gebhart/patrepeval huggingface dataset:
Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells (1997)

Human CD8+ memory- and effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8+ T cell subset. First, CD45RA-CD45R0(+) cells are reminiscent of memory-type T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon gamma, tumor necrosis factor alpha, and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8+CD45RA+CD27- population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFN-gamma and TNF-alpha. In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8+CD45RA+CD27- cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.
Transcriptional regulation of plant cell wall degradation by filamentous fungi (2004)

Plant cell wall consists mainly of the large biopolymers cellulose, hemicellulose, lignin and pectin. These biopolymers are degraded by many microorganisms, in particular filamentous fungi, with the aid of extracellular enzymes. Filamentous fungi have a key role in degradation of the most abundant biopolymers found in nature, cellulose and hemicelluloses, and therefore are essential for the maintenance of the global carbon cycle. The production of plant cell wall degrading enzymes, cellulases, hemicellulases, ligninases and pectinases, is regulated mainly at the transcriptional level in filamentous fungi. The genes are induced in the presence of the polymers or molecules derived from the polymers and repressed under growth conditions where the production of these enzymes is not necessary, such as on glucose. The expression of the genes encoding the enzymes is regulated by various environmental and cellular factors, some of which are common while others are more unique to either a certain fungus or a class of enzymes. This review summarises our current knowledge on the transcriptional regulation, focusing on the recently characterized transcription factors that regulate genes coding for enzymes involved in the breakdown of plant cell wall biopolymers.
A PET radiotracer for studying serotonin uptake sites: carbon-11-McN-5652Z. (1993)

A radioligand for imaging central serotonin (5-hydroxytryptamine; 5-HT) uptake sites by positron emission tomography (PET) has yet to be developed. Such a tracer would be useful for the study of normal and altered serotonergic neurotransmission as well as for the detection of serotonergic neurotoxicity. This paper describes the labeling of the highly potent serotonin (5-HT) uptake blocker, McN-5652-Z (trans-1,2,3,5,6,10 beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline; racemic mixture), with 11C and the evaluation of this radiotracer in rodents with respect to its in vivo binding characteristics. In mouse brain, 11C-McN-5652-Z accumulated rapidly in regions with high densities of 5-HT uptake sites. The ratio between hypothalamus and cerebellum was 1.5:1 at 15 min and increased with time to 4.6:1 at 90 min after injection. The distribution of 11C-McN-5652 in rat brain at 60 min correlated well with regional concentrations of 5-HT uptake sites (r = 0.86). The specificity and selectivity of 11C-McN-5652 binding to the 5-HT transporter were tested by preinjecting blocking doses of known 5-HT, dopamine and norepinephrine uptake inhibitors, and a 5-HT2 receptor blocker before injection of the radiotracer. Preinjection of increasing doses of unlabeled McN-5652-Z inhibited 11C-McN-5652-Z binding in a dose-dependent fashion. These results suggest that the in vivo binding of the radiotracer was specific, selective for 5-HT uptake sites, saturable and that 11C-McN-5652-Z holds promise as a radiotracer for PET imaging of 5-HT uptake sites in the mammalian brain.
Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae (2010)

In order to better understand the broad applicability of adenovirus (Ad) as a vector for human vaccine studies, we compared four adenovirus (Ad) vectors from families C (Ad human serotype 5 [HAdV-5; here referred to as AdHu5]), D (HAdV-26; here referred to as AdHu26), and E (simian serotypes SAdV-23 and SAdV-24; here referred to as chimpanzee serotypes 6 and 7 [AdC6 and AdC7, respectively]) of the Adenoviridae. Seroprevalence rates and titers of neutralizing antibodies to the two human-origin Ads were found to be higher than those reported previously, especially in countries of sub-Saharan Africa. Conversely, prevalence rates and titers to AdC6 and AdC7 were markedly lower. Healthy human adults from the United States had readily detectable circulating T cells recognizing Ad viruses, the levels of which in some individuals were unexpectedly high in response to AdHu26. The magnitude of T-cell responses to AdHu5 correlated with those to AdHu26, suggesting T-cell recognition of conserved epitopes. In mice, all of the different Ad vectors induced CD8(+) T-cell responses that were comparable in their magnitudes and cytokine production profiles. Prime-boost regimens comparing different combinations of Ad vectors failed to indicate that the sequential use of Ad vectors from distinct families resulted in higher immune responses than the use of serologically distinct Ad vectors from the same family. Moreover, the transgene product-specific antibody responses induced by the AdHu26 and AdC vectors were markedly lower than those induced by the AdHu5 vector. AdHu26 vectors and, to a lesser extent, AdC vectors induced more potent Ad-neutralizing antibody responses. These results suggest that the potential of AdHu26 as a vaccine vector may suffer from limitations similar to those found for vectors based on other prevalent human Ads.
The Bethesda Classification for Squamous Intraepithelial Lesions (1992)

In applying the Bethesda System of classification to cervical squamous lesions, we evaluated the Papanicolaou smears, cervical biopsies, and human papillomavirus (HPV) DNA status of 76 clinic patients. The biopsy specimens and concurrent Papanicolaou smears were analyzed using criteria for low-grade and high-grade squamous intraepithelial lesions, and the biopsies were analyzed for HPV DNA by in situ hybridization. Two independent observers produced good agreement in both cytologic (kappa = 0.62) and histologic (kappa = 0.71) diagnoses. Predictive values of high-grade cytology (for high-grade histology) were high (0.95 for reviewer 1; 0.97 for reviewer 2), and both high-grade cytology and histology correlated strongly with certain "high-risk" HPV types. In contrast, the predictive value of low-grade cytology for either low-grade histology or HPV types other than "high risk" was poor. This study supports the use of certain histologic criteria for distinguishing squamous intraepithelial lesions into two grades. Limitations in cytologic-histologic correlation appear to reflect the absence of cytologic criteria for distinguishing well-differentiated precursor lesions associated with high-risk HPV types.
Cost-effectiveness of three different strategies for the treatment of first recurrent Clostridium difficile infection diagnosed in a community setting (2018)

Vancomycin alone appears to be the most cost-effective regimen for the treatment of first recurrence of CDI. Fidaxomicin alone led to the highest QALY gained, but at a cost beyond what is considered cost-effective.
Identification and molecular characterization of ZAG1, the maize homolog of the Arabidopsis floral homeotic gene AGAMOUS. (1993)

Recent genetic and molecular studies in Arabidopsis and Antirrhinum suggest that mechanisms controlling floral development are well conserved among dicotyledonous species. To assess whether similar mechanisms also operate in more distantly related monocotyledonous species, we have begun to clone homologs of Arabidopsis floral genes from maize. Here we report the characterization of two genes, designated ZAG1 and ZAG2 (for Zea AG), that were cloned from a maize inflorescence cDNA library by low stringency hybridization with the AGAMOUS (AG) cDNA from Arabidopsis. ZAG1 encodes a putative polypeptide of 286 amino acids having 61% identity with the AGAMOUS (AG) protein. Through a stretch of 56 amino acids, constituting the MADS domain, the two proteins are identical except for two conservative amino acid substitutions. The ZAG2 protein is less similar to AG, with 49% identity overall and substantially less similarity than ZAG1 outside the well-conserved MADS domain. Like AG, ZAG1 RNA accumulates early in stamen and carpel primordia. In contrast, ZAG2 expression begins later and is restricted to developing carpels. Hybridization to genomic DNA with the full-length ZAG1 cDNA under moderately stringent conditions indicated the presence of a large family of related genes. Mapping data using maize recombinant inbreds placed ZAG1 and ZAG2 near two loci that are known to affect maize flower development, Polytypic ear (Pt) and Tassel seed4 (Ts4), respectively. The ZAG1 protein from in vitro translations binds to a consensus target site that is recognized by the AG protein. These data suggest that maize contains a homolog of the Arabidopsis floral identity gene AG and that this gene is conserved in sequence and function.
A filtering technique to lower LC oscillator phase noise (2001)

Based on a physical understanding of phase-noise mechanisms, a passive LC filter is found to lower the phase-noise factor in a differential oscillator to its fundamental minimum. Three fully integrated LC voltage-controlled oscillators (VCOs) serve as a proof of concept. Two 1.1-GHz VCOs achieve -153 dBc/Hz at 3 MHz offset, biased at 3.7 mA from 2.5 V. A 2.1-GHz VCO achieves -148 dBc/Hz at 15 MHz offset, taking 4 mA from a 2.7-V supply. All oscillators use fully integrated resonators, and the first two exceed discrete transistor modules in figure of merit. Practical aspects and repercussions of the technique are discussed.
Effect of brimonidine on rabbit trabecular meshwork hyaluronidase activity. (2000)

The finding of endogenous hyaluronidase activity in rabbit trabecular meshwork supports the hypothesis that this tissue can metabolize its own glycosaminoglycan (GAG) products. The present results suggest, however, that the hypotensive effect of brimonidine could be mediated, at least in part, by its ability to increase GAG catabolism, probably through a cAMP-independent mechanism.
Prediction Over the Evolution of the Health System (2006)

The predictive analysis included in the present work begins with identifying the main areas of interest for the future situation of the public health system in Romania, or in any other European state for that matter; these areas of interest relate to the most arduously debated issues, either on a national level or in the proficient institutions of the European Union. However, as previously argued, we consider such an approach to be insufficient for an appropriate description of the potentialities existing at the level of the health systems; accordingly, we consider more relevant the approach of the prediction of future changes by using four variables that have to do, on the one hand, with all the problems of the national systems of public health, and on the other hand, with offering useful information to all states, irrespective of issues such as differences in giving funds, and/or inconsistencies related to the most prominent subjects.
Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally (2017)

Candidiasis, which includes both superficial infections and invasive disease, is the most common cause of fungal infection worldwide. Candida bloodstream infections (BSI) cause significant mortality and elicit a major threat to intensive care unit (ICU) patients The annual global burden of Candida spp. BSIs is about 400,000 cases, with most cases reported from the developed world. Although Candida albicans remains the most frequently isolated Candida species in the clinical setting, in some countries, a marked shift towards species of Candida that have increased resistance to azoles such as fluconazole (FLU), the standard antifungal drug of choice in many countries, and to the recently introduced antifungals known as echinocandins, is reported. Several species of non-albicans Candida, such as C. tropicalis, C. glabrata, and C. parapsilosis, are well-recognized pathogens in BSIs in different geographic locations. More recently, Candida auris, a multidrug-resistant (MDR) yeast that exhibits resistance to FLU and markedly variable susceptibility to other azoles, amphotericin B (AMB), and echinocandins, has globally emerged as a nosocomial pathogen (Fig Alarmingly, in a span of only 7 years, this yeast, which is difficult to treat and displays clonal inter-and intra-hospital transmission, has become widespread across several countries, causing a broad range of healthcare-associated invasive infections
Synthesis and Tubulin-Binding Properties of Some AC- and ABC-Ring Analogs of Allocolchicine (1992)

Fourteen analogues [compounds (8), (9) and (11)-(22)] of the powerful antimitotic agent allocolchicine (5) have been prepared and evaluated for their ability to prevent tubulin polymerization. The X-ray structure of one of the more active compounds, tricycle (20), is reported.
Synthesis and Biological Evaluation of Novel Bisheterocycle‐Containing Compounds as Potential Antiinfluenza Virus Agents. (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.
Identification of the Hyaluronan Receptor for Endocytosis (HARE) (2000)

Rat liver sinusoidal endothelial cells (LECs) express two hyaluronan (HA) receptors, of 175 and 300 kDa, responsible for the endocytic clearance of HA. We have characterized eight monoclonal antibodies (mAbs) raised against the 175-kDa HA receptor partially purified from rat LECs. These mAbs also cross-react with the 300-kDa HA receptor. The 175-kDa HA receptor is a single protein, whereas the 300-kDa species contains three subunits, alpha, beta, and gamma at 260, 230, and 97 kDa, respectively (Zhou, B., Oka, J. A., and Weigel, P. H. (1999) J. Biol. Chem. 274, 33831-33834). The 97-kDa subunit was not recognized by any of the mAbs in Western blots. Based on their cross-reactivity with these mAbs, the 175-, 230-, and 260-kDa proteins appear to be related. Two of the mAbs inhibit (125)I-HA binding and endocytosis by LECs at 37 degrees C. All of these results confirm that the mAbs recognize the bone fide LEC HA receptor. Indirect immunofluoresence shows high protein expression in liver sinusoids, the venous sinuses of the red pulp in spleen, and the medullary sinuses of lymph nodes. Because the tissue distribution for this endocytic HA receptor is not unique to liver, we propose the name HARE (HA receptor for endocytosis).
Gene Expression Profile Changes in Cotton Root and Hypocotyl Tissues in Response to Infection with Fusarium oxysporum f. sp. vasinfectum (2004)

Microarray analysis of large-scale temporal and tissue-specific plant gene expression changes occurring during a susceptible plant-pathogen interaction revealed different gene expression profile changes in cotton root and hypocotyl tissues. In hypocotyl tissues infected with Fusarium oxysporum f. sp. vasinfectum, increased expression of defense-related genes was observed, whereas few changes in the expression levels of defense-related genes were found in infected root tissues. In infected roots, more plant genes were repressed than were induced, especially at the earlier stages of infection. Although many known cotton defense responses were identified, including induction of pathogenesis-related genes and gossypol biosynthesis genes, potential new defense responses also were identified, such as the biosynthesis of lignans. Many of the stress-related gene responses were common to both tissues. The repression of drought-responsive proteins such as aquaporins in both roots and hypocotyls represents a previously unreported response of a host to pathogen attack that may be specific to vascular wilt diseases. Gene expression results implicated the phytohormones ethylene and auxin in the disease process. Biochemical analysis of hormone level changes supported this observation.
Reduction of Antigen Expression from DNA Vaccines by Coadministered Oligodeoxynucleotides (1998)

Bacterial DNA or synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides within the context of certain flanking bases (CpG motifs) have potent stimulatory effects on the vertebrate immune system. CpG ODN with a synthetic nuclease-resistant phosphorothioate backbone (S-ODN) can be used as an adjuvant to augment both humoral and cell-mediated immune responses against a protein antigen. It has also been shown that the presence of CpG motifs in DNA vaccines may be responsible, at least in part, for their efficacy. Here we evaluate the possibility of using CpG ODN as an adjuvant with DNA vaccines to further improve their efficacy. We show that it is not possible to directly mix S-ODN with plasmid DNA because this will result in an ODN dose-dependent reduction in gene expression from the plasmid, possibly because of competitive interference at binding sites on the surface of target cells. Although ODN with a phosphorothioate-phosphodiester chimeric backbone (SDS-ODN) do not adversely effect the level of gene expression (except when certain sequences, such as a poly G, are present), this is not useful, as SDS-ODN are apparently also not sufficiently nuclease resistant to exert a strong CpG adjuvant effect. Neither is it possible to augment responses to DNA vaccines by administering the CpG S-ODN at a different time or site than the plasmid DNA. Thus, at least for the present, it appears necessary to clone CpG motifs into DNA vaccine vectors to take advantage of their adjuvant effect.
Highly Efficient Catalytic Microengines: Template Electrosynthesis of Polyaniline/Platinum Microtubes (2011)

Highly efficient catalytic microtubular engines are synthesized rapidly and inexpensively using an electrochemical growth of bilayer polyaniline/platinum microtubes within the conically shaped pores of a polycarbonate template membrane. These mass-produced microtubular engines are only 8 μm long, are self-propelled at an ultrafast speed (of over 350 body lengths s(-1)), and can operate in very low levels of the hydrogen peroxide fuel (down to 0.2%). The propulsion characteristics and optimization of these microtubular engines are described, along with their efficient operation in different biological environments which holds great promise for biomedical applications.
In situactivation of bis-dialkylaminophosphines—a new method for synthesizing deoxyoligonucleotides on polymer supports (1984)

Deoxynucleoside phosphoramidites can be prepared in good yield from deoxynucleosides, bis- dialkylaminophosphines , and the corresponding dialkylamine hydrotetrazolide or tetrazole as catalysts. These phosphoramidites generated in situ lead to the direct synthesis of deoxyoligonucleotides on polymer supports.
Hepatitis C Virus Envelope Glycoprotein E1 Originates in the Endoplasmic Reticulum and Requires Cytoplasmic Processing for Presentation by Class I MHC Molecules (1999)

We investigated whether hepatitis C virus envelope glycoprotein E1 is transported from the endoplasmic reticulum (ER) to the cytoplasm of infected cells for class I MHC processing. Target cells expressing E1 were killed by CTL lines from a hepatitis C virus-infected chimpanzee, and synthetic peptides were used to define an epitope (amino acids 233-GNASRCWVA-241) presented by the Patr-B*1601 class I MHC molecule. An unusually high concentration (>100 nM) of this nonameric peptide was required for target cell lysis, but this could be reduced at least 1000-fold by replacing the asparagine at amino acid position 234 (Asn234) with aspartic acid (Asp), the anticipated anchor residue for NH2-terminal peptide binding to Patr-B*1601. Conspicuously, position 234 is part of an N-glycosylation motif (Asn-Xaa-Ser/Thr), suggesting that the Asn234 to Asp substitution might occur naturally within the cell due to deglycosylation/deamidation of this amino acid by the cytosolic enzyme peptide N-glycanase. In support of this model, we demonstrate that presentation of the epitope depended on 1) cotranslational synthesis of E1 in the ER, 2) glycosylation of the E1 molecule, and 3) a functional TAP transporter to shuttle peptide from the cytosolic to ER compartment. These results indicate for the first time that during infection of the host, viral envelope glycoproteins originating in the ER are processed in the cytoplasm for class I MHC presentation. That a posttranslational change in amino acid sequence from Asn to Asp alters the repertoire of peptides presented to CD8+ CTL has implications for the design of antiviral vaccines.
Reverse Engineering of Bioadhesion in Marine Mussels (1999)

Marine mussels (Mytilus) are experts at bonding to a variety of solid surfaces in a wet, saline and turbulent environment. Bonding is rapid, permanent, versatile and protein-based. In mussels, adhesive bonding takes the form of a byssus--a bundle of extracorporeal threads--each connected to living tissues of the animal at one end and secured by an adhesive plaque at the other. We have investigated the composition and formation of byssal plaques and threads with the hope of discovering technologically relevant innovations in chemistry and materials science. All proteins isolated from the byssus to date share the quality of containing the unusual amino acid, 3,4-dihydroxyphenylalanine. This residue appears to have a dual functionality with significant consequences for adsorption and cohesion. On the one hand, it forms a diverse array of weaker molecular interactions such as metal chelates, H-bonds, and pi-cations: these appear to dominate in surface behavior (adsorption). On the other hand, 3,4-dihydroxyphenylalanine and its redox couple, dopaquinone, can mediate formation of covalent cross-links among byssal proteins (cohesion). One of the challenges in making functional biomimetic versions of byssal adhesion is to understand how these two reactivities are balanced.
Potential Target Found for Antimetastasis Drugs (1999)

In the July issue of
 Nature Medicine,
 researchers report that they have finally cloned the gene for the enzyme heparanase, which helps cancer cells escape to new sites in the body and may thus be a good target for anticancer drugs. In previous work, researchers had cloned several genes for the enzymes, called proteases, that cancer cells use to break down the protein portion of the extracellular matrix, the glue that holds cells together in tissues, and the basement membranes that surround the blood vessels. Although metastasizing cancer cells may produce as many as 15 different matrix-digesting proteases, the new work suggests that there is only one heparanase. Thus, if its activity can be inhibited--and indications are that it can be--other heparanases shouldn9t be around to cover for it.