gebhart/patrepeval huggingface dataset:
Genetic immunization generates cellular and humoral immune responses against the nonstructural proteins of the hepatitis C virus in a murine model. (1998)

Exposure to hepatitis C virus (HCV) is associated with a high prevalence of persistent viral infection and the development of chronic liver disease and hepatocellular carcinoma. Recovery from acute infection may depend upon the generation of broad-based cellular immune responses to viral structural and nonstructural proteins. We used the DNA-based immunization approach in BALB/c mice to determine whether the HCV nonstructural proteins NS3, NS4, and NS5 will induce Ab responses, CD4+ Th cell proliferation, and cytokine release in response to stimulation by recombinant proteins as well as generate CD8+ CTL activity both in vitro and in vivo. We found that the nonstructural proteins were particularly good immunogens and produced cellular immune responses when administered as a DNA construct. Indeed, a tumor model was established following inoculation of syngenic SP2/0 cells stably transfected with NS5. We observed protection against tumor formation and growth only in mice immunized with the NS5-encoding DNA construct, establishing the generation of significant CTL activity in vivo by this technique. The results indicate that genetic immunization may define the cellular immune response of the host to HCV nonstructural proteins and is a promising approach for vaccine development.
Type III secretion systems and pathogenicity islands (2001)

Some bacterial pathogens have evolved by acquiring pathogenicity islands (PIs), which are clusters of genes encoding virulence traits. PIs encoding the secretion of effector molecules via type III secretion (TTS) systems have been discovered in several gram-negative pathogens. TTS systems are involved in contact-dependent secretion of virulence factors and can facilitate delivery of toxins directly into target cells. The expanding list of bacteria found to contain clusters of TTS genes includes members of the genera Yersinia, Salmonella, Shigella, Escherichia, Pseudomonas, Bordetella, Burkholderia, Chlamydia and a number of plant pathogens or symbionts. This review discusses the current knowledge of the role of TTS PIs in pathogenicity, the genetic organisation and evolution of such systems,and the potential for using TTS systems as targets for novel treatments.
The Design of Cationic Lipids for Gene Delivery (2005)

Synthetic gene delivery vectors are gaining increasing importance in gene therapy as an alternative to recombinant viruses. Among the various types of non-viral vectors, cationic lipids are especially attractive as they can be prepared with relative ease and extensively characterised. Further, each of their constituent parts can be modified, thereby facilitating the elucidation of structure-activity relationships. In this forward-looking review, cationic lipid-mediated gene delivery will mainly be discussed in terms of the structure of the three basic constituent parts of any cationic lipid: the polar headgroup, hydrophobic moiety and linker. Particular emphasis will be placed on recent advances in the field as well as on our own original contributions. In addition to reviewing critical physicochemical features (such as headgroup hydration) of monovalent lipids, the use of headgroups with known nucleic-acid binding modes, such as linear and branched polyamines, aminoglycosides and guanidinium functions, will be comprehensively assessed. A particularly exciting innovation in linker design is the incorporation of environment-sensitive groups, the intracellular hydrolysis of which may lead to more controlled DNA delivery. Examples of pH-, redox- and enzyme-sensitive functional groups integrated into the linker are highlighted and the benefits of such degradable vectors can be evaluated in terms of transfection efficiency and cationic lipid-associated cytotoxicity. Finally, possible correlations between the length and type of hydrophobic moiety and transfection efficiency will be discussed. In conclusion it may be foreseen that in order to be successful, the future of cationic lipid-based gene delivery will probably require the development of sophisticated virus-like systems, which can be viewed as "programmed supramolecular systems" incorporating the various functions required to perform in a chronological order the different steps involved in gene transfection.
Être médiéviste au xxie siècle (2008)

Être médiéviste au xxie siècle... Avec une telle formulation, la présidente et le bureau de la Société des médiévistes font à nouveau preuve du dynamisme optimiste avec lequel ils se projettent dans l’avenir au gouvernail d’une association en pleine croissance. S’agit-il même d’une interrogation ? Pourtant, rien ne garantit que les médiévistes auront encore très longtemps droit de cité dans un xxie siècle où les institutions culturelles paraissent devoir vivre des jours plutôt troublés. Mais ...
N-linked neutral sugar chains of aminopeptidase N purified from rat small intestinal brush-border membrane (1991)

Neutral oligosaccharides, which accounted for 74% of the total N-linked sugar chains released by hydrazinolysis of rat small intestinal aminopeptidase N, were investigated on a structural basis. They are mainly composed of complex-type sugar chains with tri- and tetraantennary structures, and small amounts of high mannose type sugar chains (7% of the total neutral sugar chains) are also included. The unique feature of the complex-type sugar chains is the most of them contain terminal N-acetylglucosamine residues and blood group H antigenic determinants in their outer chain moieties, and bisecting N-acetylglucosamine residues in their trimannosyl cores. Both the type 1H and type 2H determinants are found, but the former is mainly expressed at the distal portions of the outer chain moieties of the oligosaccharides.
Investigating the allosterism of acyl-CoA:cholesterol acyltransferase (ACAT) by using various sterols: in vitro and intact cell studies (2005)

ACAT1 (acyl-CoA:cholesterol acyltransferase 1) is thought to have two distinct sterol-binding sites: a substrate-binding site and an allosteric-activator site. In the present work, we investigated the structural features of various sterols as substrates and/or activators in vitro. The results show that without cholesterol, the plant sterol sitosterol is a poor substrate for ACAT. In the presence of cholesterol, ACAT1-mediated esterification of sitosterol is highly activated while ACAT2-mediated esterification of sitosterol is only moderately activated. For ACAT1, we show that the stereochemistry of the 3-hydroxy group at steroid ring A is a critical structural feature for a sterol to serve as a substrate, but less critical for activation. Additionally, enantiomeric cholesterol, which has the same biophysical properties as cholesterol in membranes, fails to activate ACAT1. Thus ACAT1 activation by cholesterol is the result of stereo-specific interactions between cholesterol and ACAT1, and is not related to the biophysical properties of phospholipid membranes. To demonstrate the relevance of the ACAT1 allosteric model in intact cells, we showed that sitosterol esterification in human macrophages is activated upon cholesterol loading. We further show that the activation is not due to an increase in ACAT1 protein content, but is partly due to an increase in the cholesterol content in the endoplasmic reticulum where ACAT1 resides. Together, our results support the existence of a distinct sterol-activator site in addition to the sterol-substrate site of ACAT1 and demonstrate the applicability of the ACAT1 allosteric model in intact cells.
Formation of thin polymeric films by electropolymerization. Reduction of metal complexes containing bromomethyl-substituted derivatives of 2,2'-bipyridine (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFormation of thin polymeric films by electropolymerization. Reduction of metal complexes containing bromomethyl-substituted derivatives of 2,2'-bipyridineSharon Gould, Geoffrey F. Strouse, Thomas J. Meyer, and B. Patrick SullivanCite this: Inorg. Chem. 1991, 30, 14, 2942–2949Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/ic00014a022https://doi.org/10.1021/ic00014a022research-articleACS PublicationsRequest reuse permissionsArticle Views1343Altmetric-Citations96LEARN 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
Intensity modulated arc therapy (IMAT) with centrally blocked rotational fields (2000)

A new technique for intensity-modulated beam (IMB) delivery that combines the features of intensity modulated arc therapy (IMAT) with the use of 'classical blocks' is proposed. The role of the blocks is to realize the high-gradient modulation of the intensity profile corresponding to the region to be protected within the body contour, while the MLC leaves or the secondary collimator defines the rest of the field and delivers intensity-modulated multiple rotational segments. The centrally blocked radiation fields are applied sequentially, in several rotations. Each rotation of the gantry is responsible for delivering one segment of the optimal intensity profile. The new IMAT technique is applied for a treatment geometry represented by an annular target volume centrally located within a circular body contour. The annulus encompasses a circular critical structure, which is to be protected. The beam opening and corresponding weight of each segment are determined in two ways. The first method applies a linear optimization algorithm to precalculated centrally blocked radial dose profiles. These radial profiles are calculated for a set of beam openings, ranging from the largest field that covers the whole planning target volume (PTV) to the smallest, which is 1 cm larger than the width of the central block. The optimization is subjected to dose homogeneity constraints imposed on a linear combination of these profiles and finally delivers the dimensions and weights of the rotational beams to be used in combination. The second method decomposes into several subfields the fluence profile of a rotational beam known to deliver a constant dose level to PTV. This fluence profile is determined by using the analytical method proposed by Brahme for the case of the annular PTV and the concentric organ at risk (OAR). The proper segmentation of this intensity profile provides the field sizes and corresponding weights of the subfields to be used in combination. Both methods show that for this particular treatment geometry, three to seven segments are sufficient to cover the PTV with the 95% dose level and to keep the dose level to the central critical structure under 30% of the maximum dose. These results were verified by experimentally delivering the calculated segments to radiotherapy verification films sandwiched between two cylindrical pieces of a pressed-wood phantom. The total beam time for a three-field irradiation was 77 s. The predicted and experimental dose profiles along the radius of the phantom agreed to within 5%. Generalization of this technique to real-patient treatment geometry and advantages over other conformal radiotherapy techniques are also discussed.
Ab initiostudy of Schottky barriers at metal-nanotube contacts (2004)

The type of barrier at a metal/CNT junction is one of the key issues in nanotube electronics. Despite the extensive experimental work done to clarify this issue, there is no consensus in the nano-electronics community. We present here the first ab initio calculation on the Schottky barrier and tunneling barrier height of an idealized metal (Au, Pd, Pt) semiconducting (8,0) nanotube junction. All three metal species form Schottky barriers when contacting small diameter nanotubes. Two most important atomic geometrical factors influencing the Schottky barrier height are identified as the metal species and its surface orientation. Pd is found to have the lowest Schottky barrier. Our simulation results give useful insight into the on going experiments.
An Alphavirus -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020)

The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale up. Here, we developed an <i>Alphavirus</i>-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with lipid inorganic nanoparticles (LIONs) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti-SARS-CoV-2 S protein IgG antibody isotypes indicative of a type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in the lung and spleen. Prime-only immunization of aged (17 months old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. In nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in five intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.
Homeodomain‐Derived Peptides: In and Out of the Cells (1999)

The internalization of homeodomains and of homeopeptides derived from the third helix of the homeodomain of Antennapedia, a Drosophila transcription factor, is used by some investigators to target exogenous hydrophilic compounds into live cells. In addition to this very practical aspect of drug delivery, translocation across biologic membranes of peptides subsequently addressed to the cell cytoplasm and nucleus raises several questions. A first series of questions pertains to the mechanism of translocation. Thanks to the synthesis of several peptides derived from the third helix of the Antennapedia homeodomain, we began to investigate the mechanism of translocation and we have shown that it is not dependent upon the presence of a chiral receptor and probably involves the formation of inverted micelles. A second series of questions is related to the physiologic significance of the phenomenon. In a first approach, we demonstrated that some full-length homeoproteins are internalized and secreted in vitro. The mechanism of internalization is probably similar to that of the homeodomain or of its third helix, but secretion involves a different mechanism which requires an association with specialized intracellular membranous structures. The existence of specific mechanisms for homeoprotein internalization and secretion suggests that this class of transcription factors may have important signaling properties.
Lymphocyte-facilitated infection of epithelia by human T-cell lymphotropic virus type I (1992)

After the addition of human T-cell lymphotropic virus type I (HTLV-I)-infected lymphocytes to enterocyte monolayers, the lymphocytes adhered via microvilli from both cell types and shed virus onto the enterocyte surface. Virus fused with the epithelial membrane and infected these cells as confirmed by electron microscopic immunocytochemistry, in situ hybridization, and amplification by polymerase chain reaction.
Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients (2009)

T-cell immunotherapy that takes advantage of Epstein-Barr virus (EBV)-stimulated immunity has the potential to fill an important niche in targeted therapy for EBV-related cancers. To address questions of long-term efficacy, safety, and practicality, we studied 114 patients who had received infusions of EBV-specific cytotoxic T lymphocytes (CTLs) at 3 different centers to prevent or treat EBV(+) lymphoproliferative disease (LPD) arising after hematopoietic stem cell transplantation. Toxicity was minimal, consisting mainly of localized swelling at sites of responsive disease. None of the 101 patients who received CTL prophylaxis developed EBV(+) LPD, whereas 11 of 13 patients treated with CTLs for biopsy-proven or probable LPD achieved sustained complete remissions. The gene-marking component of this study enabled us to demonstrate the persistence of functional CTLs for up to 9 years. A preliminary analysis indicated that a patient-specific CTL line can be manufactured, tested, and infused for $6095, a cost that compares favorably with other modalities used in the treatment of LPD. We conclude that the CTL lines described here provide safe and effective prophylaxis or treatment for lymphoproliferative disease in transplantation recipients, and the manufacturing methodology is robust and can be transferred readily from one institution to another without loss of reproducibility.
IL-17 cytokines in immunity and inflammation (2013)

Interleukin 17 (IL-17) and its closest relative, IL-17F, have recently drawn much attention in the field of immunology. IL-17 and IL-17F are expressed by a distinct type of T cells, T helper 17 cells and certain other lymphocytes. These cytokines play key regulatory roles in host defense and inflammatory diseases. In this review, we summarize the recent findings in IL-17 biology and the progress towards understanding the regulatory mechanisms of IL-17 expression and signaling mechanisms. This knowledge will benefit the development of novel immune modulators that enhance immunity to various infections and reduce inflammatory damage in infected patients.
Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength (1991)

The effect of recombinant DNA human growth hormone (rhGH) treatment in adults with growth hormone (GH) deficiency was studied in 24 patients in a double-blind placebo-controlled trial. The dose was 0.07 U/kg body wt daily. After 6 mo of treatment, significant increases were noted in the rhGH group for total cross-sectional area of thigh muscle (+11.2 +/- 3.1 vs. -0.5 +/- 3.0 cm2; P = 0.015 vs. placebo) and quadriceps muscle (+4.1 +/- 0.8 vs. +0.4 +/- 1.2 cm2; P = 0.031) measured by computerized tomography. Strong correlations were noted between lean body mass (measured as total body potassium) and total thigh muscle area in normal and GH-deficient adults both before and after rhGH treatment. Strength of hip flexors (+1.25 +/- 0.27 vs. +0.25 +/- 0.12 z-scores; P = 0.004) and limb girdle muscles increased (P = 0.02) in the rhGH group. We conclude that 1) rhGH increases lean tissue and skeletal muscle mass in adults with human GH deficiency, 2) this suggests a role for GH in the regulation of body composition of adult humans, 3) the increase in strength of limb girdle muscles after rhGH treatment suggests that adults with GH deficiency may have a proximal myopathy, and 4) the failure to demonstrate an increase in strength in other muscle groups may require the study of larger numbers of patients.
Isolation of thrombin inhibitor from the leech Hirudinaria manillensis (1991)

The leech Hirudinaria manillensis belongs to the same family as the medicinal leech Hirudo medicinalis, which has been widely used for the study of hirudin, a specific thrombin inhibitor. A similar inhibitor has now been isolated from the heads of the Hirudinaria leech by acetone/acid extraction and further purified to near homogeneity by ion exchange chromatography followed by affinity chromatography on thrombin-agarose and reverse phase HPLC. The purified material was recovered at about 10-15% yield and had a specific activity of about 12,000-14,000 ATU/mg, similar to other hirudin variants. The inhibitor was shown to be homogenous by sodium dodecyl sulphate/polyacrylamide gel electrophoresis in the presence of 8 M urea with an apparent molecular mass of about 7000 daltons under reducing conditions. Comparison of the anticoagulant effect on human plasma by partial thromboplastin time assay have shown that the inhibitor from Hirudinaria has similar potency as hirudin variant 1 at equivalent dosage. However, it does not cross-react with monoclonal antibodies towards recombinant hirudin variant 1. Comparison of the N-terminal amino acid sequence up to residue 25 also indicates differences at positions 2, 13, 17 and 24 between the two thrombin inhibitors. These findings indicate that the primary anticoagulant present in the leech Hirudinaria is a potent thrombin inhibitor (Bufrudin) with biological activity similar to hirudin, but differs in its structural and immunological properties.
Systemic Iron Homeostasis (2013)

The iron hormone hepcidin and its receptor and cellular iron exporter ferroportin control the major fluxes of iron into blood plasma: intestinal iron absorption, the delivery of recycled iron from macrophages, and the release of stored iron from hepatocytes. Because iron losses are comparatively very small, iron absorption and its regulation by hepcidin and ferroportin determine total body iron content. Hepcidin is in turn feedback-regulated by plasma iron concentration and iron stores, and negatively regulated by the activity of erythrocyte precursors, the dominant consumers of iron. Hepcidin and ferroportin also play a role in host defense and inflammation, and hepcidin synthesis is induced by inflammatory signals including interleukin-6 and activin B. This review summarizes and discusses recent progress in molecular characterization of systemic iron homeostasis and its disorders, and identifies areas for further investigation.