gebhart/patrepeval huggingface dataset:
Monocyte Subpopulations in Angiogenesis (2014)

Growing understanding of the role of the tumor microenvironment in angiogenesis has brought monocyte-derived cells into focus. Monocyte subpopulations are an increasingly attractive therapeutic target in many pathologic states, including cancer. Before monocyte-directed therapies can be fully harnessed for clinical use, understanding of monocyte-driven angiogenesis in tissue development and homeostasis, as well as malignancy, is required. Here, we provide an overview of the mechanisms by which monocytic subpopulations contribute to angiogenesis in tissue and tumor development, highlight gaps in our existing knowledge, and discuss opportunities to exploit these cells for clinical benefit.
Synthesis of Novel 2,4-Diaminopyrrolo[2,3-d]pyrimidines with Antioxidant, Neuroprotective, and Antiasthma Activity (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Novel 2,4-Diaminopyrrolo[2,3-d]pyrimidines with Antioxidant, Neuroprotective, and Antiasthma ActivityGordon L. Bundy, Donald E. Ayer, Lee S. Banitt, Kenneth L. Belonga, Stephen A. Mizsak, John R. Palmer, James M. Tustin, Jia En Chin, Edward D. Hall, and Cite this: J. Med. Chem. 1995, 38, 21, 4161–4163Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October 1995https://pubs.acs.org/doi/10.1021/jm00021a004https://doi.org/10.1021/jm00021a004research-articleACS PublicationsRequest reuse permissionsArticle Views342Altmetric-Citations42LEARN 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
Diels‐Alder reactions II: The Reaction Mechanism (1967)

Abstract The possible mechanisms of the preparatively so productive Diels‐Alder reactions are discussed critically on the basis of experimental data. Although most of the facts can be explained readily by a synchronous mechanism, a number of problems remains.
Effect of Low Dose Atorvastatin Versus Diet-Induced Cholesterol Lowering on Atherosclerotic Lesion Progression and Inflammation in Apolipoprotein E*3–Leiden Transgenic Mice (2004)

Low-dose atorvastatin cholesterol-dependently reduces lesion progression in the aortic root but shows antiinflammatory vascular activity and tends to retard atherogenesis in the aortic arch beyond its cholesterol-lowering effect.
Syntheses of amine derivatives of phencyclidine (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSyntheses of amine derivatives of phencyclidinePeter Y. Johnson, Robert Pan, Jing Quan Wen, and Clarke J. HalfmanCite this: J. Org. Chem. 1981, 46, 10, 2049–2054Publication Date (Print):May 1, 1981Publication History Published online1 May 2002Published inissue 1 May 1981https://pubs.acs.org/doi/10.1021/jo00323a014https://doi.org/10.1021/jo00323a014research-articleACS PublicationsRequest reuse permissionsArticle Views627Altmetric-Citations11LEARN 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
Protective Effects of 10-nitro-oleic Acid in a Hypoxia-Induced Murine Model of Pulmonary Hypertension (2014)

Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert potent anti-inflammatory effects. The current study investigated the role of 10-nitro-oleic acid (OA-NO2) in modulating the pathophysiology of PAH in mice. Mice were kept for 28 days under normoxic or hypoxic conditions, and OA-NO2 was infused subcutaneously. Right ventricular systolic pressure (RVPsys) was determined, and right ventricular and lung tissue was analyzed. The effect of OA-NO2 on cultured pulmonary artery smooth muscle cells (PASMCs) and macrophages was also investigated. Changes in RVPsys revealed increased pulmonary hypertension in mice on hypoxia, which was significantly decreased by OA-NO2 administration. Right ventricular hypertrophy and fibrosis were also attenuated by OA-NO2 treatment. The infiltration of macrophages and the generation of reactive oxygen species were elevated in lung tissue of mice on hypoxia and were diminished by OA-NO2 treatment. Moreover, OA-NO2 decreased superoxide production of activated macrophages and PASMCs in vitro. Vascular structural remodeling was also limited by OA-NO2. In support of these findings, proliferation and activation of extracellular signal-regulated kinases 1/2 in cultured PASMCs was less pronounced on application of OA-NO2.Our results show that the oleic acid nitroalkene derivative OA-NO2 attenuates hypoxia-induced pulmonary hypertension in mice. Thus, OA-NO2 represents a potential therapeutic agent for the treatment of PAH.
Genome-wide computational prediction of transcriptional regulatory modules reveals new insights into human gene expression (2006)

The identification of regulatory regions is one of the most important and challenging problems toward the functional annotation of the human genome. In higher eukaryotes, transcription-factor (TF) binding sites are often organized in clusters called cis-regulatory modules (CRM). While the prediction of individual TF-binding sites is a notoriously difficult problem, CRM prediction has proven to be somewhat more reliable. Starting from a set of predicted binding sites for more than 200 TF families documented in Transfac, we describe an algorithm relying on the principle that CRMs generally contain several phylogenetically conserved binding sites for a few different TFs. The method allows the prediction of more than 118,000 CRMs within the human genome. A subset of these is shown to be bound in vivo by TFs using ChIP-chip. Their analysis reveals, among other things, that CRM density varies widely across the genome, with CRM-rich regions often being located near genes encoding transcription factors involved in development. Predicted CRMs show a surprising enrichment near the 3' end of genes and in regions far from genes. We document the tendency for certain TFs to bind modules located in specific regions with respect to their target genes and identify TFs likely to be involved in tissue-specific regulation. The set of predicted CRMs, which is made available as a public database called PReMod (http://genomequebec.mcgill.ca/PReMod), will help analyze regulatory mechanisms in specific biological systems.
High rate space-time block coded scheme: performance and improvement in correlated fading channels (2003)

In this paper, we study the performance of space-time block coding, also known as space-time transmit diversity (STTD) scheme for high data rate applications with 4 transmit antennas. The scheme consists of two STTD units at the transmitter and an interference-resistant detector at the receiver, termed the double-STTD (DSTTD) scheme. We compare the performance of DSTTD to general multi-input multi-output (GMIMO) signaling for a given data rate and under different channel correlation profiles. It is demonstrated that DSTTD outperforms GMIMO in all cases. In addition, additional performance gain can be attained for DSTTD in correlated channels by selectively ordering the transmit antennas to minimize the average interference terms.
Monolithic Polychromatic Light-Emitting Diodes Based on InGaN Microfacet Quantum Wells toward Tailor-Made Solid-State Lighting (2008)

Monolithic polychromatic light-emitting diodes (LEDs) based on micro-structured InGaN/GaN quantum wells are demonstrated. The microstructure is created through regrowth on SiO2 mask stripes along the [1100] direction and consists of (0001) and {1122} facets. The LEDs exhibit polychromatic emission, including white, due to the additive color mixture of facet-dependent emission colors. Altering the growth conditions and mask geometry easily controls the apparent emission color. Furthermore, simulations predict high light extraction efficiencies due to their three-dimensional structures. Those observations suggest that the proposed phosphor-free LEDs may lead to highly efficient solid-state lighting in which the color spectra of light sources are synthesized to satisfy specific requirements for illuminations.
Sequences required for cell-type specific thyroid hormone regulation of rat growth hormone promoter activity. (1986)

We have located sequences within the rat growth hormone (rGH) promoter region which are required for pituitary cell-type specific responsiveness to T3 (thyroid hormone, 3,5,3'-L-triiodothyronine). Transient transfections with a series of plasmids containing as few as 202 nucleotides upstream of the start site of the rat growth hormone mRNA showed specific induction by T3 in rat pituitary cell lines. Both the magnitude and the kinetics of this response were similar to those of the endogenous rGH gene, showing a strong early induction followed by a decline in T3 effect. Deletion of an additional 19 base pairs (to -183 relative to the start site) eliminated this induction. Plasmids containing sequences up to -237 or -202 showed significant promoter activity but no T3 responsiveness in transfections of mouse fibroblasts or monkey kidney cells. The presence of high affinity nuclear T3 binding proteins was demonstrated in both cell types. These results show that sequences between -183 and -202 are required for pituitary cell specific T3 regulation of the rGH promoter. The lack of T3 responsiveness in non-pituitary cells suggests that such regulation may be mediated by factors present in pituitary cells and absent in other cells.
Predicting functionally important residues from sequence conservation (2007)

Data sets and code for all conservation measures evaluated are available at http://compbio.cs.princeton.edu/conservation/
Recurrent Neural Network Regularization (2014)

We present a simple regularization technique for Recurrent Neural Networks (RNNs) with Long Short-Term Memory (LSTM) units. Dropout, the most successful technique for regularizing neural networks, does not work well with RNNs and LSTMs. In this paper, we show how to correctly apply dropout to LSTMs, and show that it substantially reduces overfitting on a variety of tasks. These tasks include language modeling, speech recognition, image caption generation, and machine translation.
Boron Therapeutics on the Horizon (2001)

No pharmaceutical based on boron has yet made it to market, but this may soon change. The new millennium has brought with it some unique classes of bioactive boron compounds that are sufficiently mature in development to be considered significant and timely advances in their respective chemotherapeutic areas. Because boron is seldom seen as a constituent of a bioactive agent, this review relates some of the pertinent biologic and physiologic properties of boron and then describes in detail those boron-based agents clearly visible on the therapeutic horizon. Highlighted agents include boronic acids and boron heterocycles as potent proteasome inhibitors, β-lactamase inhibitors, dipeptidyl peptidase inhibitors, inositol trisphosphate receptor modulators, antibacterials, and antiestrogens. As these new agents are welcomed into the therapeutic armamentarium, others will surely follow and the prescribing clinician will already have an awareness and appreciation of the unique benefits that these compounds have to offer.
Neuroaxonal Dystrophy in Calcium-Independent Phospholipase A2β Deficiency Results from Insufficient Remodeling and Degeneration of Mitochondrial and Presynaptic Membranes (2011)

Infantile neuroaxonal dystrophy (INAD) is a fatal neurodegenerative disease characterized by the widespread presence of axonal swellings (spheroids) in the CNS and PNS and is caused by gene abnormality in PLA2G6 [calcium-independent phospholipase A(2)β (iPLA(2)β)], which is essential for remodeling of membrane phospholipids. To clarify the pathomechanism of INAD, we pathologically analyzed the spinal cords and sciatic nerves of iPLA(2)β knock-out (KO) mice, a model of INAD. At 15 weeks (preclinical stage), periodic acid-Schiff (PAS)-positive granules were frequently observed in proximal axons and the perinuclear space of large neurons, and these were strongly positive for a marker of the mitochondrial outer membrane and negative for a marker of the inner membrane. By 100 weeks (late clinical stage), PAS-positive granules and spheroids had increased significantly in the distal parts of axons, and ultrastructural examination revealed that these granules were, in fact, mitochondria with degenerative inner membranes. Collapse of mitochondria in axons was accompanied by focal disappearance of the cytoskeleton. Partial membrane loss at axon terminals was also evident, accompanied by degenerative membranes in the same areas. Imaging mass spectrometry showed a prominent increase of docosahexaenoic acid-containing phosphatidylcholine in the gray matter, suggesting insufficient membrane remodeling in the presence of iPLA(2)β deficiency. Prominent axonal degeneration in neuroaxonal dystrophy might be explained by the collapse of abnormal mitochondria after axonal transportation. Insufficient remodeling and degeneration of mitochondrial inner membranes and presynaptic membranes appear to be the cause of the neuroaxonal dystrophy in iPLA(2)β-KO mice.
Regulation of inflammation by collagen-binding integrins α1β1 and α2β1 in models of hypersensitivity and arthritis (2000)

Adhesive interactions play an important role in inflammation by promoting leukocyte attachment and extravasation from the vasculature into the peripheral tissues. However, the importance of adhesion molecules within the extracellular matrix-rich environment of peripheral tissues, in which cells must migrate and be activated, has not been well explored. We investigated the role of the major collagen-binding integrins, alpha1beta1 and alpha2beta1, in several in vivo models of inflammation. mAb's against murine alpha1 and alpha2 were found to significantly inhibit effector phase inflammatory responses in animal models of delayed-type hypersensitivity (DTH), contact hypersensitivity (CHS), and arthritis. Mice that were alpha1-deficient also showed decreased inflammatory responses in the CHS and arthritis models when compared with wild-type mice. Decreased leukocyte infiltration and edema formation accompanied inhibition of antigen-specific models of inflammation, as nonspecific inflammation induced by croton oil was not inhibited. This study demonstrates the importance in vivo of alpha1beta1 and alpha2beta1, the collagen-binding integrins, in inflammatory diseases. The study also extends the role of integrins in inflammation beyond leukocyte attachment and extravasation at the vascular endothelial interface, revealing the extracellular matrix environment of peripheral tissues as a new point of intervention for adhesion-based therapies.
Cyclic Nucleotide Compartmentalization: Contributions of Phosphodiesterases and ATP-Binding Cassette Transporters (2011)

Cyclic nucleotides [e.g., cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)] are ubiquitous second messengers that affect multiple cell functions from maturation of the egg to cell division, growth, differentiation, and death. The concentration of cAMP can be regulated by processes within membrane domains (local regulation) as well as throughout a cell (global regulation). The phosphodiesterases (PDEs) that degrade cAMP have well-known roles in both these processes. It has recently been discovered that ATP-binding cassette (ABC) transporters contribute to both local and global regulation of cAMP. This regulation may require the formation of macromolecular complexes. Some of these transporters are ubiquitously expressed, whereas others are more tissue restricted. Because some PDE inhibitors are also ABC transporter inhibitors, it is conceivable that the therapeutic benefits of their use result from the combined inhibition of both PDEs and ABC transporters. Deciphering the individual contributions of PDEs and ABC transporters to such drug effects may lead to improved therapeutic benefits.
Yersinia pseudotuberculosis Harbors a Type IV Pilus Gene Cluster That Contributes to Pathogenicity (2002)

Fimbriae have been shown to play an essential role in the adhesion of pathogenic gram-negative bacteria to host cells. In the enteroinvasive bacterium Yersinia pseudotuberculosis, we characterized a previously unknown 11-kb chromosomal locus involved in the synthesis of type IV pili. The locus consists of 11 open reading frames forming a polycistronic unit and encoding putative Pil proteins, PilLMNOPQRSUVW. When introduced into Escherichia coli, the Y. pseudotuberculosis operon reconstituted bundles of filaments at a pole on the bacterial surface, demonstrating that the pil locus was functional in a heterogenous genetic background. Environmental factors regulated transcription of the Y. pseudotuberculosis operon; in particular, temperature, osmolarity, and oxygen tension were critical cues. Deletion of the type IV pilus gene cluster was associated with a reduction of Y. pseudotuberculosis pathogenicity for mice infected orally. Forty-one percent of Y. pseudotuberculosis strains isolated from human or animal sources harbored the type IV pilus locus. Therefore, the pil locus of Y. pseudotuberculosis might constitute an "adaptation island," permitting the microorganism to colonize a vast reservoir.
Improvement of H2O2 stability of manganese peroxidase by combinatorial mutagenesis and high-throughput screening using in vitro expression with protein disulfide isomerase (2003)

A functional expression system for a heme protein of Phanerochaete chrysosporium, manganese peroxidase (MnP), was developed using the Escherichia coli in vitro coupled transcription/translation system in the presence of hemin and fungal protein disulfide isomerase. This system has allowed the high-throughput construction and screening of a large diversity of mutant heme enzymes and has made it possible to improve the enzymatic function efficiently. Here we increased the H2O2 stability of MnP using this system; a mutant MnP library containing three randomized amino acid residues located in the H2O2-binding pocket of MnP was designed and constructed on a 384-well plate using SIMPLEX (single-molecule-PCR-linked in vitro expression). The screening of 10(4) samples independently expressed for improved H2O2 stability led to four positive mutants, the H2O2 stability of which was nine times higher than that of the wild-type.
Red mud as an iron-based catalyst for catalytic cracking of naphthalene (2017)

Reducing the tar content in the producer gas of biomass gasification processes remains one of the main challenges in the commercialization of this technology and, hence, the development of clean and economical tar-removing technologies is becoming increasingly important. Catalytic tar removal has the advantage of avoiding expensive gas cleaning systems while maintaining the sensible heat in the producer gas. Commercial catalysts based on noble metals and metal oxides have shown good activity towards tar destruction, but are prone to rapid deactivation. This in addition to the high replacement cost provide the rationale for the development of low-cost alternatives. Red mud, a by-product from bauxite processing, has received considerable attention in this regard due to its high iron content in the form of ferric oxide (Fe₂O₃), high surface area, and its resistance to sintering and poisoning. However, very few studies have been conducted to investigate red mud as a potential catalyst for catalytic tar removal. The aim of this study was to develop a catalyst from red mud for the removal of naphthalene, as a model compound for gasification tar. Red mud catalyst pellets were produced from raw red mud slurry, and their properties were investigated by measuring the chemical composition, surface area, and pore size distribution. Subsequently, the ability for tar decomposition was studied by passing naphthalene-nitrogen and naphthalene-hydrogen mixtures through a bed of the catalyst at five space velocities in the range of 4500-19,000 h-¹, and at reactor temperatures of 500, 600, 700 and 800°C. Catalytic cracking tests confirmed that red mud possesses a very high intrinsic catalytic activity for naphthalene conversion even at temperatures as low as 500°C and space velocities as high as 19,000 h-¹. Kinetic analysis was also performed to determine the apparent reaction order, the kinetic rate constants as well as the activation energy of the reaction. Long term tests of the catalyst showed that the activity of the catalyst diminished over time when no hydrogen was present in the system; however, in the presence of H₂ the activity was found to remain &gt; 90% for 14 h.
Desipramine Facilitation of Initial Cocaine Abstinence (1989)

We conducted a double-blind, random assignment, six-week comparison of desipramine hydrochloride (n = 24), lithium carbonate (n = 24), and placebo (n = 24) treatments for cocaine dependence. Subjects were 72 outpatient cocaine abusers who met DSM-III-R dependence criteria for cocaine but not for other substance abuse. Subjects in each treatment group were similar in history of cocaine and other substance abuse, cocaine craving, sociodemographics, and other psychiatric comorbidity. Desipramine, compared with both other treatments, substantially decreased cocaine use. Lithium treatment outcome did not differ from that of placebo. Desipramine-treated subjects attained contiguous periods of abstinence substantially more frequently than subjects receiving lithium or placebo. Fifty-nine percent of the desipramine-treated subjects were abstinent for at least three to four consecutive weeks during the six-week study period, compared with 17% for placebo and 25% for lithium. Cocaine craving reductions were also substantially greater in the desipramine-treated subjects. Establishment of initial abstinence is the first stage in recovery from cocaine dependence. Our findings indicate that desipramine is an effective general treatment, for this first treatment stage, in actively cocaine-dependent outpatients.