gebhart/patrepeval huggingface dataset:
Ex Vivo Isolation and Characterization of Cd4+Cd25+ T Cells with Regulatory Properties from Human Blood (2001)

It has been known for years that rodents harbor a unique population of CD4(+)CD25(+) "professional" regulatory/suppressor T cells that is crucial for the prevention of spontaneous autoimmune diseases. Here we demonstrate that CD4(+)CD25(+)CD45RO(+) T cells (mean 6% of CD4(+) T cells) are present in the blood of adult healthy volunteers. In contrast to previous reports, these CD4(+)CD25(+) T cells do not constitute conventional memory cells but rather regulatory cells exhibiting properties identical to their rodent counterparts. Cytotoxic T lymphocyte-associated antigen (CTLA)-4 (CD152), for example, which is essential for the in vivo suppressive activity of CD4(+)CD25(+) T cells, was constitutively expressed, and remained strongly upregulated after stimulation. The cells were nonproliferative to stimulation via their T cell receptor for antigen, but the anergic state was partially reversed by interleukin (IL)-2 and IL-15. Upon stimulation with allogeneic (but not syngeneic) mature dendritic cells or platebound anti-CD3 plus anti-CD28 the CD4(+)CD25(+) T cells released IL-10, and in coculture experiments suppressed the activation and proliferation of CD4(+) and CD8(+) T cells. Suppression proved IL-10 independent, yet contact dependent as in the mouse. The identification of regulatory CD4(+)CD25(+) T cells has important implications for the study of tolerance in man, notably in the context of autoimmunity, transplantation, and cancer.
Comment on “The Pro-Factor D Cleaving Activity of MASP-1/-3 Is Not Required for Alternative Pathway Function” (2014)

We would like to express our deepest gratitude to the editor for giving us the opportunity to discuss Degn and colleagues’ argument. We previously claimed ([1][1]) in the Journal of Experimental Medicine that mannan-binding lectin (MBL)–associated serine protease (MASP)-1 has an essential role
A synthetic gene coding for the green fluorescent protein (GFP) is a versatile reporter in Chlamydomonas reinhardtii† (1999)

The use of Chlamydomonas reinhardtii as a model system has been hindered by difficulties encountered in expressing foreign genes. We have synthesised a gene encoding green fluorescent protein (GFP) adapted to the codon usage of C. reinhardtii (cgfp). After verifying the gene was functional in Escherichia coli, the cgfp was fused in frame to the phleomycin resistance gene ble from Streptoalloteichus hindustanus and expressed in C. reinhardtii under control of the rbcS2 promoter and intron sequences. The GFP-fluorescence was seen only in the nucleus demonstrating the nuclear accumulation of the Ble-GFP fusion protein. The cgfp was also fused to the chlamyopsin gene, cop, and expressed in C. reinhardtii under control of the cop promoter. The eyespot became fluorescent indicating that the opsin-GFP fusion protein was correctly directed into the eyespot along with the endogenous unmodified opsin. We conclude that cgfp provides a useful tool to visualize protein synthesis and localisation in vivo in C. reinhardtii and possibly in related green algal species.
Perforated monolayers: porous and cohesive monolayers from mercurated calix[6]arenes (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPerforated monolayers: porous and cohesive monolayers from mercurated calix[6]arenesMichael A. Markowitz, Roman. Bielski, and Steven L. RegenCite this: J. Am. Chem. Soc. 1988, 110, 22, 7545–7546Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/ja00230a049https://doi.org/10.1021/ja00230a049research-articleACS PublicationsRequest reuse permissionsArticle Views227Altmetric-Citations44LEARN 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
RETRACTED: Mutant surfactant A2 proteins associated with familial pulmonary fibrosis and lung cancer induce TGF-β1 secretion (2012)

Mutations in the genes encoding the lung surfactant proteins are found in patients with interstitial lung disease and lung cancer, but their pathologic mechanism is poorly understood. Here we show that bronchoalveolar lavage fluid from humans heterozygous for a missense mutation in the gene encoding surfactant protein (SP)-A2 (SFTPA2) contains more TGF-β1 than control samples. Expression of mutant SP-A2 in lung epithelial cells leads to secretion of latent TGF-β1, which is capable of autocrine and paracrine signaling. TGF-β1 secretion is not observed in lung epithelial cells expressing the common SP-A2 variants or other misfolded proteins capable of increasing cellular endoplasmic reticulum stress. Activation of the unfolded protein response is necessary for maximal TGF-β1 secretion because gene silencing of the unfolded protein response transducers leads to an ∼50% decrease in mutant SP-A2-mediated TGF-β1 secretion. Expression of the mutant SP-A2 proteins leads to the coordinated increase in gene expression of TGF-β1 and two TGF-β1-binding proteins, LTBP-1 and LTBP-4; expression of the latter is necessary for secretion of this cytokine. Inhibition of the TGF-β autocrine positive feedback loop by a pan-TGF-β-neutralizing antibody, a TGF-β receptor antagonist, or LTBP gene silencing results in the reversal of TGF-β-mediated epithelial-to-mesenchymal transition and cell death. Because secretion of latent TGF-β1 is induced specifically by mutant SP-A2 proteins, therapeutics targeted to block this pathway may be especially beneficial for this molecularly defined subgroup of patients.
The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. (1994)

The metabolism of the anticonvulsant drug mephenytoin exhibits a genetic polymorphism in humans, with the poor metabolizer trait being inherited in an autosomal recessive fashion. There are large interracial differences in the frequency of the poor metabolizer phenotype, with Oriental populations having a 5-fold greater frequency compared to Caucasians. Impaired metabolism of mephenytoin and a number of other currently used drugs results from a defect in a cytochrome P450 enzyme recently identified as CYP2C19. Attempts over the past decade to define the molecular genetic basis of the polymorphism have, however, been unsuccessful. We now report that the principal defect in poor metabolizers is a single base pair (G-->A) mutation in exon 5 of CYP2C19, which creates an aberrant splice site. This change alters the reading frame of the mRNA starting with amino acid 215 and produces a premature stop codon 20 amino acids downstream, which results in a truncated, non-functional protein. We further demonstrate that 7/10 Caucasian and 10/17 Japanese poor metabolizers are homozygous for this defect, indicating that this is the major defect responsible for the poor metabolizer phenotype. Finally, the familial inheritance of the deficient allele was found to be concordant with that of the phenotypic trait.
Breeding for Modified Fatty Acid Composition in Soybean (2007)

ABSTRACT Genetic modification of the fatty acid composition of soybean [ Glycine max (L.) Merr.] oil has been successful in better meeting the needs of end users than is possible with conventional oil. Three modified oils are or have been sold commercially. Oil in which the linolenic acid (18:3) content has been reduced from 8 to 1% makes it possible to reduce or eliminate the need for chemical hydrogenation to achieve the stability and shelf life necessary for some food applications. Elimination of chemical hydrogenation and the trans‐ fatty acids produced by the process is important for human health. Oil in which the oleic acid (18:1) has been increased from 25 to &gt;80% also have increased its stability and shelf life. An oil with palmitic acid (16:0) reduced from 11 to &lt;4% makes it possible to achieve a low content of saturated fatty acids, which is desirable for cardiovascular health. The genetic changes in soybean oil were achieved by conventional breeding and genetic engineering. Mutagenesis was the conventional breeding method used to develop the major genes for reduced palmitic and linolenic acids that are in the cultivars currently grown for commercial production. Genetic engineering was used to elevate oleic acid to &gt;80%. The purpose of this paper is to review the methods that have been used to develop the fatty acid modifications, the inheritance of the modifications, the impact of the trait on agronomic and seed characteristics, the methods of phenotypic and genotypic selection, and the commercial status of the modified oils.
The Effects of Dexmedetomidine on Cardiac Electrophysiology in Children (2008)

DEX significantly depressed sinus and atrioventricular nodal function in pediatric patients. Heart rate decreased and arterial blood pressure increased during administration of DEX. The use of DEX may not be desirable during electrophysiology study and may be associated with adverse effects in patients at risk for bradycardia or atrioventricular nodal block.
“ Candidatus Cloacamonas Acidaminovorans”: Genome Sequence Reconstruction Provides a First Glimpse of a New Bacterial Division (2008)

Many microorganisms live in anaerobic environments. Most of these microorganisms have not yet been cultivated. Here, we present, from a metagenomic analysis of an anaerobic digester of a municipal wastewater treatment plant, a reconstruction of the complete genome of a bacterium belonging to the WWE1 candidate division. In silico proteome analysis indicated that this bacterium might derive most of its carbon and energy from the fermentation of amino acids, and hence, it was provisionally classified as "Candidatus Cloacamonas acidaminovorans." "Candidatus Cloacamonas acidaminovorans" is probably a syntrophic bacterium that is present in many anaerobic digesters. This report highlights how environmental sequence data might provide genomic and functional information about a new bacterial clade whose members are involved in anaerobic digestion.
Connectionist Music Composition Based on Melodic and Stylistic Constraints (1990)

We describe a recurrent connectionist network, called CONCERT, that uses a set of melodies written in a given style to compose new melodies in that style. CONCERT is an extension of a traditional algorithmic composition technique in which transition tables specify the probability of the next note as a function of previous context. A central ingredient of CONCERT is the use of a psychologically-grounded representation of pitch.
Inhibitors of neutral cholesteryl ester hydrolase. (1990)

p-Nitrophenyl N-butyl, N-octyl, and N-dodecyl carbamates and a newly synthesized diethyl phosphate compound were studied as potential inhibitors of the cholesteryl ester hydrolases of Fu5AH rat hepatoma cells. Whole homogenates of Fu5AH cells were used as an enzyme source for the assay of cholesteryl ester hydrolase activity. All four compounds led to marked inhibition (70-80%) of neutral cholesteryl ester hydrolase activity (assayed at pH 7) at concentrations where the activity of acid cholesteryl ester hydrolase (assayed at pH 4) was unaffected. Cholesteryl ester hydrolysis was also evaluated in intact cultured cells induced to accumulate cholesteryl esters in cytoplasmic lipid droplets by exposure to cholesterol-rich phospholipid dispersions. Hydrolysis was then assessed during subsequent incubations in the presence of an inhibitor of cholesterol esterification. All compounds caused significant inhibition of cholesterol ester hydrolysis with the diethyl phosphate being the most effective. At a concentration that caused greater than 90% inhibition of the hydrolysis of cytoplasmic cholesteryl esters, the compound had only a minimal effect on lysosomal hydrolysis of cholesteryl esters. These results suggest that diethyl phosphates and N-alkylcarbamates may be of value in future studies on the substrate specificities, regulation, and physiological role(s) of cholesteryl ester hydrolases.
Centrifugal Compressor Stability Prediction Using a New Physics Based Approach (2010)

The accurate prediction of centrifugal compressor stability continues to be an important area of interest in the oil and gas industries. Ensuring stability is critical to the cost-effective installation and operation of these machines in remote environments, where field stability problems are much more expensive to diagnose and correct. Current industry standards and tools for the prediction of impeller destabilizing forces are based on empirical methods that, to date, have served fairly well for systems with reasonable stability margins. However, as stability margins are decreased, use of a modeling method that is more physics based and can better represent the observed trends in machine behavior at low stability margins is required. Furthermore, the development of megaclass liquefied natural gas (LNG) compressors and ultra-high pressure re-injection compressors provides further motivation to improve accuracy. In this paper, a new physics based expression for the prediction of impeller cross-coupling, previously described by Moore et al. (“Rotordynamic Force Prediction of Centrifugal Compressor Impellers Using Computational Fluid Dynamics,” ASME Paper No. GT2007-28181), is further investigated by analyzing several classes and scale factors of impellers ranging from 2D designs used in re-injection to full 3D impellers typically used in LNG. The new expression is based on both computational fluid dynamics simulation and experimental test data from a known instability. These results are then applied to two case studies of marginally stable and unstable compressors in the field that were studied by the authors’ company. For each case study, the system stability is evaluated using both the new physics based expression as well as the more traditional empirical approaches. Comparisons are made for overall stability prediction as well as sensitivity to system changes. Conclusions are made regarding the applicability and limits of this new approach.
Burnout and Career Satisfaction Among American Surgeons (2009)

Burnout is common among American surgeons and is the single greatest predictor of surgeons' satisfaction with career and specialty choice. Additional research is needed to identify individual, organizational, and societal interventions that preserve and promote the mental health of American surgeons.
Immunization with Pneumocystis carinii gpA Is Immunogenic but Not Protective in a Mouse Model of P. carinii Pneumonia (1998)

Immunization with whole Pneumocystis carinii has been shown to protect mice from the development of P. carinii pneumonia (PCP) when they are subsequently immunosuppressed and challenged with viable organisms. To determine whether these results could be duplicated by using a subunit vaccine, we examined the immunogenicity and efficacy of an immunization strategy based on P. carinii gpA. This antigen was chosen for study because passive immunoprophylaxis, based on gpA, has been shown to be partially protective in various animal models of infection. Immunization with gpA produced an anti-gpA specific antibody response comparable to that resulting from immunization with whole organisms. However, in contrast to immunization with whole P. carinii, which was protective, immunization with gpA did not protect T-cell-depleted mice from the development of PCP. These studies suggest that other antigens in addition to gpA need to be evaluated for their role in protective immunity against P. carinii.
13-cis-Retinoic Acid and Interferon -2a: Effective Combination. Therapy for Advanced Squamous Cell Carcinoma of the Skin (1992)

These results indicate that combined systemic therapy with 13-cRA and IFN alpha-2a is highly effective in patients with advanced squamous cell carcinoma of the skin.
Effects of ced-9 dsRNA on <i>Caenorhabditis elegans</i> and <i>Meloidogyne incognita</i> (2011)

Problem Statement: In metazoans Programmed Cell Death (PCD) is essential for proper development. Suppression of PCD is needed to guarantee cell survival and in the nematode Caenorhabditis elegans the regulation of PCD is accomplished by the function of the ced-9 gene. Approach: In this work the use of double stranded RNA (dsRNA) to knock-down ced-9 gene function was tested as means to induce PCD. Results: Our results indicate that dsRNA targeting the cell death protection gene ced-9 is effective at decreasing the fecundity of C. elegans by up to 21%. The decreased fecundity correlated with an increased presence of cell corpses in developing embryos. Endogenous ced-9 transcript levels were reduced in progeny of ced-3 mutant nematodes fed bacteria expressing ced-9 dsRNA. These data suggest that nematode fecundity can be reduced by ingestion and exposure to dsRNAs targeting regulation of the cell death pathway. In an attempt to determine if plant parasitic nematodes are susceptible to the targeting of the PCD regulatory pathway we exposed Meloidogyne incognita, a plant parasitic nematode, to ced-9 dsRNA; here we show that this exposure results in decreased gall formation in the tobacco plants. Conclusion/Recommendations: Our results provide the first steps toward using RNAi technologies to attempt nematode control by targeting cell death pathways. Ongoing research with transgenic plants designed to express dsRNA for ced-9-like sequences will further test the feasibility of generating plants with RNAi-based resistance to parasitic nematodes.
Conjugated Thiophene-Containing Polymer Zwitterions: Direct Synthesis and Thin Film Electronic Properties (2012)

We report a direct and facile synthesis of novel conjugated polymeric zwitterions (CPZs) as a simple route to electronically active homopolymers and copolymers containing dipole-inducing pendent zwitterions. Sulfobetaine-containing polythiophenes (PTSB-1 and PTSB-2) and alternating thiophene–benzothiadiazoles (PTBTSB-1 and PTBTSB-2) were prepared and characterized relative to alkylated polymer analogues (POT-a-T and POT-a-BT). The polar zwitterionic side chains make these polymers hydrophilic and salt-responsive, with interesting electronic properties that depend on zwitterion distance from the conjugated polymer backbone (tether length), as characterized by UV–vis absorption and ultraviolet photoelectron spectroscopy (UPS). Close proximity (CH2 spacer) of the sulfobetaine groups to the polymer backbone results in increased ionization potential and enlarged band gaps of 2.19 and 2.04 eV for PTSB-1 and PTBTSB-1, respectively. On Au and Ag surfaces, the zwitterionic pendent groups significantly alter the work function due to the presence of an interfacial dipole, with the largest interfacial dipoles measuring −1.29 eV (PTBTSB-1/Au) and −0.69 eV (PTBTSB-1/Ag).
A Changing Perspective on the Role of Neuroinflammation in Alzheimer's Disease (2012)

Alzheimer's disease (AD) is a complex, neurodegenerative disorder characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain. Glial cells, particularly microglial cells, react to the presence of the amyloid plaques and neurofibrillary tangles producing an inflammatory response. While once considered immunologically privileged due to the blood-brain barrier, it is now understood that the glial cells of the brain are capable of complex inflammatory responses. This paper will discuss the published literature regarding the diverse roles of neuroinflammation in the modulation of AD pathologies. These data will then be related to the well-characterized macrophage phenotypes. The conclusion is that the glial cells of the brain are capable of a host of macrophage responses, termed M1, M2a, M2b, and M2c. The relationship between these states and AD pathologies remains relatively understudied, yet published data using various inflammatory stimuli provides some insight. It appears that an M1-type response lowers amyloid load but exacerbates neurofibrillary tangle pathology. In contrast, M2a is accompanied by elevated amyloid load and appears to ameliorate, somewhat, neurofibrillary pathology. Overall, it is clear that more focused, cause-effect studies need to be performed to better establish how each inflammatory state can modulate the pathologies of AD.
Interactions between non-classical β-lactam compounds and the β-lactamases of Actinomadura R39 and Streptomyces albus G (1981)

6-Aminopenicillanic acid, 7-aminocephalosporanic acid, mecillinam and quinacillin have varying substrate activities for both the R39 beta-lactamase (excreted by Actinomadura R39) and the G beta-lactamase (excreted by Streptomyces albus G). Cefoxitin and quinacillin sulphone are not recognized by the G beta-lactamase and are weak inactivators of the R39 beta-lactamase. N-Formimidoylthienamycin is a poor substrate for the G beta-lactamase and a potent inactivator of the R39 beta-lactamase. The high value of the bimolecular rate constant for enzyme inactivation is mainly due to a very low dissociation constant (1 microM). Clavulanate is an inactivator of both G and R39 beta-lactamases. The reaction with this latter enzyme is a branched pathway where normal turnover and permanent enzyme inactivation occur concomitantly. Between 28 and 43 molecules of clavulanate are hydrolysed before one of them has the opportunity to inactivate one molecule of enzyme.
Diffusion of isolated DNA molecules: Dependence on length and topology (2006)

The conformation and dynamics of circular polymers is a subject of considerable theoretical and experimental interest. DNA is an important example because it occurs naturally in different topological states, including linear, relaxed circular, and supercoiled circular forms. A fundamental question is how the diffusion coefficients of isolated polymers scale with molecular length and how they vary for different topologies. Here, diffusion coefficients D for relaxed circular, supercoiled, and linear DNA molecules of length L ranging from approximately 6 to 290 kbp were measured by tracking the Brownian motion of single molecules. A topology-independent scaling law D approximately L(-nu) was observed with nu(L) = 0.571 +/- 0.014, nu(C) = 0.589 +/- 0.018, and nu(S) = 0.571 +/- 0.057 for linear, relaxed circular, and supercoiled DNA, respectively, in good agreement with the scaling exponent of nu congruent with 0.588 predicted by renormalization group theory for polymers with significant excluded volume interactions. Our findings thus provide evidence in support of several theories that predict an effective diameter of DNA much greater than the Debye screening length. In addition, the measured ratio D(Circular)/D(Linear) = 1.32 +/- 0.014 was closer to the value of 1.45 predicted by using renormalization group theory than the value of 1.18 predicted by classical Kirkwood hydrodynamic theory and agreed well with a value of 1.31 predicted when incorporating a recently proposed expression for the radius of gyration of circular polymers into the Zimm model.