gebhart/patrepeval huggingface dataset:
Synergism between cAMP and ATP in signal transduction in cardiac myocytes (1992)

ATP transiently increases the intracellular Ca2+ concentration in cardiac myocyte suspensions. Pretreatment with norepinephrine (NE) greatly potentiates the ATP response. We performed experiments on adult rat myocyte suspensions loaded with fura-2 to investigate the mechanism of NE potentiation. We found that forskolin (an activator of adenylate cyclase), 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase), and permeative adenosine 3',5'-cyclic monophosphate (cAMP) analogues potentiate the increase in cytosolic Ca2+ concentration induced by ATP. NE, forskolin, and 8-(4-chlorophenylthio)-cAMP all increase Vmax of the Ca2+ response curve of ATP. Measurement of cAMP by radioimmunoassay confirmed that the changes in the ATP response were accompanied by an increase in cAMP. These results suggest that the noradrenergic potentiation of the ATP-induced Ca2+ mobilization involves cAMP as a second messenger. Patch-clamp studies of isolated myocytes showed that neither NE nor forskolin alters the inward current elicited by ATP, but rather they increase the duration of secondary slow action potentials elicited by ATP. NE also increases the Ca2+ current through L-type Ca2+ channels in the myocytes. We conclude that NE potentiates the ATP-induced Ca2+ transient by increasing cAMP levels and that one of the early events is the increase of the inward Ca2+ current during the action potential.
Post-harvest biological control by Pantoea agglomerans (CPA-2) on Golden Delicious apples (2002)

Pantoea agglomerans could be used effectively on apples under a wide range of temperature and atmosphere conditions. SIGNIFICANCE AND IMAPCT OF THE STUDY Pantoea agglomerans can be used as a biocontrol agent on apples at 8 x 10(7) cfu ml-1, the same concentration as in pears. This will facilitate the application of this biological control agent by the growers in packing houses.
Evaluation of the dual exposure technique (2001)

Phase-shift masks are an important factor in the extension of optical lithography to the 50nmmode. A critical factor in their implementation is the "Dual reticle exposure technique." This technique uses two reticles: one is typically the high-resolution phase-shift reticle, and the other, a clearing or trimming reticle to remove unwanted phase edge patterns. This paper examines the result ofimplementing this technique on a very-high numerical aperture 193 nm-catadioptric-exposure system. Examples are given for the application of the "Dual Reticle Technique" including applications in which two phase-shift reticles are used to print advanced memory cells. Chromeless phase-shift masks are also shown. Issues with the implementation ofthe technique are examined. These include exposure delay effects, pattern registration, and the impact of the technique on exposure system throughput. Exposure system design developments are reported that will improve exposure system throughput with the dual reticle exposure technique. These include: Double Reticle Stages; and a new concept of exposing the two reticles simultaneously. It is noted that this dual simultaneous exposure system, when combined with a dual wafer stage system, has the potential for exposing 300mm wafers at rates up tp 150 wafers/hour in dual reticle exposure mode.
Synthesis of combinatorial libraries with only one representation of each structure. (1994)

A technique of generating libraries in which every compound is displayed only once and all possible combinations are prepared with absolute certainty is presented. The method is based on the stepwise division of a continuous carrier in each step of randomization. Polypropylene membrane and cotton thread were evaluated as potential supports for this approach to library construction. Cotton thread accommodates 400 nmol of test compound per cm, but its mechanical properties limit the dimension of libraries. An alternative combinatorial library of "restructurable toothbrushes" is suggested.
Abstract 3650: PI3-kinase gamma controls the macrophage M1-M2 switch, thereby promoting tumor immunosuppression and progression (2014)

Abstract Innate immune cells (macrophages, monocytes and neutrophils) rapidly migrate to sites of tissue damage where they initially activate T cells (M1 classical response). These cells gradually transition to suppress T cell responses, while stimulating wound healing (M2 alternative response). In tumors, however, the normal immune response is chronically disrupted and an exaggerated immunosuppressive, wound healing, tumor-promoting (M2) response prevails. In order to identify the mechanisms regulating this M2 response in tumor inflammation and to develop novel therapeutics to control it, we set out to explore the role of macrophage signaling in control of the M1-M2 switch. Using RNA seq analysis of gene expression patterns in M1 and M2 macrophages in vitro and gene expression analysis of myeloid cells in spontaneous and orthotopic mouse models of lung, pancreatic and breast cancer, we found that myeloid cell PI3Kinase gamma controls the switch between the M1-M2 phenotype in human and murine macrophages. PI3Kinase gamma signaling stimulates an immunosuppressive, wound healing gene expression program exemplified by expression of immunosuppressive and pro-angiogenic factors, such as Arginase1, TGFbeta1, PDGFBB, MMP9, and MMP13, and suppression of pro-inflammatory factors such as IL12, iNos, and interferon gamma. Blockade of this pathway by genetic or pharmacological inhibition of PI3Kgamma blocks this immunosuppressive, wound healing gene expression program and stimulates instead a T cell activating gene expression program as well as T cell mediated tumor cell killing. PI3Kgamma blockade inhibits tumor growth and metastasis in mouse models of lung, pancreatic and breast carcinoma. Our studies demonstrate the critical role of PI3Kgamma signaling in the control of the M1-M2 macrophage switch and demonstrate that this kinase is an important therapeutic target to suppress tumor growth by targeting inflammation that is associated with all solid tumors. Citation Format: Megan Kaneda, Sara Gorjestani, Judith A. Varner. PI3-kinase gamma controls the macrophage M1-M2 switch, thereby promoting tumor immunosuppression and progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3650. doi:10.1158/1538-7445.AM2014-3650
Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR (1994)

A series of HIV protease inhibitors containing a novel C2 symmetrical "aminodiol" core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (Ki = 100 nM; ED50 (HIV-1) = 80 nM) containing P1/P1 benzyl and P2/P2 Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After i.v. and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).
Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product (1987)

We identified a conditional transcriptional enhancer in the long control region (LCR) of human papillomavirus type 16 (HPV-16). This conditional enhancer requires activation in trans by a product of the viral early-region open reading frames (ORFs). Primer extension analysis of chloramphenicol acetyltransferase RNA isolated from transiently transfected CV-1 cells demonstrated that trans-activation of the HPV-16 LCR enhancer operated at the transcriptional level. Mutational analysis of the early ORFs demonstrated that the conditional enhancer of the LCR was trans-activated by the product of the E2 ORF. The E2 gene product of bovine papillomavirus type 1, which can trans-activate the conditional enhancer in the bovine papillomavirus type 1 LCR, was also capable of trans-activating the E2-responsive enhancer of HPV-16. The activity of the HPV-16 LCR enhancer was also assayed in two human cervical carcinoma cell lines, HeLa and SiHa, which harbor transcriptionally active, integrated HPV-18 and HPV-16 DNA sequences, respectively. No endogenous E2 or E2-like activity was detected in either cell line.
LOAD SENSING HYDRAULIC SYSTEM SIMULATION (1997)

A nonlinear model of a hydraulic system containing a load sensing piston pump, state-of-the-art directionalcontrol valve, and motor was created using Simulink, a software package designed for dynamic system simulation.Validation was accomplished by comparison with field test results for the boom swing function of a log loader with highinertia load. Instability due to feedback interaction and to the inertia of the load were successfully simulated. Twomechanisms for correcting the instability were included in the model: an orifice restriction in the load sensing feedbackline, and a feedback piston in the valve spool designed to reduce the metering area at higher load pressures.
Dendrimer-Enabled Modulation of Gene Expression in Chlamydia trachomatis (2012)

The obligate intracellular bacterium Chlamydia trachomatis is an important human pathogen. The genome of this organism is small but encodes many genes of currently unknown function that are thought to be involved in virulence. Lack of a system for genetic manipulation has been a key challenge to advancing the understanding of molecular genetics underlying virulence for this bacterium. We developed a dendrimer-enabled system for transformation of C. trachomatis, and used it to demonstrate the efficient and highly specific knockdown of transcript levels from targeted genes. Antisense, sense, and other control oligonucleotides targeting two sets of duplicated genes on the chlamydial chromosome were designed, commercially synthesized, and complexed with generation-4 polyamidoamine (PAMAM) dendrimers. The complexes were given to HEp-2 cell cultures infected for 16 h with C. trachomatis serovar K and then removed three hours later. Infected cultures were harvested 6 h after pulsing, and DNA and RNA/cDNA were prepared for assessment of transcript levels compared to those for the same genes in infected cultures, without dendrimer complexation. In all cases, the targeted gene complexed to dendrimer, but not its duplicate, showed up to 90% transcript attenuation. The duration of attenuation can be extended by repeated pulsing, and in some cases transcript levels from multiple genes can be attenuated in the same organism. This system will allow study of chlamydial gene function in pathogenesis, leading to more effective therapies to treat Chlamydia-induced diseases in a targeted manner.
Storing and querying ordered XML using a relational database system (2002)

XML is quickly becoming the de facto standard for data exchange over the Internet. This is creating a new set of data management requirements involving XML, such as the need to store and query XML documents. Researchers have proposed using relational database systems to satisfy these requirements by devising ways to "shred" XML documents into relations, and translate XML queries into SQL queries over these relations. However, a key issue with such an approach, which has largely been ignored in the research literature, is how (and whether) the ordered XML data model can be efficiently supported by the unordered relational data model. This paper shows that XML's ordered data model can indeed be efficiently supported by a relational database system. This is accomplished by encoding order as a data value. We propose three order encoding methods that can be used to represent XML order in the relational data model, and also propose algorithms for translating ordered XPath expressions into SQL using these encoding methods. Finally, we report the results of an experimental study that investigates the performance of the proposed order encoding methods on a workload of ordered XML queries and updates.
N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, a novel activator of protein kinase C (1986)

Naphthalenesulfonamide derivatives were used to study the mechanism of regulation of Ca2+-dependent smooth muscle myosin light chain phosphorylation catalyzed by Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) and myosin light chain kinase. Derivatives such as N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide (SC-9), with a hydrophobic residue at the end of a hydrocarbon chain, stimulated Ca2+-activated, phospholipid-dependent myosin light chain phosphorylation in a Ca2+-dependent fashion. There was no significant effect of these compounds on Ca2+-calmodulin (CaM) dependent myosin light chain phosphorylation. On the other hand, derivatives with the guanidino or amino residue at the same position had an inhibitory effect on both Ca2+-phospholipid- and Ca2+-CaM-dependent myosin light chain phosphorylation. These observations suggest that activation of Ca2+-activated, phospholipid-dependent myosin light chain phosphorylation by naphthalenesulfonamide derivatives depends on the chemical structure at the end of hydrocarbon chain of each compound. SC-9 was similar to phosphatidylserine with regard to activation, and the apparent Km values for Ca2+ of the enzyme with this compound and phosphatidylserine were 40 microM and 80 microM, respectively. Kinetic analysis indicated that 12-O-tetradecanoylphorbol 13-acetate increased the affinity of the enzyme with SC-9 for calcium ion. However, kinetic constants revealed that the Km value of protein kinase C activated by SC-9 for substrate myosin light chain was 5.8 microM, that is, about 10 times lower than that of the enzyme with phosphatidylserine, and that the Vmax value with SC-9 was 0.13 nmol X min-1, that is, 3-fold smaller than that seen with phosphatidylserine.(ABSTRACT TRUNCATED AT 250 WORDS)
The Structure and Pharmacological Functions of Coumarins and Their Derivatives (2009)

Coumarins are of many different structures. They constitute an important class of pharmacological agents possessing a range of different physiological activities including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti-coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently, coumarins have attracted intense research interest. Of great interest is the possibility that this class of molecules could be a source of drugs for the therapy of several diseases. These include recent insights into inhibiting cell proliferation by interfering with mitotic spindle microtubule function, decrease Matrix Metalloproteinase (MMP) activity, block the cell cycle in the S or G2/M phases to interfere with processes of cell division, suppress O2(-) generation in leukocytes, inhibit different protein kinases, modulate the signalings, induce carcinogen-detoxifying enzymes glutathione S-transferases (GSTs) and/or NAD(P)H quinine oxidoreductase (NQO1), suppress the phosphorylation of Akt/PKB as a mechanism inhibiting inflammation, progress in structure modification to increase in anti-fungal action, to broaden against bacteria spectrum, to enhance inhibiting activities of nitric oxide synthase (NOS) and cyclooxygenase (COX), to strengthen anti-oxidant activity and to exhibite a much higher cytotoxicity against human umbilical vein endothelial cell (HUVEC). With fewer non-hemorrhagic side effects than the indanedione derivatives, they can be applied as an oral anticoagulant commonly for preventing venous thromboembolism following orthopedic surgery, recurrent myocardial infarction and the treatment of systemic embolism in atrial fibrillation, together with the significant advances in the basis of drug action. It is therefore useful to build up some correlations with the data available in order to better explore the molecular and cellular mechanism of coumarin action in the treatment of diseases. This review will focus on recent advances in molecular and cellular mechanisms of coumarin action involved with the relationship between structure and activity.
The Design and Application of Free Radical Chain Reactions in Organic Synthesis. Part 2 (1988)

The successful application of free radical transformations requires a basic knowledge of elementary radical reactions and an understanding of the principles of free radical chain reactions. Using illustrative examples from the recent literature as a framework, this review provides an introduction to the design and application of free radical reactions for use in organic synthesis. While a few non-chain reactions are discussed, the primary focus is on four of the most important and versatile methods to conduct radical chain reactions. These are: the tin hydride method, the fragmentation method, the thiohydroxamate ester method (the Barton method), and the atom transfer method. Particular emphasis is placed on the selectivity requirements which must be met for the design of sequences of radical reactions. The review appears in two parts in consecutive issues. Part 1 contains Sections 1 (Introduction) and 2 (The Tin Hydride Method), and Part 2 contains Sections 3 (The Fragmentation Method), 4 (The Thiohydroxamate Ester Method), 5 (The Atom-Transfer Method), and 6 (Non-Chain Methods). Part 1 1. Introduction 1.1. Chain Reactions and Synthetic Planning 2. The Tin Hydride Method 2.1. Intramolecular Cyclizations 2.2.Intermolecular Additions 2.3.Combination Sequences Part 2 3.The Fragmentation Method 4.The Thiohydroxamate Ester Method 5.The Atom-Transfer Method 5.1.Hydrogen Atom Transfer Addition and Cyclization 5.2. Halogen Atom Transfer 5.2.1. Halogen Atom Transfer Addition 5.2.2. Halogen Atom Transfer Cyclization 5.2.3. Halogen Atom Transfer Annulation 5.3.Heteroatom-Halogen Donors 5.4.Organocobalt Group Transfer 6. Non-Chain Methods 7. Summary and Conclusions
BlindCall: ultra-fast base-calling of high-throughput sequencing data by blind deconvolution (2014)

We directly formulate base-calling as a blind deconvolution problem and implemented BlindCall as an efficient solver to this inverse problem. BlindCall produced base-calls at accuracy comparable to state-of-the-art probabilistic methods while processing data at rates 10 times faster in most cases. The computational complexity of BlindCall scales linearly with read length making it better suited for new long-read sequencing technologies.
Programmable repression and activation of bacterial gene expression using an engineered CRISPR-Cas system (2013)

The ability to artificially control transcription is essential both to the study of gene function and to the construction of synthetic gene networks with desired properties. Cas9 is an RNA-guided double-stranded DNA nuclease that participates in the CRISPR-Cas immune defense against prokaryotic viruses. We describe the use of a Cas9 nuclease mutant that retains DNA-binding activity and can be engineered as a programmable transcription repressor by preventing the binding of the RNA polymerase (RNAP) to promoter sequences or as a transcription terminator by blocking the running RNAP. In addition, a fusion between the omega subunit of the RNAP and a Cas9 nuclease mutant directed to bind upstream promoter regions can achieve programmable transcription activation. The simple and efficient modulation of gene expression achieved by this technology is a useful asset for the study of gene networks and for the development of synthetic biology and biotechnological applications.
Structural and Dynamic Characterization of the Heterodimeric and Homodimeric Complexes of Distamycin and 1-Methylimidazole-2-carboxamide-netropsin Bound to the Minor Groove of DNA (1994)

NMR spectroscopy combined with molecular modeling was used to characterize a heterodimeric complex with Dst and 2-ImN bound in the minor groove of d(GCCTAACAAGG).d(CCTTGTTAGGC) (1:1:1 2-ImN.Dst.DNA complex). The imidazole-pyrrole-pyrrole ligand 2-ImN spans 5'-GTTA-3' of the TAACA.TGTTA binding site with the imidazole nitrogen specifically recognizing the guanine amino group. The Dst ligand lies along the 5'-AACA-3' sequence and complements the 2-ImN ligand in the formation of the antiparallel side-by-side heterodimeric complex. Titrations of the same site with Dst or 2-ImN alone yield homodimeric complexes (2:1 ligand.DNA) of lower stability than the 1:1:1 2-ImN.Dst.DNA complex. Dst and 2-ImN binding to d(CGCAAACTGGC).d(GCCAGTTTGCG) was also investigated. The 1:1:1 2-ImN.Dst.DNA complex is again the most stable complex with the AAACT.AGTTT site and is similar to the TAACA.TGTTA complex. No monomeric binding of either 2-ImN or Dst was observed to either site.
Specific Resistance of Body Tissues (1956)

The resistive properties of various tissues surrounding the heart were investigated in a number of living dogs. Alternating currents of a frequency varying between 10 and 10,000 c.p.s. have been used for this purpose. Technical problems associated with such measurements are analyzed. The results show that the resistive properties of most tissues are comparable and that the resistivity decreases slowly as the frequency increases.
Light-Emitting Diodes (LEDs) in Dermatology (2008)

Light-emitting diode photobiomodulation is the newest category of nonthermal light therapies to find its way to the dermatologic armamentarium. In this article, we briefly review the literature on the development of this technology, its evolution within esthetic and medical dermatology, and provide practical and technical considerations for use in various conditions. This article also focuses on the specific cell-signaling pathways involved and how the mechanisms at play can be put to use to treat a variety of cutaneous problems as a stand-alone application and/or complementary treatment modality or as one of the best photodynamic therapy light source.
Generalized Bienenstock–Cooper–Munro rule for spiking neurons that maximizes information transmission (2005)

Maximization of information transmission by a spiking-neuron model predicts changes of synaptic connections that depend on timing of pre- and postsynaptic spikes and on the postsynaptic membrane potential. Under the assumption of Poisson firing statistics, the synaptic update rule exhibits all of the features of the Bienenstock-Cooper-Munro rule, in particular, regimes of synaptic potentiation and depression separated by a sliding threshold. Moreover, the learning rule is also applicable to the more realistic case of neuron models with refractoriness, and is sensitive to correlations between input spikes, even in the absence of presynaptic rate modulation. The learning rule is found by maximizing the mutual information between presynaptic and postsynaptic spike trains under the constraint that the postsynaptic firing rate stays close to some target firing rate. An interpretation of the synaptic update rule in terms of homeostatic synaptic processes and spike-timing-dependent plasticity is discussed.