gebhart/patrepeval huggingface dataset:
Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design (1994)

The results reported here show that the two meningococcal transferrin-binding proteins (TBP1 and TBP2) generate different immune responses in different host species and that there is variation in response dependent on the method of antigen preparation and possibly the route of administration. Mice immunized with either whole cells of Neisseria meningitidis SD (B:15:P1.16) or the isolated TBP1-TBP2 complex from the same strain produced antisera which, when tested against a representative panel of meningococcal isolates by Western blotting (immunoblotting), recognized some but not all heterologous TBP2 molecules. In contrast, rabbit antisera raised to the same preparations were cross-reactive with almost all the TBP2 molecules. The immune response to TBP1 was also host species dependent. Western blot analysis with denatured TBP1 failed to detect antibodies in antisera raised in mice to whole cells or in a rabbit to the TBP1-TBP2 complex but detected broadly cross-reactive antibodies in mouse anti-TBP1-TBP2 complex sera and strain-specific antibodies in rabbit anti-whole-cell serum. Human convalescent-phase sera obtained from five patients infected with meningococci of different serogroups and serotypes contained fully cross-reactive antibodies to TBP2 but no anti-TBP1 antibodies, when examined on Western blots. However, on dot immunoblots, the same patients' sera, as well as the mouse anti-whole cell and the rabbit anti-TBP1-TBP2 complex sera, reacted with purified biologically active TBP1 of strain SD. This indicates that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that humans generate cross-reactive antibodies to native epitopes. These observations have important implications for assessing the vaccine potential of TBPs and other meningococcal antigens. Conclusions regarding the usefulness of TBPs as candidate components of meningococcal serogroup B vaccines based on results from certain animal species such as mice, or on methods such as Western blotting, may have little bearing on the situation in humans and may lead to some potentially useful antigens being disregarded.
Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target? (2014)

Nano-sized therapeutic agents have several advantages over low molecular weight agents such as a larger loading capacity, the ability to protect the payload until delivery, more specific targeting due to multivalency and the opportunity for controlled/sustained release. However, the delivery of nano-sized agents into cancer tissue is problematic because it mostly relies on the enhanced permeability and retention (EPR) effect that depends on the leaky nature of the tumor vasculature and the prolonged circulation of nano-sized agents, allowing slow but uneven accumulation in the tumor bed. Delivery of nano-sized agents is dependent on several factors that influence the EPR effect; 1. Regional blood flow to the tumor, 2. Permeability of the tumor vasculature, 3. Structural barriers imposed by perivascular tumor cells and extracellular matrix, 4. Intratumoral pressure. In this review, these factors will be described and methods to enhance nano-agent delivery will be reviewed.
Evidence for Positive Selection in the C-terminal Domain of the Cholesterol Metabolism Gene PCSK9 Based on Phylogenetic Analysis in 14 Primate Species (2007)

These results suggest that among primates, differential selective pressure has shaped evolutionary patterns in the functional domains of PCSK9, an important regulator of cholesterol homeostasis.
Photochemical and Electrochemical Properties of Zinc Chlorin−C60Dyad as Compared to Corresponding Free-Base Chlorin−C60, Free-Base Porphyrin−C60, and Zinc Porphyrin−C60Dyads (2001)

The photochemical and electrochemical properties of four chlorin-C60 or porphyrin-C60 dyads having the same short spacer between the macrocycle and the fullerene are examined. In contrast with all the previous results on porphyrin-fullerene dyads, the photoexcitation of a zinc chlorin-C60 dyad results in an unusually long-lived radical ion pair which decays via first-order kinetics with a decay rate constant of 9.1 x 10(3) x s(-1). This value is 2-6 orders of magnitude smaller than values reported for all other porphyrin or chlorin donor-acceptor of the molecule dyad systems. The formation of radical cations of the donor part and the radical anion of the acceptor part was also confirmed by ESR measurements under photoirradiation at low temperature. The photoexcitation of other dyads (free-base chlorin-C60, zinc porphyrin-C60, and free-base porphyrin-C60 dyads) results in formation of the ion pairs which decay quickly to the triplet excited states of the chlorin or porphyrin moiety via the higher lying radical ion pair states as is expected from the redox potentials.
In Situ Modification of Plain Liposomes with Lipidated Coiled Coil Forming Peptides Induces Membrane Fusion (2013)

Complementary coiled coil forming lipidated peptides embedded in liposomal membranes are able to induce rapid, controlled, and targeted membrane fusion. Traditionally, such fusogenic liposomes are prepared by mixing lipids and lipidated peptides in organic solvent (e.g., chloroform). Here we prepared fusogenic liposomes in situ, i.e., by addition of a lipidated peptide solution to plain liposomes. As the lipid anchor is vital for the correct insertion of lipidated peptides into liposomal membranes, a small library of lipidated coiled coil forming peptides was designed in which the lipid structure was varied. The fusogenicity was screened using lipid and content mixing assays showing that cholesterol modified coiled coil peptides induced the most efficient fusion of membranes. Importantly, both lipid and content mixing experiments demonstrated that the in situ modification of plain liposomes with the cholesterol modified peptides yielded highly fusogenic liposomes. This work shows that existing membranes can be activated with lipidated coiled coil forming peptides, which might lead to highly potent applications such as the fusion of liposomes with cells.
A mutant p53 protein is required for maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs. (1992)

Mutant p53 and activated ras cDNA clones cooperate to fully transform primary rat embryo fibroblasts in cell culture, whereas neither cDNA alone results in the full transformation of these cells. The mutant p53 protein may be required to initiate the transformation event with ras. Alternatively, mutant p53 gene expression may be required to maintain the properties of the transformed phenotype. To distinguish between these possibilities, primary rat embryo fibroblasts were transformed with mutant p53 plus ras cDNAs, where the expression of the p53 gene was regulated by an isopropyl beta-D-thiogalactoside-responsive promoter. When expression of the mutant p53 cDNA was inhibited and no detectable exogenous p53 protein was produced, both the growth rate and the morphology of the cells reverted to a normal phenotype. These results demonstrate that a mutant p53 protein is required for the maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs.
Recombinant Human Growth Hormone in Patients with HIV-Associated Wasting (1996)

Treatment with growth hormone increases body weight, lean body mass, and treadmill work output and appears to be a safe and potentially effective therapy in patients with HIV-associated wasting.
Negotiating the liminal divide: some Italian- Australian diasporic poets (2013)

This essay offers a survey of some of the leading first-generation Italian-Australian poets, and does not attempt to be definitive. As Adam Aitken points out in his ‘Asian-Australian Diasporic Poets: A Commentary’ (Cordite, 1 August 2012), ‘Diasporic poetics raise more questions than they answer and are just as much about dis-placement as about place, just as much about a ‘poetics of uncertainty’ as about certainties of style/nation/identity.’ Diasporic poetics is, arguably, also very much a poetics of engagement with the liminal divide, a process that is not linear but cyclic, as crossings in liminal space and time join an implicit, complex and not altogether unproblematic but nevertheless positive Australian present to the recall of the joys and sorrows of an ever-present pre-migration past.
Stereoselective nucleophilic additions to the carbon-nitrogen double bond. 3. Chiral acyliminium ions (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective nucleophilic additions to the carbon-nitrogen double bond. 3. Chiral acyliminium ionsRichard P. Polniaszek, Stephen E. Belmont, and Ramon AlvarezCite this: J. Org. Chem. 1990, 55, 1, 215–223Publication Date (Print):January 1, 1990Publication History Published online1 May 2002Published inissue 1 January 1990https://doi.org/10.1021/jo00288a036Request reuse permissionsArticle Views1179Altmetric-Citations73LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Primary Sclerosing Cholangitis, Inflammatory Bowel Disease, and Colon Cancer (2006)

The prevalence of inflammatory bowel disease (IBD) in patients with PSC differs in various part of the world. Ulcerative colitis (UC) is most common, but 1 to 14% of all primary sclerosing cholangitis (PSC) patients have Crohn disease with colonic involvement. Many PSC patients without clinical symptoms of IBD have colonoscopic and histological findings compatible with IBD, and the subclinical phase may last several years before onset of symptoms of active colitis. The characteristics of UC in patients with PSC are different from those in UC patients without PSC. The colitis is usually substantial, the clinical course of the colitis is quiescent, and rectal sparing is common. Moreover, PSC patients with UC have a higher risk of developing colorectal dysplasia/carcinoma than UC patients without PSC. In patients having an ileal pelvic pouch with ileal anal anastomosis, PSC is a risk factor for development of pouchitis. It is important that all PSC patients with UC are included in colonoscopic surveillance programs.
Update on active specific immunotherapy with melanoma vaccines (1997)

Although a randomized clinical trial has yet to show a statistically significant improvement in the survival of patients receiving vaccine therapy for malignant melanoma, several studies have shown enhanced survival of patients developing an immune response to a melanoma vaccine. The knowledge and techniques of modern molecular biology and immunology suggest multiple strategies to augment this response. The challenge of immunotherapy research is to determine which combination of approaches leads to a favorable clinical response and how to monitor that response effectively. This review identifies components of a successful vaccine, discusses new ways to modulate and stimulate the immune system, and summarizes some of the more interesting clinical trials of melanoma vaccine immunotherapy.
Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice (2005)

Obstructive sleep apnea (OSA), a condition tightly linked to obesity, leads to chronic intermittent hypoxia (CIH) during sleep. There is emerging evidence that OSA is independently associated with insulin resistance and fatty liver disease, suggesting that OSA may affect hepatic lipid metabolism. To test this hypothesis, leptin-deficient obese (ob/ob) mice were exposed to CIH during the light phase (9 AM-9 PM) for 12 wk. Liver lipid content and gene expression profile in the liver (Affymetrix 430 GeneChip with real-time PCR validation) were determined on completion of the exposure. CIH caused a 30% increase in triglyceride and phospholipid liver content (P < 0.05), whereas liver cholesterol content was unchanged. Gene expression analysis showed that CIH upregulated multiple genes controlling 1) cholesterol and fatty acid biosynthesis [malic enzyme and acetyl coenzyme A (CoA) synthetase], 2) predominantly fatty acid biosynthesis (acetyl-CoA carboxylase and stearoyl-CoA desaturases 1 and 2), and 3) triglyceride and phospholipid biosynthesis (mitochondrial glycerol-3-phosphate acyltransferase). A majority of overexpressed genes were transcriptionally regulated by sterol regulatory element-binding protein (SREBP) 1, a master regulator of lipogenesis. A 2.8-fold increase in SREBP-1 gene expression in CIH was confirmed by real-time PCR (P = 0.001). Expression of major genes of cholesterol biosynthesis, SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase, was unchanged. In conclusion, we have shown that CIH may exacerbate preexisting fatty liver of obesity via upregulation of the pathways of lipid biosynthesis in the liver.
Effect of Microbial Inoculants on the Indigenous Actinobacterial Endophyte Population in the Roots of Wheat as Determined by Terminal Restriction Fragment Length Polymorphism (2004)

The effect of single actinobacterial endophyte seed inoculants and a mixed microbial soil inoculant on the indigenous endophytic actinobacterial population in wheat roots was investigated by using the molecular technique terminal restriction fragment length polymorphism (T-RFLP). Wheat was cultivated either from seeds coated with the spores of single pure actinobacterial endophytes of Microbispora sp. strain EN2, Streptomyces sp. strain EN27, and Nocardioides albus EN46 or from untreated seeds sown in soil with and without a commercial mixed microbial soil inoculant. The endophytic actinobacterial population within the roots of 6-week-old wheat plants was assessed by T-RFLP. Colonization of the wheat roots by the inoculated actinobacterial endophytes was detected by T-RFLP, as were 28 to 42 indigenous actinobacterial genera present in the inoculated and uninoculated plants. The presence of the commercial mixed inoculant in the soil reduced the endophytic actinobacterial diversity from 40 genera to 21 genera and reduced the detectable root colonization by approximately half. The results indicate that the addition of a nonadapted microbial inoculum to the soil disrupted the natural actinobacterial endophyte population, reducing diversity and colonization levels. This was in contrast to the addition of a single actinobacterial endophyte to the wheat plant, where the increase in colonization level could be confirmed even though the indigenous endophyte population was not adversely affected.
Comparative Activity of Oral and Parenteral Topotecan in Murine Tumor Models: Efficacy of Oral Topotecan (1994)

Studies were performed using several tumor models to determine the oral efficacy of topotecan. These studies were direct comparisons of oral administration with parenteral treatment by the intravenous, intraperitoneal, or subcutaneous routes. Treatment schedules included bolus treatments at 4- or 7-day intervals and a split-dose regimen (q3hx4) repeated at 4- or 7-day intervals. On the various schedules, the maximally tolerated dose of topotecan was either equivalent to or at most 1.7-fold that of parenteral administration, indicative of excellent oral bioavailability in the mouse. Orally administered topotecan was comparable in efficacy to parenteral treatment in four of five tumor models tested (i.v. L1210 leukemia, i.v. B16 melanoma, i.v. and s.c. Lewis lung carcinoma). The M5076 reticulum cell sarcoma implanted i.p. responded to i.p. and s.c. but not to orally administered topotecan. These studies provide convincing support for the clinical evaluation of orally administered topotecan.
The Cytoplasmic, Transmembrane, and Stem Regions of Glycosyltransferases Specify Their in Vivo Functional Sublocalization and Stability in the Golgi (1999)

We provide evidence for the presence of targeting signals in the cytoplasmic, transmembrane, and stem (CTS) regions of Golgi glycosyltransferases that mediate sorting of their intracellular catalytic activity into different functional subcompartmental areas of the Golgi. We have constructed chimeras of human alpha1, 3-fucosyltransferase VI (FT6) by replacement of its CTS region with those of late and early acting Golgi glycosyltransferases and have stably coexpressed these constructs in BHK-21 cells together with the secretory reporter glycoprotein human beta-trace protein. The sialyl Lewis X:Lewis X ratios detected in beta-trace protein indicate that the CTS regions of the early acting GlcNAc-transferases I (GnT-I) and III (GnT-III) specify backward targeting of the FT6 catalytic domain, whereas the CTS region of the late acting human alpha1,3-fucosyltransferase VII (FT7) causes forward targeting of the FT6 in vivo activity in the biosynthetic glycosylation pathway. The analysis of the in vivo functional activity of nine different CTS chimeras toward beta-trace protein allowed for a mapping of the CTS donor glycosyltransferases within the Golgi/trans-Golgi network: GnT-I < (ST6Gal I, ST3Gal III) < GnT-III < ST8Sia IV < GalT-I < (FT3, FT6) < ST3Gal IV < FT7. The sensitivity or resistance of the donor glycosyltransferases toward intracellular proteolysis is transferred to the chimeric enzymes together with their CTS regions. Apparently, there are at least three different signals contained in the CTS regions of glycosyltransferases mediating: first, their Golgi retention; second, their targeting to specific in vivo functional areas; and third, their susceptibility toward intracellular proteolysis as a tool for the regulation of the intracellular turnover.
Iron Deficiency in Children With Attention-Deficit/Hyperactivity Disorder (2004)

These results suggest that low iron stores contribute to ADHD and that ADHD children may benefit from iron supplementation.
Bordetella pertussis induces apoptosis in macrophages: role of adenylate cyclase-hemolysin (1993)

Bordetella pertussis, the causative agent of whooping cough, has been shown recently to enter and survive in epithelial cells and macrophages in vitro. In the present study, we show that B. pertussis is cytotoxic for J774A.1 cells, a monocyte-macrophage cell line, and for murine alveolar macrophages. We demonstrate that cell cytotoxicity mediated by B. pertussis occurred through apoptosis, as shown by changes in nuclear morphology and by host cell DNA fragmentation. Parental strains and a mutant deficient in pertussis toxin expression are able to induce apoptosis, whereas avirulent mutant or adenylate cyclase-hemolysin-deficient mutants are not cytotoxic. Both adenylate cyclase and hemolytic activities are required for programmed cell death. These results show that induction of apoptosis is dependent on the expression of adenylate cyclase-hemolysin. The infection of murine alveolar macrophages in primary culture with B. pertussis leads to apoptosis, suggesting that this process might be relevant in vivo. The ability of B. pertussis to promote cell death may be important for the initiation of infection, bacterial survival, and escape of the host immune response.
Design and Use of an Oxazolidine Silyl Enol Ether as a New Homoalanine Carbanion Equivalent for the Synthesis of Carbon-Linked Isosteres of O-Glycosyl Serine and N-Glycosyl Asparagine (1999)

A trimethylsilyl enol ether carrying the N-Boc 2,2-dimethyloxazolidine ring was designed to serve as a synthetic equivalent of the homoalanine carbanion for the introduction of the alpha-amino acid side chain at the anomeric carbon of sugars. This new functionalized silyl enol ether was prepared in multigram scale and high enantiomeric purity starting from methyl N-Boc-L-threoninate (six steps, 49% yield). This reagent was employed in two synthetic approaches to C-glycosyl amino acids. In one approach, the BF(3).Et(2)O-promoted coupling with tetra-O-benzyl-D-galactopyranosyl trichloroacetimidate afforded the alpha-linked C-glycoside as main product (30% isolated yield), which upon treatment with tert-butyllithium was converted into the beta-linked isomer. Deoxygenation of these compounds by the Barton-McCombie method and unmasking of the glycyl moiety from the oxazolidine ring by oxidative cleavage with the Jones reagent gave the C-glycosyl serine isosteres alpha- and beta-Gal-CH(2)()-Ser. In a similar way were prepared alpha- and beta-Glc-CH(2)()-Ser starting from tetra-O-benzyl-D-glucopyranosyl trichloroacetimidate. In a second approach, the same oxazolidine silyl enol ether was condensed with formyl tetra-O-benzyl-beta-D-C-galactopyranoside in the presence of BF(3).Et(2)O to give the beta-linked C-glycoside in 78% yield without any anomerization. The deoxygenation of this product and the cleavage of the oxazolidine ring as described above afforded the glycosyl asparagine isostere beta-Gal-(CH(2)())(2)()-Asn. The same reaction sequence was applied to convert formyl tetra-O-benzyl-beta-D-C-glucopyranoside and mannopyranoside into the C-glycosyl amino acids beta-Glc-(CH(2)())(2)()-Asn and beta-Man-(CH(2)())(2)()-Asn, respectively.
Conformationally Constrained PNA Analogues:  Structural Evolution toward DNA/RNA Binding Selectivity (2005)

Since its discovery 12 years ago, aminoethylglycyl peptide nucleic acid (aeg-PNA) has emerged as one of the successful DNA mimics for potential therapeutic and diagnostic applications. An important requisite for in vivo applications that has received inadequate attention is engineering PNA analogues for able discrimination between DNA and RNA as binding targets. Our approach toward this aim is based on structural preorganization of the backbone to hybridization-competent conformations to impart binding selectivity. This strategy has allowed us to design locked PNAs to achieve specific hybridization with DNA or RNA with aims to increase the binding strength without losing the binding specificity. This Account presents results of our rationale in design of different conformationally constrained PNA analogues, their synthesis, and evaluation of hybridization specificities.
Miniature SAW antenna duplexer for 800-MHz portable telephone used in cellular radio systems (1988)

A description is given of a low-loss, high-power surface acoustic wave (SAW) filter developed for an antenna duplexer used in an 800-MHz portable telephone transceiver. The ladder-type configuration uses SAW resonators and capacitors between electrode fingers and ground. The device is fabricated on a 20-mm-square LiTaO/sub 3/ chip. This configuration provides insertion loss as low as 1.0-1.2 dB and output power up to 2 W at 800 MHz. Experimental results from a miniature antenna duplexer-module using this SAW filter as a transmitter filter and previously published high-performance SAW filters as receiver filters are also presented and compared.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>