gebhart/patrepeval huggingface dataset:
Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney (2006)

Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.
A Robust High-Content Imaging Approach for Probing the Mechanism of Action and Phenotypic Outcomes of Cell-Cycle Modulators (2011)

High-content screening is increasingly used to elucidate changes in cellular biology arising from treatment with small molecules and biological probes. We describe a cell classifier for automated analysis of multiparametric data from immunofluorescence microscopy and characterize the phenotypes of 41 cell-cycle modulators, including several protein kinase inhibitors in preclinical and clinical development. This method produces a consistent assessment of treatment-induced phenotypes across experiments done by different biologists and highlights the prevalence of nonuniform and concentration-dependent cellular response to treatment. Contrasting cell phenotypes from high-content screening to kinase selectivity profiles from cell-free assays highlights the limited utility of enzyme potency ratios in understanding the mechanism of action for cell-cycle kinase inhibitors. Our cell-level approach for assessing phenotypic outcomes is reliable, reproducible and capable of supporting medium throughput analyses of a wide range of cellular perturbations.
Designing for Patient-Centeredness: the Design of Hemodialysis Equipment (2003)

The aim of this study was to gain an insight into the use and application of patient-centeredness to medical equipment design. Hemodialysis (HD) equipment was therefore chosen as a 'case' to identify the differences in the end-products resulting from clinician-centered (traditional design methods) and patient-centered to design. The story of HD equipment evolution demonstrated that the design of HD equipment should be influenced not only by technology-push or/and market-pull but also by the needs of the patients or clinicians. The appropriateness of the patient-centeredness and its application to HD has also been identified in this study. Finally, the study suggests a radical change is required for the design of HD equipment. The learned lessons from the patient are the finest basis of discussion for how to get benefits back to the patient.
Multipotent hematopoietic cell lines derived from C/EBPα(−/−) knockout mice display granulocyte macrophage–colony-stimulating factor, granulocyte– colony-stimulating factor, and retinoic acid–induced granulocytic differentiation (2001)

The transcription factor C/EBPalpha is an important mediator of granulocyte differentiation and regulates the expression of multiple granulocyte-specific genes including the granulocyte-colony-stimulating factor (G-CSF) receptor, neutrophil elastase, and myeloperoxidase. Indeed C/EBPalpha knockout mice display a profound block in granulocyte differentiation. To study this block in granulocytic differentiation in more detail, retroviral vector-mediated transduction of a dominant-negative retinoic acid receptor was used to establish hematopoietic growth factor-dependent, lympho-myeloid progenitor cell lines from the fetal livers of both the C/EBPalpha knockout animals (C/EBPalpha(-/-)) and their heterozygous littermates (C/EBPalpha(+/-)). Surprisingly, the C/EBPalpha(-/-) cell lines displayed significant spontaneous granulocytic differentiation, and this differentiation was markedly enhanced when the cells were stimulated with granulocyte macrophage (GM)-CSF. This GM-CSF-mediated differentiation was associated with the up-regulation of G-CSF receptor mRNA, and the combination of GM-CSF and G-CSF generated more than 95% mature neutrophils in the C/EBPalpha(-/-) cultures. The addition of all-trans retinoic acid also enhanced this granulocytic differentiation of the cultured C/EBPalpha(-/-) cells, indicating that the activated retinoic acid receptors can enhance granulocytic differentiation through a molecular pathway that is independent of C/EBPalpha. These studies clearly indicate that terminal granulocytic differentiation associated with the up-regulation of C/EBPalpha-responsive genes can occur in the absence of C/EBPalpha, and they indicate the existence of multiple independent molecular pathways potentially used by primitive hematopoietic precursors that can lead to the development of mature granulocytes.
Exactly-once delivery in a content-based publish-subscribe system (2003)

This paper presents a general knowledge model for propagating information in a content-based publish-subscribe system. The model is used to derive an efficient and scalable Protocol for exactly-once delivery to large numbers (tens of thousands per broker) of content-based subscribers in either publisher order or uniform total order Our protocol allows intermediate content filtering at each hop, but requires persistent storage only at the publishing site. It is tolerant of message drops, message reorderings, node failures, and link failures, and maintains only "soft" state at intermediate nodes. We evaluate the performance of our implementation both under failure-free conditions and with fault injection.
Management of a Solitary Thyroid Nodule (1993)

The solitary thyroid nodule, defined as a palpably discrete swelling within an otherwise apparently normal gland, is usually a benign lesion. However, patient and physician alike are typically concerned about the possibility of thyroid cancer. This review describes a strategy for the treatment of clinically euthyroid patients who have a solitary thyroid nodule that prevents unnecessary testing while identifying the few patients who require therapy. Management has changed in recent years, but important differences of opinion remain over which nodules should be surgically excised. Several recent reviews address these issues comprehensively13.Prevalence of Thyroid Nodules and CancerThe . . .
Stabilised G protein-coupled receptors in structure-based drug design: a case study with adenosine A2A receptor (2012)

The first example of structure-based drug design with stabilised GPCRs has enabled the identification of a preclinical candidate for the treatment of Parkinson's disease.
Using Wireless Communications in Business (1994)

From the Publisher:
This one-of-a-kind guide offers applications from a business perspective toward a complete understanding of wireless communication systems. In clear, non-technical language, Using Wireless Communications in Business explains what technologies are available now and what will be available in the future, the capabilities of wireless communication systems, and the legal issues involved.
FUNCTIONAL POLYMER BRUSHES* (2002)

*Reprinted from Supramolecular Polymers; Ciferri, A., Ed.; Marcel Dekker, Inc.: New York; 2000, 565–613. ACKNOWLEDGMENTS The authors wish to thank their coworkers Dr. O. Prucker, Dr. J. Habicht, Dr. M. Schimmel, Dr. M. Biesalski, Dr. N. Bunjes, F. Hofmann, I. Homann, Dr. H. Murata, Dr. S. Paul, B. Peng, Dr. D. Johannsmann, Dr. A. Offenhäusser, Dr. C. Sprößler, Dr. M. Schmidt, and Dr. G. Tovar. Financial support by the Deutsche Forschungsgemeinschaft (Projects "Polymerschichten," "Polyelektrolytbürsten," "Orientierungsschichten") and the Max–Buchner Foundation are gratefully acknowledged. Notes *Reprinted from Supramolecular Polymers; Ciferri, A., Ed.; Marcel Dekker, Inc.: New York; 2000, 565–613.
Feedback systems using non-binary LDPC codes with a limited number of transmissions (2014)

One advantage of incremental transmissions with feedback in point-to-point memoryless channels is a reduction in average blocklength required to approach capacity. This paper optimizes the size of each incremental transmission for non-binary (NB) LDPC codes to maximize throughput in VLFT and two-phase VLF settings. The optimization problem uses an approximation based on the inverse-Gaussian p.d.f. of the blocklength required for successful decoding. By using the optimized incremental transmission lengths (with an average blocklength of less than 500 bits), NB-LDPC codes for VLFT setting limited to 5 transmissions achieve a throughput greater than 96% of that obtained by an unlimited-transmission VLFT scheme with the same average blocklength. With a similar average blocklength, a two-phase VLF system limited to five transmissions (with optimized lengths) using the binary image of NB-LDPC codes achieves greater than 90% of the capacity of binary-input AWGN channel with SNR=2 dB. Two-phase VLF does not match the throughput of VLFT, but it is more practical than VLFT because it does not assume noiseless transmitter confirmation.
Nanostructures in Biodiagnostics (2005)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNanostructures in BiodiagnosticsNathaniel L. Rosi and Chad A. MirkinView Author Information Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113 Cite this: Chem. Rev. 2005, 105, 4, 1547–1562Publication Date (Web):March 23, 2005Publication History Received23 November 2004Published online23 March 2005Published inissue 1 April 2005https://pubs.acs.org/doi/10.1021/cr030067fhttps://doi.org/10.1021/cr030067fresearch-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views34466Altmetric-Citations4159LEARN 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:Assays,Biopolymers,Genetics,Metal nanoparticles,Nanoparticles Get e-Alerts
Management of malignant pleural mesothelioma: a critical review (2000)

Malignant mesothelioma remains a uniformly fatal disease and best supportive care continues to be the standard treatment. Neither chemotherapy nor surgery has been shown to prolong survival. Radiotherapy is not curative but is useful for prophylaxis against needle-track metastases and for symptom palliation. Combinations of therapies have been tried but most studies were uncontrolled and selection bias makes the results impossible to interpret. The combination of extrapleural pneumonectomy, chemotherapy, and radiotherapy attracted much interest, but the subsequent results were disappointing in a highly selected group of patients. Randomized controlled trials are desperately needed to provide definitive information on experimental treatments. It is also important to develop better measures of disease response and to assess quality of life issues in clinical trials. If patients are to receive therapies other than palliation, they should only do so in the setting of randomized controlled trials under approved protocols.
Mediators of oligodendrocyte differentiation during remyelination (2011)

Myelin, a dielectric sheath that wraps large axons in the central and peripheral nervous systems, is essential for proper conductance of axon potentials. In multiple sclerosis (MS), autoimmune-mediated damage to myelin within the central nervous system (CNS) leads to progressive disability primarily due to limited endogenous repair of demyelination with associated axonal pathology. While treatments are available to limit demyelination, no treatments are available to promote myelin repair. Studies examining the molecular mechanisms that promote remyelination are therefore essential for identifying therapeutic targets to promote myelin repair and thereby limit disability in MS. Here, we present our current understanding of the critical extracellular and intracellular pathways that regulate the remyelinating capabilities of oligodendrocyte precursor cells (OPCs) within the adult CNS.
Transduction of Human Progenitor Hematopoietic Stem Cells by Human Immunodeficiency Virus Type 1-Based Vectors Is Cell Cycle Dependent (1999)

Human immunodeficiency virus (HIV) type 1 vectors are highly efficient in their ability to transduce human progenitor hematopoietic stem cells (PHSC). Although mitosis was not required for transduction of these cells, transduction rates were much greater once cells had been cultured in the presence of cytokines. Transduction rates, however, rarely exceeded 70%. We demonstrate here that there is a distinct subpopulation that is more easily transduced by HIV vectors. These cells were distinguished by a disproportionate population in the S/G2/M phases of the cell cycle. By sorting them prior to transduction, we found that those cells in either the G1 or S/G2/M fraction were more readily transduced than G0 cells. Maintaining the cells in G0 by omitting cytokines from the medium reduced transduction rates by up to 10-fold. Addition of cytokines to the medium immediately after transduction did not improve the transduction efficiency as measured by expression of the transgene. Analysis of replication intermediates indicated that the block to transduction of G0 cells operated near the time of initiation of reverse transcription. These results suggest that although lentivirus vectors can transduce nondividing PHSC, transduction efficiency is severalfold greater once the cells exit G0 and enter G1. Further characterization of these more transducible cells and identification of the cellular factors responsible may enhance transduction while maintaining the pluripotentiality of the PHSC.
Synthesis of Some 2(3H)‐Benzoxazolone Derivatives and their in‐vitro Effects on Human Leukocyte Myeloperoxidase Activity (2005)

Myeloperoxidase (MPO), a heme protein expressed by polymorphonuclear leukocytes, generates potent oxidants which are proposed to contribute to tissue damage during inflammation and certain pathogenesis such as neurodegenerative disorders. In this study, twenty omega-[2-oxo-3H-benzoxazol-3-yl]-N-phenylacetamide and propionamide derivatives having substituents of different lipophilic and electronic nature on the N-phenyl ring were synthesized to evaluate the inhibitory effects on in vitro leukocyte MPO chlorinating activity. The most active compounds in the series were the derivatives bearing 2-methyl and 4-nitro substituent on the N-phenyl ring.
Structure of Human Phytanoyl-CoA 2-Hydroxylase Identifies Molecular Mechanisms of Refsum Disease* (2005)

Refsum disease (RD), a neurological syndrome characterized by adult onset retinitis pigmentosa, anosmia, sensory neuropathy, and phytanic acidaemia, is caused by elevated levels of phytanic acid. Many cases of RD are associated with mutations in phytanoyl-CoA 2-hydroxylase (PAHX), an Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase that catalyzes the initial alpha-oxidation step in the degradation of phytenic acid in peroxisomes. We describe the x-ray crystallographic structure of PAHX to 2.5 A resolution complexed with Fe(II) and 2OG and predict the molecular consequences of mutations causing RD. Like other 2OG oxygenases, PAHX possesses a double-stranded beta-helix core, which supports three iron binding ligands (His(175), Asp(177), and His(264)); the 2-oxoacid group of 2OG binds to the Fe(II) in a bidentate manner. The manner in which PAHX binds to Fe(II) and 2OG together with the presence of a cysteine residue (Cys(191)) 6.7 A from the Fe(II) and two further histidine residues (His(155) and His(281)) at its active site distinguishes it from that of the other human 2OG oxygenase for which structures are available, factor inhibiting hypoxia-inducible factor. Of the 15 PAHX residues observed to be mutated in RD patients, 11 cluster in two distinct groups around the Fe(II) (Pro(173), His(175), Gln(176), Asp(177), and His(220)) and 2OG binding sites (Trp(193), Glu(197), Ile(199), Gly(204), Asn(269), and Arg(275)). PAHX may be the first of a new subfamily of coenzyme A-binding 2OG oxygenases.
Combinatorial and High‐Throughput Materials Science (2007)

There is increasing acceptance of high-throughput technologies for the discovery, development, and optimization of materials and catalysts in industry. Over the years, the relative synchronous development of technologies for parallel synthesis and characterization has been accompanied by developments in associated software and information technologies. This Review aims to provide a comprehensive overview on the state of the art of the field by selected examples. Technologies developed to aid research on complex materials are covered as well as databases, design of experiment, data-mining technologies, modeling approaches, and evolutionary strategies for development. Different methods for parallel synthesis provide single sample libraries, gradient libraries for electronic or optical materials, similar to polymers and catalysts, and products produced through formulation strategies. Many examples illustrate the variety of isolated solutions and document the barely recognized variety of new methods for the synthesis and analysis of almost any material. The Review ends with a summary of success stories and statements on still-present problems and future tasks.
Practical Total Synthesis of the Anti-Influenza Drug GS-4104 (1998)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTPractical Total Synthesis of the Anti-Influenza Drug GS-4104John C. Rohloff, Kenneth M. Kent, Michael J. Postich, Mark W. Becker, Harlan H. Chapman, Daphne E. Kelly, Willard Lew, Michael S. Louie, Lawrence R. McGee, Ernest J. Prisbe, Lisa M. Schultze, Richard H. Yu, and Lijun ZhangView Author Information Gilead Sciences Inc., Process Chemistry, 353 Lakeside Drive, Foster City, California 94404 Cite this: J. Org. Chem. 1998, 63, 13, 4545–4550Publication Date (Web):June 5, 1998Publication History Received23 February 1998Published online5 June 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/jo980330qhttps://doi.org/10.1021/jo980330qbrief-reportACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views8366Altmetric-Citations169LEARN 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:Anions,Crystallization,Ethers,Ethyl groups,Mixtures Get e-Alerts
The Recirculation of Naive and Memory Lymphocytes (1998)

It has been clearly shown that continuous recirculation of lymphocytes is crucial for the development of primary immune responses and that naive CD4 cells are distinguished from memory CD4 cells by differences in expression of several adhesion molecules. These findings suggest that changes in migratory behavior accompany the naive to memory cell transition. This area is first reviewed and then to evaluate this hypothesis, we compare the tissue distributions of highly purified naive and memory CD4 cells after transfer to syngeneic recipients. Naive cells which express high levels of L-selectin, and low levels of alpha 4 and beta 2 integrins, and CD44 localized in secondary lymphoid organs and were detectable in these tissues and in the blood for several weeks after transfer. Memory cells, which have a reciprocal phenotype, showed a markedly different distribution, particularly with respect to tissues where entry is controlled through high endothelial venules.
Flow cytometry: An improved method for the selection of highly productive gene‐amplified CHO cells using flow cytometry (2001)

In previous work, we clarified the relationship between the productivity and stability of gene-amplified cells and the location of the amplified gene. The location of the amplified gene enabled us to classify resistant cells into two types. One type of resistant cell group, in which the amplified genes were observed near the telomeric region, was named the "telomere type." The other type of cell group, in which the amplified genes were observed in other chromosomal regions, was named the "other type." The phenotypes of these two types of cells are very different. In this experiment, using a fluorescein isothiocyanate-labeled methotrexate (F-MTX) reagent with flow cytometry, we were easily able to distinguish between highly productive cells and the other types of cells. The level of fluorescence differed according to the difference in resistance to MTX. Based on this new finding, highly productive gene-amplified cells could be isolated from heterogeneous gene-amplified cell pools more easily than by the method of limiting-dilution assay. The limiting-dilution method requires several months to obtain highly productive gene-amplified cells, while our flow-cytometry-based method of selection requires only a few weeks.
Route Knowledge in Complex Environments: An Analysis of Pedestrian Recall Using Stereoscopic Panoramic Interactive Navigation (2006)

In this study, we investigate whether data collected on route knowledge is influenced by the method of data collection. The results of stereoscopic panoramic interactive navigation re-enactment sessions and conventional paper and pencil maps are compared against observational tracing data of pedestrian route choice behavior in the city center of Eindhoven, The Netherlands. The findings of the study suggest that the data collected through maps better describe empirical observations of pedestrian route choice behavior that the data collected through stereoscopic panoramic interactive navigation sessions.