gebhart/patrepeval huggingface dataset:
Sulfur-substituted dienes and the silylene protecting group in synthesis. Deoxypillaromycinone (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSulfur-substituted dienes and the silylene protecting group in synthesis. DeoxypillaromycinoneBarry M. Trost, Charles G. Caldwell, Eigoro Murayama, and Denis HeisslerCite this: J. Org. Chem. 1983, 48, 19, 3252–3265Publication Date (Print):September 1, 1983Publication History Published online1 May 2002Published inissue 1 September 1983https://pubs.acs.org/doi/10.1021/jo00167a020https://doi.org/10.1021/jo00167a020research-articleACS PublicationsRequest reuse permissionsArticle Views1422Altmetric-Citations68LEARN 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
Cell cycle correlated genes dictate the prognostic power of breast cancer gene lists (2008)

These data indicate that the discriminative ability of breast cancer classifiers is dependent upon genes that correlate with cell cycle progression.
Metal‐ and Chemical‐Oxidant‐Free CH/CH Cross‐Coupling of Aromatic Compounds: The Use of Radical‐Cation Pools (2012)

Pool and couple: A method for oxidative C-H/C-H cross-coupling has been developed using "radical-cation pools". Aromatic compounds react with aryl radical cations, which are generated and accumulated by low-temperature electrolysis (see scheme). This method avoids both the nonselective oxidation of substrates and oxidation of products and effects the C-H/C-H cross-coupling of aromatic compounds without metal complexes and chemical oxidants.
Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage (2013)

We report on crystal structures of ternary Thermus thermophilus Argonaute (TtAgo) complexes with 5'-phosphorylated guide DNA and a series of DNA targets. These ternary complex structures of cleavage-incompatible, cleavage-compatible, and postcleavage states solved at improved resolution up to 2.2 Å have provided molecular insights into the orchestrated positioning of catalytic residues, a pair of Mg(2+) cations, and the putative water nucleophile positioned for in-line attack on the cleavable phosphate for TtAgo-mediated target cleavage by a RNase H-type mechanism. In addition, these ternary complex structures have provided insights into protein and DNA conformational changes that facilitate transition between cleavage-incompatible and cleavage-compatible states, including the role of a Glu finger in generating a cleavage-competent catalytic Asp-Glu-Asp-Asp tetrad. Following cleavage, the seed segment forms a stable duplex with the complementary segment of the target strand.
The Membrane Phospholipid Concept of Schizophrenia (1999)

The membrane phospholipid hypothesis suggests that the primary abnormality in schizophrenia is in phospholipid biochemistry. This particularly applies to mechanisms regulating highly unsaturated fatty acid metabolism at the Sn2 position of phospholipid molecules. As a consequence there are abnormalities of neuronal membrane structure and cell signalling. These lead secondarily to disturbances in neurotransmitter and ion channel-related mechanisms. Two separate abnormalities of phospholipid metabolism are proposed. They are present throughout the body and can be detected in red blood cells and also in the skin during stimulation of arachidonic acid metabolism by niacin. One of them may also be identified by abnormal P50 gating. Novel therapies based on this concept have yielded good results in clinical trials with none of the usual side effects of either typical or atypical neuroleptics. The phospholipid concept offers a new approach to the problems of understanding and treating schizophrenia.
ERα-Dependent E2F Transcription Can Mediate Resistance to Estrogen Deprivation in Human Breast Cancer (2011)

Most estrogen receptor α (ER)-positive breast cancers initially respond to antiestrogens, but many eventually become estrogen-independent and recur. We identified an estrogen-independent role for ER and the CDK4/Rb/E2F transcriptional axis in the hormone-independent growth of breast cancer cells. ER downregulation with fulvestrant or small interfering RNA (siRNA) inhibited estrogen-independent growth. Chromatin immunoprecipitation identified ER genomic binding activity in estrogen-deprived cells and primary breast tumors treated with aromatase inhibitors. Gene expression profiling revealed an estrogen-independent, ER/E2F-directed transcriptional program. An E2F activation gene signature correlated with a lesser response to aromatase inhibitors in patients' tumors. siRNA screening showed that CDK4, an activator of E2F, is required for estrogen-independent cell growth. Long-term estrogen-deprived cells hyperactivate phosphatidylinositol 3-kinase (PI3K) independently of ER/E2F. Fulvestrant combined with the pan-PI3K inhibitor BKM120 induced regression of ER(+) xenografts. These data support further development of ER downregulators and CDK4 inhibitors, and their combination with PI3K inhibitors for treatment of antiestrogen-resistant breast cancers.
Tumor growth in vivo selects for resistance to tumor necrosis factor. (1989)

The relationship between in vivo tumor growth and resistance to TNF in WEHI-164 cells has been examined. When a highly TNF-sensitive clone of WEHI-164 was grown in vivo in syngeneic mice it became resistant to rTNF such that a 4 to 5 log higher concentration of TNF was required to produce tumor lysis in vitro. When compared with an in vitro selected TNF-resistant variant, the in vivo selected line was significantly more tumorigenic. The resistant phenotype of both the in vivo and in vitro selected variants was stable in culture and both selected lines were also resistant to lysis by syngeneic spleen cells with natural cytotoxic activity. The parental clone and the two variants were equally sensitive to lysis by allo-CTL and expressed similar levels of MHC class I Ag. Resistance to TNF in the two variants was not a function of de novo production of TNF measured as supernatant TNF activity or TNF mRNA expression. These studies are the first to demonstrate that in vivo tumor growth results in resistance to TNF and therefore may have direct relevance to the efficacy of TNF in the treatment of human neoplasms.
Disappearing and Reappearing Polymorphs. The Benzocaine:Picric Acid System (2001)

The low-melting polymorphic modification of the 1:1 complex of benzocaine (BC) and picric acid (PA) had earlier been reported to be an example of a "disappearing polymorph". The BC:PA system has been reinvestigated by thermomicroscopy, calorimetry, solid-state NMR, and X-ray crystallography. The phase diagram has been derived, and robust procedures for the crystallization of the two 1:1 complexes, a hydrate of the 1:1 complex, and a 2:1 complex have been devised. The structures of all four phases have been determined and compared using graph set analysis to characterize the hydrogen-bonding patterns. It is shown that the thorough microscopic investigation of the thermal behavior, combined with calorimetric methods, can lead to the development of strategies to crystallize metastable polymorphic forms which may be difficult to obtain once their stable congeners have been obtained.
Reduction of the periplasmic disulfide bond isomerase, DsbC, occurs by passage of electrons from cytoplasmic thioredoxin (1997)

The Escherichia coli periplasmic protein DsbC is active both in vivo and in vitro as a protein disulfide isomerase. For DsbC to attack incorrectly formed disulfide bonds in substrate proteins, its two active-site cysteines should be in the reduced form. Here we present evidence that, in wild-type cells, these two cysteines are reduced. Further, we show that a pathway involving the cytoplasmic proteins thioredoxin reductase and thioredoxin and the cytoplasmic membrane protein DsbD is responsible for the reduction of these cysteines. Thus, reducing potential is passed from cytoplasmic electron donors through the cytoplasmic membrane to DsbC. This pathway does not appear to utilize the cytoplasmic glutathione-glutaredoxin pathway. The redox state of the active-site cysteines of DsbC correlates quite closely with its ability to assist in the folding of proteins with multiple disulfide bonds. Analysis of the activity of mutant forms of DsbC in which either or both of these cysteines have been altered further supports the role of DsbC as a disulfide bond isomerase.
Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. (1996)

A methodology has been developed for the study of molecular recognition at the level of single events and for the localization of sites on biosurfaces, in combining force microscopy with molecular recognition by specific ligands. For this goal, a sensor was designed by covalently linking an antibody (anti-human serum albumin, polyclonal) via a flexible spacer to the tip of a force microscope. This sensor permitted detection of single antibody-antigen recognition events by force signals of unique shape with an unbinding force of 244 +/- 22 pN. Analysis revealed that observed unbinding forces originate from the dissociation of individual Fab fragments from a human serum albumin molecule. The two Fab fragments of the antibody were found to bind independently and with equal probability. The flexible linkage provided the antibody with a 6-nm dynamical reach for binding, rendering binding probability high, 0.5 for encounter times of 60 ms. This permitted fast and reliable detection of antigenic sites during lateral scans with a positional accuracy of 1.5 nm. It is indicated that this methodology has promise for characterizing rate constants and kinetics of molecular recognition complexes and for molecular mapping of biosurfaces such as membranes.
Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication (2000)

Prostacyclin is an endothelially derived vasodilator and inhibitor of platelet aggregation. Despite its therapeutic potential for peripheral arterial disease, the short half-life and chemical instability are barriers to routine therapy. Accordingly, prostacyclin analogs are being evaluated in patients with peripheral arterial disease. State-of-the-art non-invasive ultrasonography allows for serial testing of the hemodynamic effects of vasoactive drugs. The safety, efficacy and hemodynamic effects of UT-15, a novel, long-acting prostacyclin analog, were studied in patients with severe intermittent claudication. A total of eight patients with stable severe intermittent claudication, Fontaine classes IIb-III, were admitted to the hospital for intravenous infusion of UT-15. A symptom-limited, dose-escalation protocol was instituted, beginning with placebo and then with increasing dosage at 60-min intervals, followed by a 2-h period of maintenance dose at the maximum well-tolerated infusion rate. The hemodynamic response in the lower limbs was assessed with serial ultrasonography, segmental arterial pressures and pulse volumes. Blood flow in the common femoral artery increased 29% (p = 0.003) by the end of the maintenance period and remained above baseline throughout the washout period (p = 0.044). Blood velocity in the lower limb increased in most of the peripheral arteries. These increases achieved statistical significance in the common femoral artery (p = 0.025) and anterior tibial artery (p = 0.019), and approached significance in the popliteal artery (p = 0.062). In two of four patients in whom blood flow was undetectable before the infusion, arterial blood flow at the ankle level became apparent on ultrasonography during maintenance infusion. UT-15 infusion improved the pulse volume recording (p = 0.016) but the ankle/brachial index did not change significantly. Common side effects at peak dose included headache and nausea. There were no serious adverse events attributable to UT-15 treatment. In most patients, the optimal infusion rate was 10-20 ng/kg per min. In conclusion, ultrasonography is a novel approach for assessing the hemodynamic response to vasoactive agents. UT-15 is well tolerated when given for up to 2 h and increases arterial blood flow and velocity in patients with severe intermittent claudication.
Activation of Gene Expression by a Ligand-induced Conformational Change of a Protein-DNA Complex (1998)

IlvY protein binds cooperatively to tandem operator sites in the divergent, overlapping, promoter-regulatory region of the ilvYC operon of Escherichia coli. IlvY positively regulates the expression of the ilvC gene in an inducer-dependent manner and negatively regulates the transcription of its own divergently transcribed structural gene in an inducer-independent manner. Although binding of IlvY protein to the tandem operators is sufficient to repress ilvY promoter-specific transcription, it is not sufficient to activate transcription from the ilvC promoter. Activation of ilvC promoter-specific transcription requires the additional binding of a small molecule inducer to the IlvY protein-DNA complex. The binding of inducer to IlvY protein does not affect the affinity of IlvY protein for the tandem operator sites. It does, however, cause a conformational change of the IlvY protein-DNA complex, which is correlated with the partial relief of an IlvY protein-induced bend of the DNA helix in the ilvC promoter region. This structural change in the IlvY protein-DNA complex results in a 100-fold increase in the affinity of RNA polymerase binding at the ilvC promoter site. The ability of a protein to regulate gene expression by ligand-responsive modulation of a protein-DNA structure is an emerging theme in gene regulation.
End-tidal Carbon Dioxide in Critically ill Patients during Changes in Mechanical Ventilation (1989)

Values of end-tidal CO2 (PETCO2) approximate PaCO2 in spontaneous breathing normal subjects and in stable patients receiving mechanical ventilatory support (MVS). Because marked inequality of ventilation/perfusion ratios in critically ill patients might affect this correlation, we assessed changes of PETCO2 in predicting changes in PaCO2 (delta PaCO2) and changes in minute ventilation (delta Ve) in this patient population. Twenty consecutive intubated patients 38 to 89 yr of age (mean, 70 yr) with respiratory failure while receiving MVS with indwelling arterial lines were studied. Settings on the mechanical ventilator were varied for frequency and tidal volume, and after a minimum of 5 to 10 min equilibration, PaCO2 and PETCO2 were measured. Vt and Ve were recorded from the digital indicator of the pneumotachygraph within the mechanical ventilator and corrected for compression volume in the respirator circuit. A total of 116 simultaneous measurements were performed. PETCO2 correlated well with PaCO2 (r = 0.78, p less than 0.001). The 95% confidence interval for the mean difference in PaCO2-PETCO2 was 4.0 +/- 0.97 mm Hg. However, delta PETCO2 (measured from baseline) did not correlate as well with delta PaCO2 (r = 0.58, p = less than 0.001). In four patients, the trend in their PETCO2 during changes in mechanical ventilation were in the opposite direction from the trend in their PaCO2. Thus, many critically ill patients, who cannto be preidentified, have an inconstant PaCO2-PETCO2 gradient with changes of ventilation. Utilization of PETCO2 as a noninvasive monitoring substitute for trends in PaCO2 in critically ill patients may be misleading despite establishing an initial PaCO2-PETCO2 relationship.
High Immunogenicity of the Human Leukocyte Antigen Peptidomes of Melanoma Tumor Cells (2012)

Human leukocyte antigens (HLA) bind peptides generated by limited proteolysis in cells and present them at the cell surfaces for recognition by T cells. Through this antigen presentation function they control the specificity of T cell responses and thereby adaptive immune responses. Knowledge of HLA-bound peptides is thus key to understanding adaptive immunity and to the development of vaccines and other specific immune intervention strategies. To gain insight into the antigenicity of melanomas, peptides were extracted from HLA isolated from the tumor cells, separated by two-dimensional HPLC, and sequenced by mass spectrometry. The spectra were analyzed by database-dependent MASCOT searches and database-independent de novo sequencing and, where required, confirmed with synthetic peptides, which were also used to determine their immunogenicity. Comparing four different melanoma cell lines, little overlap of the HLA-bound peptides was found, suggesting a high degree of individualization of the HLA peptidomes. This notwithstanding, the peptidomes were highly immunogenic in the patients from whom the tumor cells had been established and in unrelated patients. This broad cross-patient immunogenicity was only exceptionally related to individual peptides. The majority of the identified epitopes were derived from low to medium abundance proteins, mostly involved in sensitive cellular processes such as cell cycle control, DNA replication, control of gene expression, tumor suppressor function, and protein metabolism. The peptidomes thus provide insights into processes potentially related to tumorigenesis. Furthermore, analyses of the peptide sequences yield information on the specificity of peptide selection by HLA applicable to the developing prediction algorithms for T cell epitopes.
Postoperative course after total hip arthroplasty: wound drainage versus no drainage. (1992)

This retrospective study of 364 patients with total hip replacements performed between 1985 and 1990 showed no benefit in the use of drains and found an increased rate of transfusion associated with the use of drains. The two study groups (171 patients with two closed-wound suction drains in the wound and 193 patients closed without drains) differed in the type but not in the rate of wound problems; the drained group had more drainage at the port site, whereas the undrained group had more ecchymosis and swelling. There was no significant difference between the groups in operative blood loss; however, the drained group did require transfusions significantly more often than the undrained group (98 of 171 [57.3%] as opposed to 83 of 193 [43%], respectively). Of the patients requiring transfusions, patients with wound drains required significantly more blood than those without drains (1.12 versus 0.62 transfusions per patient for men; 1.73 versus 1.03 transfusions per patient for women).
Multiple Organ Failure as a Cause of Death in Patients With Severe Burns (2011)

The aim of this study was to investigate the causes of death in patients with burns using both medicolegal autopsy reports and clinical data collected during treatment to specify irreversible organ dysfunctions leading to death. Burn deaths occurring in the Helsinki Burn Center from 1995 to 2005 were identified in the hospital database. The clinical charts and medicolegal autopsy reports were retrieved and compared. The data were evaluated by plastic surgeons specialized in burn care, an intensivist, and a pathologist, with special reference to organ-specific changes in the autopsy reports. From 1999 to 2005, there were 71 burn deaths in the Helsinki Burn Center of which 40% was caused by multiple organ failure (MOF). Death from untreatable burn injury was recorded in 28 patients, whereas other causes were scarce. MOF patients displayed approximately four organ failures on average, ranging from three to eight. All 28 MOF patients were recorded to have acute renal failure, followed by liver damage, of which four patients had acute or chronic liver failure. Sepsis was always affiliated with MOF as a cause of death. In conclusion, careful examination of MOF as a cause of death revealed several organ failures: four organ failures per patient. Acute renal failure was noted in all MOF patients. Sepsis was always affiliated with MOF.
Expression Profiles of Epithelial-Mesenchymal Transition-Associated Proteins in Epithelial Ovarian Carcinoma (2014)

Epithelial-mesenchymal transition (EMT) has been suggested to contribute to tumor progression and acquisition of therapeutic resistance. To assess the clinical significance of EMT-associated proteins, we evaluated the expression of Snail and Slug, the key regulators of EMT, in the primary ovarian cancer samples (n = 103) by immunohistochemistry. Snail was differentially expressed according to the histologic subtype (P = 0.001) and was predominantly expressed in serous and endometrioid types. In the serous and endometrioid adenocarcinomas, the expression of Snail remained high across the stage and grade, suggesting its role in the early phase of carcinogenesis. However, the expression of Snail and Slug was not related to chemoresistance and poor prognosis and did not serve as independent predictive or prognostic marker.
Dry-etch damage and its recovery in InGaN/GaN multi-quantum-well light-emitting diodes (2003)

Etch-induced damage in GaN/InGaN multi-quantum well light-emitting diodes (LEDs) caused by a Cl2-base plasma and its recovery by means of a N2-plasma and annealing process of n-GaN is described. The photoluminescence intensity of etched n-type GaN was decreased by several orders of magnitude due to etch-induced damage, giving rise to an increase in the leakage current in LED current–voltage curves. However, treatment of the LEDs with a N2 plasma along with a rapid thermal annealing process led to an enhancement in the I–V characteristics of the LEDs due to the suppression of the leakage current. The electroluminescence intensity of LEDs which was etched at dc bias of −200 V was also improved by a factor of two relative to the as-etched LEDs, as a result of this treatment.
Design of enhancement mode single-gate and doublegate multi-channel GaN HEMT with vertical polarity inversion heterostructure (2013)

We propose the design and simulation study of novel gallium nitride (GaN) devices, consisting of nitride stacks with different polarity, to provide multiple channels by flexible gate(s) control. Calibrated TCAD device simulations visualize device characteristics of 0.62-μm-gate-length multi-channel transistors. E-mode operations demonstrate a positive small threshold voltage V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> below 2 V at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ds</sub> = 0.1 V for all multichannel devices, and a high on-state current I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</sub> (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">gs</sub> = V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ds</sub> = 4 V) up to 4 A/mm achieved by 4 channels induced within the device.