gebhart/patrepeval huggingface dataset:
Sorafenib With Interferon Alfa-2b As First-Line Treatment of Advanced Renal Carcinoma: A Phase II Study of the Southwest Oncology Group (2007)

The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.
Transport phenomena in amorphous silicon doped by ion implantation of 3d metals (1986)

Charge transport in amorphous silicon (aSi) doped with ion implantation of Mn+, Ni+, Fe+, and Cu+ ions is studied using ESR technique, temperature dependence of conductivity σ(T), and thermopower α(T) measurements. With increasing of impurity (Mn, Ni, Fe) concentration (from 1018to 1019 cm−3) the localized state density and σ decrease owing to the passivation of silicon dangling bonds with impurity atoms. An analysis of conductivity and thermopower data allows to reveal three temperature regions. 1) At 250 < T < 500 K σ is due to holes excited from the acceptor impurity states. 2) At T > 500 K electron transport dominates. 3) At T < 250 K hopping conductivity with variable range hopping near Fermi level prevails. For a-Si:Mn in the region of 4 < T < 80 K Coulomb correlations are detected in the behaviour of σ(T). The Coulomb gap is foundto reach a maximum value 25 meV which appears to be one order of value larger than the known (one) in semiconductors doped with shallow impurity levels. [Russian Text Ignored].
Cold Atmospheric Plasma Induces a Predominantly Necrotic Cell Death via the Microenvironment (2015)

These observations will need to be taken into account when studying in vitro plasma/cell interaction and may have implications for the design and future evaluation of the efficacy and safety of this new treatment strategy.
The Network Audio System: make your applications sing (as well as dance)! (1994)

Audio input and output is rapidly becoming a standard feature in desktop devices and an expected element of user interfaces. Workstations, X terminals, and personal computers now typically include hardware capabilities ranging from 8 kHz mono &amp;quot;voice quality&amp;quot; up through 48 kHz stereo. Unfortunately, application programming interfaces vary widely across platforms, limiting the types of applications that can be developed in X environments. The Network Audio System, commonly but unimaginatively known as NetworkAudio, was developed by NCD for playing, recording, and manipulating audio data over a network. Like the X Window System [Scheifler92], it uses the client/server model to separate applications from the specific drivers that control audio input and output devices. A free, sample implementation of the NetworkAudio server and programming library is available for Sun and SGI platforms; additional product versions are available or have been announced for NCD X terminals, NCD PC-X servers,...
Studies on Monooxygenases (1972)

Abstract Crystalline l-lysine monooxygenase from Pseudomonas fluorescens catalyzes the incorporation of 1 atom of molecular oxygen into the substrate, l-lysine, concomitant with a decarboxylation to form δ-amino-n-valeramide. In addition to l-lysine, the l isomers of several basic amino acids such as 2,7-diaminoheptanoate, arginine, δ-hydroxylysine, and S-aminoethylcysteine serve as the substrate for the monooxygenation catalyzed by the enzyme. When l-ornithine was incubated with the enzyme, however, it was converted to α-keto-δ-amino-n-valerate with the consumption of oxygen and with the formation of ammonia and hydrogen peroxide in stoichiometric amounts. These findings suggest that l-lysine monooxygenase can catalyze an oxidative deamination of l-ornithine similar to that catalyzed by l-amino acid oxidase. 2,8-Diaminooctanoate appeared to be degraded in the same way as l-ornithine as evidenced by a 50% reduction in the rate of oxygen uptake upon the addition of catalase. Evidence indicating that both activities, monooxygenation and oxidation of amino acids, are attributable to a single enzyme includes the constant ratio of the two activities during the course of the enzyme purification and the parallel inactivation by —SH inhibitors or by sodium dodecyl sulfate. A competitive type inhibition of lysine monooxygenation by ornithine suggests that both amino acids bind to the enzyme at the same site.
BET inhibitors induce apoptosis through a MYC independent mechanism and synergise with CDK inhibitors to kill osteosarcoma cells (2015)

Osteosarcoma (OS) survival rates have plateaued in part due to a lack of new therapeutic options. Here we demonstrate that bromodomain inhibitors (BETi), JQ1, I-BET151, I-BET762, exert potent anti-tumour activity against primary and established OS cell lines, mediated by inhibition of BRD4. Strikingly, unlike previous observations in long-term established human OS cell lines, the antiproliferative activity of JQ1 in primary OS cells was driven by the induction of apoptosis, not cell cycle arrest. In further contrast, JQ1 activity in OS was mediated independently of MYC downregulation. We identified that JQ1 suppresses the transcription factor FOSL1 by displacement of BRD4 from its locus. Loss of FOSL1 phenocopied the antiproliferative effects of JQ1, identifying FOSL1 suppression as a potential novel therapeutic approach for OS. As a monotherapy JQ1 demonstrated significant anti-tumour activity in vivo in an OS graft model. Further, combinatorial treatment approaches showed that JQ1 increased the sensitivity of OS cells to doxorubicin and induced potent synergistic activity when rationally combined with CDK inhibitors. The greater level of activity achieved with the combination of BETi with CDK inhibitors demonstrates the efficacy of this combination therapy. Taken together, our studies show that BET inhibitors are a promising new therapeutic for OS.
Brain drug delivery of small molecules using immunoliposomes (1996)

Immunoliposomes (antibody-directed liposomes) were used in the present study for delivery of the antineoplastic agent daunomycin to the rat brain. A coupling procedure was introduced, which allows conjugation of a thiolated antibody to maleimide-grafted 85-nm liposomes sterically stabilized with PEG. Antibody was thereby coupled to the terminal end of a PEG-conjugated linker lipid. No brain uptake of PEG-conjugated liposomes carrying [3H]daunomycin was observed. However, brain targeting of immunoliposomes carrying [3H]daunomycin was mediated by the OX26 monoclonal antibody to the rat transferrin receptor, which is selectively enriched at the brain microvascular endothelium that comprises the blood-brain barrier in vivo. Coupling of 30 OX26 antibodies per liposome resulted in optimal brain delivery. Saturation of delivery was observed at higher antibody densities. Determination of brain levels of immunoliposomes over 24 h revealed that immunoliposomes accumulate in brain tissue. Brain targeting of immunoliposomes was not observed in immunoliposomes conjugated with a mouse IgG2a isotype control. In addition, coinjection of free OX26 saturated plasma clearance of immunoliposomes. Since a single liposome may carry > or = 10,000 drug molecules, the use of PEG-conjugated immunoliposomes increases the drug carrying capacity of the monoclonal antibody by up to 4 logarithmic orders in magnitude. In summary, specific OX26-mediated targeting of daunomycin to the rat brain was achieved by the use of an immunoliposome-based drug delivery system.
A prospective investigation of the impact of smoking bans on tobacco cessation and relapse (2001)

Employees in workplaces with smoking bans have higher rates of smoking cessation than employees where smoking is permitted, but relapse is similar between these two groups of employees. The results of this investigation have international applicability for policy makers, clinicians, employers, and employees. Countries should review smoking policies in workplaces in light of their own smoking patterns and efforts to deal with environmental tobacco smoke.
Organic disulfides and related substances. 42. Synthesis and properties of some tertiary disulfides, especially involving penicillamine (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganic disulfides and related substances. 42. Synthesis and properties of some tertiary disulfides, especially involving penicillamineLamar Field and Ramanathan RavichandranCite this: J. Org. Chem. 1979, 44, 15, 2624–2629Publication Date (Print):July 1, 1979Publication History Published online1 May 2002Published inissue 1 July 1979https://pubs.acs.org/doi/10.1021/jo01329a007https://doi.org/10.1021/jo01329a007research-articleACS PublicationsRequest reuse permissionsArticle Views407Altmetric-Citations14LEARN 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
Susceptibility of Six Bacterial Pathogens of Channel Catfish to Six Antibiotics (1995)

Two hundred eight bacterial isolates from diseased channel catfish Ictalurus punctatus were screened for susceptibility to apramycin, enrofloxacin, cephalothin, oxytetracycline, sulfadimethoxine-ormetoprim, and tilmicosin by the Kirby-Bauer disk diffusion method. Bacteria evaluated were Edwardsiella ictaluri, E. tarda, Aeromonas sp., A. hydrophila, A. sobria, and Pseudomonas sp. All bacteria were most susceptible to enrofloxacin (99.0%) and apramycin (97.6%), but only 86.5% were susceptible to sulfadimethoxine-ormetoprim, 84.1%o to oxytetracycline, and 75.5% to cephalothin. Edwardsiella ictaluri, E. tarda, A. hydrophila, and A. sobria were 100% susceptible to enrofloxacin. Aeromonas sp., E. ictaluri and E. tarda were 100% susceptible to apramycin. Resistance was detected in all bacterial species to cephalothin, oxytetracycline, sulfadimethoxine-ormetoprim, and tilmicosin. Testing E. ictaluri against sulfadimethoxine-ormetoprim gave larger zones of inhibition on Mueller-Hinton medium than on brain-heart infusion agar.
Simple Charts to Determine Hole Cleaning Requirements in Deviated Wells (1994)

ABSTRACT Optimization of hole cleaning remains one of the major challenges when planning and drilling high angle and extended reach wells. In this paper, a simple rig-site graphical technique is presented for determining hole cleaning requirements for a range of hole sizes. The method uses a set of charts which have been derived from a computer model based on both laboratory and field measurements. Access to the technology at the rig-site has been greatly improved by the development of the simplified charts. Examples are presented which illustrate how the charts can be applied to determine the influence of the major drilling variables on hole cleaning requirements. Mud rheology is shown to be a key variable for optimising hole cleaning in deviated wells. The charts can also be used to quantify the effect of hole enlargement which adversely affects hole cleaning. In addition, the paper discusses the detailed methodology behind the development of the charts from the original physically-based model. The charts presented in the paper are valid for the typical North Sea drilling conditions.
Role of glycosylation on the secretion and biological activity of erythropoietin (1992)

The erythropoietin (EPO) molecule contains four carbohydrate chains. Three contain N-linkages to asparagines at positions 24, 38, and 83, and one contains an O-linkage to a serine at position 126. We constructed human EPO variants that eliminated the three N-glycosylation sites by replacing the asparagines with glutamines singly or in combination. The O-linked carbohydrate chain was removed by replacing the serine with glutamine, valine, histidine, or alanine. A variant with a double mutation (Gln38,83) and another with a triple mutation (Gln24,38,83) were secreted poorly from COS1 and CHO cells even though RNA encoding these variants was present. All other variants with mutations in N-linked glycosylation sites were secreted normally. Removal of any of the N-glycosylation sites reduced the in vivo but not the in vitro biological activity of the EPO molecule. All the mutations at Ser126, the O-glycosylation site, were secreted normally. In vitro activity was also unaffected except for Ala126 which had a 50-fold decrease. The Val126 variant was tested in vivo, and its specific activity was only slightly less than that of the native EPO, which indicates that the O-linked carbohydrate is not essential for activity.
Learning from data: a tutorial with emphasis on modern pattern recognition methods (2002)

The purposes of this tutorial are twofold. First, it reviews the classical statistical learning scenario by highlighting its fundamental taxonomies and its key aspects. The second aim of the paper is to introduce some modern (ensembles) methods developed inside the machine learning field. The tutorial starts by putting the topic of supervised learning into the broader context of data analysis and by reviewing the classical pattern recognition methods: those based on class-conditional density estimation and the use of the Bayes theorem and those based on discriminant functions. The fundamental topic of complexity control is treated in some detail. Ensembles techniques have drawn considerable attention in recent years: a set of learning machines increases classification accuracy with respect to a single machine. Here, we introduce boosting, in which classifiers adaptively concentrate on the harder examples located near to the classification boundary and output coding, where a set of independent two-class machines solves a multiclass problem. The first successful applications of these methods to data produced by the Pico-2 electronic nose (EN), developed at the University of Brescia, Brescia, Italy, are also briefly shown.
Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity (1991)

In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony-stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the "autonomous" colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder.
Baseline Measurement of Bone Mass Predicts Fracture in White Women (1989)

A single bone mass measurement of the radius is predictive of future nonspine fractures at all sites, and at both the forearm and the hip. Baseline age was not a significant predictor of fracture within either cohort. Relative-risk estimates were not dissimilar across fracture sites.
AMPA receptor activation is rapidly toxic to cortical astrocytes when desensitization is blocked (1996)

Although cultured astrocytes express functional glutamate receptors, they are generally resistant to excitotoxic cell death. We explored the role of receptor desensitization in glutamate-mediated astrocyte injury. In cultures of type 1 astrocytes from mouse neocortex, brief application of AMPA evoked small, rapidly desensitizing inward currents, whereas kainate evoked small, sustained currents. Neither agonist increased cytosolic calcium, and astrocyte toxicity occurred only after 24 hr exposure to high (500-1000 microM) concentrations of kainate but not to AMPA or glutamate. Cyclothiazide, a drug that selectively blocks AMPA receptor desensitization, greatly potentiated AMPA- or kainate-gated currents and intracellular calcium elevation. Coapplication of 10-100 microM cyclothiazide with glutamate, AMPA, or kainate produced widespread astrocyte cell death within 2 hr or application. The enhancement of toxicity by cyclothiazide, which alone was not toxic, was concentration-dependent for each of the tested agonists (EC50 30-100 microM) and was blocked by further addition of the selective AMPA/kainate antagonist 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX). NMDA caused no injury even in the presence of cyclothiazide. Cyclothiazide-enhanced injury varied with the age of astrocyte cultures; the maximal effect occurred at approximately 2 weeks in vitro, and little death was seen after 4 weeks. Type 1 astrocytes express AMPA-type glutamate receptors that are unmasked by reducing their desensitization with cyclothiazide. Although overactivation of AMPA receptors can be rapidly lethal to astrocytes, rapid desensitization normally limits this toxicity. The extent of AMPA receptor desensitization may be an important determinant of glial vulnerability to excitotoxic insults.
Nα-Alloc temporary protection in solid-phase peptide synthesis. The use of amine–borane complexes as allyl group scavengers (1999)

The use of a combination of amine–borane complexes and soluble palladium catalyst allows the fast deprotection of allyl carbamates under near-to-neutral conditions and without any side-formation of allylamine. Preliminary experiments indicate that palladium catalyst–amine–borane systems seem ideally suited for removal of Nα-Alloc terminal groups during solid phase peptide synthesis according to the N α-Alloc temporary protection strategy.
The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy (2017)

Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by targeted therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, we report clonal shifts (change >0.1 in clonal cancer cell fraction, Q < 0.1) in 31% of patients during the first year of therapy, associated with adverse outcome. We also observe transcriptional downregulation of pathways mediating energy metabolism, cell cycle, and B cell receptor signaling. Known and previously undescribed mutations in BTK and PLCG2, or uncommonly, other candidate alterations are present in seventeen subjects at the time of progression. Thus, the frequently observed clonal shifts during the early treatment period and its potential association with adverse outcome may reflect greater evolutionary capacity, heralding the emergence of drug-resistant clones.
Advanced Mobile Phone Service: Mobile Telephone Switching Office (1979)

The Mobile Telephone Switching Office provides centralised control of the Advanced Mobile Phone Service. Using a No. 1/1A Electronic Switching System, the Mobile Telephone Switching Office coordinates and controls the activities of the cell sites, interconnects the mobile telephones with the land telephone network, and maintains system integrity through automated maintenance. This paper gives an overview of the Mobile Telephone Switching Office and addresses the unique call processing and maintenance aspects of mobile telephony.
TCR-Induced Transmembrane Signaling by Peptide/MHC Class II Via Associated Ig-α/β Dimers (2001)

Previous findings suggest that during cognate T cell-B cell interactions, major histocompatability complex (MHC) class II molecules transduce signals, leading to Src-family kinase activation, Ca2+ mobilization, and proliferation. Here, we show that antigen stimulation of resting B cells induces MHC class II molecules to associate with Immunoglobulin (Ig)-alpha/Ig-beta (CD79a/CD79b) heterodimers, which function as signal transducers upon MHC class II aggregation by the T cell receptor (TCR). The B cell receptor (BCR) and MHC class II/Ig-alpha/Ig-beta are distinct complexes, yet class II-associated Ig-alpha/beta appears to be derived from BCR. Hence, Ig-alpha/beta are used in a sequential fashion for transduction of antigen and cognate T cell help signals.
The role of chromosome 21 in hematology and oncology (2010)

Newborns and children with Down syndrome (DS) often present with congenital transient leukemia and have an increased risk of acute myeloid leukemia and acute lymphoblastic leukemia. Thus, constitutional trisomy 21 represents an excellent model to study the origin and progression of leukemia. However, trisomy 21 can also occur as a somatic chromosome aberration leading to sporadic leukemia. During the 50 years, since the discovery of constitutional trisomy 21 in DS, we have also learned that this small chromosome 21, harboring about 300 genes, may be involved in numerous structural aberrations, e.g., translocations, deletions, and amplifications, in leukemias, lymphomas, and solid tumors. Moreover, genes located on chromosome 21 have been identified that play an important role in tumorigenesis. Somatic mutations of several of these genes have been shown to be associated with different solid tumors, but also constitutional mutations of a specific gene on chromosome 21 leading to myelodysplastic syndromes and acute myeloid leukemia have been described. In this review, the specific forms of myeloid leukemia as well as of acute lymphoblastic leukemia in children with DS will be presented and possible explanations for the paucity of solid tumors in DS will be given. Somatic numerical as well as structural chromosome 21 aberrations in association with leukemias will be described. Finally, the nature and function of specific genes, like RUNX1, TMPRSS2, and TFF, located in 21q, and their role in tumorigenesis will be exemplified.