gebhart/patrepeval huggingface dataset:
Templated Regioselective and Stereoselective Synthesis in Fullerene Chemistry (1999)

ADVERTISEMENT RETURN TO ISSUEPREVArticleTemplated Regioselective and Stereoselective Synthesis in Fullerene ChemistryFrançois Diederich and Roland KessingerView Author Information Laboratorium für Organische Chemie, ETH Zürich, Universitätstrasse 16, 8092 Zürich, Switzerland Cite this: Acc. Chem. Res. 1999, 32, 6, 537–545Publication Date (Web):March 2, 1999Publication History Received28 October 1998Published online2 March 1999Published inissue 1 June 1999https://pubs.acs.org/doi/10.1021/ar970321ohttps://doi.org/10.1021/ar970321oresearch-articleACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1956Altmetric-Citations240LEARN 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 SUBJECTS:Adducts,Carbon nanomaterials,Functionalization,Nanospheres,Reaction products Get e-Alerts
Intranasal Vaccination of Recombinant Adeno-Associated Virus Encoding Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Spike Protein Induces Strong Mucosal Immune Responses and Provides Long-Term Protection against SARS-CoV Infection (2008)

We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-gamma-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile.
Tumor‐specific shared antigenic peptides recognized by human T cells (2002)

The first tumor-specific shared antigens and the cancer-germline genes that code for these antigens were identified with antitumor cytolytic T lymphocytes obtained from cancer patients. A few HLA class I-restricted antigenic peptides were identified by this 'direct approach'. A large set of additional cancer-germline genes have now been identified by purely genetic approaches or by screening tumor cDNA expression libraries with the serum of cancer patients. As a result, a vast number of sequences are known that can code for tumor-specific shared antigens, but most of the encoded antigenic peptides have not yet been identified. We review here recent 'reverse immunology' approaches for the identification of new antigenic peptides. They are based on in vitro stimulation of naive T cells with dendritic cells that have either been loaded with a cancer-germline protein or that have been transduced with viruses carrying cancer-germline coding sequences. These approaches have led to the identification of many new antigenic peptides presented by class I or class II molecules. We also describe some aspects of the processing and presentation of these antigenic peptides.
Efficacy and safety of rebamipide for the treatment of dry mouth symptoms in patients with Sjögren’s syndrome: a double-blind placebo-controlled multicenter trial (2009)

The effects of rebamipide on dry mouth and salivary secretion in Sjögren’s syndrome patients were investigated in a double-blind placebo-controlled study. Rebamipide (100 mg TID) or placebo was administered for eight weeks and patient-assessed improvement of dry mouth and increase in salivary secretion measured by the Saxon test were evaluated. At two, four, and eight weeks, dry mouth improvement rates were, respectively, 26.0, 44.0, and 46.9% for rebamipide and 20.0, 27.1, and 39.1% for placebo, and mean increases in salivary secretion were, respectively, 0.14, 0.24, and 0.35 g for rebamipide and 0.03, 0.09, and 0.17 g for placebo, indicating higher values in the rebamipide group for both parameters at all timepoints but no significant differences between the two groups. Analysis by baseline characteristics suggested a statistically significant salivary secretion increasing effect of rebamipide in cases of primary Sjögren’s syndrome. No difference in the incidence of adverse events was seen between the two groups, confirming the safety of rebamipide. As a salivary secretion increasing effect was strongly suggested in cases of primary Sjögren’s syndrome, further study on the administration of rebamipide for the treatment of dry mouth in patients with Sjögren’s syndrome is required.
Random sequential addition of hard spheres in high Euclidean dimensions (2006)

Sphere packings in high dimensions have been the subject of recent theoretical interest. Employing numerical and theoretical methods, we investigate the structural characteristics of random sequential addition (RSA) of congruent spheres in d -dimensional Euclidean space R{d} in the infinite-time or saturation limit for the first six space dimensions (1< or =d < or =6) . Specifically, we determine the saturation density, pair correlation function, cumulative coordination number and the structure factor in each of these dimensions. We find that for 2< or =d <or =6 , the saturation density phi{s} scales with dimension as phi{s}=c{1}/2{d}+c{2}d/2{d} , where c{1}=0.202048 and c{2}=0.973872 . We also show analytically that the same density scaling is expected to persist in the high-dimensional limit, albeit with different coefficients. A byproduct of this high-dimensional analysis is a relatively sharp lower bound on the saturation density for any d given by phi{s}> or =(d+2)(1-S{0})2;{d+1} , where S{0}[0,1] is the structure factor at k=0 (i.e., infinite-wavelength number variance) in the high-dimensional limit. We demonstrate that a Palàsti-type conjecture (the saturation density in R{d} is equal to that of the one-dimensional problem raised to the d th power) cannot be true for RSA hyperspheres. We show that the structure factor S(k) must be analytic at k=0 and that RSA packings for 1< or =d< or =6 are nearly "hyperuniform." Consistent with the recent "decorrelation principle," we find that pair correlations markedly diminish as the space dimension increases up to six. We also obtain kissing (contact) number statistics for saturated RSA configurations on the surface of a d -dimensional sphere for dimensions 2< or =d< or =5 and compare to the maximal kissing numbers in these dimensions. We determine the structure factor exactly for the related "ghost" RSA packing in R{d} and demonstrate that its distance from "hyperuniformity" increases as the space dimension increases, approaching a constant asymptotic value of 12 . Our work has implications for the possible existence of disordered classical ground states for some continuous potentials in sufficiently high dimensions.
Activity of quinupristin/dalfopristin against gram-positive bacteria: clinical applications and therapeutic potential (1997)

In recent years there has been a dramatic worldwide increase in the prevalence of multiple drug-resistant strains of common Gram-positive bacteria. This highlights the need for a new class of antibiotic with activity against these organisms. Quinupristin/dalfopristin, the first injectable streptogramin antibiotic, has a unique spectrum of activity, encompassing most Gram-positive cocci (including multi-drug-resistant strains), respiratory pathogens and anaerobes, Gram-positive, and a prolonged post-antibiotic effect. Quinupristin/ dalfopristin is active in vitro against multi-drug-resistant isolates of Staphylococcus aureus, coagulase-negative staphylococci, penicillin-resistant pneumococci and vancomycin-resistant Enterococcus faecium. Clinical case reports have shown that the combination is active against intra-abdominal, aortic graft, bacteraemia and hydrocephalus shunt infections caused by multi-drug-resistant enterococci, particularly E. faecium. In almost all of these clinical situations the enterococcal infection had displayed resistance to all other antimicrobial therapies. Preliminary clinical data have demonstrated the activity of quinupristin/ dalfopristin against S. aureus bacteraemia, and quinupristin/dalfopristin may also prove useful in the treatment of pneumococcal infections. Thus, possible future applications of the combination include the treatment of multi-drug-resistant strains of staphylococci, streptococci and enterococci. Quinupristin/dalfopristin may prove useful in the treatment of staphylococcal infections in children, invasive systemic pneumococcal infections, and nosocomial and community-acquired Gram-positive infections in patients unable to tolerate beta-lactam antimicrobial agents or glycopeptide antibiotics.
Astroglial permissivity for neuritic outgrowth in neuron–astrocyte cocultures depends on regulation of laminin bioavailability (2001)

The molecular determinants underlying the failure of axons to regenerate in the CNS after injury were studied in an in vitro model of astrogliosis and neuronal coculture. Mechanically lesioned neuron-astrocyte mouse cortical cocultures were treated with antisense glial fibrillary acidic protein (GFAP)-mRNA in order to inhibit the formation of gliofilaments that occurs in response to injury. This inhibition relieves the blockage of neuron migration and neuritic outgrowth observed after lesion, and migrating neurons reappeared, supported by a laminin-labeled extracellular network (permissive conditions). We then questioned the relationship between this permissivity and laminin production. Follow-up studies on the concentration of laminin indicated that, after antisense treatment, the laminin level was increased in the cocultures and was under the control of astrocyte-neuron interactions. The addition of exogenous laminin favored neuronal migration and neurite outgrowth, whereas neutralizing laminin bioavailability with antibodies recognizing the astroglial laminin resulted in an inhibition of both neuronal access to the lesion site and neurite outgrowth, suggesting an active role for laminin in the permissive process. This permissive process could be associated with modulation of extracellular matrix (ECM) molecule degradation by proteinases. Among the latter, matrix metalloproteinases (MMPs) are involved in the breakdown of the ECM component. Our investigation showed a net decrease of the matrix metalloproteinase MMP-2 expression and activity and an increase of its endogenous inhibitor TIMP-2 expression. Both proteins associated with permissivity should be involved in the laminin stabilization and cell-matrix interactions. High levels of laminin and laminin bioavailability, consequent to a reduction in astrogliosis, may be important permissive elements for neuronal migration and neurite outgrowth postlesion.
Widespread Site-Dependent Buffering of Human Regulatory Polymorphism (2012)

The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within any given transcription factor recognition sequence. To address this, we comprehensively analyzed heritable genome-wide binding patterns of a major sequence-specific regulator (CTCF) in relation to genetic variability in binding site sequences across a multi-generational pedigree. We localized and quantified CTCF occupancy by ChIP-seq in 12 related and unrelated individuals spanning three generations, followed by comprehensive targeted resequencing of the entire CTCF-binding landscape across all individuals. We identified hundreds of variants with reproducible quantitative effects on CTCF occupancy (both positive and negative). While these effects paralleled protein-DNA recognition energetics when averaged, they were extensively buffered by striking local context dependencies. In the significant majority of cases buffering was complete, resulting in silent variants spanning every position within the DNA recognition interface irrespective of level of binding energy or evolutionary constraint. The prevalence of complex partial or complete buffering effects severely constrained the ability to predict reliably the impact of variation within any given binding site instance. Surprisingly, 40% of variants that increased CTCF occupancy occurred at positions of human-chimp divergence, challenging the expectation that the vast majority of functional regulatory variants should be deleterious. Our results suggest that, even in the presence of "perfect" genetic information afforded by resequencing and parallel studies in multiple related individuals, genomic site-specific prediction of the consequences of individual variation in regulatory DNA will require systematic coupling with empirical functional genomic measurements.
Mcl-1 Is Required for Melanoma Cell Resistance to Anoikis (2009)

Melanoma is a particularly aggressive tumor type that exhibits a high level of resistance to apoptosis. The serine/threonine kinase B-RAF is mutated in 50% to 70% of melanomas and protects melanoma cells from anoikis, a form of apoptosis induced by lack of adhesion or adhesion to an inappropriate matrix. Mutant B-RAF down-regulates two BH3-only proapoptotic proteins, Bim(EL) and Bad. BH3-only proteins act, at least in part, by sequestering prosurvival Bcl-2 family proteins and preventing them from inhibiting the mitochondrial apoptotic pathway. Several Bcl-2 proteins are up-regulated in melanoma; however, the mechanisms of up-regulation and their role in melanoma resistance to anoikis remain unclear. Using RNA interference, we show that depletion of Mcl-1 renders mutant B-RAF melanoma cells sensitive to anoikis. By contrast, minor effects were observed following depletion of either Bcl-2 or Bcl-(XL). Mcl-1 expression is enhanced in melanoma cell lines compared with melanocytes and up-regulated by the B-RAF-MEK-extracellular signal-regulated kinase 1/2 pathway through control of Mcl-1 protein turnover. Similar to B-RAF knockdown cells, adhesion to fibronectin protected Mcl-1 knockdown cells from apoptosis. Finally, expression of Bad, which does not sequester Mcl-1, further augmented apoptosis in nonadherent Mcl-1 knockdown cells. Together, these data support the notion that BH3 mimetic compounds that target Mcl-1 may be effective for the treatment of melanoma in combinatorial strategies with agents that disrupt fibronectin-integrin signaling.
Study of the Human Visual Cortex: Direct Cortical Evoked Potentials and Stimulation (2007)

The authors studied the visual cortex of 15 patients undergoing studies for medically intractable epilepsy. Although the subdural and strip electrode placement varied in each of these patients, there were enough electrodes over the visual cortex to complete studies involving evoked potentials and direct cortical stimulation. Visual evoked potentials were elicited using two check sizes (50 and 16 min) for pattern reversal studies, 50 min checks for on-off stimulation, 50 min checks for horizontal and vertical hemifields and simple flash for the VEP. These studies demonstrated that the pattern reversal and on-off stimuli caused very complex, multipotential waveforms in striate and vision associational cortex that do not resemble the response obtained at the scalp. Different volumes of visual cortex are activated by stimulation with 16 min checks, 50 min checks and simple flash. Flash activates the largest volume of visual cortex and it is likely that this finding is what makes this test of so little value clinically. Direct cortical stimulation shows that colored responses are generated primarily in the posterior striate cortex and inferior occipital lobe, while movement is primarily generated by the visual association cortex. No complex visual images were obtained by stimulation of either the striate cortex or visual association cortex. The brain mechanisms that lead to formed visual images remain to be identified.
Spatially selective photocoagulation of biological tissues: feasibility study utilizing cryogen spray cooling (1996)

Successful laser treatment of selected dermatoses such as hemangiomas requires thermally induced damage to blood vessels while protecting the epidermis. We present and test a procedure in a rabbit liver tissue model that utilizes cryogen spray cooling during continuous Nd:YAG laser irradiation to induce deep photocoagulation necrosis while protecting superficial tissues from thermal injury. Gross and histologic observations are consistent with calculated thicknesses of protected and photocoagulated tissues and demonstrate the feasibility of inducing spatially selective photocoagulation when cryogen spray cooling is used in conjunction with laser irradiation. This procedure may be useful in the thermal treatment of some pathological conditions for which it is desired that deep photocoagulation be induced while protecting superficial tissues.
Steroid requirement for androgen receptor dimerization and DNA binding. Modulation by intramolecular interactions between the NH2-terminal and steroid-binding domains. (1993)

Infection of Spodoptera frugiperda Sf9 insect cells with recombinant human androgen receptor (AR) baculovirus results in expression of a 118-kDa phosphoprotein that displays high affinity androgen binding and androgen-dependent targeting to the nucleus. Using the DNA mobility shift assay, specific in vitro binding of full-length AR to androgen response element DNA (ARE) requires intracellular hormone exposure. The ability of a variety of steroids to induce ARE binding paralleled their transcriptional potential. Certain antihormones, cyproterone acetate and RU486, promote ARE binding, but a pure antiandrogen, hydroxyflutamide, inhibits AR binding to ARE DNA. AR dimerization requires incubation of recombinant baculovirus-infected insect cells with androgen, but only when one or both components of the dimer contain the NH2-terminal domain. Based on the intensities of ARE binding and lack of binding to an ARE half-site, it appears that, unlike the glucocorticoid receptor, AR binds DNA primarily as a dimer. Thus, full-length baculovirus-expressed AR requires intracellular hormone exposure for dimerization and ARE binding to overcome inhibition imposed by the AR NH2-terminal domain. Antihormones with agonist activity promote dimerization and ARE binding, while a pure antiandrogen blocks AR DNA binding. It is concluded that intramolecular interactions between the NH2-terminal and steroid-binding domains are regulated by the specificity of hormone binding and modulate receptor dimerization and DNA binding.
The social and economic publicity and propaganda of the labour governments of 1945–51 (1992)

This article outlines the use of the Central Office of Information and other parts of the Government Information Sevices and media in the publicising of the legislation making up the core of what has been called the Welfare State. Different parts of the legislation, which came into force in 1948, required different treatment according to its purpose, and the article shows how those requirements affected the campaigns, the media through which the campaigns were conducted, and an estimate of the success or otherwise of those campaigns.
Robust Concurrent Remote Entanglement Between Two Superconducting Qubits (2016)

Communication that relies on quantum carriers, like single photons, can achieve a level of privacy unattainable by classical communication methods. In a new experiment, single microwave photons are used as carriers of quantum information in a manner robust to loss.
Immune Evasion by Muscle-Specific Gene Expression in Dystrophic Muscle (2001)

Muscle tissue from Duchenne muscular dystrophy patients and the Dmd(mdx/mdx) (hereafter referred to as mdx) mouse is characterized by an abundance of necrotic myofibers and infiltrating macrophages. Both features may provide additional stimulus to the immune response directed against novel antigens, such as those delivered by gene therapy vectors. It has previously been shown that the immune evasion achieved by adeno-associated virus in healthy muscle fails in one model of muscular dystrophy. Here, we examined the immune response to adenoviral vectors and their transgenes in normal and mdx mice. We found that mdx mouse muscles contain 20 times more macrophages and 7 times more dendritic cells than healthy muscles. This higher professional antigen-presenting cell content results in a stronger immune response to antigens that can be directly presented by those cells, including viral antigens and constitutively expressed transgene products. However, we did not detect a significant immune response to beta-galactosidase expressed specifically in muscle, even at high expression levels. This result suggests that cross-presentation is not more effective in mdx mouse muscle, and that targeted vectors and tissue-specific promoters may be useful tools for evasion of the immune response in dystrophic muscle.