gebhart/patrepeval huggingface dataset:
Air traffic control: satellites and artificial intelligence promise improved safety and efficiency (1991)

Longer-term solutions to air traffic management are examined. These include global networks of satellites for communications, navigation, and surveillance,which may upstage ground radars in the next century. Greater capability in the cockpits (including collision avoidance systems and flight computers with extensive libraries), better weather prediction and information transfer, and plans to artificial intelligence in the system are also reviewed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A model for heterogeneous growth of Si1−xGex films from hydrides (1991)

Growth rates for Si1−xGex films (0≤x≤0.19) have been measured between 610–750 °C using low pressure H2/SiH4/GeH4 mixtures and at different temperatures these rates show different dependencies on composition x. A model attributes this complex behavior to competition between an increasing rate for desorption of surface hydrogen and a decreasing sticking probability for the reactive hydrides as x increases. The latter effect is explicitly reported for the first time. GeH4 is found to be ∼4.7 times more reactive than SiH4, and relative surface hydrogen coverages on Si and Si0.87Ge0.13 films measured by secondary ion mass spectroscopy are compared with the model.
An active-site mutation (Gly633 .fwdarw. Arg) of dipeptidyl peptidase IV causes its retention and rapid degradation in the endoplasmic reticulum (1992)

Dipeptidyl peptidase IV (DPPIV), a serine protease expressed on the cell surface, is deficient in a Fischer rat substrain. Northern blot analysis showed no difference in the size and amount of DPPIV mRNA between normal (344/NC) and deficient (344/CRJ) rats. Cloning and sequencing of DPPIV cDNAs revealed a G to A transition at nucleotide 1897 in the cDNA sequence of 344/CRJ, which leads to substitution of Gly633-->Arg in the active-site sequence Gly629-Trp-Ser-Tyr-Gly633 determined for the wild-type DPPIV [Ogata, S., Misumi, Y., Takami, N., Oda, K., & Ikehara, Y. (1992) Biochemistry 31, 2582-2587]. Pulse-chase experiments with hepatocytes showed that the wild-type DPPIV was initially synthesized as a 103-kDa form with high-mannose-type oligosaccharides, which was processed to a mature form of 109 kDa with the complex type during intracellular transport. In contrast, the mutant DPPIV, although being synthesized as the 103-kDa form, was rapidly degraded without being processed to the mature form. Site-directed mutagenesis of the wild-type and mutant cDNAs and their transfection/expression in COS-1 cells confirmed that the single substitution of Gly633-->Arg is sufficient to cause the rapid intracellular degradation of DPPIV. Immunoelectron-microscopic observations showed that the mutant DPPIV was detectable only in the endoplasmic reticulum (ER), in contrast to the distribution of the wild-type DPPIV in the Golgi complex and on the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)
Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear RNAs (1998)

In several forms of beta-thalassemia, mutations in the second intron of the beta-globin gene create aberrant 5' splice sites and activate a common cryptic 3' splice site upstream. As a result, the thalassemic beta-globin pre-mRNAs are spliced almost exclusively via the aberrant splice sites leading to a deficiency of correctly spliced beta-globin mRNA and, consequently, beta-globin. We have designed a series of vectors that express modified U7 snRNAs containing sequences antisense to either the aberrant 5' or 3' splice sites in the IVS2-705 thalassemic pre-mRNA. Transient expression of modified U7 snRNAs in a HeLa cell line stably expressing the IVS2-705 beta-globin gene restored up to 65% of correct splicing in a sequence-specific and dose-dependent manner. Cell lines that stably coexpressed IVS2-705 pre-mRNA and appropriately modified U7 snRNA exhibited up to 55% of permanent restoration of correct splicing and expression of full-length beta-globin protein. This novel approach provides a potential alternative to gene replacement therapies.
Reaction of saturated organic compounds with acetyl and trifluoroacetyl nitrate (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReaction of saturated organic compounds with acetyl and trifluoroacetyl nitrateRobert D. Bach, Thomas H. Taaffee, and Joseph W. HolubkaCite this: J. Org. Chem. 1980, 45, 17, 3439–3442Publication Date (Print):August 1, 1980Publication History Published online1 May 2002Published inissue 1 August 1980https://pubs.acs.org/doi/10.1021/jo01305a013https://doi.org/10.1021/jo01305a013research-articleACS PublicationsRequest reuse permissionsArticle Views432Altmetric-Citations9LEARN 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
The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins (2013)

Thalidomide-like drugs such as lenalidomide are clinically important treatments for multiple myeloma and show promise for other B cell malignancies. The biochemical mechanisms underlying their antitumor activity are unknown. Thalidomide was recently shown to bind to, and inhibit, the cereblon ubiquitin ligase. Cereblon loss in zebrafish causes fin defects reminiscent of the limb defects seen in children exposed to thalidomide in utero. Here we show that lenalidomide-bound cereblon acquires the ability to target for proteasomal degradation two specific B cell transcription factors, Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). Analysis of myeloma cell lines revealed that loss of IKZF1 and IKZF3 is both necessary and sufficient for lenalidomide's therapeutic effect, suggesting that the antitumor and teratogenic activities of thalidomide-like drugs are dissociable.
USES OF THE FRIES REARRANGEMENT FOR THE PREPARATION OF HYDROXYARYLKETONES. A REVIEW (1992)

(1992). USES OF THE FRIES REARRANGEMENT FOR THE PREPARATION OF HYDROXYARYLKETONES. A REVIEW. Organic Preparations and Procedures International: Vol. 24, No. 4, pp. 369-435.
X-ray powder diffraction data of lapatinib ditosylate monohydrate (2009)

The room temperature powder pattern of lapatinib ditosylate monohydrate (active ingredient in Tykerb used to treat refractory breast cancer) was indexed and the cell from the single crystal X-ray diffraction structure was refined using the experimental capillary data. Unit-cell parameters for the orthorhombic compound with space group Pbca refined from powder diffraction data are a =9.6850±0.0009 Å, b =29.364±0.003 Å, and c =30.733±0.003 Å, α = β = γ =90°, z =8, V =8740.1 Å 3 . Values of 2 θ , d , I , and Miller indices are reported.
Requirement for Enhancer Specificity in Immunoglobulin Heavy Chain Locus Regulation (2008)

The intronic Emicro enhancer has been implicated in IgH locus transcription, VDJ recombination, class switch recombination, and somatic hypermutation. How Emicro controls these diverse mechanisms is still largely unclear, but transcriptional enhancer activity is thought to play a central role. In this study we compare the phenotype of mice lacking the Emicro element (DeltaEmicro) with that of mice in which Emu was replaced with the ubiquitous SV40 transcriptional enhancer (SV40eR mutation) and show that SV40e cannot functionally complement Emu loss in pro-B cells. Surprisingly, in fact, the SV40eR mutation yields a more profound defect than DeltaEmicro, with an almost complete block in micro0 germline transcription in pro-B cells. This active transcriptional suppression caused by enhancer replacement appears to be specific to the early stages of B cell development, as mature SV40eR B cells express micro0 transcripts at higher levels than DeltaEmicro mice and undergo complete DNA demethylation at the IgH locus. These results indicate an unexpectedly stringent, developmentally restricted requirement for enhancer specificity in regulating IgH function during the early phases of B cell differentiation, consistent with the view that coordination of multiple independent regulatory mechanisms and elements is essential for locus activation and VDJ recombination.
Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. (1994)

E2F-1 is a transcription factor suspected of activating genes required for S phase and a known target for the action of RB, the retinoblastoma gene product. Its induction in quiescent fibroblasts led to S-phase entry followed by apoptosis. E2F-1-mediated apoptosis was suppressed by coexpression of wild-type RB or a transdominant negative mutant species of p53. In contrast, coexpression of a naturally occurring loss-of-function RB mutant or wild-type p53 did not suppress the induction of apoptosis under these conditions. Thus, deregulated E2F-1 activity gives rise to proliferative and apoptotic signals. p53 appears to participate in the execution of the latter.
Segmented polyurethanes derived from novel siloxane–carbonate soft segments for biomedical applications (2011)

Abstract A novel macrodiol based on mixed silicone and carbonate chemistries was synthesized and used as a soft segment precursor in the synthesis of two series of segmented polyurethane (PU) copolymers varying in hard segment content and soft segment molecular weight. The hard segments in these copolymers were derived from 4,4‐methylene diphenyl diisocyanate and 1,4‐butane diol. The phase transitions, microphase separation behavior, and mechanical properties of the copolymers were investigated using a variety of experimental methods. When compared with segmented PU copolymers having predominately poly(dimethyl siloxane) soft segments, these siloxane–carbonate soft segment copolymers exhibit enhanced intersegment mixing, and consequently relatively low mechanical modulus. With relatively low modulus and siloxane units in the soft phase, the siloxane–carbonate PUs have potential for use in cardiac and orthopedic biomedical applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011
Alteration in the agonist/antagonist balance of antiestrogens by activation of protein kinase A signaling pathways in breast cancer cells: antiestrogen selectivity and promoter dependence. (1994)

We find that stimulation of the protein kinase A (PKA) signaling pathway in MCF-7 human breast cancer cells changes the agonist/antagonist activity of tamoxifen and related antiestrogens; it activates or enhances their estrogen agonist activity and reduces their ability to antagonize the effects of estradiol (E2). In MCF-7 human breast cancer cells which contain high levels of endogenous estrogen receptor (ER), the antiestrogen trans-hydroxy-tamoxifen (TOT) fails to stimulate transcription of the estrogen-responsive promoter-reporter constructs estrogen response element (ERE)-TATA-chloramphenicol acetyl transferase (CAT), (ERE)2-TATA-CAT, and pS2-CAT. However, when cells are treated with isobutyl methylxanthine plus cholera toxin (which increases intracellular cAMP approximately 10-fold), or with 8-bromo-cAMP, or are transfected with expression vectors for the PKA catalytic subunits, the transcriptional activity of the antiestrogen-ER complex is now increased, to levels 20-75% that of E2, and TOT also becomes much less effective in antagonizing the stimulation of transcription by E2. Although this alteration in the agonist and antagonist activity of TOT is observed with three promoter-reporter constructs, containing a simple TATA promoter or a more complex, pS2 promoter, elevation of cAMP did not enhance the transcription by either TOT or E2 of the reporter plasmid ERE-thymidine kinase-CAT. Thus, this phenomenon is promoter specific. The maximal stimulatory effects of isobutylmethylxanthine plus cholera toxin and PKA catalytic subunits on TOT and E2 transcriptional enhancement were not additive, consistent with the hypothesis that they are both acting via stimulation of the same signal transduction pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Saturation, Competition, and Specificity in Interaction of Heat Shock Proteins (hsp) gp96, hsp90, and hsp70 with CD11b+ Cells (2000)

Heat shock proteins (hsp(s)) have been postulated to interact with APCs through specific receptors, although the receptors are yet to be identified. Specificity, saturation, and competition are the three defining attributes of a receptor-ligand interaction. We demonstrate here that the interaction of the heat shock proteins gp96 and hsp90 with CD11b+ cells is specific and saturable and that gp96 can compete with itself in gp96-macrophage interaction. Interestingly, the phylogenetically related hsp90 also competes quite effectively with gp96 for binding to macrophages, whereas the unrelated hsp70 does so relatively poorly, although it binds CD11b+ cells just as effectively. These data provide evidence that the heat shock proteins interact with APCs with specificity and for the existence of at least two distinct receptors, one for gp96 and hsp90 and the other for hsp70.
Generation of insulin-producing β-like cells from human iPS cells in a defined and completely xeno-free culture system (2014)

Human induced pluripotent stem (hiPS) cells are considered a potential source for the generation of insulin-producing pancreatic β-cells because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently differentiate hiPS cells into insulin-producing cells in vitro. We found that a high NOGGIN concentration is crucial for specifically inducing the differentiation first into pancreatic and duodenal homeobox-1 (PDX1)-positive pancreatic progenitors and then into neurogenin 3 (NGN3)-expressing pancreatic endocrine progenitors, while suppressing the differentiation into hepatic or intestinal cells. We also found that a combination of 3-isobutyl-1-methylxanthine (IBMX), exendin-4, and nicotinamide was important for the differentiation into insulin single-positive cells that expressed various pancreatic β-cell markers. Most notably, the differentiated cells contained endogenous C-peptide pools that were released in response to various insulin secretagogues and high levels of glucose. Therefore, our results demonstrate the feasibility of generating hiPS-derived pancreatic β-cells under xeno-free conditions and highlight their potential to treat patients with type 1 diabetes.
Development of Adoptive Cell Therapy for Cancer: A Clinical Perspective (2010)

Adoptive cellular therapy provides the promise of a potentially powerful general treatment for cancer. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. However, these trials are also identifying new challenges and this review focuses on these clinical issues. For tumors such as melanoma, in which tumor-specific T cells can be readily identified and isolated, the adoptive transfer of "tumor-infiltrating lymphocytes" (TILs) already appears to offer significant patient benefit and this approach now warrants further development. Genetically engineered T cells offer a means to endow peripheral blood T cells with antitumor activity and in principle these techniques could allow the treatment of a wide range of cancers. Genetic engineering also offers the means to endow T cells with new properties and enhanced functions. There have been clear proof-of-principle trials showing responses with T cell receptor (TCR)-engineered T cells and this can be built on with further development. By contrast, other trials have produced significant toxicity related to expression of target antigen on normal tissue, particularly with enhanced receptors. The challenge ahead lies in understanding how to achieve the balance between targeted antitumor immune responses while avoiding toxicity associated with on-target destruction of antigen-expressing normal tissues. Cellular therapy of cancer will need continued preclinical evaluation as well as carefully designed clinical trials addressing the various issues. For these challenges to be fully assessed, and for progression to a widely used, effective and safe therapy, development as cooperative groups is an appropriate way forward.
Herpes simplex virus 1 protein kinase is encoded by open reading frame US3 which is not essential for virus growth in cell culture (1987)

Earlier reports have described a novel protein kinase in cells infected with herpes simplex or pseudorabies viruses. These novel enzymes were characterized by their acceptance of protamine as a substrate and by their differential chromatographic behavior in anion-exchange chromatography. We report that this activity was not present in extracts of uninfected cells or of cells infected with a mutant constructed so as to contain a deletion in the US3 open reading frame mapping in the small component of herpes simplex virus 1 DNA. The activity was present in extracts of cells infected with wild-type virus and with a recombinant in which the US3 open reading frame had been rescued. Our results are consistent with the observation reported earlier that the coding sequences predict an amino acid motif common to protein kinases and lead to the conclusion that the US3 open reading frame encodes a virus-specific protein kinase that is not required for virus growth in cells in culture.
Characterization of DNA polymerase from Pyrococcus sp. strain KOD1 and its application to PCR (1997)

The DNA polymerase gene from the archaeon Pyrococcus sp. strain KOD1 (KOD DNA polymerase) contains a long open reading frame of 5,013 bases that encodes 1,671 amino acid residues (GenBank accession no. D29671). Similarity analysis revealed that the DNA polymerase contained a putative 3'-5' exonuclease activity and two in-frame intervening sequences of 1,080 bp (360 amino acids; KOD pol intein-1) and 1,611 bp (537 amino acids; KOD pol intein-2), which are located in the middle of regions conserved among eukaryotic and archaeal alpha-like DNA polymerases. The mature form of the DNA polymerase gene was expressed in Escherichia coli, and the recombinant enzyme was purified and characterized. 3'-5' exonuclease activity was confirmed, and although KOD DNA polymerase's optimum temperature (75 degrees C) and mutation frequency (3.5 x 10(-3)) were similar to those of a DNA polymerase from Pyrococcus furiosus (Pfu DNA polymerase), the KOD DNA polymerase exhibited an extension rate (100 to 130 nucleotides/s) 5 times higher and a processivity (persistence of sequential nucleotide polymerization) 10 to 15 times higher than those of Pfu DNA polymerase. These characteristics enabled the KOD DNA polymerase to perform a more accurate PCR in a shorter reaction time.
Serological Diagnosis of Scrub Typhus by Indirect Immunofluorescence (1963)

SummaryThe indirect fluorescent antibody test, in which dilutions of sera from patients with scrub typhus were tested on smears of Rickettsia tsutsugamushi, gave results which were serologically diagnostic of the disease in each instance. Non-specific reactions did not occur when the scrub typhus sera were exposed to antigens of other species of Rickettsia. Likewise, there was no reaction between R. tsutsugamushi smears and sera from other rickettsial infections, or with sera from patients with Proteus OXK agglutinins of non-rickettsial origin with one exception, i.e., a case of leptospirosis from Puerto Rico.
Clinical pharmacology of tocilizumab for the treatment of patients with rheumatoid arthritis (2011)

Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody for the treatment of rheumatoid arthritis (RA). A dose of 8 mg/kg produces adequate blockade of IL-6 receptors throughout a dosing interval, as confirmed by sustained high levels of tocilizumab-bound soluble IL6-R complex and normalization of C-reactive protein levels. Studies have confirmed 8 mg/kg every 4 weeks as the optimal dose and 4 mg/kg as the starting dose for the treatment of RA, with favorable efficacy and acceptable safety profiles. After 8 mg/kg, steady-state peak and trough concentrations were 183 ± 86 and 9.7 ± 11 µg/ml, respectively. Tocilizumab serum exposures increased more than proportionally to the dose increase from 2-10 mg/kg. Total clearance is concentration dependent, with non-linear receptor-mediated clearance dominant at low concentrations (<25 µg/ml). Tocilizumab exposures are not affected by common concomitant medications in RA patients, but decreased IL-6 activity resulted in increased CYP3A4 activity and hence decreased exposures of CYP3A4 substrates.
Long-Term Land Application of Activated Sludge from a Petrochemical Wastewater Treatment Plant: I - Leachate Quality (1991)

Excess activated sludge from SITEL, the wastewater treatment plant of Polo Petroquímico do Sul (South Petrochemical Complex), Triunfo, State of Rio Grande do Sul (RS), Brazil, is disposed of by subsurface injection on pangola grass and rye grass fields at an average annual rate of 24 tons/ha (dry basis). In order to assess absorption of sludge constituents by plants, modifications of soil properties and leachate quality, a microplot growth-leaching experiment is being conducted at the Department of Soils of UFRGS since 1985. Pangola grass (Digitariadecumbens, Stent) and rye grass (Loliummultiflorum, Lam) are grown in summer and winter respectively. Some microplots have been loaded with sludge enriched with Cu, Zn, Cr, Ni, Cd, Pb and Hg since 1988. Plant nutrients such as K, Cu, Zn and B did not increase in leachate, even at the higher application rates employed. Ammonium and pH were not affected either, whilst nitrates increased at the highest application rates. Ca and Mg increased in leachate during the third and the fourth years of the experiment, probably due to the liming of the microplots. Electrical conductivity of leachate increased with sludge application. Na, chloride and sulphate, the more soluble ions, increased slowly during the first year and more rapidly during the subsequent years. Heavy metals Cr, Ni, Cd, Pb and Hg in leachate were not consistently affected by application of pure sludge or metals-enriched sludge. The concentrations of these constituents in leachate were found to be generally below accepted limits for potable water. Exacerbation of loading of metals, bringing about introduction of total amounts that exceed current limits of addition of metals to soil, did not produce significant alterations in leachate quality. This suggests that these limits are very safe with respect to protection of aquifers. The determination of nitrates in leachate at different sludge application rates made possible the adoption of 40 tons/ha.year as the maximum allowable sludge loading rate (on dry basis) for the real sludge farms at SITEL. This figure is approximately double the operational sludge application rate at SITEL.