gebhart/patrepeval huggingface dataset:
Monocyte-derived cytokines in multiple sclerosis (2003)

MS is an inflammatory, presumably autoimmune, disease mediated by the activation of T cells, B cells and monocytes (MO). Inflammation is thought to occur early during the relapsing-remitting phase of MS (RRMS), whereas in the later phases of MS such as secondary progressive MS (SPMS), inflammation tends to diminish. Our objective was to compare the types and amounts of proinflammatory and regulatory cytokines produced by MO from relapsing-remitting patients with or without treatment with IFN-beta (RRMS+ therapy, RRMS- therapy), respectively, from secondary progressive patients (SPMS) and from healthy controls (HC). MO were isolated by a density-gradient technique and three different techniques (RNase protection assay, ELISA and intracellular cytokine staining) were used to assess cytokine levels. An increase in IL6, IL12 and TNF-alpha was observed by all three methods for RRMS- therapy and for SPMS patients compared to HC and RRMS+ therapy patients. We conclude that proinflammatory and regulatory monokines can be derived from MO of MS patients and that these levels are modulated by IFN-beta therapy. Although it is believed that inflammation tends to diminish in SPMS patients, our data show that inflammatory cytokines continue to be released at high levels, suggesting that IFN-beta or IL10 treatment may be beneficial for this group.
N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis (2014)

The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography-mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding microRNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis.
Sphingosine‐1‐Phosphate in Cell Growth and Cell Deatha (1998)

Recent evidence suggests that branching pathways of sphingolipid metabolism may mediate either apoptotic or mitogenic responses depending on the cell type and the nature of the stimulus. While ceramide has been shown to be an important regulatory component of apoptosis induced by tumor necrosis factor alpha and Fas ligand, sphingosine-1-phosphate (SPP), a further metabolite of ceramide, has been implicated as a second messenger in cellular proliferation and survival induced by platelet-derived growth factor, nerve growth factor, and serum. SPP protects cells from apoptosis resulting from elevations of ceramide. Inflammatory cytokines stimulate sphingomyelinase, but not ceramidase, leading to accumulation of ceramide, whereas growth signals also leading to accumulation of ceramide, whereas growth signals also stimulate ceramidase and sphingosine kinase leading to increased SPP levels. We propose that the dynamic balance between levels of sphingolipid metabolites, ceramide, and SPP, and consequent regulation of different family members of mitogen-activated protein kinases (JNK versus ERK), is an important factor that determines whether a cell survives or dies.
Discovery of a Potent, Selective, and Orally Efficacious Pyrimidinooxazinyl Bicyclooctaneacetic Acid Diacylglycerol Acyltransferase-1 Inhibitor (2009)

Inhibition of DGAT-1 is increasingly seen as an attractive mechanism with the potential for treatment of obesity and other elements of the metabolic syndrome. We report here a bicyclooctaneacetic acid derivative in the pyrimidinooxazine structural class of DGAT-1 inhibitors that has good potency, selectivity, and pharmacokinetic characteristics across a variety of species. This compound is an effective inhibitor of DGAT-1 in both intestinal and adipose tissue, which results in a reduction in body weight or body weight gain following oral administration in both mouse and rat models of dietary-induced obesity.
Synthesis of Nucleoside Phosphate and Phosphonate Prodrugs (2014)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTSynthesis of Nucleoside Phosphate and Phosphonate ProdrugsUgo Pradere†, Ethel C. Garnier-Amblard‡, Steven J. Coats‡, Franck Amblard†, and Raymond F. Schinazi*†View Author Information† Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Atlanta, Georgia 30322, United States‡ RFS Pharma LLC, Tucker, Georgia 30084, United States*E-mail: [email protected]Cite this: Chem. Rev. 2014, 114, 18, 9154–9218Publication Date (Web):August 21, 2014Publication History Received11 April 2014Published online21 August 2014Published inissue 24 September 2014https://doi.org/10.1021/cr5002035Copyright © 2014 American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceArticle Views29407Altmetric-Citations386LEARN 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 InReddit PDF (13 MB) Get e-AlertsSUBJECTS:Monomers,Nucleic acids,Organophosphorus compounds,Pharmaceuticals,Reaction products Get e-Alerts
3,4-diaminopyridine for the treatment of Lambert–Eaton myasthenic syndrome (2010)

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which antibodies against voltage-gated calcium channels inhibit cholinergic neurotransmission. LEMS is clinically characterized by muscle weakness and autonomic dysfunction. 3,4-diaminopyridine (3,4-DAP) blocks potassium channels in nerve terminals, resulting in an increase in acetylcholine release. This article describes the four randomized placebo-controlled trials of 3,4-DAP in patients with LEMS. All trials demonstrated a significant effect on muscle strength and compound muscle action potential amplitude. Furthermore, the safety and tolerability of 3,4-DAP are reviewed. The side effects of 3,4-DAP are generally mild and most frequently consist of paresthesias, but epileptic seizures and arrhythmias have been described in patients using high doses. Given the efficacy and safety of 3,4-DAP in LEMS, this drug is the mainstay for symptomatic treatment of LEMS.
A novel biotinylated adenylate analog derived from pyrazolo[3,4-d]pyrimidine for labeling DNA probes (1991)

A novel dATP analogue, 3-[5-[(N-biotinyl-6- amiocaproyl)amino]pentyl]-1-(2-deoxy-beta-D-erythro-pentofuranosyl )-1H-pyrazolo[3,4-d]pyrimidin-4-amine 5'-triphosphate (9, bio-13-dAPPTP), which is modified at the 3-position with a flexible linker arm bearing a terminal biotin moiety, has been synthesized. This nucleotide is readily incorporated into DNA probes by nick translation. These probes hybridize to complementary targets as well as probes labeled with bio-dUTP, as judged by slot blot. When incorporated into oligonucleotides, they do not cause the loss of hybridization efficiency that an N-6-substituted adenine nucleotide does when incorporated into the same sites in the oligonucleotide.
Recognition of position-specific properties of tectal cell membranes by retinal axons in vitro (1987)

In order to test the preference of growing axons for membrane-associated positional specificity a new in vitro assay was developed. In this assay, membrane fragments of two different sources are arranged as a carpet of very narrow alternating strips. Axons growing on such striped carpets are simultaneously confronted with the two substrates at the stripe borders. If there is a preference of axons for one or the other substrate they become oriented by the stripes and grow within the lanes of the preferred substrate. Such preferential growth could, in principle, be due to affinity to attractive factors on the preferred stripes or avoidance of repulsive factors on the alternate stripes. This assay system was used to investigate growth of chick retinal axons on tectal membranes. Tissue strips cut from various areas of the retina were explanted and the extending axons were confronted with stripes of cell membranes from various areas within the optic tectum. Tectal cell membranes prove to be an excellent substrate for the growth of retinal axons. Nasal and temporal axons can grow well on membranes of both posterior and anterior tectal cells. If, however, temporal axons are given a choice and encounter the border between anterior and posterior membranes they show a marked preference for growth on membranes of the anterior tectum, their natural target area. Nasal axons do not show a preference in this assay system. The transition from nasal to temporal properties within the retina is abrupt. In contrast, the transition from anterior to posterior properties of the tectal cell membranes occurs as a smooth gradient. Significantly, the positional differences of tectal membrane properties are only seen during the period of development of the retinotectal projection and are independent of tectal innervation by retinal axons. These anterior-posterior differences disappear by embryonic day 14.
Molecular Architecture Influences the Thermally Induced Aggregation Behavior of Elastin-like Polypeptides (2011)

Elastin-like polypeptides are thermally responsive polymers that exhibit phase separation above a transition temperature. The effect of molecular architecture on the temperature responsive behavior of elastin-like polypeptide solutions was investigated by characterization of solutions of three-armed star polypeptides, linear polypeptides, and their mixtures. These biosynthesized polypeptides have precise lengths and amino acid sequences. Transition temperatures were measured as a function of molecular weight and solution concentration and compared to their linear counterparts. Like their linear counterparts, the transition temperature is linearly related to log concentration. A mathematical relationship was used to fit the transition temperature data of different polypeptide lengths to a volume-based concentration using the polymer coil volume. The results of this model suggest that the linear ELP is in a random coil conformation at the transition temperature while the three-armed ELP is in a compact extended coil conformation, consistent with different pathways for aggregation. Solutions containing both trimer and linear constructs have two transition temperatures, further supporting differing aggregation behaviors.
Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults (2012)

Skeletal muscle atrophy during bed rest is attributed, at least in part, to slower basal muscle protein synthesis (MPS). Essential amino acids (EAA) stimulate mammalian target of rapamycin (mTORC1) signaling, amino acid transporter expression, and MPS and are necessary for muscle mass maintenance, but there are no data on the effect of inactivity on this anabolic mechanism. We hypothesized that bed rest decreases muscle mass in older adults by blunting the EAA stimulation of MPS through reduced mTORC1 signaling and amino acid transporter expression in older adults. Six healthy older adults (67 ± 2 yr) participated in a 7-day bed rest study. We used stable isotope tracers, Western blotting, and real-time qPCR to determine the effect of bed rest on MPS, muscle mTORC1 signaling, and amino acid transporter expression and content in the postabsorptive state and after acute EAA ingestion. Bed rest decreased leg lean mass by ∼4% (P < 0.05) and increased postabsorptive mTOR protein (P < 0.05) levels while postabsorptive MPS was unchanged (P > 0.05). Before bed rest acute EAA ingestion increased MPS, mTOR (Ser(2448)), S6 kinase 1 (Thr(389), Thr(421)/Ser(424)), and ribosomal protein S6 (Ser(240/244)) phosphorylation, activating transcription factor 4, L-type amino acid transporter 1 and sodium-coupled amino acid transporter 2 protein content (P < 0.05). However, bed rest blunted the EAA-induced increase in MPS, mTORC1 signaling, and amino acid transporter protein content. We conclude that bed rest in older adults significantly attenuated the EAA-induced increase in MPS with a mechanism involving reduced mTORC1 signaling and amino acid transporter protein content. Together, our data suggest that a blunted EAA stimulation of MPS may contribute to muscle loss with inactivity in older persons.
Theoretical and electrophysiological evidence for axial loading about aortic baroreceptor nerve terminals in rats (2007)

Arterial baroreceptors are essential for neurocirculatory control, providing rapid hemodynamic feedback to the central nervous system. The pressure-dependent discharge of carotid and aortic baroreceptor afferents has been extensively studied. A common assumption has been that circumferential deformation of the arterial wall is the predominant mechanical force affecting baroreceptor discharge. However, in vivo the arterial tree is under significant longitudinal tension, leading to the hypothesis that axially directed forces may contribute to baroreceptor function. To test this hypothesis, we utilized a combination of finite element modeling methods and an in vitro rat aortic arch preparation. Model formulation utilized traditional analytic constructs available in the literature followed by refinement of model material parameters through direct comparison of computationally and experimentally generated pressure-diameter curves. The numerical simulations strongly indicated a functional role for axial loading within the region of the baroreceptive nerve terminal. This prediction was confirmed through single-fiber recording of baroreceptor nerve discharge under conditions with and without longitudinal tension in the vessel preparation. The recordings (n = 5) demonstrated that longitudinal tension significantly (P < 0.02) lowered both the pressure threshold (P(th), mmHg) for baroreceptor discharge and sensitivity (S(th), Hz/mmHg). The effect was nearly instantaneous and sustained; i.e., under longitudinal tension average P(th) was 84 +/- 3 mmHg and S(th) was 0.71 +/- 0.15 Hz/mmHg, which immediately increased to a P(th) of 94 +/- 4 mmHg and a S(th) of 1.20 +/- 0.32 Hz/mmHg with loss of axial tension. Possible explanations of how an abrupt change in axial loading could result in a synchronized increase in afferent drive of the baroreceptor reflex, and the potentiating effect this could have on neurogenically mediated orthostatic intolerance are discussed.
Structural Determinants of Heparin's Growth Inhibitory Activity (1989)

The glycosaminoglycan heparin inhibits the growth of several cell types in vitro including smooth muscle cells and rat cervical epithelial cells. The commercially available heparin which has antiproliferative activity is a structurally heterogeneous polymer that undergoes extensive modifications during maturation. In this report we have performed structure-function studies on heparin's antiproliferative activity using three different cell types: both rat and calf vascular aortic smooth muscle cells and rat cervical epithelial cells. The minimal oligosaccharide size requirements for antiproliferative activity were determined for the three cell types by using oligosaccharide fragments of defined length prepared by nitrous acid cleavage and gel filtration and a synthetic pentasaccharide. The size requirements are similar but not identical for the different cell types. Hexasaccharide fragments are antiproliferative for all three cell types but the synthetic pentasaccharide inhibits the growth of only the rat and calf vascular aortic smooth muscle cells. The interdependence between size and charge for antiproliferative activity was investigated using chemically modified oligosaccharides as well as oligosaccharides prepared from heparin and separated into fractions of differing charge by ion-exchange chromatography. There is a strong interdependence between size and charge for antiproliferative activity. For example, increasing the charge of inactive tetrasaccharide fragments by O-oversulfation makes them antiproliferative whereas reducing the charge of active larger fragments causes them to loose their antiproliferative activity. Finally the importance of 2-O-sulfate glucuronic acid moieties for antiproliferative activity was investigated using heparin preparations that lack 2-O-sulfate glucuronic acid. These compounds possess antiproliferative activity indicating that 2-O-sulfate glucuronic acid is not required for antiproliferative activity.
Single Sub-20 nm Wide, Centimeter-Long Nanofluidic Channel Fabricated by Novel Nanoimprint Mold Fabrication and Direct Imprinting (2007)

We report and demonstrate a new method to fabricate single fluidic-channels of uniform channel width (11-50 nm) and over 1.5 cm in length, which are essential to developing innovative bio/chemical sensors but have not been fabricated previously. The method uses unconventional nanofabrication (a combination of crystallographic anisotropic etching, conformal coating, and edge patterning, etc.) to create an imprint mold of a channel pattern and nanoimprint to duplicate such channel. The centimeter-long channel continuity is verified by flowing fluorescent dye-stained water and stretching and transporting DNAs. The 18 by 20 nm channel cross-section was confirmed by measuring the liquid conductance in the channel.
Synthesis of mesoporous silica nanoparticle‐encapsulated alginate microparticles for sustained release and targeting therapy (2013)

This study reports the synthesis of mesoporous silica nanoparticle-encapsulated alginate microparticles (MSN@Alg) for sustained release and targeting therapy. The MSN@Alg was synthesized by air dynamical atomization, and the effects of several critical factors including concentration of alginate solution, flow rate of alginate solution, flow rate of air, the distance between nozzle and calcium bath, and stirring rate of calcium on the particle size of the synthesized MSN@Alg were investigated. For studying the sustained release properties of the MSN@Alg, rhodamine 6G (R6G) was used as a model drug, and we compared the release properties of R6G/MSN and R6G/MSN@Alg using different concentrations of alginate, concentrations and volumes of phosphate-buffered saline (PBS) buffer solutions. The sustained release behavior of the R6G/MSN@Alg system can be prolonged to 20 days with an optimal condition of 1 mg R6G/MSN@Alg to 2 mL PBS (10 mM). To achieve targeting therapy, an anticancer drug, doxorubicin (Dox), was loaded into MSN@Alg, and a arginine, glycine, and aspartic acid (RGD)-based peptide was functionalized onto the surface of MSN@Alg for the purpose of specific targeting. The results showed that the intracellular drug delivery efficiency was greatly enhanced (i.e., 3.5-folds) for the Dox/MSN@Alg-RGD drug delivery system.
<title>Advantage of single-lens stereopsis</title> (1992)

That stereopsis is scalable is often misunderstood. Because stereopsis is scalable, the Carter single lens system offers many advantages over dual lens imaging in the accuracy and timing of mechanical tasks. Before a typical application is described, the bias against, and the human factors issues surrounding stereopsis are examined. This single lens solution is offered and its application to microscopic probes is detailed.
Nanosecond laser amplification via degenerate multiwave mixing in silicon (1988)

We present the results of a detailed study of degenerate multiwave mixing mediated nanosecond 1.06 μm pulse amplification in silicon, taking into account higher order diffracted beams, self-phase modulation, pump depletions, intensity-dependent absorption losses, electron-hole plasma attenuation, and other geometrical optical parameters. Excellent agreements between theory and experiment are obtained.
Epitope mapping of a monoclonal antibody directed against the α-subunit of phosphofructokinase-1 fromSaccharomyces cerevisiae by screening phage display libraries (1999)

Phosphofructokinase-1 from Saccharomyces cerevisiae is composed of two types of subunits, alpha and beta. Subunit-specific monoclonal antibodies were raised to elucidate structural and functional properties of both subunits. One monoclonal antibody, alpha-F3, binds to an epitope either at the C-terminal or at the N-terminal part of the alpha-polypeptide chain. By screening a heptapeptide library with this monoclonal antibody, a set of heptapeptides was selected, which contained the consensus sequences D-A-F and D-S-F. Two heptapeptides with these motifs were synthesized in order assess their capacity to inhibit the binding of antibody alpha-F3 to native phosphofructokinase-1. The peptide G-I-K-D-A-F-L inhibited the binding more strongly (IC50 = 1.5 microM) than the peptide A-P-W-H-D-S-F (IC50 = 33.3 microM). Sequence matching revealed the presence of the D-A-F motif in the polypeptide chain of phosphofructokinase-1 at amino acid position 172-174. As a control, the nonapeptide A-P-T-S-K-D-A-F-L which corresponds to the sequence of the putative epitope was tested in the inhibition assay. In view of the high inhibitory capacity (IC50 = 0.3 microM) it was concluded that this nonapeptide represents the continuous epitope of phosphofructokinase-1 that is recognized by antibody alpha-F3.
The role of viruses in human cancer development and antiviral approaches for intervention. (2002)

Viruses are estimated to be linked to at least 15% of human cancers. Hepatitis B and C viruses, human papilloma viruses, Epstein-Barr virus, human herpes virus-8 and human T-cell leukemia virus have been definitively linked to human cancer. A brief overview of the molecular mechanisms of carcinogenesis elucidated for these viruses and antiviral approaches which may provide clues to reducing the occurrence or progression of the resulting virally derived cancers are described.
14.6 A 1.42TOPS/W deep convolutional neural network recognition processor for intelligent IoE systems (2016)

In this paper, we present an energy-efficient CNN processor with 4 key features: (1) a CNN-optimized neuron processing engine (NPE), (2) a dual-range multiplyaccumulate (DRMAC) block for low-power convolution operations, (3) an on-chip memory architecture and a utilization scheme for reducing off-chip memory accesses, (4) kernel data compression for further reducing off-chip memory accesses.