gebhart/patrepeval huggingface dataset:
Treatment with Trichuris suis soluble products during monocyte‐to‐macrophage differentiation reduces inflammatory responses through epigenetic remodeling (2016)

Helminths have strong immunoregulatory properties that may be exploited in treatment of chronic immune disorders, such as multiple sclerosis and inflammatory bowel disease. Essential players in the pathogenesis of these diseases are proinflammatory macrophages. We present evidence that helminths modulate the function and phenotype of these innate immune cells. We found that soluble products derived from the Trichuris suis (TsSP) significantly affect the differentiation of monocytes into macrophages and their subsequent polarization. TsSPs reduce the expression and production of inflammatory cytokines, including IL-6 and TNF, in human proinflammatory M1 macrophages. TsSPs induce a concomitant anti-inflammatory M2 signature, with increased IL-10 production. Furthermore, they suppress CHIT activity and enhance secretion of matrix metalloproteinase 9. Short-term triggering of monocytes with TsSPs early during monocyte-to-macrophage differentiation imprinted these phenotypic alterations, suggesting long-lasting epigenetic changes. The TsSP-induced effects in M1 macrophages were completely reversed by inhibiting histone deacetylases, which corresponded with decreased histone acetylation at the TNF and IL6 promoters. These results demonstrate that TsSPs have a potent and sustained immunomodulatory effect on human macrophage differentiation and polarization through epigenetic remodeling and provide new insights into the mechanisms by which helminths modulate human immune responses.-Hoeksema, M. A., Laan, L. C., Postma, J. J., Cummings, R. D., de Winther, M. P. J., Dijkstra, C. D., van Die, I., Kooij, G. Treatment with Trichuris suis soluble products during monocyte-to-macrophage differentiation reduces inflammatory responses through epigenetic remodeling.
Transmucosal Electrical Stimulation of Laryngeal Muscles (1989)

A new technique is described that enables discrete activation of individual laryngeal muscles by electrical stimulation across overlying mucosa. In 15 dogs, we defined six distinct motor points by transmucosal stimulation at 3 mA while observing the resulting characteristic position of the arytenoid and true vocal cord. Five dogs were then paralyzed with succinylcholine in order to simulate bilateral vocal cord paralysis. Application of a 3-mA stimulus at each motor point yielded no motion of the cords, but when the current was increased to 20 mA, characteristic responses were elicited. In five other dogs, botulinum toxin was injected directly into laryngeal muscles. Stimulation was used in an attempt to quantify the degree of neuromuscular blockade. In the last group of five dogs, we simulated cricoarytenoid arthritis by scarifying the joint. The extent and nature of the joint's impairment could be demonstrated by stimulation. Transmucosal stimulation appears promising as a clinical technique for correlating particular vocal cord movements and thresholds of activation with specific laryngeal disorders. Additionally, such a technique may be useful in clarifying how each laryngeal muscle acts upon the cricoarytenoid joint.
Carcinogenic tobacco-specific N-nitrosamines in snuff and in the saliva of snuff dippers. (1981)

Human data indicate an increased risk for cancer of the oral cavity for snuff dippers. Popular snuff products from the United States, Germany, Sweden, and Denmark were analyzed for tobacco-specific N-nitrosamines (TSNA). These compounds are formed during tobacco processing from nicotine, nornicotine, and anatabine and represent the only known carcinogens in snuff. N'-Nitrosonornicotine, a moderately active carcinogen, ranged in dry snuff from 3.5 to 77 ppm; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a relatively strong carcinogen, ranged from 0.6 to 7.0 ppm; and N'-nitrosoanatabine, thus far not bioassayed, ranged from 0.8 to 44 ppm. The concentrations of TSNA in a given snuff product can vary widely, and aging in the open air can lead to an increase in TSNA. Analysis of the saliva of snuff dippers revealed that these nitrosamines are extracted from the tobacco plug during snuff dipping and that their concentrations in saliva can vary widely between users. Efforts should be made to reduce the TSNA in snuff by modifications of the production process and by wrapping individual snuff portions in airtight packets.
Modulation of Kv4 channels, key components of rat ventricular transient outward K+ current, by PKC (1997)

Current evidence suggests that members of the Kv4 subfamily may encode native cardiac transient outward current (I(to)). Antisense hybrid-arrest with oligonucleotides targeted to Kv4 mRNAs specifically inhibited rat ventricular I(to), supporting this hypothesis. To determine whether protein kinase C (PKC) affects I(to) by an action on these molecular components, we compared the effects of PKC activation on Kv4.2 and Kv4.3 currents expressed in Xenopus oocytes and rat ventricular I(to). Phorbol 12-myristate 13-acetate (PMA) suppressed both Kv4.2 and Kv4.3 currents as well as native I(to), but not after preincubation with PKC inhibitors (e.g., chelerythrine). An inactive stereoisomer of PMA had no effect. Phenylephrine or carbachol inhibited Kv4 currents only when coexpressed, respectively, with alpha1C-adrenergic or M1 muscarinic receptors (this inhibition was also prevented by chelerythrine). The voltage dependence and inactivation kinetics of Kv4.2 were unchanged by PKC, but small effects on the rates of inactivation and recovery from inactivation of native I(to) were observed. Thus Kv4.2 and Kv4.3 proteins are important subunits of native rat ventricular I(to), and PKC appears to reduce this current by affecting the molecular components of the channels mediating I(to).
A Review of Solid Materials as Alternative Ammonia Sources for Lean NOx Reduction with SCR (2009)

&lt;div class="htmlview paragraph"&gt;The need for improved emissions control in lean exhaust to meet tightening, world-wide NOx emissions standards has led to the development of selective catalytic reduction of NOx with ammonia as a major technology for emissions control. Current systems are being designed to use a solution of urea (32.5 wt %) dissolved in water or Diesel Exhaust Fluid (DEF) as the ammonia source. While DEF or AdBlue® is widely used as a source of ammonia, it has a number of issues at low temperatures, including freezing below −12 °C, solid deposit formation in the exhaust, and difficulties in dosing at exhaust temperatures below 200 °C. Additionally creating a uniform ammonia concentration can be problematic, complicating exhaust packaging and usually requiring a discrete mixer. A number of other materials have been proposed as alternative sources of ammonia that would improve many of these issues; materials such as solid urea, ammonium carbamate, and metal ammine chloride salts allow for the direct injection of ammonia gas into the exhaust.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;We have examined the relevant properties of a range of ammonia source materials for their ability to provide ammonia for use in SCR. Important properties, including volumetric efficiency (moles of ammonia/liter), mass efficiency (moles of ammonia/gram), and ammonia release temperatures were evaluated. A number of materials provide an equivalent number of moles of ammonia to AdBlue® in roughly one third the volume or one third the mass. After a careful review of these materials, we have found that ammonium salts (e.g., ammonium carbamate) and metal ammine chlorides (e.g., strontium ammine chloride) offer the most desirable range of properties for use as ammonia source materials. Further issues relating to the use of these materials will be discussed.&lt;/div&gt;
Prevention of insulin resistance by n-3 polyunsaturated fatty acids (2009)

n-3 PUFA supplementation has clinical significance in the prevention and reversal of insulin resistance. However, increased intake of n-3 PUFA should be part of an overall healthy lifestyle that includes weight control, exercise, and reduction in the intake of refined sugars, n-6, saturated, and trans fatty acids.
In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20) (2009)

These observations provide a rational basis for in vitro testing of microbicide candidate molecule combinations, including anti-HIV-1 and cytotoxic cellular assays.
Rule-based expert systems for network management and operations: an introduction (1988)

The functions that can be performed by an integrated communication network management expert system are identified. Expert systems are defined, and knowledge representation, knowledge acquisition, and inference engines are discussed. A sample application problem using OPS5 is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Impact of Hyperhomocysteinemia as a Cardiovascular Risk Factor in the Prediction of Coronary Heart Disease (2003)

Coronary heart disease often occurs in the absence of traditional risk factors. Consequently, epidemiological studies exploring novel risk factors are necessary to improve the prediction of coronary heart disease. This study evaluated five promising markers of cardiovascular risk: homocysteine, C-reactive protein, fibrinogen, lipoprotein(a) (Lp(a)), free apolipoprotein(a) (apo(a)) and Lp(a) phenotypes. The study included 135 patients with angiographically confirmed atherosclerosis. The control group consisted of 93 sex- and age-matched individuals. The Mann-Whitney U-test was used for group comparison. New risk factors were evaluated by binary logistic regression. The odds ratios were calculated continuously for homocysteine in dependence on C-reactive protein. Low density lipoprotein (LDL)-cholesterol was nearly identical in controls and patients. Homocysteine, C-reactive protein, fibrinogen, high density lipoprotein (HDL)-cholesterol and Lp(a) discriminated highly significantly between both groups. The continuously calculated odds ratio for homocysteine demonstrated a distinct influence of C-reactive protein. In the group with high C-reactive protein levels, homocysteine levels above 9.6 micromol/l resulted in a markedly elevated risk (odds ratio 12), in the group with C-reactive protein levels below 5 mg/dl, a comparable risk increase was observed at a homocysteine level of 16.6 micromol/l. This data strongly suggests that plasma homocysteine helps identify individuals at risk, especially among those with elevated C-reactive protein levels.
c-di-AMP Secreted by Intracellular Listeria monocytogenes Activates a Host Type I Interferon Response (2010)

Intracellular bacterial pathogens, such as Listeria monocytogenes, are detected in the cytosol of host immune cells. Induction of this host response is often dependent on microbial secretion systems and, in L. monocytogenes, is dependent on multidrug efflux pumps (MDRs). Using L. monocytogenes mutants that overexpressed MDRs, we identified cyclic diadenosine monophosphate (c-di-AMP) as a secreted molecule able to trigger the cytosolic host response. Overexpression of the di-adenylate cyclase, dacA (lmo2120), resulted in elevated levels of the host response during infection. c-di-AMP thus represents a putative bacterial secondary signaling molecule that triggers a cytosolic pathway of innate immunity and is predicted to be present in a wide variety of bacteria and archea.
The Growth Factor Granulin Interacts with Cyclin T1 and Modulates P-TEFb-Dependent Transcription (2003)

Cyclin T1, together with the kinase CDK9, is a component of the transcription elongation factor P-TEFb which binds the human immunodeficiency virus type 1 (HIV-1) transactivator Tat. P-TEFb facilitates transcription by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II. Cyclin T1 is an exceptionally large cyclin and is therefore a candidate for interactions with regulatory proteins. We identified granulin as a cyclin T1-interacting protein that represses expression from the HIV-1 promoter in transfected cells. The granulins, mitogenic growth factors containing repeats of a cysteine-rich motif, were reported previously to interact with Tat. We show that granulin formed stable complexes in vivo and in vitro with cyclin T1 and Tat. Granulin bound to the histidine-rich domain of cyclin T1, which was recently found to bind to the CTD, but not to cyclin T2. Binding of granulin to P-TEFb inhibited the phosphorylation of a CTD peptide. Granulin expression inhibited Tat transactivation, and tethering experiments showed that this effect was due, at least in part, to a direct action on cyclin T1 in the absence of Tat. In addition, granulin was a substrate for CDK9 but not for the other transcription-related kinases CDK7 and CDK8. Thus, granulin is a cellular protein that interacts with cyclin T1 to inhibit transcription.
Hyaluronan Synthase of Chlorella Virus PBCV-1 (1997)

Sequence analysis of the 330-kilobase genome of the virus PBCV-1 that infects a chlorella-like green algae revealed an open reading frame, A98R, with similarity to several hyaluronan synthases. Hyaluronan is an essential polysaccharide found in higher animals as well as in a few pathogenic bacteria. Expression of the A98R gene product in Escherichia coli indicated that the recombinant protein is an authentic hyaluronan synthase. A98R is expressed early in PBCV-1 infection and hyaluronan is produced in infected algae. These results demonstrate that a virus can encode an enzyme capable of synthesizing a carbohydrate polymer and that hyaluronan exists outside of animals and their pathogens.
Fluctuating Enzymes: Lessons from Single‐Molecule Studies (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Wavelength division multiplexing and demultiplexing with photonic crystal waveguide couplers (2001)

A multiplexer-demultiplexer (MUX-DEMUX) based on PC waveguide couplers is proposed, and its wavelength demultiplexing properties are theoretically investigated. First, a two-channel MUX-DEMUX is designed and characterized, and then, by cascading, two stages of photonic crystal (PC) waveguide couplers with different coupling coefficients are constructed. The device sizes are expected to be drastically reduced from a scale of a few tens of micrometers to a scale of a few hundreds of micrometers in a MUX-DEMUX.
HEL Cells: A New Human Erythroleukemia Cell Line with Spontaneous and Induced Globin Expression (1982)

A new human erythroleukemia cell line has been established. This line, designated HEL, is capable of spontaneous and induced globin synthesis, producing mainly G gamma and A gamma chains. Embryonic chains (epsilon, zeta) and alpha chains are detectable in very small amounts; beta chains are undetectable. This line provides a new model system for studying aspects of erythroid cell differentiation and differential globin gene expression.
Luminescence decay time of the 1.945 eV centre in type Ib diamond (1983)

The luminescence decay time of the 1.945 eV centre has been determined as 13+or-0.5 ns for natural type Ib diamonds. For synthetic diamonds the value is slightly lower, probably because of competitive non-radiative recombination in these relatively impure crystals. The similarity of the decay time to that for the H3 centre further supports the model proposed for the vacancy-enhanced aggregation of nitrogen in diamond. No temperature dependence of the 1.945 eV decay time has been detected in the range 77-700K, and this result is not inconsistent with the energy level scheme used to interpret ESR data for the 1.945 eV centre.
Regioselective conversion of 3‐cyano‐6‐hydroxy‐2‐pyridones into 3‐cyano‐6‐amino‐2‐pyridones (1995)

Abstract The reaction of a tautomeric mixture of 1‐butyl‐1,2‐dihydro‐6‐hydroxy‐4‐methyl‐2‐oxopyridine‐3‐carbonitrile and its 2‐hydroxy‐6‐oxo analog with phosphorus oxychloride gave 1‐butyl‐6‐chloro‐1,2‐dihydro‐4‐methyl‐2‐oxopyridine‐3‐carbonitrile (68%) and 1‐butyl‐2‐chloro‐1,6‐dihydro‐4‐methyl‐6‐pyridine‐3‐car‐bonitrile (3%). Both chloropyridones were converted to their corresponding aminopyridones by reaction with liquid ammonia. Strong support for the molecular structure of 6‐amino‐1‐butyl‐1,2‐dihydro‐4‐methyl‐2‐oxopyridine‐3‐carbonitrile was obtained on the basis of nmr techniques.
Work-Related Interests Among Industrial Pharmacists (1987)

A mail survey of 1,505 pharmacists in every major work setting and position was conducted. The purpose of this paper is to report the vocational interest profiles for 364 industrial pharmacists, 288 males and 76 females, employed in sales, marketing, administration, manufacturing/quality control, and research and development. Limitations include small samples for three female groups and the lack of a random sample. Patterns of interest profiles were remarkably consistent in most instances with respect to sex role differences, associated scales and related work activities. Among males, there were several group differences on the enterprising, social and realistic general interest scales, and on the sciences, mathematics, public speaking, law/politics, merchandising, business management and sales basic interest scales. Among females, there were group differences on the enterprising, conventional and sales scales. Group comparisons were made using the LSD procedure and alpha = 0.01. There were fewer significant differences among female groups primarily because of small cell samples. The most significant aspect of this study was that reliable vocational interest profiles were constructed to serve as a guide for students and practitioners in selecting an area of industrial pharmacy to pursue.
Liquid-crystal phase modulator for unpolarized light (1993)

A simple method for phase modulating unpolarized light with a double pass through a nematic liquid crystal retarder is described.
Identification of destabilizing residues in HLA class II-selected bacteriophage display libraries edited by HLA-DM (1999)

HLA-DM (DM) functions as a peptide editor by catalyzing the release of class II-associated invariant chain peptides (CLIP) and other unstable peptides, thus supporting the formation of stable class II-peptide complexes for presentation. To investigate the general features that determine the DM susceptibility of HLA-DR1/peptide complexes, we generated a large DM-sensitive peptide repertoire from an M13 bacteriophage display library using a novel double selection protocol: we selected bacteriophage capable of binding to DR1 molecules and, subsequently, we enriched DR1-bound bacteriophage susceptible to elution by purified DM molecules. Sequence and mutational analyses of the DR1/DM double-selected peptides revealed that the amino acids Gly and Pro play a destabilizing role in the dissociation kinetics of DR1 ligands. This observation was confirmed also in natural peptide sequences such as CLIP 89-101, HA 307-319 and bovine collagen II (CII) 261-273. Our results demonstrate that DM susceptibility does not only depend on the number and nature of anchor residues, or the peptide length. Instead, less obvious sequence characteristics play a major role in the DM editing process and ultimately in the composition of peptide repertoires presented to T cells.
Direct and selective elimination of specific prions and amyloids by 4,5-dianilinophthalimide and analogs (2008)

Mechanisms to safely eliminate amyloids and preamyloid oligomers associated with many devastating diseases are urgently needed. Biophysical principles dictate that small molecules are unlikely to perturb large intermolecular protein-protein interfaces, let alone extraordinarily stable amyloid interfaces. Yet 4,5-dianilinophthalimide (DAPH-1) reverses Abeta42 amyloidogenesis and neurotoxicity, which is associated with Alzheimer's disease. Here, we show that DAPH-1 and select derivatives are ineffective against several amyloidogenic proteins, including tau, alpha-synuclein, Ure2, and PrP, but antagonize the yeast prion protein, Sup35, in vitro and in vivo. This allowed us to exploit several powerful new tools created for studying the conformational transitions of Sup35 and decipher the mechanisms by which DAPH-1 and related compounds antagonize the prion state. During fibrillization, inhibitory DAPHs alter the folding of Sup35's amyloidogenic core, preventing amyloidogenic oligomerization and specific recognition events that nucleate prion assembly. Select DAPHs also are capable of attacking preformed amyloids. They remodel Sup35 prion-specific intermolecular interfaces to create morphologically altered aggregates with diminished infectivity and self-templating activity. Our studies provide mechanistic insights and reinvigorate hopes for small-molecule therapies that specifically disrupt intermolecular amyloid contacts.
Turkey ovomucoid third domain inhibits eight different serine proteinases of varied specificity on the same ...Leu18-Glu19... reactive site (1985)

We show that eight different serine proteinases--bovine chymotrypsins A and B, porcine pancreatic elastase I, proteinase K, Streptomyces griseus proteinases A and B, and subtilisins BPN' and Carlsberg--interact with turkey ovomucoid third domain at the same Leu18-Glu19 peptide bond, the reactive site of the inhibitor. Turkey ovomucoid third domain was converted to modified (the reactive site peptide bond hydrolyzed) form as documented by sequencing. Complexes of all eight enzymes both with virgin and with modified inhibitor were prepared. All 16 complexes were subjected to kinetically controlled dissociation, and all 16 produced predominantly virgin (greater than 90%) inhibitor, thus proving our point. During this investigation, we found that both alpha-chymotrypsin and especially S. griseus proteinase B convert virgin to modified turkey ovomucoid third domain, even in the pH range 1-2, a much lower pH than we expected. We have also measured rate constants kon and kon* for the association of virgin and modified turkey ovomucoid third domain with several serine proteinases. The kon/kon* ratio is 4.8 X 10(6) for chymotrypsin, but it is only 1.5 for subtilisin Carlsberg. A number of generalizations concerning reactive sites of protein proteinase inhibitor are proposed and discussed.
Prostatic Acid Phosphatase in Serum of Patients with Prostatic Cancer Is a Specific Phosphotyrosine Acid Phosphatase (1990)

We developed an assay to measure at acid pH the phosphotyrosine phosphatase activity in sera from patients with prostatic cancer. The method used quantifies the inorganic phosphate liberated from phosphotyrosine after incubation with serum, followed by the deproteinization of the reaction mixture. A high acid phosphatase (EC 3.1.3.2) activity towards phosphotyrosine was observed in all sera from patients with increased activity of prostatic acid phosphatase. This activity represented 96% of prostatic acid phosphatase and 77% of total acid phosphatase activities. Moreover, it was correlated (r = 0.91) with the amount of serum prostatic acid phosphatase determined by radioimmunoassay. When serum acid phosphatase activity was measured on several phosphorylated substrates, preferential hydrolysis was demonstrated for those in which the phosphate group was esterified on an aromatic ring rather than those presenting an aliphatic chain. Among phosphoamino acids, only phosphotyrosine was a good substrate, with little or no activity observed with phosphoserine and phosphothreonine. Human seminal plasma and partially purified prostatic acid phosphatase, tested for their activity on some of these substrates, gave similar results. On the other hand, sera from patients with above-normal alkaline phosphatase activity and no prostatic disease showed little or no activity on phosphotyrosine at both acid and alkaline pH values. Evidence is presented that the prostatic acid phosphatase in serum is a specific phosphotyrosine acid phosphatase.