gebhart/patrepeval huggingface dataset:
Sustained Sympathoinhibitory Effects of Cardiac Resynchronization Therapy in Severe Heart Failure (2004)

Evidence is available that in heart failure, cardiac resynchronization therapy by biventricular pacing improves myocardial function and exercise capacity. Whether this is accompanied by a sustained inhibition of heart failure-dependent sympathoexcitation is uncertain. In 11 heart failure patients (mean+/-SEM age, 68.4+/-1.5 years) in New York Heart Association (NYHA) class III and IV under medical treatment with an intraventricular conduction delay (QRS duration > or =130 ms), with a markedly depressed left ventricular ejection fraction, and undergoing implantation of a biventricular pacemaker, we measured beat-to-beat blood pressure and muscle sympathetic nerve traffic. Measurements, which also included echocardiographic and clinical variables, were performed before and approximately 10 weeks after successful resynchronization therapy. Ten age- and NYHA class-matched heart failure patients who were under medical treatment for the same time period served as controls. Long-term resynchronization therapy improved cardiac function and caused a significant increase in systolic blood pressure coupled with an improvement in maximal oxygen consumption and exercise capacity. These effects were coupled with a significant and marked reduction in sympathetic nerve traffic when expressed both as burst frequency over time (44.1+/-3.6 vs 30.7+/-3.0 bs/min, -30.5%, P<0.02) and as burst frequency corrected for heart rate (68.3+/-5.9 vs 47.3+/-4.3 bs/100 beats, -32.1%, P<0.02). No significant change in the aforementioned parameters was seen in the control group. These data provide the first direct evidence that in severe heart failure, resynchronization therapy exerts a marked and sustained sympathoinhibition. Because in heart failure sympathetic overactivity adversely affects prognosis, this may have important clinical implications.
Design, construction and characterization of a set of insulated bacterial promoters (2010)

We have generated a series of variable-strength, constitutive, bacterial promoters that act predictably in different sequence contexts, span two orders of magnitude in strength and contain convenient sites for cloning and the introduction of downstream open-reading frames. Importantly, their design insulates these promoters from the stimulatory or repressive effects of many 5'- or 3'-sequence elements. We show that different promoters from our library produce constant relative levels of two different proteins in multiple genetic contexts. This set of promoters should be a useful resource for the synthetic-biology community.
Functionalized PEG–PEI Copolymers Complexed to Exon-Skipping Oligonucleotides Improve Dystrophin Expression in mdx Mice (2008)

Exon-skipping oligonucleotides (ESOs) with 2'-O-methyl modifications are promising compounds for the treatment of Duchenne muscular dystrophy (DMD). However, the usefulness of these compounds is limited by their poor delivery profile to muscle tissue in vivo. We previously established that copolymers made of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) enhanced ESO transfection in skeletal muscle of mdx mice, resulting in widespread distribution of dystrophin-positive fibers, but limited dystrophin expression by Western blot. In an attempt to improve ESO delivery and dystrophin expression, a new formulation of PEG-PEI copolymer was used, along with functionalized derivatives containing either the cell-penetrating peptide TAT (trans-activator of transcription), adsorbed colloidal gold (CG), or both TAT and CG. Tibialis anterior muscles were given three intramuscular injections of various PEG-PEI-ESO polyplexes (3 days apart; 5 microg of ESO per injection) and muscles were harvested 3 weeks after the first injection. Surface modifications of PEG-PEI copolymers with TAT showed the highest level of dystrophin recovery, with a 6-fold increase in dystrophin-positive fibers compared with ESO alone and up to 30% of normal dystrophin expression by Western blot. The adsorption of CG to either PEG-PEI or TAT-PEG-PEI copolymers showed no further improvement in dystrophin expression. Our data indicate that TAT-modified PEG-PEI copolymers are effective carriers for delivery of ESOs to skeletal muscle and are promising compounds for the therapeutic treatment of DMD.
ChemInform Abstract: Facile Transformation of Aromatic Aldehydes to Acids Mediated by Tetraethylammonium Superoxide. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer. (1995)

Changes in estrogen receptor (ER) expression and function may explain the development of tamoxifen resistance in breast cancer. ER expression was measured by an immunohistochemical assay, validated for use in tamoxifen-treated tumors against a biochemical enzyme immunoassay, in 72 paired biopsies taken before treatment and at progression or relapse on tamoxifen. Progesterone receptor (PgR) and pS2 gene expression were also measured immunohistochemically as an indicator of ER function. Overall the frequency of ER expression was reduced from 37 of 72 (51%) pretamoxifen to 21 of 72 (29%) at progression or relapse, with a significant reduction in the quantitative level of ER (P < 0.0001; Wilcoxon signed rank sum test). Tumors treated with primary tamoxifen that responded but then developed acquired resistance frequently remained ER positive (ER+) at relapse: 16 of 18 (89%) were ER+ pretamoxifen (75% of these expressed either PgR or pS2) and 11 of 18 (61%) were ER+ at relapse (82% continued to express PgR or pS2). In contrast, only 3 of 20 (15%) tumors that progressed on primary tamoxifen with de novo resistance were ER+ pretamoxifen, and all tumors were ER- at progression. At progression, 6 of 20 (30%) of these tumors expressed high levels of PgR (mean H-score, 98) and/or pS2 (mean, 50% cells positive), despite being ER-. In tumors that recurred during adjuvant tamoxifen therapy, including locoregional and metastatic lesions, ER expression was significantly reduced from 18 of 34 (53%) in the original primary tumor to 10 of 34 (29%) at relapse (P = 0.002). PgR expression was likewise significantly reduced in this group (P = 0.001). This study confirms that expression of a functional ER in breast cancer is a strong predictor for primary response to tamoxifen. Although ER was reduced in tamoxifen-resistant tumors overall, the development of acquired resistance was associated with maintained ER expression and function in many tumors, whereas de novo resistance remained related to lack of ER expression. Recurrence during adjuvant tamoxifen was associated with development of an ER/PgR-negative phenotype in some tumors. These data imply that separate mechanisms of resistance may occur in these different clinical subgroups.
Structures of Shikimate Dehydrogenase AroE and Its Paralog YdiB (2003)

Shikimate dehydrogenase catalyzes the fourth step of the shikimate pathway, the essential route for the biosynthesis of aromatic compounds in plants and microorganisms. Absent in metazoans, this pathway is an attractive target for nontoxic herbicides and drugs. Escherichia coli expresses two shikimate dehydrogenase paralogs, the NADP-specific AroE and a putative enzyme YdiB. Here we characterize YdiB as a dual specificity quinate/shikimate dehydrogenase that utilizes either NAD or NADP as a cofactor. Structures of AroE and YdiB with bound cofactors were determined at 1.5 and 2.5 A resolution, respectively. Both enzymes display a similar architecture with two alpha/beta domains separated by a wide cleft. Comparison of their dinucleotide-binding domains reveals the molecular basis for cofactor specificity. Independent molecules display conformational flexibility suggesting that a switch between open and closed conformations occurs upon substrate binding. Sequence analysis and structural comparison led us to propose the catalytic machinery and a model for 3-dehydroshikimate recognition. Furthermore, we discuss the evolutionary and metabolic implications of the presence of two shikimate dehydrogenases in E. coli and other organisms.
Large-Scale MIMO Detection for 3GPP LTE: Algorithms and FPGA Implementations (2014)

Large-scale (or massive) multiple-input multiple-out put (MIMO) is expected to be one of the key technologies in next-generation multi-user cellular systems based on the upcoming 3GPP LTE Release 12 standard, for example. In this work, we propose-to the best of our knowledge-the first VLSI design enabling high-throughput data detection in single-carrier frequency-division multiple access (SC-FDMA)-based large-scale MIMO systems. We propose a new approximate matrix inversion algorithm relying on a Neumann series expansion, which substantially reduces the complexity of linear data detection. We analyze the associated error, and we compare its performance and complexity to those of an exact linear detector. We present corresponding VLSI architectures, which perform exact and approximate soft-output detection for large-scale MIMO systems with various antenna/user configurations. Reference implementation results for a Xilinx Virtex-7 XC7VX980T FPGA show that our designs are able to achieve more than 600 Mb/s for a 128 antenna, 8 user 3GPP LTE-based large-scale MIMO system. We finally provide a performance/complexity trade-off comparison using the presented FPGA designs, which reveals that the detector circuit of choice is determined by the ratio between BS antennas and users, as well as the desired error-rate performance.
thick tassel dwarf1encodes a putative maize ortholog of theArabidopsis CLAVATA1leucine-rich repeat receptor-like kinase (2005)

Development in higher plants depends on the activity of meristems, formative regions that continuously initiate new organs at their flanks. Meristems must maintain a balance between stem cell renewal and organ initiation. In fasciated mutants, organ initiation fails to keep pace with meristem proliferation. The thick tassel dwarf1 (td1) mutation of maize affects both male and female inflorescence development. The female inflorescence, which results in the ear, is fasciated, with extra rows of kernels. The male inflorescence, or tassel, shows an increase in spikelet density. Floral meristems are also affected in td1 mutants; for example, male florets have an increase in stamen number. These results suggest that td1 functions in the inflorescence to limit meristem size. In addition, td1 mutants are slightly shorter than normal siblings, indicating that td1 also plays a role in vegetative development. td1 encodes a leucine-rich repeat receptor-like kinase (LRR-RLK) that is a putative ortholog of the Arabidopsis CLAVATA1 protein. These results complement previous work showing that fasciated ear2 encodes a CLAVATA2-like protein, and suggest that the CLAVATA signaling pathway is conserved in monocots. td1 maps in the vicinity of quantitative trait loci that affect seed row number, spikelet density and plant height. We discuss the possible selection pressures on td1 during maize domestication.
How Do Cells Know What They Want to Be When They Grow Up? Lessons from Epidermal Patterning in Arabidopsis (2003)

Because the plant epidermis is readily accessible and consists of few cell types on most organs, the epidermis has become a well-studied model for cell differentiation and cell patterning in plants. Recent advances in our understanding of the development of three epidermal cell types, trichomes, root hairs, and stomata, allow a comparison of the underlying patterning mechanisms. In Arabidopsis, trichome development and root epidermal patterning use a common mechanism involving closely related cell fate transcription factors and a similar lateral inhibition signaling pathway. Yet the resulting patterns differ substantially, primarily due to the influence of a prepattern derived from subepidermal cortical cells in root epidermal patterning. Stomatal patterning uses a contrasting mechanism based primarily on control of the orientation of cell divisions that also involves an inhibitory signaling pathway. This review focuses on comparing and contrasting these patterning pathways to identify and illustrate general themes that may be broadly applicable to other systems. Where these pathways occur in the same tissue, interaction and competition between these pathways is also discussed.
Composite piezoelectric sensors (1984)

Abstract Various types of composite piezoelectric transducers are reviewed with emphasis on the hydrophone figure of merit dhgh . Composites containing piezoceramic fibers, or skeletons in a polymer matrix, are superior to single-phase polymer or ceramic transducers.
Functionalized flexible MOFs as fillers in mixed matrix membranes for highly selective separation of CO2 from CH4 at elevated pressures (2011)

Mixed matrix membranes (MMMs) composed of a glassy polymer (polysulfone) and the flexible metal organic framework NH(2)-MIL-53(Al) exhibit excellent separation properties. In contrast to most reported membranes, CO(2)/CH(4) separation selectivity increases with pressure, related to the flexibility of the filler.
Direct Condensation of Carboxylic Acids with Alcohols Catalyzed by Hafnium(IV) Salts (2000)

In order to promote atom efficiency in synthesis and to avoid the generation of environmental waste, the use of stoichiometric amounts of condensing reagents or excess substrates should be avoided. In esterification, excesses of either carboxylic acids or alcohols are normally needed. We show that the direct condensation of equimolar amounts of carboxylic acids and alcohols can be achieved with the use of hafnium(IV) salts, such as commercially available hafnium(IV) chloride and hafnium(IV) tert-butoxide. The present method can be applied to direct polyesterification and may be suitable for large-scale operations.
The Oct-2 glutamine-rich and proline-rich activation domains can synergize with each other or duplicates of themselves to activate transcription. (1994)

The B-cell POU homeodomain protein Oct-2 contains two transcriptional activation domains, one N terminal and the other C terminal of the central DNA-binding POU domain. The synergistic action of these two activation domains makes Oct-2 a more potent activator of mRNA promoters than the related broadly expressed octamer motif-binding protein Oct-1, which contains an N-terminal but not a C-terminal Oct-2-like activation domain. Both Oct-2 mRNA promoter activation domains were delineated by truncation analysis: the N-terminal Q domain is a 66-amino-acid region rich in glutamines, and the C-terminal P domain is a 42-amino-acid region rich in prolines. The Q and P domains synergized with each other or duplicates of themselves, independently of their N-terminal or C-terminal position relative to the POU domain. The C-terminal P domain, which differentiates Oct-2 from Oct-1, also activated transcription in conjunction with the heterologous GAL4 DNA-binding domain. Oct-2 thus contains three modular functional units, the DNA-binding POU domain and the two P and Q activation domains. An electrophoretic mobility shift assay with a variety of these Oct-2 activators revealed a distinct complex called QA that was dependent on the presence of an active glutamine-rich activation domain and migrated more slowly than the Oct-2-DNA complexes. Formation of the QA complex is consistent with interaction of the glutamine-rich activation domains with a regulatory protein important for the process of transcriptional activation.
Prediction of response to chemotherapy in acute myelocytic leukemia (1980)

Marrow specimens obtained from 23 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and/or daunorubicin in vitro, and the effects of these agents on colony formation in vitro was determined. Thymidine suicide indices were determined as well, which permitted a distinction to be made between kinetic and metabolic resistance to cytosine arabinoside. The sensitivity of the colony- forming cells to the two chemotherapeutic agents did not correlate with each other, indicating that sensitivity to each was independently determined. The relationship between in vitro sensitivity to daunorubicin and cytosine arabinoside and response to 25 courses of in vivo therapy with these two agents administered to 21 patients was determined. These studies indicated a clear-cut relationship between in vitro drug sensitivity and in vivo response with patients whose leukemic cells were sensitive to both agents entering complete remission, whereas patients whose leukemic cells were insensitive to one or both drugs in vitro failed to enter remission.
ELA1 and CUL3 Are Required Along with ELC1 for RNA Polymerase II Polyubiquitylation and Degradation in DNA-Damaged Yeast Cells (2007)

Treatment of yeast and human cells with DNA-damaging agents elicits lysine 48-linked polyubiquitylation of Rpb1, the largest subunit of RNA polymerase II (Pol II), which targets Pol II for proteasomal degradation. However, the ubiquitin ligase (E3) responsible for Pol II polyubiquitylation has not been identified in humans or the yeast Saccharomyces cerevisiae. Here we show that elongin A (Ela1) and cullin 3 (Cul3) are required for Pol II polyubiquitylation and degradation in yeast cells, and on the basis of these and other observations, we propose that an E3 comprised of elongin C (Elc1), Ela1, Cul3, and the RING finger protein Roc1 (Rbx1) mediates this process in yeast cells. This study provides, in addition to the identification of the E3 required for Pol II polyubiquitylation and degradation in yeast cells, the first evidence for a specific function in yeast for a member of the elongin C/BC-box protein/cullin family of ligases. Also, these observations raise the distinct possibility that the elongin C-containing ubiquitin ligase, the von Hippel-Lindau tumor suppressor complex, promotes Pol II polyubiquitylation and degradation in human cells.
Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit coexpression: changes in blocker sensitivity, activation/relaxation and inactivation kinetics, and protein kinase A modulation. (1996)

A human homolog of the large-conductance calcium-activated potassium (BK) channel beta subunit (hSlobeta) was cloned, and its effects on a human BK channel (hSlo) phenotype are reported. Coexpression of hSlo and hSlobeta, in both oocytes and human embryonic kidney 293 cells, resulted in increased Ca2+ sensitivity, marked slowing of BK channel activation and relaxation, and significant reduction in slow inactivation. In addition, coexpression changed the pharmacology of the BK channel phenotype: hSlo-mediated currents in oocytes were more sensitive to the peptide toxin iberiotoxin than were hSlo + hSlobeta currents, and the potency of blockade by the alkaloid BK blocker tetrandrine was much greater on hSlo + hSlobeta- mediated currents compared with hSlo currents alone. No significant differences in the response to charybdotoxin or the BK channel opener NS1619 were observed. Modulation of BK channel activity by phosphorylation was also affected by the presence of the hSlobeta subunit. Application of cAMP-dependent protein kinase increased P(OPEN) of hSlo channels, but decreased P(OPEN)of most hSlo + hSlobeta channels. Taken together, these altered characteristics may explain some of the wide diversity of BK channel phenotypes observed in native tissues.
Image interpretation using multi-relational grammars (2002)

An approach to computational vision that is based on multiple levels of interpretation is presented. The step between each level is seen as taking place in three stages-parsing (in which features and groups of features in an image are given labels), interpreting (in which several interpretations are built, assuring that each feature is given at most one explanation in terms of a higher-level label), and pruning (in which some interpretations are discarded because of global constraints). The parsing and pruning steps are guided by multirelational grammars, a generalization of ordinary attribute grammars and of graph grammars. A bottom-up parsing algorithm for this class of grammars is presented, and their usefulness in image interpretation is illustrated by examples using both synthetic and real-world data.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Estimation of Breast Cancer Disease-Probability by Difference of Individual Susceptibility (2003)

The availability of previous Western models was limited for Korean female due to the differences inhazard-rates and the characteristics of breast cancer between Asian and Western females. Due to limited basic data, i.e. incidence, hazard-rate and cancer-cohorts, the developing-probability of breast cancer for Korean females was not calculated. Therefore, the disease-probability was calculated instead. This approach might be more beneficial for Koreans, and help in the decision- making for regular screening or hospital visit-interval, counseling in breast-cancer clinics, prescribing high-risk population, and in educating for primary prevention, although it over-estimates the relative probability compared to the developing-probability and the 65% predictive validity.
A2A Adenosine Receptor Gene Deletion or Synthetic A2A Antagonist Liberate Tumor-Reactive CD8+ T Cells from Tumor-Induced Immunosuppression (2018)

Tumor hypoxia-driven accumulation of extracellular adenosine was shown to facilitate tumor evasion by engaging the immunosuppressive, intracellular cAMP-elevating A<sub>2</sub> adenosine receptors (A<sub>2</sub>R) on tumor-reactive effector T cells, but there remains a need for careful evaluation of the limiting factors and properties of A<sub>2</sub>R blockade-enabled antitumor immunity. In studies of A<sub>2A</sub>R and/or A<sub>2B</sub>R gene-deficient mice, we found that A<sub>2A</sub>R deletion-but not A<sub>2B</sub>R deletion-liberates endogenous CD8<sup>+</sup> T cell antitumor immunity against weakly immunogenic MCA205 sarcomas. Studies of adoptively transferred A<sub>2A</sub>R<sup>-/-</sup>, A<sub>2B</sub>R<sup>-/-</sup>, or A<sub>2A</sub>R<sup>-/-</sup>/A<sub>2B</sub>R<sup>-/-</sup> tumor-reactive T cells confirmed that immunosuppression in the tumor microenvironment was mediated by A<sub>2A</sub>R on CD8<sup>+</sup> T cells. Treatment with A<sub>2A</sub>R antagonist mimicked A<sub>2A</sub>R gene deletion in adoptive T cell immunotherapy. This therapeutic benefit of targeting A<sub>2A</sub>R was independent of the anatomical location of tumor growth. The enhanced antitumor reactivity also led to the eradication of established intracranial tumors, which was associated with mouse survival and the maintenance of long-lasting, tumor-specific immunological memory. The blockade of the A<sub>2A</sub>R on adoptively transferred T cells by synthetic A<sub>2A</sub>R antagonist led to higher levels of IFN-γ secretion by tumor-infiltrating CD8<sup>+</sup> T cells. These data clarify the mechanism of hypoxia-driven immunosuppression in the tumor microenvironment by A<sub>2A</sub>R on tumor-reactive CD8<sup>+</sup> T cells and show that selective A<sub>2A</sub>R antagonists can be effective in improving the outcomes of T cell-based immunotherapies. Demonstration of the T cell dose dependency of tumor rejection points to a major limitation of current cancer immunotherapies, in which the presence of sufficient numbers of tumor-reactive T cells in a patient is not known.