gebhart/patrepeval huggingface dataset:
Quantitative PCR analysis of HbF inducers in primary human adult erythroid cells (2000)

The development and evaluation of drugs to elevate fetal hemoglobin in the treatment of the genetic diseases of hemoglobin would be facilitated by the availability of reliable cell assays. We have used real-time, quantitative polymerase chain reaction (PCR) analyses of globin messenger RNA (mRNA) levels in a biphasic, erythropoietin-dependent primary culture system for human adult erythroid cells in order to assay compounds for their ability to modulate levels of adult (beta) and fetal (gamma) globin mRNA. Complementary DNA synthesized from total RNA extracted at timed intervals from aliquots of cells were assayed throughout the period that the culture was studied. gamma-globin mRNA levels were found to be much lower (less than 1%) than beta-globin mRNA levels. At concentrations of agents chosen for minimal effect on cell division, we find that the 3 drugs studied, 5-azacytidine (5 micromol/L), hydroxyurea (40 micromol/L), and butyric acid (0.5 mmol/L), significantly increase gamma-globin mRNA levels. Interestingly, hydroxyurea also had a small stimulatory effect on beta-globin mRNA levels, while butyric acid caused a twofold inhibition of beta-globin mRNA levels, and 5-azacytidine had little effect on beta-globin mRNA levels. The net result of all 3 drugs was to increase the gamma/(gamma + beta) mRNA ratios by threefold to fivefold. These data suggest that the mechanism is distinct for each drug. The profile of butyric-acid-induced changes on globin gene expression is also quite distinct from changes produced by trichostatin A, a known histone deacetylase inhibitor. Quantitative PCR analyses of human erythroid cells should prove useful for studying the mechanism(s) of action of known inducers of gamma-globin and identifying new drug candidates.
An Improved Artificial Intelligence Based on Gray Wolf Optimization and Cultural Algorithm to Predict Demand for Dairy Products: A Case Study (2019)

This paper provides an integrated framework based on statistical tests, time series neural network and improved multi-layer perceptron neural network (MLP) with novel meta-heuristic algorithms in order to obtain best prediction of dairy product demand (DPD) in Iran. At first, a series of economic and social indicators that seemed to be effective in the demand for dairy products is identified. Then, the ineffective indices are eliminated by using Pearson correlation coefficient, and statistically significant variables are determined. Then, MLP is improved with the help of novel meta-heuristic algorithms such as gray wolf optimization and cultural algorithm. The designed hybrid method is used to predict the DPD in Iran by using data from 2013 to 2017. The results show that the MLP offers 71.9% of the coefficient of determination, which is better compared to the other two methods if no improvement is achieved.
A Reattachment Analysis for Closure of the Supersonic Base Flow Problem (1975)

Technical Briefs A Reattachment Analysis for Closure of the Supersonic Base Flow Problem Philip M. Gerhart, Philip M. Gerhart The University of Akron, Akron, Ohio Search for other works by this author on: This Site PubMed Google Scholar Robert A. White, Robert A. White University of Illinois, Urbana, Ill. Search for other works by this author on: This Site PubMed Google Scholar H. H. Korst H. H. Korst Department of Mechanical and Industrial Engineering, University of Illinois, Urbana, Ill. Search for other works by this author on: This Site PubMed Google Scholar Author and Article Information Philip M. Gerhart The University of Akron, Akron, Ohio Robert A. White University of Illinois, Urbana, Ill. H. H. Korst Department of Mechanical and Industrial Engineering, University of Illinois, Urbana, Ill. J. Fluids Eng. Mar 1975, 97(1): 124-126 (3 pages) https://doi.org/10.1115/1.3447191 Published Online: March 1, 1975 Article history Received: December 2, 1974 Online: October 12, 2010
Characterization of Bacterial and Fungal Soil Communities by Automated Ribosomal Intergenic Spacer Analysis Fingerprints: Biological and Methodological Variability (2001)

Automated rRNA intergenic spacer analysis (ARISA) was used to characterise bacterial (B-ARISA) and fungal (F-ARISA) communities from different soil types. The 16S-23S intergenic spacer region from the bacterial rRNA operon was amplified from total soil community DNA for B-ARISA. Similarly, the two internal transcribed spacers and the 5.8S rRNA gene (ITS1-5.8S-ITS2) from the fungal rRNA operon were amplified from total soil community DNA for F-ARISA. Universal fluorescence-labeled primers were used for the PCRs, and fragments of between 200 and 1,200 bp were resolved on denaturing polyacrylamide gels by use of an automated sequencer with laser detection. Methodological (DNA extraction and PCR amplification) and biological (inter- and intrasite) variations were evaluated by comparing the number and intensity of peaks (bands) between electrophoregrams (profiles) and by multivariate analysis. Our results showed that ARISA is a high-resolution, highly reproducible technique and is a robust method for discriminating between microbial communities. To evaluate the potential biases in community description provided by ARISA, we also examined databases on length distribution of ribosomal intergenic spacers among bacteria (L. Ranjard, E. Brothier, and S. Nazaret, Appl. Environ. Microbiol. 66:5334-5339, 2000) and fungi.
Parallel concatenated systematic polar codes (2015)

A parallel concatenated coding structure, which can improve the performance of polar codes in finite‐length regime, is proposed. In the proposed structure, the encoder is built using two systematic polar codes (SPCs), and the decoder adopts iterative belief propagation decoding algorithm. Numerical results in the binary‐input additive white Gaussian noise channel indicate that the proposed coding scheme can improve BER performance of polar codes significantly. Specially, BER of the proposed coding scheme with length 192 is almost equal to that of original SPCs with length 256, when the code rate is 1/3.
A phase I trial of BKM120 combined with vemurafenib in BRAFV600<sup>E/k</sup> mutant advanced melanoma. (2014)

9101 Background: Vemurafenib induces transient objective responses in half of BRAFV600Emutant melanoma patients and a median PFS of 5.3 months. PTEN loss and PI3K activation are common in BRAF mutant metastatic melanoma, and PI3K activation has been implicated as a cause acquired resistance to BRAF inhibitors. This phase I study tested the safety of combining the BRAF inhibitor, vemurafenib, with the PI3K inhibitor, BKM120, in patients with metastatic BRAF mutant melanoma. Methods: Vemurafenib-naïve patients receive a single dose of oral BKM120 (d -7) then vemurafenib twice daily with BKM120 daily (starting on c1d1). Patients with prior progression on vemurafenib received both vemurafenib and BKM120 starting on c1d1 after a vemurafenib washout of at least 14 days. Serial biopsies prior to treatment, on cycle 1 day 15, and at progression were obtained for pharmacodynamics analysis in patients with visible or palpable tumors. 3 + 3 dose escalation was planned starting at vemurafenib 720 mg PO twice daily with BKM120 60 mg daily. Results: Four BRAF inhibitor naïve patients andfour BRAF inhibitor refractory patients were treated on study with vemurafenib 720 mg PO bid and BKM120 60 mg PO daily. Two BRAF inhibitor naïve patient experienced DLTs (myalgias, DRESS syndrome). One vemurafenib naïve patient was inevaluable due to non-compliance and had minimal exposure to study drug. Two of four BRAF inhibitor refractory patients experienced DLTs (myalgias, febrile neutropenia). One BRAF inhibitor-resistant patient had a mixed response to treatment with a 35.9% reduction in target lesions and two new small subcutaneous lesions. Conclusions: Combination therapy with vemurafenib and BKM120 in BRAF-V600E/K mutant melanoma was not tolerated in either BRAF inhibitor naïve or BRAF inhibitor resistant patients. Clinical trial information: NCT01512251.
Reducing access latency of MLC PCMs through line striping (2014)

Although phase change memory with multi-bit storage capability (known as MLC PCM) offers a good combination of high bit-density and non-volatility, its performance is severely impacted by the increased read/write latency. Regarding read operation, access latency increases almost linearly with respect to cell density (the number of bits stored in a cell). Since reads are latency critical, they can seriously impact system performance. This paper alleviates the problem of slow reads in the MLC PCM by exploiting a fundamental property of MLC devices: the Most-Significant Bit (MSB) of MLC cells can be read as fast as SLC cells, while reading the Least-Significant Bits (LSBs) is slower. We propose Striped PCM (SPCM), a memory architecture that leverages this property to keep MLC read latency in the order of SLC's. In order to avoid extra writes onto memory cells as a result of striping memory lines, the proposed design uses a pairing write queue to synchronize write-back requests associated with blocks that are paired in striping mode. Our evaluation shows that our design significantly improves the average memory access latency by more than 30% and IPC by up to 25% (10%, on average), with a slight overhead in memory energy (0.7%) in a 4-core CMP model running memory-intensive benchmarks
Stein Variational Gradient Descent: A General Purpose Bayesian Inference Algorithm (2016)

We propose a general purpose variational inference algorithm that forms a natural counterpart of gradient descent for optimization. Our method iteratively transports a set of particles to match the target distribution, by applying a form of functional gradient descent that minimizes the KL divergence. Empirical studies are performed on various real world models and datasets, on which our method is competitive with existing state-of-the-art methods. The derivation of our method is based on a new theoretical result that connects the derivative of KL divergence under smooth transforms with Stein's identity and a recently proposed kernelized Stein discrepancy, which is of independent interest.
Solid-Phase Library Synthesis of Alkoxyprolines (2001)

The library synthesis of alkoxyprolines was achieved using an acid-stable, nucleophile-cleavable solid support. A hydroxythiophenol linker derived from Merrifield resin was esterified with the corresponding ethers of BOC-hydroxyproline. Removal of the BOC protecting group with trifluoroacetic acid followed by acylation gave solid-supported hydroxyproline derivatives. Cleavage from the solid support with excess primary amines or excess secondary amines followed by purification of the crude products from the excess amine by supported liquid-liquid extraction gave the alkoxyproline library in high purity.
On a fractional distributed-order oscillator (2005)

We consider a viscoelastic rod with a concentrated mass at its end. The mass is moving along the straight line that coincides with the rod axis. The mass is connected by a linear spring and a known active force is acting on it. We assume that the rod is light and described by fractional dissipation. The dynamics of such a system constitutes a problem of a fractional oscillator. In this paper, we shall study some properties of the solutions for the distributed-order fractional derivative viscoelastic rod.
Improved Methodologies for the Preparation of Highly Substituted Pyridines (2005)

[reaction: see text] Two separate strategies have been developed for the preparation of highly substituted pyridines from 1,2,4-triazines via the inverse-electron-demand Diels-Alder reaction: a microwave-promoted, solvent-free procedure and a tethered imine-enamine (TIE) approach. Both routes avoid the need for a discrete aromatization step and offer significant advantages over the classical methods, giving a wide variety of tri-, tetra-, and penta-substituted pyridines in high, optimized yields.
Advances in Development of Dopaminergic Aporphinoids (2006)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTAdvances in Development of Dopaminergic AporphinoidsAo Zhang, Yi Zhang, Alan R. Branfman, Ross J. Baldessarini, and John L. NeumeyerView Author Information Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China, The Branfman Family Foundation, 418 Queen Anne Road, Cherry Hill, New Jersey 08003, Department of Psychiatry & Neuroscience Program, Harvard Medical School, Boston, Massachusetts 02114, Neuropharmacology Laboratory Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, Massachusetts 02478-9106, and Medicinal Chemistry Laboratory, Alcohol & Drug Abuse Research Center, McLean Division of Massachusetts General Hospital, Belmont, Massachusetts 02478-9106. Cite this: J. Med. Chem. 2007, 50, 2, 171–181Publication Date (Web):December 16, 2006Publication History Received8 August 2006Published online16 December 2006Published inissue 1 January 2007https://pubs.acs.org/doi/10.1021/jm060959ihttps://doi.org/10.1021/jm060959ireview-articleACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views1646Altmetric-Citations95LEARN 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:Agonists,Antagonists,Receptors,Rodent models,Selectivity Get e-Alerts
Physician recruitment after Hermann Hospital. (1995)

The state of physician recruitment changed after the Internal Revenue Service required Hermann Hospital to publish its closing agreement with the IRS. The closing agreement released the long-awaited IRS "Hospital Physician Recruitment Guidelines." The IRS' recently proposed revenue ruling provides additional insight on acceptable physician recruitment practices as well.
Discrimination of Breast Cancer with Microcalcifications on Mammography by Deep Learning (2016)

Microcalcification is an effective indicator of early breast cancer. To improve the diagnostic accuracy of microcalcifications, this study evaluates the performance of deep learning-based models on large datasets for its discrimination. A semi-automated segmentation method was used to characterize all microcalcifications. A discrimination classifier model was constructed to assess the accuracies of microcalcifications and breast masses, either in isolation or combination, for classifying breast lesions. Performances were compared to benchmark models. Our deep learning model achieved a discriminative accuracy of 87.3% if microcalcifications were characterized alone, compared to 85.8% with a support vector machine. The accuracies were 61.3% for both methods with masses alone and improved to 89.7% and 85.8% after the combined analysis with microcalcifications. Image segmentation with our deep learning model yielded 15, 26 and 41 features for the three scenarios, respectively. Overall, deep learning based on large datasets was superior to standard methods for the discrimination of microcalcifications. Accuracy was increased by adopting a combinatorial approach to detect microcalcifications and masses simultaneously. This may have clinical value for early detection and treatment of breast cancer.
The mRNA interferases, MazF‐mt3 and MazF‐mt7 from <i>Mycobacterium tuberculosis</i> target unique pentad sequences in single‐stranded RNA (2008)

mRNA interferases are sequence-specific endoribonucleases encoded by toxin-antitoxin (TA) systems in bacterial genomes. Previously, we demonstrated that Mycobacterium tuberculosis contains at least seven genes encoding MazF homologues (MazF-mt1 to -mt7) and determined cleavage specificities for MazF-mt1 and MazF-mt6. Here we have developed a new general method for the determination of recognition sequences longer than three bases for mRNA interferases with the use of phage MS2 RNA as a substrate and CspA, an RNA chaperone, which prevents the formation of secondary structures in the RNA substrate. Using this method, we determined that MazF-mt3 cleaves RNA at UU CCU or CU CCU and MazF-mt7 at U CGCU ( indicates the cleavage site). As pentad sequence recognition is more specific than those of previously characterized mRNA interferases, bioinformatics analysis was carried out to identify M. tuberculosis mRNAs that may be resistant to MazF-mt3 and MazF-mt7 cleavage. The pentad sequence was found to be significantly underrepresented in several genes, including members of the PE and PPE families, large families of proteins that play a role in tuberculosis immunity and pathogenesis. These data suggest that MazF-mt3 and MazF-mt7 or other mRNA interferases that target longer RNA sequences may alter protein expression through differential mRNA degradation, a regulatory mechanism that may allow adaptation to environmental conditions, including those encountered by pathogens such as M. tuberculosis during infection.
X7R Multilayer Ceramic Capacitors with Nickel Electrodes (1991)

Electrical properties and microstructures of a holmium-doped (Ba 1.01 Mg 0.01 )O 1.02 (Ti 0.98 Zr 0.02 )O 2 system were studied. Additions of Ho 2 O 3 had little effect in preventing the dielectrics from reducing at high temperature, but the resistivity at low temperature increased with increasing amount of Ho 2 O 3 when treated in oxidizing atmosphere at the cooling stage. From transmission electron micrograph (TEM) observation, it was noted that the microstructure exhibited a grain core-grain shell structure. Newly developed X7R multilayer ceramic capacitors with Ni electrodes revealed highly reliable electrical properties.
Geometrical structure of traveling-wave electroabsorption modulator with enhanced performance (2005)

Effect of microwave characteristics on optical response and nonlinearity of traveling-wave electroabsorption modulator (TW-EAM) is analyzed. TW-EAM having the thickness and the width of 0.4/spl mu/m and 2/spl mu/m with 30/spl Omega/ termination resistor, respectively, is shown as appropriate for millimeter-wave application.
Development of Hardening Depth Evaluation Technique using Eddy Current – Establishment and Introduction of In-line Hardening Depth Inspection System – (2009)

<div class="htmlview paragraph">A hardening depth evaluation technique using eddy current has been developed, which can be applied to a mass production line for destructive (cutting) inspections. Using this technique, changes in the hardness of the induction-hardened structure can be detected based on the changes in magnetic permeability. This technique reduces the thermal effect and improves measurement accuracy through a multi-frequency exciting method and a difference method algorithm.</div>
Stimulation of pulmonary immune responses by the TLR2/6 agonist MALP‐2 and effect on melanoma metastasis to the lung (2011)

Given that metastasized melanoma is a fatal disease in most cases, it is tempting to develop strategies to a priori prevent metastasis. We have stimulated the pulmonary innate immune system by macrophage-activating lipopeptide-2 (MALP-2), a specific agonist at Toll-like receptor (TLR) 2/6, and investigated its impact on experimental melanoma metastasis. In C57BL/6 mice, intratracheal application of MALP-2 induced a profound influx of neutrophils and macrophages into the lung, which peaked after 24 h (sixfold increase) and returned to baseline within 72 h. Further analysis revealed that MALP-2 also markedly induced VCAM-1 expression on pulmonary blood vessels. In vitro experiments demonstrated that this adhesion molecule mediates binding of B16F10 melanoma cells. Furthermore, in vivo or in vitro treatment with MALP-2 did not significantly affect the ability of immune cells to lyse melanoma cells. As a consequence, notwithstanding the profound pulmonary immune response induction and in contrast to conclusions drawn from some previous publications, the net extent of experimental metastasis did not change significantly, regardless of the application regimen of MALP-2 prior to, concomitant with or after tumor cell inoculation. Melanoma cells stably transfected with green fluorescent protein allowed tracking of early events after tumor cell dissemination and showed that MALP-2-mediated TLR2/6 activation did not interfere with pulmonary melanoma cell arrest. Likewise, boosting the immune induction after establishment of metastases did not change the clinical outcome. These unexpected results vividly counsel caution regarding predictions of immunomodulating therapies, as multiple intertwined effects may influence the net outcome.
Mucin 1 is a potential therapeutic target in cutaneous T-cell lymphoma (2015)

Cutaneous T-cell lymphoma (CTCL) is an aggressive neoplasm with limited treatments for patients with advanced disease. The mucin 1 C-terminal subunit (MUC1-C) oncoprotein plays a critical role in regulating cell proliferation, apoptosis, and protection from cytotoxic injury mediated by reactive oxygen species (ROS). Although CTCL cells exhibit resistance to ROS-induced apoptosis, the expression and functional significance of MUC1 in CTCL have not been previously investigated. Present studies demonstrate that MUC1-C is overexpressed in CTCL cell lines and primary CTCL cells but is absent in resting T cells from healthy donors and B-cell lymphoma cells. We have developed a cell-penetrating peptide that disrupts homodimerization of the MUC1-C subunit necessary for its nuclear translocation and downstream signaling. We show that treatment of CTCL cells with the MUC1-C inhibitor is associated with downregulation of the p53-inducible regulator of glycolysis and apoptosis and decreases in reduced NAD phosphate and glutathione levels. In concert with these results, targeting MUC1-C in CTCL cells increased ROS and, in turn, induced ROS-mediated late apoptosis/necrosis. Targeting MUC1-C in CTCL tumor xenograft models demonstrated significant decreases in disease burden. These findings indicate that MUC1-C maintains redox balance in CTCL cells and is thereby a novel target for the treatment of patients with CTCL.