gebhart/patrepeval huggingface dataset:
Data from VS-5584, a Novel and Highly Selective PI3K/mTOR Kinase Inhibitor for the Treatment of Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR (IC&lt;sub&gt;50&lt;/sub&gt; = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC&lt;sub&gt;50&lt;/sub&gt;: PI3Kα = 16 nmol/L; PI3Kβ = 68 nmol/L; PI3Kγ = 25 nmol/L; PI3Kδ = 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials. &lt;i&gt;Mol Cancer Ther; 12(2); 151–61. ©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Acute phase response in the horse: plasma protein changes associated with adjuvant induced inflammation. (1988)

The induction of an acute phase response in four horses by adjuvant administration was used to examine the effect on the levels of plasma proteins. Blood parameters (packed cell volume, total plasma protein, red blood cell count, haemoglobin concentration) were monitored to follow the progress of the acute phase response in parallel with the examination of plasma proteins. Plasma protein levels were determined by densitometry from the electrophoretic patterns of three different gel systems. Haptoglobin and alpha 1 B glycoprotein were shown to be positive acute phase reactants whereas albumin was a negative acute phase reactant. Plasma esterase and proteins of the Pi system did not change following the experimental inflammation.
Biexcitonic Bound and Continuum States of Homogeneously and Inhomogeneously Broadened Exciton Resonances (2002)

We investigate the influence of excitonic localization on the corresponding biexcitonic states in GaAs quantum wells by spectrally resolved four-wave mixing. With increasing localization, the biexciton binding energy increases, while the biexciton continuum shifts to higher energies. The localization leads to an inhomogeneous broadening of the biexciton binding energy and the biexciton continuum edge. Simultaneously, the oscillator strength of the biexciton continuum-edge is reduced. This is interpreted as a result of the different localization of biexcitonic and excitonic states by the random disorder potential.
ChemInform Abstract: Synthesis of the C1—C12 Fragment of Fostriecin. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Impact of Immediate Primary Lung Allograft Dysfunction on Bronchiolitis Obliterans Syndrome (2006)

Primary graft dysfunction is associated with an increased risk of bronchiolitis obliterans syndrome independent of acute rejection, lymphocytic bronchitis, and community-acquired respiratory viral infections, and this risk is directly related to the severity of primary graft dysfunction.
Cloning, Sequence Analysis, and Expression of Active Phrixothrix Railroad-Worms Luciferases:  Relationship between Bioluminescence Spectra and Primary Structures, (1999)

Phrixothrix railroad-worms emit yellow-green light through 11 pairs of lateral lanterns along the body and red light through two cephalic lanterns. The cDNAs for the lateral lanterns luciferase of Phrixothrix vivianii, which emit green light (lambda max= 542 nm), and for the head lanterns of P. hirtus, which emit the most red-shifted bioluminescence (lambda max= 628 nm) among luminescent beetles, were cloned. Positive clones which emitted green (PvGR: lambda max= 549 nm) and red (PhRE: lambda max= 622 nm) bioluminescence were isolated. The lucifereases coded by PvGR (545 amino acid residues) and PhRE (546 amino acid residues) cDNAs share 71% identity. PvGR and PhRE luciferases showed 50-55% and 46-49% identity with firefly luciferases, respectively, and 47-49% with click-beetle luciferases. PhRE luciferase has some unique residues which replace invariant residues in other beetle luciferases. The additional residue Arg 352 in PhRE, which is deleted in PvGR polypeptide, seems to be another important structural feature associated with red light production. As in the case of other railroad-worms and click-beetle luciferases studied, Phrixothrix luciferases do not undergo the typical red shift suffered by firefly luciferases upon decreasing pH, a property which might be related to the many amino acid residues shared in common between railroad-worm and click-beetle luciferase.
Mechanically Induced Generation of Counterions Inside Surface‐Grafted Charged Macromolecular Films: Towards Enhanced Mechanotransduction in Artificial Systems (2006)

Brushing up on films: A simple model, based on strong ion-pairing interactions of a dye probe (bromothymol blue, BTB) within surface-grafted charged polyelectrolyte brushes, provides evidence that physical forces can be easily mechanotransducted into chemical signals (see picture, PDMS=poly(dimethylsiloxane)). The application of a mechanical force results in a shift of the equilibrium for BTB, which can be monitored by UV/Vis spectroscopy.
Disparate Effects of Roscovitine on Renal Tubular Epithelial Cell Apoptosis and Senescence: Implications for Autosomal Dominant Polycystic Kidney Disease (2008)

Data in this study provide a mechanistic explanation of how roscovitine is effective in PKD, and suggest that further study of this agent should focus on assessment of dose response. Furthermore, our discovery of senescence induced by a PKD effective drug suggests a new area of therapeutic investigation in this disease.
Glycinin A5A4B3 mRNA: cDNA cloning and nucleotide sequencing of a splitting storage protein subunit of soybean (1985)

The complete nucleotide sequence of a cloned cDNA, designated pGA5A4B3822, corresponding to glycinin A5A4B3 mRNA was determined. Analysis of the cDNA insert revealed that it contained 1899 nucleotides of mRNA sequence with a 5'-terminal non-translated region of 31 nucleotides, a signal peptide region corresponding to 23 amino acids, an acidic subunit region (A5) corresponding to 97 amino acids, an acidic subunit region (A4) corresponding to 257 amino acids followed by a basic subunit region (B3) corresponding to 185 amino acids, and a 3'-terminal non-translated region of 182 nucleotides. These results show that the glycinin A4 subunit, which is not found to be linked to a basic subunit via a disulfide bond, is synthesized as a full-sized precursor, i.e. the A5A4B3 subunit complex, from a single mRNA, followed by post-translational processing to generate an intermediary subunit complex (A5-B3), covalently linked by a disulfide bond, and the mature A4 subunit, which may associate with the above subunit complex by non-covalent interactions. From the results obtained by the Chou-Fasman rules we speculated that the two post-translational cleavage sites of this subunit precursor might be processed by the same proteolytic enzyme.
Chemical Vapor Deposition of Tungsten Carbide, Molybdenum Carbide Nitride, and Molybdenum Nitride Films (1997)

Tungsten carbides, β‐ and WC, molybdenum carbide nitride, Mo(C, N), and molybdenum nitride, MoN, films were prepared by chemical vapor deposition using and with , and . The reaction of with and yielded WC films at 700–800°C and β‐ films at 400–600°C. This reaction did not give tungsten carbide nitride, probably because of the higher structural instability of the tungsten nitride than the carbide. The interaction of with and , however, gave a molybdenum carbide nitride film at 700°C though the crystallinity was lower than that of cubic molybdenum nitride prepared at the same temperature. Cubic molybdenum nitride MoN films were obtained at 500–700°C from the reactions of with and using Ar as a carrier gas. The powder product obtained at 800°C by the same reaction was composed of cubic and hexagonal MoN phases, while that prepared at 850°C was hexagonal MoN and metallic molybdenum. Molybdenum nitrides contained nitrogen atoms trapped in the grain boundary in addition to those occupying lattice points. Vickers hardness values of the MoN films prepared at 600–750°C were in the range of 1300 to 1400 kgf mm−2.
Calculations of three-dimensional distributions of current density, electric field, and power deposition in externally sustained electrical discharges. [For calculating performance of CO/sub 2/ laser] (1982)

In the design of larger and larger CO/sub 2/ laser amplifiers, the problem of attaining the ideal uniform discharge in these large discharge volumes becomes increasingly difficult and expensive to solve. The practical solution is a compromise between uniformity and other design considerations. In order to judge the adequacy of each compromise, a method of predicting the distribution of current density and electric field throughout the discharge volume is needed. When these electrical distributions are known, population inversions can be calculated and the amplifier performance evaluated. This report describes a method of calculating the three-dimensional distributions of electric field and current density for externally sustained discharges. Two-dimensional calculations have been reported previously.
Detection and Tracking of Multiple Pedestrians in Automotive Applications (2007)

We present a method for tracking an unknown and changing number of far away pedestrians in a video stream. Multiple particle filter instances are utilized which track single pedestrians independently from each other. The tracking is guided by a cascade classifier which is integrated into the particle filter framework. In order to be able to detect hardly visible pedestrians and to filter out isolated false positives of the classifier, we developed a detection criterion for particle filters which follows the track-before-detect paradigm. The system nearly works in real time.
ANT1, Twinkle, POLG, and TP (2001)

Since Albrecht Von Graefe’s description of chronic progressive external ophthalmoplegia (CPEO) in 1868, the classification of diseases with PEO has been the subject of controversy. Weakness of extraocular muscles has been attributed to oculomotor nuclear dysfunction, ocular myopathy, or both.1 Lumpers have grouped patients with PEO under the broad diagnosis of “PEO-plus”, whereas splitters have attempted to delineate specific syndromes.

Clearly, some diseases with PEO can be sorted out because of characteristic features: congenital myasthenic syndromes, congenital myopathies, and oculopharyngeal muscular dystrophy. Thus, congenital myopathies are defined by abnormal histochemical structures, such as central cores, multicores, central nuclei, myotubes, nemaline rods, and tubular aggregates. Mitochondrial myopathies are usually defined by ragged-red fibers, cytochrome c oxidase (COX)-deficient fibers, and ultrastructurally abnormal mitochondria.

Recent breakthroughs in molecular genetics allow a more specific genetic classification of PEO. For example, the heterogeneous group of congenital myasthenic syndromes has been redefined based on mutations in different structures of the neuromuscular junction.2

Similarly, molecular genetic studies of mitochondrial PEO have uncovered mutations in many different genes. Such studies began in 1988 with the seminal discovery by Holt et al.3 of single large-scale deletions of mitochondrial DNA (mtDNA) in patients with mitochondrial myopathy. Later that …
Monolithic Light Guide Optics for See-through Smart Glasses & Smart Headphones (2015)

Optinvent has developed a unique see-through display technology based on thin monolithic plastic light guide enabling AR and Thin form factor Smart glasses. New Smart headphones integrating this technology will be presented and discussed.
Hemodynamic effects of a counterpulsation device implanted on the ascending aorta in severe cardiogenic shock. (1989)

A valveless, single orifice counterpulsation device (CD) with maximum stroke volume of 100 ml was implanted on the ascending aorta of nine dogs. Its pneumatic driver was gaited by the ECG to provide aortic diastolic augmentation, with a stroke volume of 60-70 ml. In the same animals a 20 ml intraaortic balloon (IAB) was placed into the descending aorta. An attempt was made to evaluate the effectiveness of the CD on severe cardiogenic shock and to compare its hemodynamic effects with those of the IABP. Severe cardiogenic shock was induced by coronary artery ligation, propranolol administration, and fluid infusion and was characterized by a LVEDP of 22.2 +/- 6.4 mmHg, ASP less than 70 mmHg and greater than or equal to 30 mmHg, and a reduction of CI by 71.7%. The CD had a significant beneficial effect in all measured parameters. The LVEDP decreased by a mean of 44.3% (P less than 0.001) below control value, and the AEDP by 60.2% (P less than 0.001). The PADA increased by 108.5% (P less than 0.001), and the CI by 155.8% (P less than 0.004). The IABP did not significantly change any of the hemodynamic variables. In conclusion, the CD has significant salutary hemodynamic effects in severe cardiogenic shock where IABP is ineffective.
Experimental quantum-state tomography of a solid-state qubit (2008)

Quantum-state tomography is used to characterize the state of an ensemble based qubit implemented through two hyperfine levels in ${\mathrm{Pr}}^{3+}$ ions, doped into a ${\mathrm{Y}}_{2}\mathrm{Si}{\mathrm{O}}_{5}$ crystal. We experimentally verify that single-qubit rotation errors due to inhomogeneities of the ensemble can be suppressed using the Roos-M\o{}lmer dark-state scheme [Roos and M\o{}lmer, Phys. Rev. A 69, 022321 (2004)] Fidelities above $&gt;90%$, presumably limited by excited state decoherence, were achieved. Although not explicitly taken care of in the Roos-M\o{}lmer scheme, it appears that also decoherence due to inhomogeneous broadening on the hyperfine transition is largely suppressed.
Idebenone in Friedreich ataxia and Leber’s hereditary optic neuropathy: close mechanisms, similar therapy?: Table 1 (2016)

Sir,

In 1999, we reported in a preliminary study that idebenone (Mnesis) decreased heart hypertrophy in three young patients with Friedreich ataxia, possibly with slight improvement in delicate movements (Rustin et al. , 1999 b ). In the vast majority of patients with Friedreich ataxia, an abnormal GAA expansion is found in the first intron of the frataxin ( FXN ) gene impairing transcription of the gene (Campuzano et al. , 1996). The resulting loss of function of the mitochondria-targeted frataxin protein leads to a deficiency of the mitochondrial iron-sulphur containing proteins (ISP), including complexes I, II and III of the respiratory chain in the heart of the patients (Rotig et al. , 1997). Defect of the ISP was shown to cause an iron-dependent oxidative stress which could be controlled in vitro by reduced idebenone (Rustin et al. , 1999 a ). In vivo , idebenone can be reduced by respiratory chain and/or NQO1 (NADH quinone oxidoreductase) activity (Haefeli et al. , 2011). Following the preliminary report of idebenone efficacy to counteract …
Parents’ Awareness of and Anticipated Responses to Their Teens’ Reports of Dating Violence (2015)

Teen dating violence (TDV) challenges families because of negative effects on youths’ well-being. This exploratory study examines parents’ awareness of TDV and their anticipated responses to adolescents’ reports. The authors used a telephonic survey of 539 Michigan adults to assess knowledge of TDV, awareness of its prevalence, and anticipated responses. More mothers than fathers viewed TDV as a major public health problem and were likely to urge their adolescents to seek formal help. Fathers were more likely to ground their children or say that things are not so bad. Findings of demographic differences influencing parental responses can inform social workers to help parents plan for responding to TDV effectively.
The Role of Ca2+-Coordinating Residues of Herring Antifreeze Protein in Antifreeze Activity (2004)

The type II antifreeze protein of Atlantic herring (Clupea harengus harengus) requires Ca(2+) as a cofactor to inhibit the growth of ice crystals. On the basis of homology modeling with Ca(2+)-dependent lectin domains, five residues of herring antifreeze protein (hAFP) are predicted to be involved in Ca(2+) binding: Q92, D94, E99, N113, and D114. The role of E99, however, is less certain. A previous study on a double mutant EPN of hAFP suggested that the Ca(2+)-binding site of hAFP was the ice-binding site. However, it is possible that Ca(2+) might function distantly to affect ice binding. Site-directed mutagenesis was performed on the Ca(2+)-coordinating residues of hAFP in order to define the location of the ice-binding site and to explore the role of these residues in antifreeze activity. Properties of the mutants were investigated in terms of their structural integrity and antifreeze activity. Equilibrium dialysis analysis demonstrated that E99 is a Ca(2+)-coordinating residue. Moreover, proteolysis protection assay revealed that removal of Ca(2+) affected the conformation of the Ca(2+)-binding loop rather than the core structure of hAFP. This finding rules out the possibility that Ca(2+) might act at a distance via a conformational change to affect the function of hAFP. Substitutions at positions 99 and 114 resulted in severely reduced thermal hysteresis activity. These data indicate that the ice-binding site of hAFP is located at the Ca(2+)-binding site and the loop region defined by residues 99 and 114 is important for antifreeze activity.
Smart contracts: terminology, technical limitations and real world complexity (2017)

If one is to believe the popular press and many “technical writings,” blockchains create not only a perfect transactional environment but also obviate the need for banks, lawyers and courts. The latter will soon be replaced by smart contracts: unbiased and infallible computer programs that form, perform and enforce agreements. Predictions of future revolutions must, however, be distinguished from the harsh reality of the commercial marketplace and the technical limitations of blockchains. The fact that a technological solution is innovative and elegant need not imply that it is commercially useful or legally viable. Apart from attempting a terminological “clean-up” surrounding the term smart contract, this paper presents some technological and legal constraints on their use. It confronts the popular claims concerning their ability to automate transactions and to ensure perfect performance. It also examines the possibility of reducing contractual relationships to code and the ability to integrate smart contracts with the complexities of the real world. A closer analysis reveals that smart contracts can hardly be regarded as a semi-mythical technology liberating the contracting parties from the shackles of traditional legal and financial institutions.
Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD (2004)

Bilateral STN stimulation is more effective than unilateral pallidotomy in reducing parkinsonian symptoms in patients with advanced PD.
U.S. Drug Firms' Profits Climbed 12% in Fourth Quarter (1986)

RETURN TO ISSUEPREVNewsNEXTU.S. Drug Firms' Profits Climbed 12% in Fourth QuarterWeaker U.S. dollar helped sales increase 11%; profitability edged up slightly to 11.5% from a year earlierDAVID WEBBERView Author Information C&EN New YorkCite this: Chem. Eng. News 1986, 64, 9, 14–15Publication Date (Print):March 3, 1986Publication History Published online7 November 2010Published inissue 3 March 1986https://pubs.acs.org/doi/10.1021/cen-v064n009.p014https://doi.org/10.1021/cen-v064n009.p014newsACS PublicationsCopyright © 1986 AMERICAN CHEMICAL SOCIETYArticle Views5Altmetric-Citations-LEARN 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 options SUBJECTS:Pharmaceuticals Get e-Alerts
Regulation of kinetic and pharmacological properties of synaptic NMDA receptors depends on presynaptic exocytosis in rat hippocampal neurones (1998)

1. Using whole-cell patch-clamp recordings of NMDA EPSCs from co-cultured rat hippocampal (CA region) neurones, developmental changes in the kinetic and pharmacological properties of synaptic NMDA receptors were investigated. During in vitro differentiation a fast decaying component increasingly contributed to NMDA EPSCs. 2. Extracellular Mg2+ (1 mM) strongly blocked NMDA EPSCs at all stages in culture. Using the NR2B subunit-specific NMDA receptor antagonist ifenprodil (3 microM), we observed a developmental decrease in ifenprodil sensitivity of NMDA EPSCs. This suggests developmental changes in the expression of NMDA receptor subtypes. 3. To transiently block presynaptic exocytosis, we incubated presynaptic explants with tetanus toxin (TeTx) prior to cultivation. In TeTx-pretreated cultures the occurrence of fast decaying components of NMDA EPSCs and the developmental decrease in ifenprodil sensitivity was inhibited. Our results indicate a regulatory role of presynaptic exocytosis in the expression of NMDA receptor subtypes.
Pituitary Carcinoma Containing Gonadotropins: Treatment by Radical Excision and Cytotoxic Chemotherapy: Case Report (2000)

This is the only documented case of a gonadotropin-staining pituitary carcinoma for which hormone production was proven in both the primary and metastatic tumors. Many benign "nonsecreting" pituitary adenomas actually produce subclinical amounts of gonadotropins, and malignant nonfunctional pituitary neoplasms may do the same.