer, and therapeutic strategies for the pharmacological rescue of p53 function in tumors. p53 emerges as a paradigm for a more general understanding of the structural organization of modular proteins and the effects of disease-causing mutations.
Long-term inhibition of murine experimental autoimmune encephalomyelitis using CTLA-4-Fc supports a key role for CD28 costimulation. (1995)

T cell activation involves not only recognition of antigen presented by the MHC, but also nonspecific interactions termed "costimulation." The costimulatory molecules B7-1 and B7-2 are ligands on antigen-presenting cells for the CD28 and CTLA-4 receptors on T cells. Previously, a fusion protein consisting of human CTLA-4 linked to human Fc was shown to bind B7-1 and B7-2 with high avidity and to prevent specific T cell activation. Here we investigated the effects of a recombinant fusion protein consisting of the extracellular domain of human CTLA-4 bound to mouse IgG2a Fc (CTLA-4-Fc) upon experimental autoimmune encephalomyelitis, a T cell-mediated disease that serves as a model for multiple sclerosis. CTLA-4-Fc prevented experimental autoimmune encephalomyelitis in 26 of 28 CTLA-4-Fc-treated mice (median maximum score 0), whereas 28 of 30 mice treated with control mouse IgG2a developed disease (median maximum score 2.75). Less inflammation and virtually no demyelination or axonal loss occurred in CTLA-4-Fc-treated compared with control-treated mice. Activated splenocytes from CTLA-4-Fc-treated mice were able to transfer disease adoptively to naive recipients. These results indicate a key role for the B7/CD28 system in the development of actively induced murine experimental autoimmune encephalomyelitis, suggesting an area of investigation with therapeutic potential for multiple sclerosis.
Overview of Sandia's fiber laser program (2008)

Sandia National Laboratories' program in high-power fiber lasers has emphasized development of enabling technologies
for power scaling and gaining a quantitative understanding of fundamental limits, particularly for high-peak-power,
pulsed fiber sources. This paper provides an overview of the program, which includes: (1) power scaling of diffraction-limited
fiber amplifiers by bend-loss-induced mode filtering to produce >1 MW peak power and >1 mJ pulse energy
with a practical system architecture; (2) demonstration of a widely tunable repetition rate (7.1-27 kHz) while
maintaining constant pulse duration and pulse energy, linear output polarization, diffraction-limited beam quality, and
<1% pulse-energy fluctuations; (3) development of microlaser seed sources optimized for efficient energy extraction; (4)
high-fidelity, three-dimensional, time-dependent modeling of fiber amplifiers, including nonlinear processes; (5)
quantitative assessment of the limiting effects of four-wave mixing and self-focusing on fiber-amplifier performance; (6)
nonlinear frequency conversion to efficiently generate mid-infrared through deep-ultraviolet radiation; (7) direct diode-bar
pumping of a fiber laser using embedded-mirror side pumping, which provides 2.0x higher efficiency and much
more compact packaging than traditional approaches employing formatted, fiber-coupled diode bars; and (8)
fundamental studies of materials properties, including optical damage, photodarkening, and gamma-radiation-induced
darkening.
Nephrotic Syndrome as a Complication of Immune Tolerance in Hemophilia B (1997)

To the Editor:

Inhibitors to factor IX (fIX) develop in approximately 1.5% to 3% of persons with severe hemophilia B and are commonly associated with the complete absence of fIX antigen due to large gene deletions or nonsense mutations.[1][1] The occurrence of high-titer inhibitors severely
The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation (2019)

Current published protocols for targeted differentiation of human stem cells toward pancreatic β-cells fail to deliver sufficiently mature cells with functional properties comparable to human islet β-cells. We aimed to assess whether Wnt-modulation could promote the final protocol stages of β-cell maturation, building our hypothesis on our previous findings of Wnt activation in immature hiPSC-derived stage 7 (S7) cells compared to adult human islets and with recent data reporting a link between Wnt/PCP and <i>in vitro</i> β-cell maturation. In this study, we stimulated canonical and non-canonical Wnt signaling in hiPSC-derived S7 cells using syntetic proteins including WNT3A, WNT4, WNT5A and WNT5B, and we inhibited endogenous Wnt signaling with the Tankyrase inhibitor G007-LK (TKi). Whereas neither canonical nor non-canonical Wnt stimulation alone was able to mature hiPSC-derived S7 cells, WNT-inhibition with TKi increased the fraction of monohormonal cells and global proteomics of TKi-treated S7 cells showed a proteomic signature more similar to adult human islets, suggesting that inhibition of endogenous Wnt contributes toward final β-cell maturation.
Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity (2013)

TRPA1, one of the transient receptor potential channels, has been reported to be involved in nociception and inflammatory pain, suggesting that this molecule could be a promising target for the development of analgesic agents. We screened several monoterpene analogs of camphor, which is known to inhibit human (h) TRPA1, to identify more effective naturally occurring TRPA1 antagonists. Borneol, 2-methylisoborneol, and fenchyl alcohol exhibited higher inhibitory effects on hTRPA1 activity than either camphor or 1,8-cineole. Our results revealed further that the S873, T874, and Y812 residues of hTRPA1 were involved in the inhibitory effects, suggesting that the hydroxyl group in the six-membered ring of the inhibitors may be interacting with these amino acids. Further research on these identified TRPA1 antagonists could lead to new pain therapeutics.
Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression (2008)

Tamm-Horsfall protein (THP) is a glycoprotein with unclear functions expressed exclusively in thick ascending limbs (TAL) of the kidney. Its role in ischemic acute kidney injury is uncertain, with previous data suggesting a possible negative effect by enhancing cast formation and promoting inflammation. Using a recently characterized THP knockout mouse (THP−/−), we investigated the role of THP in renal ischemia-reperfusion injury (IRI). In wild-type mice (THP+/+), THP expression was increased by injury. THP−/− mice developed more functional and histological renal damage after IRI compared with THP+/+. THP−/− kidneys showed more inflammation and tubular necrosis. Cast formation correlated with the severity of injury and was independent of THP presence. THP absence was associated with a more necrotic, rather than apoptotic, phenotype of cell death. The outer medulla was predominantly affected, where significant interstitial neutrophil infiltration was detected in proximity to injured S3 proximal tubular segments and TAL. This coincided with an enhanced expression of the innate immunity receptor Toll-like receptor 4 (TLR4) in S3 segments of THP−/− compared with THP+/+ mice. Specifically, a basolateral S3 expression of TLR4 was more evident in THP−/− kidneys compared with a more apical distribution in THP+/+. Such basolateral location for TLR4 allows a greater interaction with proinflammatory ligands present in the interstitium during ischemia. In conclusion, we are showing a completely novel role for a very old protein in the setting of renal injury. Our data suggest that THP stabilizes the outer medulla in the face of injury by decreasing inflammation, possibly through an effect on TLR4.
Single-Cell Western Blotting after Whole-Cell Imaging to Assess Cancer Chemotherapeutic Response (2014)

Intratumor heterogeneity remains a major obstacle to effective cancer therapy and personalized medicine. Current understanding points to differential therapeutic response among subpopulations of tumor cells as a key challenge to successful treatment. To advance our understanding of how this heterogeneity is reflected in cell-to-cell variations in chemosensitivity and expression of drug-resistance proteins, we optimize and apply a new targeted proteomics modality, single-cell western blotting (scWestern), to a human glioblastoma cell line. To acquire both phenotypic and proteomic data on the same, single glioblastoma cells, we integrate high-content imaging prior to the scWestern assays. The scWestern technique supports thousands of concurrent single-cell western blots, with each assay comprised of chemical lysis of single cells seated in microwells, protein electrophoresis from those microwells into a supporting polyacrylamide (PA) gel layer, and in-gel antibody probing. We systematically optimize chemical lysis and subsequent polyacrylamide gel electrophoresis (PAGE) of the single-cell lysate. The scWestern slides are stored for months then reprobed, thus allowing archiving and later analysis as relevant to sparingly limited, longitudinal cell specimens. Imaging and scWestern analysis of single glioblastoma cells dosed with the chemotherapeutic daunomycin showed both apoptotic (cleaved caspase 8- and annexin V-positive) and living cells. Intriguingly, living glioblastoma subpopulations show up-regulation of a multidrug resistant protein, P-glycoprotein (P-gp), suggesting an active drug efflux pump as a potential mechanism of drug resistance. Accordingly, linking of phenotype with targeted protein analysis with single-cell resolution may advance our understanding of drug response in inherently heterogeneous cell populations, such as those anticipated in tumors.
DBTGR: a database of tunicate promoters and their regulatory elements (2005)

The high similarity of tunicates and vertebrates during their development coupled with the transparency of tunicate larvae, their well-studied cell lineages and the availability of simple and efficient transgenesis methods makes of this subphylum an ideal system for the investigation of vertebrate physiological and developmental processes. Recently, the sequencing of two different Ciona genomes has lead to the identification of numerous genes. In order to better understand the regulation of these genes, a database was created containing information on regulation of tunicate genes collected from literature. It includes for instance information regarding the minimal promoter length, the transcription factors involved and their binding sites, as well as the localization of the gene expression. Additionally, binding sites for characterized transcription factors were predicted based on published in vitro recognition sites. Comparison of the promoters of homologous genes in different species is also provided to allow identification of conserved cis elements. At the time of writing, information about 184 promoters, containing 73 identified binding sites and >2000 newly predicted binding sites is available. This database is accessible at http://dbtgr.hgc.jp.
On the asymptotic capacity of MIMO systems with fixed length linear antenna arrays (2004)

There has been significant interest in the capacity of multiple element antenna (MEA) wireless systems. Previous authors have shown that the asymptotic capacity of a system with N transmit and N receive antennas (termed an (N,N) MEA) grows linearly with N if, for all l, the correlation of the fading for two antennas whose indices differ by l remains fixed as antennas are added to the array. However, in practice, the total size of the array is often fixed, and thus the correlation of the fading for two elements separated in index by some value l changes as the number of antenna elements is increased. In this paper, under the condition that the length of a linear array of antennas is fixed, the asymptotic properties of the instantaneous mutual information I/sub N,N/ of an (N,N) MEA wireless system are derived analytically and tested for accuracy for finite N through simulations. Two different cases are considered: (1) when the fixed array size constraint is imposed at the mobile unit, and (2) when the fixed array size constraint is imposed at both the base station and the mobile unit. For the first case, simulation results indicate that the analytical approximations are very accurate for moderate values of N, especially at high signal-to-noise-ratios (SNR). For the second case, the predicted non-convergence of I/sub N,N/ is observed in simulations, as well.
Transcription factors as drug targets: opportunities for therapeutic selectivity. (1995)

Many traditional drugs target cell surface receptors. Medicinal chemists and pharmacologists have not ventured into the field of transcription regulation due to the fear that drugs that interfere with transcription regulation may not be selective or efficacious. The past 5 years have seen some exciting developments in the field of signal transduction in general, and transcription regulation in particular. Our understanding of mechanisms of regulated and basal transcription is advanced to a degree that it should be possible to selectively modulate a target gene directly. In this review we have argued that sufficient diversity exists in the combinatorial interplay of the transcription factors to offer opportunities for selective therapeutic intervention. We have focused our attention on transcriptional factors that play a role in three different therapeutic areas: osteoporosis, immune modulation, and cardiovascular diseases. Human estrogen receptor is considered as a model transcription factor. The role of estrogen in bone remodeling is discussed. Opportunities for tissue-specific modulation of estrogen receptors are described. For selective immune modulation, we have discussed the role of NF-AT (nuclear factors for activated T cells) transcription factors in interleukin-2 gene regulation. The last section focuses on the transcriptional mechanisms conferring tissue specificity in regulated expression of the apoAI gene, a major component of HDL, in liver. We have highlighted opportunities for rational development of transcription-based drugs useful for raising HDL plasma levels and atherosclerosis prevention.
The coagulase of Staphylococcus aureus 8325‐4. Sequence analysis and virulence of site‐specific coagulase‐deficient mutants (1990)

The sequence of the coagulase gene (coa) from Staphylococcus aureus strain 8325-4 is reported. The deduced amino acid sequence of the coagulase protein is compared with previously reported sequences of coagulases from strains 213 and BB. The secreted mature forms of coagulase proteins are composed of three distinct segments: (i) the N-terminal 150-270 residues, which are c. 50% identical, (ii) a central region with high (greater than 90%) residue identities, and (iii) a C-terminal region composed of repeated 27-amino-acid residue sequences. The variable N-terminal sequences are probably responsible for antigenic differences among coagulases of different serotype. The region of coagulase which binds to prothrombin and activates it to form staphylothrombin is also located in the N-terminal half of the protein. A site-specific substitution mutation in the coa gene, which abolished plasma clotting activity, was isolated by recombinational allele-replacement in strains 8325-4 and M60. The Coa- mutants did not show diminished virulence in subcutaneous and intramammary infections of mice. No evidence for a role for coagulase in virulence of toxigenic or nontoxigenic strains was obtained. This contradicts findings of several groups using Coa- mutants generated by chemical mutagenesis and suggests that the earlier results were obtained with strains that had suffered additional mutations in virulence-related genes.