gebhart/patrepeval huggingface dataset:
CD47‐signal regulatory protein α signaling system and its application to cancer immunotherapy (2018)

Tumor cells evade immune surveillance through direct or indirect interactions with various types of immune cell, with much recent attention being focused on modifying immune cell responses as the basis for the development of new cancer treatments. Signal regulatory protein α (SIRPα) and CD47 are both transmembrane proteins that interact with each other and constitute a cell-cell communication system. SIRPα is particularly abundant in myeloid cells such as macrophages and dendritic cells, whereas CD47 is expressed ubiquitously and its expression level is elevated in cancer cells. Recent studies have shown that blockade of CD47-SIRPα interaction enhances the phagocytic activity of phagocytes such as macrophages toward tumor cells in vitro as well as resulting in the efficient eradication of tumor cells in a variety of xenograft or syngeneic mouse models of cancer. Moreover, CD47 blockade has been shown to promote the stimulation of tumor-specific cytotoxic T cells by macrophages or dendritic cells. Biological agents, such as Abs and recombinant proteins, that target human CD47 or SIRPα have been developed and are being tested in preclinical models of human cancer or in clinical trials with cancer patients. Preclinical studies have also suggested that CD47 or SIRPα blockade may have a synergistic antitumor effect in combination with immune checkpoint inhibitors that target the adaptive immune system. Targeting of the CD47-SIRPα signaling system is thus a promising strategy for cancer treatment based on modulation of both innate and acquired immune responses to tumor cells.
Clustering strategy and method selection (2015)

This paper is a chapter in the forthcoming Handbook of Cluster Analysis, Hennig et al. (2015). For definitions of basic clustering methods and some further methodology, other chapters of the Handbook are referred to. To read this version of the paper without the Handbook, some knowledge of cluster analysis methodology is required. The aim of this chapter is to provide a framework for all the decisions that are required when carrying out a cluster analysis in practice. A general attitude to clustering is outlined, which connects these decisions closely to the clustering aims in a given application. From this point of view, the chapter then discusses aspects of data processing such as the choice of the representation of the objects to be clustered, dissimilarity design, transformation and standardization of variables. Regarding the choice of the clustering method, it is explored how different methods correspond to different clustering aims. Then an overview of benchmarking studies comparing different clustering methods is given, as well as an out- line of theoretical approaches to characterize desiderata for clustering by axioms. Finally, aspects of cluster validation, i.e., the assessment of the quality of a clustering in a given dataset, are discussed, including finding an appropriate number of clusters, testing homogeneity, internal and external cluster validation, assessing clustering stability and data visualization.
Intelligent Agents for Flexible Workflow Systems (1998)

Many practitioners and researchers in workflow systems have stressed the importance of flexibility in such systems. On the one hand, organizational control requires detailed modeling of workflow processes and stringent procedural guidelines. On the other hand, dramatic organizational changes and frequent exceptions demand system flexibility. Few satisfactory solutions have been provided thus far to deal with this issue of flexibility because workflow systems developed using conventional software techniques are costly to modify and offer limited flexibility in general. However, recent progress in intelligent agents, especially autonomous and adaptive agents, seems to hold promise in providing increased flexibility in software systems. In this paper, we discuss the problem of flexibility in workflow systems, overview the features of intelligent agents, survey their applications in workflow system prototypes, and propose several research issues on the development of agent-based workflow systems to achieve increased flexibility.
2013 ESH/ESC Guidelines for the management of arterial hypertension (2013)

The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) follow the guidelines jointly issued by the two societies in 2003 and 2007 [1,2]. Publication of a new document 6 years after the previous one was felt to be timely because, over this period, important studies have been conducted and many new results&#13;\nhave been published on both the diagnosis and treatment of individuals with an elevated blood pressure (BP), making refinements, modifications and expansion of the previous recommendations necessary.
Single-Cell Microarray Analysis in Hippocampus CA1: Demonstration and Validation of Cellular Heterogeneity (2003)

Laser capture microdissection in combination with microarrays allows for the expression analysis of thousands of genes in selected cells. Here we describe single-cell gene expression profiling of CA1 neurons in the rat hippocampus using a combination of laser capture, T7 RNA amplification, and cDNA microarray analysis. Subsequent cluster analysis of the microarray data identified two different cell types: pyramidal neurons and an interneuron. Cluster analysis also revealed differences among the pyramidal neurons, indicating that even a single cell type in vivo is not a homogeneous population of cells at the gene expression level. Microarray data were confirmed by quantitative RT-PCR and in situ hybridization. We also report on the reproducibility and sensitivity of this combination of methods. Single-cell gene expression profiling offers a powerful tool to tackle the complexity of the mammalian brain.
Cellular‐Level Body Composition Model: A New Approach to Studying Fat‐free Mass Hydration (2000)

Fat-free mass hydration, the ratio of total body water (TBW) to fat-free mass (FFM), is stable at approximately 0.73 in mammals, and this constancy provides a means of estimating total body fat in vivo. As there is no mechanistic theory to explain the magnitude and variability in TBW/FFM, the present investigation describes a cellular-level model indicating that FFM hydration is determined by four factors: body cell mass hydration, extracellular fluid hydration, ratio of extracellular solids to TBW, and ratio of extracellular water to intracellular water. According to the model, TBW/FFM can be predicted for adult humans as a mean of 0.73, and a variation range 0.69-0.77. The suggested modeling approach provides a conceptual framework for TBW-fat estimation method and identifies important areas that remain to be studied.
Interaction of polyamine gene vectors with RNA leads to the dissociation of plasmid DNA‐carrier complexes (2006)

These data suggest that RNA induces pDNA dissociation from the polyamine gene vectors. Furthermore, this process apparently occurs in the cytoplasm before the gene vectors enter the nucleus.
Unusual DNA duplex and hairpin motifs (2003)

Single-stranded DNA or double-stranded DNA has the potential to adopt a wide variety of unusual duplex and hairpin motifs in the presence (trans) or absence (cis) of ligands. Several principles for the formation of those unusual structures have been established through the observation of a number of recurring structural motifs associated with different sequences. These include: (i) internal loops of consecutive mismatches can occur in a B-DNA duplex when sheared base pairs are adjacent to each other to confer extensive cross- and intra-strand base stacking; (ii) interdigitated (zipper-like) duplex structures form instead when sheared G*A base pairs are separated by one or two pairs of purine*purine mismatches; (iii) stacking is not restricted to base, deoxyribose also exhibits the potential to do so; (iv) canonical G*C or A.T base pairs are flexible enough to exhibit considerable changes from the regular H-bonded conformation. The paired bases become stacked when bracketed by sheared G.A base pairs, or become extruded out and perpendicular to their neighboring bases in the presence of interacting drugs; (v) the purine-rich and pyrimidine-rich loop structures are notably different in nature. The purine-rich loops form compact triloop structures closed by a sheared G*A, A*A, A*C or sheared-like G(anti)*C(syn) base pair that is stacked by a single residue. On the other hand, the pyrimidine-rich loops with a thymidine in the first position exhibit no base pairing but are characterized by the folding of the thymidine residue into the minor groove to form a compact loop structure. Identification of such diverse duplex or hairpin motifs greatly enlarges the repertoire for unusual DNA structural formation.
The Preparation of N-Mono-substituted and Unsymmetrically Disubstituted Piperazines (1944)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation of N-Mono-substituted and Unsymmetrically Disubstituted PiperazinesRichard Baltzly, Johannes S. Buck, Emil Lorz, and William SchönCite this: J. Am. Chem. Soc. 1944, 66, 2, 263–266Publication Date (Print):February 1, 1944Publication History Published online1 May 2002Published inissue 1 February 1944https://pubs.acs.org/doi/10.1021/ja01230a031https://doi.org/10.1021/ja01230a031research-articleACS PublicationsRequest reuse permissionsArticle Views720Altmetric-Citations37LEARN 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
Semi-Preparative HPLC Separations of E and Z Isomers of New Aromatic Retinoids (1984)

Abstract Semi-preparative scale HPLC separations of E and Z isomers of new aromatic retinoids with α ⋍1 are reported. Clean separations with quantitative yields were achieved in less than 1 hour by normal phase HPLC using an analytical instrument.
DLFM (2000)

The DataLinks technology developed at IBM Almaden Research Center and now available in DB2 UDB 5.2 introduces a new data type called DATALINK for a database to reference and manage files stored external to the database. An external file is put under a database control by “linking” the file to the database. Control to a file can also be removed by “unlinking” it. The technology provides transactional semantics with respect to linking or unlinking the file when DATALINK value is stored or updated. Further more, it provides the following set of properties: (1) managing access control to linked files, (2) enforcing referential integrity, such as referenced file cannot be deleted or renamed as long as it is referenced from the RDBMS, and (3) providing coordinated backup and recovery of RDBMS data with the file data. DataLinks File Manager (DLFM) is a key component of the DataLinks technology. DLFM is a sophisticated SQL application with a set of daemon processes residing at a file server node that work cooperatively with the host database server(s) to manage external files. To reduce the number of messages between database server and DLFM, DLFM maintains a set of meta data on the file system and the files that are under database control. One of the major decisions we made was to build DLFM on top of an existing database manager, such as DB2, instead of implementing a proprietary persistent data store. We have mixed feelings about using the RDBMS to build such a resource manager. One of the major challenges is to support transactional semantics for DLFM operations. To do this, we implemented the two-phase commit protocol in DLFM and designed an innovative scheme to enable rolling back transaction update after local database commit. Also a major gotchas is that the RDBMS' cost based optimizer generates the access plan, which does not take into account the locking costs of a concurrent workload. Using the RDBMS as a black box can cause “havoc” in terms of causing the lock timeouts and deadlocks and reducing the throughput of a concurrent workload. To solve the problem, we came up with a simple but effective way of influencing the optimizer to generate access plans matching the needs of DLFM implementation. Also several precautions had to be taken to ensure that lock escalation did not take place; next key locking was disabled to avoid deadlocks on heavily used indexes and SQL tables; and timeout mechanism was applied to break global deadlocks. We were able to run 100-client workload for 24 hours without much deadlock/timeout problem in system test. This paper describes the motivation for building the DLFM and the lessons that we have learned from this experience.
C1 inhibitor deficiency: consensus document (2005)

We present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis is confirmed by the presence of a low serum C4 and absent or greatly reduced C1 inhibitor level or function. The condition can cause fatal laryngeal oedema and features indistinguishable from gastrointestinal tract obstruction. Attacks can be precipitated by trauma, infection and other stimulants. Treatment is graded according to response and the clinical site of swelling. Acute treatment for severe attack is by infusion of C1 inhibitor concentrate and for minor attack attenuated androgens and/or tranexamic acid. Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There are a number of new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist. Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification.
Inhibition of the Subgenomic Hepatitis C Virus Replicon in Huh-7 Cells by 2′-Deoxy-2′-Fluorocytidine (2004)

2'-Deoxy-2'-fluorocytidine (FdC) is a potent inhibitor of the hepatitis C virus RNA replicon in culture, and FdC-5'-triphosphate is an effective inhibitor of the NS5B polymerase. Dynamic profiling of cell growth in an antiviral assay showed that FdC caused cytostasis due to an S-phase arrest. These observations demonstrate that FdC treatment is affecting both a viral target and a cellular target.
The use of CAD/CAM technology in prosthetics and orthotics--current clinical models and a view to the future. (2001)

This report examines the current clinical uses of CAD/CAM in prosthetics and orthotics. We conducted interviews to contrast patterns of CAD/CAM use in different private practice settings, at two different teaching institutions, and within two large Prosthetic and Orthotic delivery systems. Investigation into these patterns of use has revealed several lessons. First, there currently exist several very different models of use in clinical practice and these different models will most likely continue. The clinical models range from all traditional techniques with no use of CAD/CAM, to full in-house suites of CAD/CAM equipment with extensive utilization, to a simplified office with minimal in-house equipment and minimal fabrication and a near total dependency on central fabrication. Second, a growing number of prosthetic and orthotic devices are successfully being fabricated and fit with CAD/CAM technology after starting the process with simple measurements instead of casted, scanned, or digitized exact anatomic data. Starting the CAD process with "by-the-numbers approach" has revealed the reality that for some devices, the "input" needed to define the shape of the residual limb or torso, may not need to be as accurate as originally thought. Third, the fabrication techniques that are currently being used with CAD/CAM systems are still rather traditional techniques. Most devices are still laminated or formed over computer carved models. Although research continues into advanced fabrication techniques, the prosthetics and orthotics industry has not yet taken advantage of the possibilities in the computer-assisted manufacturing side of the equation. Finally, the business of manufacturing and selling up-to-date CAD/CAM equipment and software has a tremendous impact on how this technology is used in prosthetics and orthotics. The size of the prosthetics and orthotics industry and the potential number of customers for major equipment are relatively small. Being in the business of providing the advanced CAD/CAM systems of tomorrow is an expensive and difficult proposition. Current users of full in-house CAD systems have expressed concern that upgrading equipment and software might not be economical with today's decreasing revenues. For all of these reasons, many believe that the number of practitioners who use a central fabrication model will grow more rapidly than the number of practitioners who own and operate a full in-house system.
Research on organization method of development activities for complicated product (2005)

In order to realize the target to analyze and control microcosmic process of product development according to different level and region in different phase, a kind of planning and design method of product development process was brought forth which based on self-organizing and organized methodology. In the process of task stratification and decomposition and product development based on restraint, the restraints and influence factors in connection with process were reflected and embodied by logic state and evaluation probability among activity nodes. By applying nature and principle of reachable matrix in graphics theory, activity sequence and its organization route of product development were analyzed quantitatively, macroscopic process management and microcosmic process control of product development were realized, and the organization mode, and make state evolution and work flow of development activity be observed and analyzed under the transparent and controllable environment all the time. All these help project manager to explicit the primary route and key point juncture of product development process, to overcome the difficulty of traditional method in the way of modeling and analysis by synthesizing multiple elementals and crossing entire process.
Real-time x-ray imaging with flat panels (1998)

To provide real-time x-ray imaging, industry relies almost entirely on the combination of the x-ray image intensifier and the high-performance television camera. Although these devices have ben pushed to remarkable degrees of performance, they remain complex electro-optical assemblies with significant built-in errors, instabilities and degradation mechanisms. We describe a replacement for these system utilizing as a sensor a large array of amorphous silicon photodiodes and thin-film switching transistors. Specifically, the equipment described is a replacement for a 9-inch dual-mode x-ray image intensifier with a high performance 2000-line digital tv camera capable of operating in both real-time video radioscopic and high-performance radiographic modes.
A set of interactions to rotate solids in 3D geometry context (2013)

Tablets with touch-screens, multi-touch interfaces and various sensors are becoming increasingly common. More and more schools are testing them with their pupils in the hope of bringing pedagogic benefits. Thanks to this new type of devices, new sets of interactions can be thought of. Yet, user reception has to be tested before any pedagogic benefits can be evaluated. In this paper, a set of interactions using multi-touch and sensors to manage rotation of solids is presented. It was largely accepted by a test group of learners aged 9 to 15.
Iron Therapy for the Treatment of Iron Deficiency in Chronic Heart Failure: Intravenous or Oral? (2015)

This article considers the use and modality of iron therapy to treat iron deficiency in patients with heart failure, an aspect of care which has received relatively little attention compared with the wider topic of anaemia management. Iron deficiency affects up to 50% of heart failure patients, and is associated with poor quality of life, impaired exercise tolerance, and mortality independent of haematopoietic effects in this patient population. The European Society of Cardiology Guidelines for heart failure 2012 recommend a diagnostic work-up for iron deficiency in patients with suspected heart failure. Iron absorption from oral iron preparations is generally poor, with slow and often inefficient iron repletion; moreover, up to 60% of patients experience gastrointestinal side effects. These problems may be exacerbated in heart failure due to decreased gastrointestinal absorption and poor compliance due to pill burden. Evidence for clinical benefits using oral iron is lacking. I.v. iron sucrose has consistently been shown to improve exercise capacity, cardiac function, symptom severity, and quality of life. Similar findings were observed recently for i.v. ferric carboxymaltose in patients with systolic heart failure and impaired LVEF in the double-blind, placebo-controlled FAIR-HF and CONFIRM-HF trials. I.v. iron therapy may be better tolerated than oral iron, although confirmation in longer clinical trials is awaited. Routine diagnosis and management of iron deficiency in patients with symptomatic heart failure regardless of anaemia status is advisable, and, based on current evidence, prompt intervention using i.v. iron therapy should now be considered.
Vascular endothelial growth factor receptor‐1 in human cancer (2010)

The human vascular endothelial growth factor receptor-1 (VEGFR-1, or Flt-1) is widely expressed in normal and pathologic tissue and contributes to the pathogenesis of both neoplastic and inflammatory diseases. In human cancer, VEGFR-1 mediated signaling is responsible for both direct tumor activation and angiogenesis. VEGFR-1 mediated activation of nonmalignant supporting cells, particularly stromal, dendritic, hematopoietic cells, and macrophages, is also likely important for cancer pathogenesis. VEGFR-1 is also hypothesized to enable the development of cancer metastases by means of activation and premetastatic localization in distant organs of bone marrow-derived hematopoietic progenitor cells, which express VEGFR-1. IMC-18F1 is a fully human IgG(1) antibody that binds to VEGFR-1 and has been associated with the inhibition of cancer growth in multiple in vitro and human tumor xenograft models. The preliminary results of phase 1 investigations have also indicated a favorable safety profile for IMC-18F1 at doses that confer antibody concentrations that are associated with relevant antitumor activity in preclinical models.