gebhart/patrepeval huggingface dataset:
Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON) (2016)

NCT01721044; Results.
The Novel Tryptamine Derivative JNJ-26854165 Induces Wild-Type p53- and E2F1-Mediated Apoptosis in Acute Myeloid and Lymphoid Leukemias (2010)

The development of small-molecule activators of p53 is currently focused on malignancies containing a wild-type p53 genotype, which is present in most leukemias. JNJ-26854165 is one such p53-activating agent, but its mechanism of action remains to be elucidated. Here, we report the effects of JNJ-26854165 in acute leukemias. JNJ-26854165 treatment induced p53-mediated apoptosis in acute leukemia cells with wild-type p53, in which p53 rapidly drives transcription-independent apoptosis followed by activation of a transcription-dependent pathway. JNJ-26854165 accelerated the proteasome-mediated degradation of p21 and antagonized the transcriptional induction of p21 by p53. Interestingly, JNJ-26854165 induced S-phase delay and upregulated E2F1 expression in p53 mutant cells, resulting in apoptosis preferentially of S-phase cells. E2F1 knockdown blocked apoptosis induced by JNJ-26854165 in p53 mutant cells. Apoptotic activity of JNJ-26854165 against primary acute leukemia cells was maintained in leukemia/stroma cocultures, unlike doxorubicin, which has reduced cytrotoxicity in coculture systems. JNJ-26854165 synergizes with 1-β-arabinofuranosylcytosine or doxorubicin to induce p53-mediated apoptosis. Our data suggest that JNJ-26854165 may provide a novel therapeutic approach for the treatment of acute leukemias. The presence of p53-independent apoptotic activity in addition to p53-mediated apoptosis induction, if operational in vivo, may prevent the selection of p53 mutant subclones during therapy.
SiGe-channel n-MOSFET by germanium implantation (1991)

The first n-SiGe-channel MOSFETs fabricated using high-dose germanium implantation and solid-phase epitaxy are reported. The polysilicon-gate MOSFETs were fabricated in the same chip in which conventional polysilicon-gate n-MOSFETs were made and their electrical characteristics are compared. The SiGe-channel MOSFETs show some significantly better electrical characteristics as compared to the silicon-channel MOSFETs. For example, the SiGe MOSFETs show higher drain conductance in the triode region and higher transconductance overall. The threshold voltage of the SiGe MOSFET appears to be smaller and the carrier mobility in the channel appears to be higher.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Active Separation Control on the Flap of a Two-Dimensional Generic High-Lift Configuration (2007)

The paper describes experimental results of controlling flow separation by periodic excitation on the flap of a generic high-lift configuration. The single slotted flap of the two-dimensional test model is equipped with a robust and reliable actuator system that fits inside the flap. The flow is excited using a pulsed wall jet that emanates from the upper surface near the flap's leading edge through a small spanwise-oriented slot By preventing the flow from separating or by reattaching the separated flow, lift and drag are substantially improved, resulting in a lift-to-drag ratio enhancement of 20-25 %. Because of the actuator assembly with spanwise individually addressable segments, the separated flow can be forced to attach only to certain parts of the flap. Local spanwise excitation is thus used to generate a rolling moment without the need to deflect an aileron.
Visitor management in the public planning policy context: A case study of Cambridge (1994)

Visitor management plans are increasingly seen by local authorities as an essential contribution they can make towards sustainable tourism. However, tourism is subject to many external influences and is only part of the system of activities and land uses at the destination. Successful visitor management must, therefore, be broadly based and rooted in a wide range of policies. The objectives for sustainable tourism in Cambridge are supported by policies at the European, national, regional, county and local level covering tourism, recreation, transport, the environment, land use and economic development. This results in an integrated policy framework that ensures consistency, encourages cooperation and long‐term planning, makes the best use of resources, opens up additional sources of finance and provides a firm justification for refusing undesirable development. Achieving integration requires the visitor management plan to be seen neither as an end nor as a beginning, but as part of a process. In Cambridge this has involved a commitment to monitoring and reviewing strategies and to ensuring a policy input on tourism issues at all levels of decision making. Appropriate ad hoc bodies have been set up. Visitor management cannot succeed in isolation: other policies must be made to work for it, not frustrate action.
Ofatumumab and its role as immunotherapy in chronic lymphocytic leukemia (2015)

The therapy of chronic lymphocytic leukemia (CLL) is in an era of momentous change from chemotherapy towards targeted therapy. The first phase was the introduction of monoclonal antibodies, especially the anti-CD20 antibodies rituximab, ofatumumab, and obinutuzumab in combination immunochemotherapy. More recently, small molecular inhibitors have emerged which target the B-cell receptor signaling pathways (ibrutinib and idelalisib), BCL-2 (ABT-199), and immunomodulation [immunomodulatory drugs (IMiDs), lenalidomide]. In this rapidly changing landscape, what is the role of the anti-CD20 monoclonal antibody ofatumumab in CLL?
Studies of two different intrachain cGMP-binding sites of cGMP-dependent protein kinase. (1983)

The binding of [3H]cGMP to purified beef lung cGMP-dependent protein kinase (cG kinase) was examined using two methods of membrane filtration which avoided loss of bound [3H]cGMP. The enzyme bound 1.6-2.0 mol of [3H]cGMP/mol of monomer. If the kinase was saturated with [3H]cGMP and then excess unlabeled cGMP was added, [3H]cGMP dissociated from the enzyme as two approximately equal components (Sites 1 and 2). When 8-bromo-cGMP or cIMP was added to the [3H]cGMP-binding reaction at a concentration sufficient to competitively inhibit binding by greater than 50%, the relative amount of the slower or faster component, respectively, of [3H]cGMP dissociation decreased during the cGMP chase. The data indicated that the cG kinase, like its cAMP-dependent protein kinase homologue, possesses two highly conserved intrachain cyclic nucleotide-binding sites which have different dissociation rates and analog specificity. The Ka of the kinase for cGMP was about 20-fold lower using histone instead of heptapeptide as substrate. Aging of the enzyme caused conversion to a higher Ka form of the kinase and an apparent increase in the Site 1 cGMP dissociation rate. Using fresh enzyme and heptapeptide as substrate, Site 1 occupation occurred at lower concentrations of cGMP than did Site 2 occupation, and was associated with an increase in protein kinase activity. However, kinase activity appeared to correlate better with total cGMP binding than with binding to either of the two sites, and the activation by cGMP exhibited positive cooperativity (n = 1.57). It is suggested that both intrachain sites are involved in protein kinase activation. E2 + 4 cGMP in equilibrium E2 . cGMP4 The cG kinase could be photoaffinity-labeled using 8-azido-[32P]cAMP. When the labeled cG kinase was trypsin-treated followed by sodium dodecyl sulfate-slab gel electrophoresis, a single major peptide of approximate Mr = 12,000 was resolved.
Accelerating Convolutional Neural Networks for Continuous Mobile Vision via Cache Reuse. (2017)

Convolutional Neural Network (CNN) is the state-of-the-art algorithm of many mobile vision fields. It is also applied in many vision tasks such as face detection and augmented reality on mobile devices. Though benefited from the high accuracy achieved via deep CNN models, nowadays commercial mobile devices are often short in processing capacity and battery to continuously carry out such CNN-driven vision applications. In this paper, we propose a transparent caching mechanism, named CNNCache, that can substantially accelerate CNN-driven mobile continuous vision tasks without any efforts from app developers. To cache and reuse the computations of the similar image regions which are consecutively captured by mobile devices, CNNCache leverages two novel techniques: an image matching algorithm that quickly identifies similar image regions between images, and a cache-aware CNN inference engine that propagates the reusable regions through varied layers and reuses the computation results at layer granularity. We implement a prototype of CNNCache to run on commodity Android devices, and evaluate it via typical CNN models. The results show that CNNCache can accelerate the execution of CNN models by 20.2% on average and up to 47.1% under certain scenarios, with no more than 3.51% accuracy loss.
Aldose Reductase Regulates Growth Factor-Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Colon Cancer Cells (2006)

Inhibition of prostaglandin E(2) (PGE(2)) and cyclooxygenase (COX)-2 by nonsteroidal anti-inflammatory drugs reduces the progression of colon cancer. Inhibition of aldose reductase (AR; EC. 1.1.1.21.) by sorbinil or by antisense ablation prevented fibroblast growth factor-induced and platelet-derived growth factor-induced up-regulation of PGE(2) synthesis in human colon cancer cells, Caco-2. AR besides reducing aldo-sugars efficiently reduces toxic lipid aldehydes and their conjugates with glutathione. Inhibition of AR prevented growth factor-induced COX-2 activity, protein, and mRNA and significantly decreased activation of nuclear factor-kappaB and protein kinase C (PKC) and phosphorylation of PKC-beta2 as well as progression of Caco-2 cell growth but had no effect on COX-1 activity. Cell cycle analysis suggests that inhibition of AR prevents growth factor-induced proliferation of Caco-2 cells at S phase. Treatment of Caco-2 cells with the most abundant and toxic lipid aldehyde 4-hydroxy-trans-2-nonenal (HNE) or its glutathione-conjugate [glutathionyl-HNE (GS-HNE)] or AR-catalyzed product of GS-HNE, glutathionyl-1,4-dihydroxynonane (GS-DHN), resulted in increased COX-2 expression and PGE(2) production. Inhibition of AR prevented HNE- or GS-HNE-induced but not GS-DHN-induced up-regulation of COX-2 and PGE(2). More importantly, in vivo studies showed that administration of AR-small interfering RNA (siRNA), but not control siRNA, to nude mice bearing SW480 human colon adenocarcinoma cells completely arrested tumor progression. Collectively, these observations suggest that AR is an obligatory mediator of growth factor-induced up-regulation of COX-2, PGE(2), and growth of Caco-2 cells, indicating that inhibition of AR may be a novel therapeutic approach in preventing the progression of colon cancer.
Evidence for At Least Four Antigenic Sites on Type O Foot-and-Mouth Disease Virus Involved in Neutralization; Identification by Single and Multiple Site Monoclonal Antibody-resistant Mutants (1989)

Neutralizing monoclonal antibodies raised against type O foot-and-mouth disease virus have been characterized on the basis of their reactivity with a panel of single site monoclonal antibody-resistant mutants which had defined three antigenic sites. Five antibodies neutralized all these mutants, but by selecting further single site mutants with one of these antibodies it was possible to define a fourth site involved in virus neutralization. Two monoclonal antibodies still neutralized these mutants and all multiple site resistant mutants. One multiple site resistant mutant was resistant to neutralization at each of four antigenic sites but was still efficiently neutralized by type O convalescent cattle sera. The relationship between sites recognized by different monoclonal antibodies generated in different laboratories is discussed.
Ontogeny of lymphocyte homing receptor expression in the mouse thymus. (1986)

The monoclonal antibody MEL-14 has been used in conjunction with immunohistology and multiparameter immunofluorescence to identify and characterize homing receptor-bearing thymocytes at various stages of embryonic and neonatal development. MEL-14hi thymocytes first appear at day 14 of gestation and come to represent about 40% of day 15 fetal thymocytes. Thereafter, the proportion of MEL-14hi thymocytes rapidly declines such that by birth (usually the 20th day of embryonic development) only about 2% of thymocytes are MEL-14hi. Although newborn thymocytes resemble adult thymocytes in this respect, the phenotypic characteristics of fetal and neonatal MEL-14hi thymocytes suggest that this unique subset undergoes a gradual transition from containing exclusively phenotypically immature cells in early gestation to containing predominantly phenotypically mature cells by young adulthood. Thus, virtually none of day 15 MEL-14hi fetal thymocytes are peanut agglutinin (PNA)lo, Ly-1hi, or either Lyt-2-/L3T4+ or Lyt-2+/L3T4-, whereas in the weeks that follow a steadily greater proportion of MEL-14hi thymocytes come to express this mature pattern (roughly 70% at 4 wk of age). Most day 15 MEL-14hi fetal thymocytes appear to express the functional homing receptor molecule, since day 15 fetal thymocytes bind to peripheral lymph node high endothelial venules about 40 to 50% as well as do adult mesenteric node lymphocytes, whereas adult thymocytes bind only about 5% as well. We have also identified a population of outer cortical MEL-14hi Lyt-2-/L3T4- lymphoblasts that appears during thymus regeneration 5 to 6 days after the administration of hydrocortisone. These lymphoblasts express the same phenotype as cells that constitute 40% of the day 15 fetal thymus and only 0.4% of normal adult thymocytes, implying that this particular subset may make up a significant fraction of thymocytes whenever there is a requirement for rapid expansion of the intrathymic and/or peripheral T cell pools. Taken together, these results are consistent with the notion that expression of the MEL-14-defined homing receptor may be closely linked to important intrathymic events that may occur early in T cell development and yet still have an overriding impact on the selection of those thymocytes that will serve as precursors of thymus emigrants.
Quantification of Cyanamide Contents in Herbaceous Plants (2006)

Cyanamide (NH2CN) is found in nature, although it has long been recognized as an industrial product. Distribution of cyanamide in the plant kingdom was investigated using a direct quantitative determination method to detect and measure cyanamide by stable isotope dilution gas chromatography-mass spectrometry (the SID-GC-MS method). The SID-GC-MS method proved to be a robust way to quantify cyanamide contents in the extracts of 101 species of herbaceous plants. The average recovery of cyanamide from all plants tested was 55.6+/-20.3%. Vicia villosa and V. cracca contained cyanamide at 369-498 microg/gFW and 3,460-3,579 microg/gFW respectively, while the other 99 species contained no detectable cyanamide (<1 microg/gFW). This result suggests that distribution of cyanamide in the plant kingdom is limited and uneven.
Anti-TNF therapy for other inflammatory conditions. (2003)

The use of biological agents in inflammatory conditions is rapidly increasing. TNFalpha blocking treatments have changed the course of rheumatoid arthritis, Crohn's disease, juvenile rheumatoid arthritis and psoriatic arthritis. Open label studies with TNFalpha inhibitors in other inflammatory conditions such as adult Still's disease, uveitis, Wegener's granulomatosis, Behçet's disease, scleroderma, Sjögren's syndrome, sarcoidosis, pyoderma gangrenosum, polymyositis/dermatomyositis have shown promising results. However, whether anti-TNFalpha therapy can be safely and efficaciously applied to these other inflammatory disorders requires further controlled studies.
Comparing fuzzy logic with classical controller designs (1987)

A unified approach for comparing the performance of fuzzy and nonfuzzy controller designs is presented. Relationships are established between the gain parameters for the two classes of controller designs. The methods presented apply equally well to proportional-plus-integral, linear multiband, and multilevel relay controllers.
CRISPR technologies and the search for the PAM-free nuclease (2021)

The ever-expanding set of CRISPR technologies and their programmable RNA-guided nucleases exhibit remarkable flexibility in DNA targeting. However, this flexibility comes with an ever-present constraint: the requirement for a protospacer adjacent motif (PAM) flanking each target. While PAMs play an essential role in self/nonself discrimination by CRISPR-Cas immune systems, this constraint has launched a far-reaching expedition for nucleases with relaxed PAM requirements. Here, we review ongoing efforts toward realizing PAM-free nucleases through natural ortholog mining and protein engineering. We also address potential consequences of fully eliminating PAM recognition and instead propose an alternative nuclease repertoire covering all possible PAM sequences.
Treatment machines for external beam radiotherapy (2005)

Since the inception of radiotherapy soon after the discovery of X rays by Roentgen in 1895, the technology of X ray production has first been aimed towards ever higher photon and electron beam energies and intensities, and more recently towards computerization and intensity modulated beam
Neurotrophic Effects of the Peptide NAP: A Novel Neuroprotective Drug Candidate (2006)

This short review outlines the scientific progression from the neuropeptide vasoactive intestinal peptide as a neuroprotective agent that acts through glial cells to increase and modulate the synthesis and secretion of novel neuroprotective substances. Recent development in the studies on activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF) and short peptide derivatives of these proteins, ADNF-9 and NAP suggest that these peptides are neurotrophic and promote neurite outgrowth. These short peptides hold promise in future neuroprotective/neurotrophic drug development. Clinical development of NAP is currently in progress by Allon Therapeutics, Inc.
Mastering Microsoft Outlook 2000 Premium Edition (1999)

From the Publisher:
Written for business people who want to move beyond the basics, this Premium Edition delivers all the basic concepts plus expanded coverage of hot and advanced topics. This definitive guide to Microsoft Outlook tackles challenging topics such as security, e-mail decoding, using Outlook with the Web, integrating Outlook with other Office applications, compatibility with email services, and setting up Outlook for a LAN and as an Exchange Server client. With a comprehensive troubleshooting section, this is the Outlook book users will turn to for answers to the tough questions. It covers Outlook for stand-alone LANs and Exchange Server environments, plus Outlook Express. Includes special bonus section300 pages on using Outlook to build custom applications! CD contains productivity-enhancing software.
ConusVenoms: A Rich Source of Novel Ion Channel-Targeted Peptides (2004)

The cone snails (genus Conus) are venomous marine molluscs that use small, structured peptide toxins (conotoxins) for prey capture, defense, and competitor deterrence. Each of the 500 Conus can express approximately 100 different conotoxins, with little overlap between species. An overwhelming majority of these peptides are probably targeted selectively to a specific ion channel. Because conotoxins discriminate between closely related subtypes of ion channels, they are widely used as pharmacological agents in ion channel research, and several have direct diagnostic and therapeutic potential. Large conotoxin families can comprise hundreds or thousands of different peptides; most families have a corresponding ion channel family target (i.e., omega-conotoxins and Ca channels, alpha-conotoxins and nicotinic receptors). Different conotoxin families may have different ligand binding sites on the same ion channel target (i.e., mu-conotoxins and delta-conotoxins to sites 1 and 6 of Na channels, respectively). The individual peptides in a conotoxin family are typically each selectively targeted to a diverse set of different molecular isoforms within the same ion channel family. This review focuses on the targeting specificity of conotoxins and their differential binding to different states of an ion channel.
Effect of Chain Persistence Length on the Moduli of Block Copolymer Films (1999)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTEffect of Chain Persistence Length on the Moduli of Block Copolymer FilmsN. DanView Author Information Department of Chemical Engineering, University of Delaware, Newark, Delaware 19716 Cite this: Macromolecules 1999, 32, 5, 1686–1690Publication Date (Web):February 9, 1999Publication History Received20 March 1998Revised14 December 1998Published online9 February 1999Published inissue 1 March 1999https://pubs.acs.org/doi/10.1021/ma980445whttps://doi.org/10.1021/ma980445wbrief-reportACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views160Altmetric-Citations1LEARN 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 SUBJECTS:Copolymers,Flexibility,Interfaces,Layers,Stiffness Get e-Alerts
Preventive Effect of Antioxidants on Lipid Peroxidation in the Retina (1991)

Lipid peroxidation was induced with porcine retinal homogenates using ferric iron or UV light. A number of lipid and aqueous-soluble antioxidants were tested and their protective effects measured after 60 min of exposure. The iron system produced up to 5 times more lipid hydroperoxides as quantified by the fluorescence thiobarbituric acid (TBA) assay. Of the three substituted dialkyl phenols evaluated, the most efficient was compound S-17224 which was able to afford greater than 90% protection at 10(-4) M concentration in the iron-induced system. At 10(-5) M, inhibition was 78% and at 10(-6) M 33%. By comparison, 10(-4) M gamma-oryzanol inhibited the reaction by 61% and alpha-tocopherol by only 14%. The combination of 10(-6) M S-17224 and 10(-4) M gamma-oryzanol potentiated the effect by another 23%. In the light-catalyzed system. S-17224 and alpha-tocopherol were more efficient (71%). The model system described here is simple and can be employed to study additional antioxidants as well as in the retinotoxic evaluation of ophthalmic drugs.