gebhart/patrepeval huggingface dataset:
Inhibition Of HDAC6 In Combination With Targeted Agents Results In Broad Synergistic Decreases In Viability In Non-Hodgkin’s Lymphoma (NHL) Cells (2013)

Abstract Histone Deacetylase (HDAC) inhibitors have demonstrated significant clinical benefit as single agents in cutaneous and peripheral T cell lymphomas, and have received FDA approval for these indications. Numerous clinical studies are also ongoing to investigate the potential benefit of combining HDAC inhibitors with other standard of care and investigational agents in various subtypes of lymphoma. ACY-1215 is a first-in-class, orally available selective inhibitor of HDAC6 (approximately 11-fold selective over class I HDAC’s) that is currently in two Phase Ib clinical trials (NCT01323751 and NCT01583283) in combination with dexamethasone and either bortezomib or lenalidomide in multiple myeloma (MM) patients. Beyond MM, preclinical studies in NHL cell lines also demonstrated increased benefit from treatment with ACY-1215 in combination with the proteasome inhibitors bortezomib or carfilzomib (Amengual, et al, ASH, 2012; Dasmahapatra, et al, ASH, 2012). In addition to standard of care therapies, a number of novel targeted agents have recently demonstrated potential clinical benefit in subtypes of NHL, including agents targeting Bruton’s tyrosine kinase (eg. ibrutinib) and the phosphatidyl inositol-3’ kinase family (eg. GS-1101, IPI-145, and GDC-0941). We describe here the therapeutic potential of ACY-1215 in a collection of NHL cell lines both as a single agent and in combination with these novel targeted agents. NHL cell lines derived from diffuse large B cell lymphomas (DLBCL; both germinal center and activated B cell type) and mantle cell lymphomas (MCL) exhibit significantly decreased viability in response to treatment with selective inhibitors of HDAC6, including both ACY-1215 and ACY-775 (approximately 300-fold selective for HDAC6 over HDAC1/2, and 1500-fold selective over HDAC3). Furthermore, combination treatment of NHL lines with ACY-1215 and either ibrutinib, GDC-0941, or GS-1101, in a dose-matrix format resulted in synergistic decreases in cell viability. The relevance of HDAC6 inhibition to this synergistic response was confirmed through the observation of similarly decreased viability when treating cells in combination with the highly selective HDAC6 inhibitor ACY-775. Detailed molecular mechanism of action studies are ongoing and will be presented. Additional studies are also underway to assess the tolerability and efficacy of combinations of these targeted agents with ACY-1215 in xenograft models of lymphoma. Overall, these data support the continued investigation of the activity of ACY-1215 in lymphoma both as a single agent and in combination with the next generation of targeted therapies for B cell lymphomas. Disclosures: Quayle: Acetylon Pharmaceuticals, Inc: Employment, Equity Ownership. Tamang:Acetylon Pharmaceuticals, Inc: Employment, Equity Ownership. Yang:Acetylon Pharmaceuticals, Inc: Employment, Equity Ownership. Jones:Acetylon Pharmaceuticals, Inc: Employment, Equity Ownership.
Identification of hidden associations among eukaryotic genes through statistical analysis of coevolutionary transitions (2023)

Coevolution at the gene level, as reflected by correlated events of gene loss or gain, can be revealed by phylogenetic profile analysis. The optimal method and metric for comparing phylogenetic profiles, especially in eukaryotic genomes, are not yet established. Here, we describe a procedure suitable for large-scale analysis, which can reveal coevolution based on the assessment of the statistical significance of correlated presence/absence transitions between gene pairs. This metric can identify coevolution in profiles with low overall similarities and is not affected by similarities lacking coevolutionary information. We applied the procedure to a large collection of 60,912 orthologous gene groups (orthogroups) in 1,264 eukaryotic genomes extracted from OrthoDB. We found significant cotransition scores for 7,825 orthogroups associated in 2,401 coevolving modules linking known and unknown genes in protein complexes and biological pathways. To demonstrate the ability of the method to predict hidden gene associations, we validated through experiments the involvement of vertebrate malate synthase-like genes in the conversion of (<i>S</i>)-ureidoglycolate into glyoxylate and urea, the last step of purine catabolism. This identification explains the presence of glyoxylate cycle genes in metazoa and suggests an anaplerotic role of purine degradation in early eukaryotes.
Green Metrics for Energy-aware IT Systems (2011)

This paper presents a novel approach to characterise applications with respect to their energy consumption by using a set of energy-related metrics, called Green Metrics. These indicators are based on energy consumption measurements, such as indexes of computing resource usage, of environmental impact, and even of development costs required to (re)design an application in order to optimise its energy consumption footprint, or of organizational factors related to application management. Our approach is framed in the GAMES (Green Active Management of Energy in IT Service centres) EU Project1 about green IT. In this paper, we define four clusters of Green Metrics enabling to feature an application in terms of the energy it consumes at run time. Such metrics are the basis for measuring the "greenness" of an application and to detect where it consumes and wastes energy. Hints are provided to improve applications design and execution. We show within an application scenario how monitoring and evaluation of the Green Metrics helps to improve energy efficiency.
Characterization of Purified Lipoxygenase Extracts from Fusarium proliferatum (1998)

A crude lipoxygenase (FI) extract from Fusarium proliferatum was partially purified by ammonium sulfate precipitation (FII). The purification of fraction FII by size-exclusion chromatography resulted in three major peaks, FIIIa, FIIIb, and FIIIc. Fraction FIIIa demonstrated the highest specific lipoxygenase activity as well as the highest recovery and was therefore further purified. The purification procedure resulted in one major fraction (FIV) by ion-exchange chromatography, and the presence of one major and two minor protein bands in both the native and sodium dodecyl sulfate−polyacrylamide gel electrophoresis patterns. The purified enzyme demonstrated approximately 2.5 times more activity toward mono- and dilinolein and 1.5 times more with linolenic and arachidonic acids than that exhibited toward linoleic acid at pH 6.0; however, at pH 10.5, this enzymatic fraction possessed an overall preference toward linoleic acid. The purified fraction produced mainly the 13-hydroperoxides (HPODs) from linoleic acid at pH 6.0 and the 9- and 13-HPODs, at a ratio of approximately 1:1, at pH 10.5. In addition, the presence of a lipoxygenase activity producing the 10- and 12-HPODs was also suggested at pH 10.5. Keywords: Lipoxygenase; Fusarium proliferatum; purification; characterization
Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus. (1995)

The contribution to systemic lupus erythematosus (SLE) of three lupus-associated polymorphisms (involving the C4A2 complement component, Humhv3005 and the T cell antigen receptor alpha chain gene) are investigated in 81 individuals from 14 multiplex SLE families, 41 unrelated lupus patients, and 88 unrelated healthy controls. The results show a strong association between C4A deletion and SLE in these families. While the current study confirms the previously reported association between hv3005 deletion and sporadic SLE, the study fails to support this association in familial SLE patients. Moreover, no correlation is detected between the occurrence of hv3005 deletion and C4A null alleles in lupus patients, suggesting that the effects of these genetic polymorphisms on predisposition to lupus are independent. The previously reported lupus-associated T cell receptor (TCR) alpha chain polymorphism is not detected in any of the individuals studied here. The combined data suggest that C4A null alleles predispose strongly to development of lupus, whereas the influence of hv3005 deletion is relatively weak. The results also suggest that contributions of weak susceptibility genes such as hv3005 to disease predisposition may be obscured by the effects of stronger genetic factors and thus need to be examined in patients lacking these factors.
Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2016 (2016)

Summary Standards are essential to the advancement of science and technology. In systems and synthetic biology, numerous standards and associated tools have been developed over the last 16 years. This special issue of the Journal of Integrative Bioinformatics aims to support the exchange, distribution and archiving of these standards, as well as to provide centralised and easily citable access to them.
A novel receptor for diadenosine polyphosphates coupled to calcium increase in rat midbrain synaptosomes (1995)

1. Diadenosine polyphosphates, Ap4A and Ap5A, as well as ATP, alpha,beta-MeATP and ADP-beta-S, were able to elicit variable intrasynaptosomal Ca2+ increases in rat midbrain synaptic terminals. The origin of the Ca2+ increment was the extra synaptosomal space since the elimination of extracellular Ca2+ abolished the effect of all the agonists. 2. The P2-purinoceptor antagonist, suramin, did not affect the Ca(2+)-increase evoked by diadenosine polyphosphates but dramatically blocked the Ca2+ entry induced by ATP and its synthetic analogues. 3. The actions of Ap5A and ATP on the intrasynaptosomal Ca2+ increase did not cross-desensitize. 4. Concentration-response studies for diadenosine polyphosphates showed pD2 values of 54.5 +/- 4.2 microM and 55.6 +/- 3.8 microM for Ap4A and Ap5A, respectively. 5. The entry of calcium induced by diadenosine polyphosphates could be separated into two components. The first represented a selective voltage-independent Ca2+ entry; the second, a sustained phase which was voltage-dependent. 6. Studies on the voltage-dependent Ca(2+)-channels involved in the effects of the diadenosine polyphosphates, demonstrated that omega-conotoxin G-VI-A inhibited the sustained Ca(2+)-entry, suggesting the participation of an N-type Ca(2+)-channel. This toxin was unable to abolish the initial cation entry induced by Ap4A or Ap5A. omega-Agatoxin IV-A, tetrodotoxin, or nifedipine did not inhibit the effects of the diadenosine polyphosphates. 7. The effect of ATP on Ca(2+)-entry was abolished by nifedipine and omega-conotoxin G-VI-A, suggesting the participation of L- and N-type Ca(2+)-channels in the response to ATP. 8. These data suggest that Ap4A, Ap5A and ATP activate the same intracellular Ca2+ signal through different receptors and different mechanisms. Ap4A and Ap5A induce a more selective Ca2+-entry in a voltage-independent process. This is the first time that a selective action of diadenosine polyphosphate through receptors other than P1 and P2-purinoceptors has been described.
Development of Organic‐Dye‐Doped Silica Nanoparticles in a Reverse Microemulsion (2004)

A new synthesis method to produce various organic‐dye‐doped silica nanoparticles using a reverse microemulsion has been developed. These nanoparticles show extremely high fluorescent signals (see Figure), excellent photostability, and size uniformity and tenability. These dye‐doped silica nanoparticles can be used for various applications, especially in ultra‐sensitive bioanalysis and in biomedical monitoring.
Partial-field decomposition analysis of full-scale supersonic jet noise using optimized-location virtual references (2018)

Supersonic jet noise reduction efforts benefit from targeted source feature extraction and high-resolution acoustic imaging. Another useful tool for feature extraction is partial field decomposition of sources into independent contributors. Since such decomposition processes are nonunique, care must be taken in the physical interpretation of decomposed partially coherent aeroacoustic fields. The optimized-location virtual reference method (OLVR) is a partial field decomposition designed to extract physically meaningful source and field information through the strategic placement of virtual references within a reconstructed field. The OLVR method is applied here to obtain spatially distinct and ordered partial sources at multiple frequencies of a full-scale, high-performance supersonic jet engine operating at 100% engine power. Partial sources are shown to mimic behaviors of the total source distributions including monotonic growth and decay. Because of finite spatial coherence, multiple partial sources are used to reproduce far-field radiation away from the main lobe, and the number of required sources increases with increasing frequency. An analytical multiwavepacket model is fitted to the partial sources to demonstrate how OLVR partial fields can be leveraged to produce reduced-order models.
Incentives for content availability in memory-less peer-to-peer file sharing systems (2005)

In this paper we address the issue of content availability in p2p file sharing systems. Content availability is a public good: the copying of a file by one peer does not prevent another peer also from copying it; but contributing files to the common pool is costly. The asymptotic analysis of certain public good models for p2p file sharing suggests that when the aim is to maximize social welfare, a fixed contribution scheme in terms of the number of files shared per unity of time can be asymptotically optimal as the number of participants n grows to infinity. However, the enforcement of such an incentive scheme is not straightforward in a realistic p2p system, where no trusted software or central entity accounting for peers' transactions can be assumed and peers are free to change their identity with no cost. We present a realistic version of the fixed contribution scheme, which does not require the use of system memory but relies only on the time peers are consuming resources to ensure that they contribute adequately. We describe the functionality that should be supported for enforcement and discuss the additional incentive issues that arise in this context, proposing some practical solutions to address them. We also formulate a suitable economic model to estimate the efficiency-loss of the proposed mechanism (compared to the one achieved using the theoretically optimal schemes under complete and incomplete information) and provide some insights for the correct tuning of its basic parameters. Our first results indicate that the proposed mechanism constitutes a good compromise between economic efficiency and implementability and should lead to some interesting and practical solutions for providing incentives for content availability in p2p systems.
Analysis of Heterogeneous Data in Ultrahigh Dimensions (2005)

This chapter contains sections titled: Introduction Data Clustering Techniques: A Brief Survey Algebraic Transformations Discrete Geometry Methods Learning Techniques Latent Semantic Indexing Experimental Results Summary Acknowledgments References
Numerical analysis of fluid flow in continuous casting mold by bubble dispersion model. (1991)

Surface and internal defects of cold rolled steel sheet attributable to steelmaking conditions arise from the entrapment, by the solidifying shell in the continuous casting mold, of alumina clusters, moid powder, and argon gas bubbles blown into the immersion nozzle. In order to prevent such defects, it is necessary to control the fluid flow of molten steel in the mold. In this study, actual-scale water model experiments were first carried out to investigate in detail the fluid flow pattern and distribution of local gas holdup in the mold. Subsequently, a hydrodynamic analysis model was developed considering the etfect of the buoyant force of gas bubbles on fluid flow and the continuity of local gas holdup (bubble dispersion model). This modelhas made it possible to estimate the liquid velocity profile, andthe distributions of local gas holdup and inclusions in the mold.
A new deterioration model for electrolytic capacitors in direct current to direct current (DC-DC) converters (2012)

The output filter aluminum electrolytic capacitor is one of the key components that determine the life of direct current to direct current (DC-DC) converters, and so, establishing a deterioration model for the electrolytic capacitor is the basis for analyzing the impact on the converters’ performances. Generally, the main parasitic parameters that indicate the electrolytic capacitor deterioration such as capacitance (C) and equivalent series resistance (ESR) are separately considered when building the model. However, taking the Buck-Boost converter as the research object, this paper discussed the impact of the two kinds of parasitic parameters simultaneous degradation on the DC-DC converters. Firstly, according to the electrolytic capacitor failure mechanisms, a joint degradation model for the C and ESR-a new deterioration model for the electrolytic capacitor was established. On the basis, this paper discussed the impact on the system pole-zero of the parasitic parameters degradation, analyzed the electrolytic capacitor deterioration on how to affect the performances of the DC-DC converter, and verified the theoretical analysis results through the software simulation experiments. The new model provides the theoretical basis for monitoring the health state of DC-DC converters.

	 

	Key words: Electrolytic capacitor, deterioration, capacitance, equivalent series resistance (ESR), joint degradation model, pole-zero.
An Executive Role Study: Investigating Expectation Enactment in the Role of the Chancellor of the University of the Nations-Kona (2001)

This research created an Expectation Enactment Analysis, which was used to study the Chancellor of a Christian, faith-based, missions-oriented university. The study was grounded in the field of managerial work, jobs, and behaviour. It also drew on symbolic interactionism, role theory, role identity theory, and enactment theory.

The framework for Expectation Enactment Analysis contains seven components viewed from three perspectives. The components are 1) identification of contextual parameters, 2) Role Episode analyses, 3) interviews of the Chancellor and his Role Set Members, 4) identification of Managerial Agenda items, tasks, and activities, 5) identification of three Expectation Enactment Programs, 6) expectations enacted, and 7) Impact Analysis. The three perspectives are organizational, interpersonal, and personal.

This Analysis developed the Expectation Enactment Program model-an open systems, role construct--integrating the managerial agenda as an internal standard for internal processing and external performance. Additionally, the Analysis linked external performance to expectation enactment and the Role Incumbent's impact on the organization, his Role Set Members, and himself.

The study employed a naturalistic, inquiry from the inside approach characterised by a longitudinal, field based, case study format relying on qualitative methods. It was an exploratory study designed to create a conceptual framework for further developing an understanding of managerial roles. This methodology involved intensive participation on the part of the researcher. As a result, it extends this type of research only occasionally seen in the field of managerial work, jobs, and behaviour.

Expectation Enactment Analysis integrates work from a breadth of related disciplines. Such an Analysis offers the possibility of understanding 1) the functioning of a Role Incumbent in role, 2) the impact of that functioning on an organization, Role Set Members, and him/herself, and 3) potential leverage points for creating change within the organization through the Role Incumbent. The Analysis offers future possibilities for application in research, management education, and executive development.
Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy (2015)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTCarbon Nanomaterials for Biological Imaging and Nanomedicinal TherapyGuosong Hong, Shuo Diao, Alexander L. Antaris, and Hongjie Dai*View Author Information Department of Chemistry, Stanford University, Stanford, California 94305, United States*E-mail: [email protected]Cite this: Chem. Rev. 2015, 115, 19, 10816–10906Publication Date (Web):May 21, 2015Publication History Received5 January 2015Published online21 May 2015Published inissue 14 October 2015https://pubs.acs.org/doi/10.1021/acs.chemrev.5b00008https://doi.org/10.1021/acs.chemrev.5b00008review-articleACS PublicationsCopyright © 2015 American Chemical SocietyRequest reuse permissionsArticle Views34513Altmetric-Citations1131LEARN 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:Biological imaging,Carbon nanomaterials,Carbon nanotubes,Fluorescence,Fluorescence imaging Get e-Alerts
Challenges, impact and the future (2019)

We are at the very beginning of understanding the respiratory microbiome and its influence on health and disease; early indications are that this might be profound. Though it builds on decades of research in other fields, including environmental microbiology, clinical microbiology, gut and oral microbiome work, currently we are describing the organisms that are present in different parts of the respiratory tract under different conditions. Few studies have done so longitudinally and the relationship with disease is largely associative, making translation to clinical applications challenging. We are beginning to understand the nature of the challenges and we can draw common problems from the chapters of this Monograph.
A Survey on Deep Learning for Named Entity Recognition (2020)

Named entity recognition (NER) is the task to identify mentions of rigid designators from text belonging to predefined semantic types such as person, location, organization etc. NER always serves as the foundation for many natural language applications such as question answering, text summarization, and machine translation. Early NER systems got a huge success in achieving good performance with the cost of human engineering in designing domain-specific features and rules. In recent years, deep learning, empowered by continuous real-valued vector representations and semantic composition through nonlinear processing, has been employed in NER systems, yielding stat-of-the-art performance. In this paper, we provide a comprehensive review on existing deep learning techniques for NER. We first introduce NER resources, including tagged NER corpora and off-the-shelf NER tools. Then, we systematically categorize existing works based on a taxonomy along three axes: distributed representations for input, context encoder, and tag decoder. Next, we survey the most representative methods for recent applied techniques of deep learning in new NER problem settings and applications. Finally, we present readers with the challenges faced by NER systems and outline future directions in this area.