gebhart/patrepeval huggingface dataset:
Luminescent (N^C^C) Gold(III) Complexes: Stabilized Gold(III) Fluorides (2015)

We report the design, synthesis, and application of a (N^C^C)-ligand framework able to stabilize highly electron-deprived gold(III) species. This novel platform enabled the preparation of C(sp(2))-gold(III) fluorides for the first time in monomeric, easy-to-handle, bench-stable form by a Cl/F ligand-exchange reaction. Devoid of oxidative conditions or stoichiometric use of toxic Hg salts, this method was applied to the preparation of multiple [C(sp(2))-Au(III)-F] complexes, which were used as mechanistic probes for the study of the unique properties and intrinsic reactivity of Au-F bonds. The improved photophysical properties of [(N^C^C)Au(III)] complexes compared to classical pincer (C^N^C)-Au systems paves the way for the design of new late-transition-metal-based OLEDs.
Establishment and Maintenance of Gammaherpesvirus Latency Are Independent of Infective Dose and Route of Infection (2003)

Gammaherpesviruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are important human pathogens that establish long-term latent infections. Understanding of the initiation and maintenance of latent infections has important implications for the prevention and treatment of gammaherpesvirus-related diseases. Although much is known about gammaherpesvirus pathogenesis, it is unclear how the infectious dose of a virus influences its ability to establish latent infection. To examine the relationship between the infectious dose and gammaherpesvirus latency, we inoculated wild-type mice with 0.01 to 10(6) PFU of murine gammaherpesvirus 68 (gammaHV68) and quantitatively measured latency and acute-phase replication. Surprisingly, during latency, the frequencies of ex vivo reactivation were similar over a 10(7)-fold range of doses for i.p. infection and over a 10(4)-fold range of doses for intranasal infection. Further, the frequencies of cells harboring viral genome during latency did not differ substantially over similar dose ranges. Although the kinetics of acute-phase replication were delayed at small doses of virus, the peak titer did not differ significantly between mice infected with a large dose of virus and those infected with a small dose of virus. The results presented here indicate that any initiation of infection leads to substantial acute-phase replication and subsequent establishment of a maximal level of latency. Thus, infections with doses as small as 0.1 PFU of gammaHV68 result in stable levels of acute-phase replication and latent infection. These results demonstrate that the equilibrium level of establishment of gammaherpesvirus latency is independent of the infectious dose and route of infection.
Sequence requirements for formation of conformational variants of tau similar to those found in Alzheimer's disease (1999)

Alz-50 and MC-1 monoclonal antibody reactivity is dependent on both the extreme N-terminus of tau (residues 7-9) and a 30-amino acid sequence of tau (amino acids 312-342) in the third microtubule binding domain, suggesting that the specificity of the Alz-50 and MC-1 antibodies for Alzheimer's disease (AD) pathological tau lies in their ability to recognize a specific conformation of the tau molecule in AD. The present study uses deletional and site-directed mutants of tau to further refine the C-terminal (third microtubule binding domain) epitope requirements for Alz-50, MC-1, and several new antibodies that recognize similar epitopes in tau to amino acids 313-322 of tau, and to demonstrate that intervening portions of the tau molecule are not required for the formation of conformational variants of tau similar to those seen in AD. Further analysis of deletional and site-directed mutations of tau demonstrate subtle variations in the epitope requirements for Alz-50, MC-1, CP-1, CP-2, and CP-28, suggesting that these antibodies, albeit different, all recognize a similar pathological conformation of tau. Additional experiments using synthetic peptides demonstrate that the NH2-terminal (amino acids 1-18) and COOH-terminal (amino acids 309-326) portions of the Alz-50, MC-1, CP-1, CP-2, and CP-28 epitopes can interact with high affinity under near physiological conditions.
Glutamic acid decarboxylase autoantibodies in preclinical insulin-dependent diabetes. (1992)

Insulin-dependent diabetes mellitus (IDDM) is associated with serum antibodies that precipitate a 64-kDa pancreatic islet cell protein reported to be glutamic acid decarboxylase (GAD; glutamate decarboxylase, EC 4.1.1.15). Previously, antibodies to GAD were found in the rare neurological disorder stiff man syndrome. To demonstrate directly antibodies to GAD, enzymatically active GAD was first purified from fresh human cerebellum. Brain GAD activity was precipitated by noninhibitory antibodies in the sera of 16/26 (62%) subjects defined as having preclinical IDDM (islet cell antibody-positive first-degree relatives of a person with IDDM), 3/13 (23%) with recent-onset IDDM, and 3/3 with the stiff man syndrome. In addition, sera of 5/26 (19%) preclinical and 2/13 (15%) recent-onset IDDM subjects contained antibodies that precipitated GAD but inhibited its activity. Thus, overall, 21/26 (81%) preclinical and 5/13 (38%) recent-onset IDDM subjects had antibodies that precipitated GAD activity. Antibodies to GAD were not detected in sera from subjects with other autoimmune diseases (n = 29) or healthy controls (n = 14). GAD affinity-purified to homogeneity (specific activity, 58 units/mg) was specifically immunoprecipitated as a single 60-kDa species by the IDDM sera. In an ELISA incorporating whole mouse brain GAD captured by the GAD-6 monoclonal antibody the frequencies of GAD antibodies for all subject groups were indistinguishable from those found by precipitation of human brain enzymatic activity. We conclude that (i) GAD is an (auto)antigen in a majority of subjects operationally defined as having preclinical IDDM, (ii) pancreatic islet and brain GAD are likely to be cross-reactive, and (iii) the majority of GAD antibodies are directed away from the catalytic site of the brain enzyme. The lower frequency of GAD antibodies in recent-onset IDDM subjects indicates either that immunoreactivity is lost with near-total beta-cell destruction or that GAD antibodies denote a low risk of progression to clinical disease.
β‐Mercaptopropionitrile (2‐Cyanoethanethiol) (2003)

Abstract β‐Mercaptopropionitrile (2‐cyanoethanethiol) intermediate: 2‐Cyanoethylthiouronium hydrochloride product: 2‐Cyanoethanethiol product: 3,3′‐Dithiobispropionitrile
Effect of Topical Basic Fibroblast Growth Factor on the Healing of Chronic Diabetic Neuropathic Ulcer of the foot: A pilot, randomized, double-blind, placebo-controlled study (1995)

Topical application of bFGF has no advantage over placebo for healing chronic neuropathic diabetic ulcer of the foot. Because diabetes causes significant wound-healing defects, we hypothesized that using a single growth factor might be insufficient to accelerate wound closure of diabetic ulcers.
Pharmacology and Toxicology of Major Constituents of Marijuana—On the Metabolic Activation of Cannabinoids and Its Mechanism (2003)

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of Cannabis sativa L. (Cannabinaceae), were pharmacologically potent, and 11‐hydroxy‐THCs, 11‐oxo‐Δ8‐THC, 7‐oxo‐Δ8‐THC, 8β,9β‐epoxyhexahydrocannabinol (EHHC), 9α,10α‐EHHC and 3'‐hydroxy‐Δ9‐THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice, indicating that these metabolites are active metabolites of THCs. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6‐hydroxymethyl‐Δ9‐THC and 3‐pentyl‐6, 7, 7a, 8, 9, 11a‐hexahydro‐1, 7‐dihydroxy‐7,10‐dimethyldibenzo[b,d]oxepin (PHDO) through 8R,9‐epoxy‐CBD and 8S, 9‐epoxy‐CBD as intermediates, respectively, identified by us. Both metabolites have some pharmacological effects comparable to Δ9‐THC. Cannabinol (CBN), the other major component, was mainly metabolized to 11‐hydroxy‐CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that 11‐hydroxylation of CBN is an activation pathway of the cannabinoid as is the case in THCs. Tolerance developed to catalepsy, hypothermia and pentobarbital‐induced sleep prolonging effects of Δ8‐THC and its active metabolite, 11‐hydroxy‐Δ8‐THC. Reciprocal cross‐tolerance also developed to pharmacological effects and the magnitude of tolerance development produced by the metabolite was significantly higher than that by Δ8‐THC indicating that 11‐hydroxy‐Δ8‐THC has important role not only in the pharmacological effects but also its tolerance development of Δ8‐THC. THCs and their metabolites competed with the specific binding of CP‐55,940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely parallel to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified for the first time by us as a major enzyme responsible for the metabolic activation of Δ8‐THC at the 11‐position in the mouse liver. cDNA of cyp2c29 was cloned from a mouse cDNA library and its sequence was determined. All of major P450s involving the metabolic activation of Δ8‐THC at the 11‐position are belonging to CYP2C subfamily in mammalian liver.
Novel Control Motif Cluster in the IgH δ-γ3 Interval Exhibits B Cell-Specific Enhancer Function in Early Development (2001)

The majority of the human Ig heavy chain (IgH) constant (C) region locus has been cloned and mapped. An exception is the region between C delta and C gamma 3, which is unstable and may be a recombination hot spot. We isolated a pBAC clone (pHuIgH3'delta-gamma 3) that established a 52-kb distance between C delta and C gamma 3. Sequence analysis identified a high number of repeat elements, explaining the instability of the region, and an unusually large accumulation of transcription factor-binding motifs, for both lymphocyte-specific and ubiquitous transcription activators (IKAROS, E47, Oct-1, USF, Myc/Max), and for factors that may repress transcription (Delta EF1, Gfi-1, E4BP4, C/EBP beta). Functional analysis in reporter gene assays revealed the importance of the C delta-C gamma 3 interval in lymphocyte differentiation and identified independent regions capable of either enhancement or silencing of reporter gene expression and interaction with the IgH intron enhancer E mu. In transgenic mice, carrying a construct that links the beta-globin reporter to the novel delta-gamma 3 intron enhancer (E delta-gamma 3), transgene transcription is exclusively found in bone marrow B cells from the early stage when IgH rearrangement is initiated up to the successful completion of H and L locus recombination, resulting in Ab expression. These findings suggest that the C delta-C gamma 3 interval exerts regulatory control on Ig gene activation and expression during early lymphoid development.
Elevated serum levels of vascular endothelial growth factor in patients with preeclampsia (1995)

Serum VEGF levels were elevated in patients with preeclampsia, which suggests that the growth factor has a role in the endothelial cell activation that occurs in the disease.
Boar proacrosin. Purification and preliminary activation studies of proacrosin isolated from ejaculated boar sperm. (1977)

Two forms of proacrosin have been purified from ejacualted boar spermatozoa. The isolation method utilized benzamidine to inhibit the premeture activation of the zymogen and included pH precipitation, ammonium sulfate fractionation, and sodium chloride precipitation. Further purification was achieved by Sephadex G-200 FILTRATION OF THE PREPARATION AFTER IT WAS TREATED WITH 8 M urea. The overall proacrosin yield was 58% with a specific acitivity of 253 units/mg of protein. The molecular weights of the proacrosins determined by sodium dodecyl sulfate disc gel electrophoresis were 55,000 and 53,000. Proacrosin autoactivation followed the classical S-shaped activation curve and calcium was not required to obtain full activation. Time course activation studies in 0.1 M Tris/HCl, pH 8.4, at 0 degrees were monitored with sodium dodecyl sulfate-disc gel eletrophoresis and anlytical gel electrophoresis with staining techniques for protein and enzymatic activity. Under the conditions used, the zymogens were sequentially degraded to three different active specise of acrosin (alpha, beta, and gamma). The approximate molecualr weights of the acrosins were 49,000, 39,000, and 25,000 for the alpha, beta, and gamma forms, respectively. The autoactivation is concentration-dependent and can be proteolytically stimulated with either alpha- or beta-acrosin and trypsin, indicating the activation of proacrosin can via a bimolecular process.
Glycolipid-bound sialic acid in serum: increased levels in mice and humans bearing mammary carcinomas. (1977)

In mice bearing transplantable mammary carcinomas, serum levels of sialic acid-containing glycolipids were elevated 2.5-fold in pooled serum samples from which gangliosides were purified by column chromatography. A method is also described by which ganglioside content was estimated on as little as 1.0 ml of whole blood to permit studies with individual tumor-bearing mice and age- and litter-matched controls. Using this method, we observed similar elevations in ganglioside levels that were independent of age and sex of the animal and appeared in advance of palpable tumors. Following excision of the tumors, the glycolipid sialic acid values dropped below control levels and remained there. Serum sialic acid of the glycolipid fraction was elevated nearly 2-fold in human carcinoma patients and appeared to decline after surgery.
Structure and Activity of Glycosylated Human Interferon-γ (1986)

Structural properties and activity of recombinant human interferon-gamma (IFN-gamma) purified from Chinese hamster ovary (CHO) cells or a natural source were determined and compared with those of Escherichia coli-derived IFN-gamma. One preparation of CHO-derived IFN-gamma showed three bands, with the middle band being a doublet, in a SDS-polyacrylamide gel. The two higher-molecular-weight bands were shown to be glycosylated. Western blot analysis indicated that the three bands are IFN-gamma and lack an intact carboxyl terminus. The circular dichroic (CD) spectra showed that conformation of the CHO-derived IFN-gamma is similar in the native state, in acid, and after renaturation from acid to the E. coli-derived IFN-gamma. These results indicate that neither glycosylation nor carboxy-terminal processing affects conformational properties of the protein, as detected by CD spectroscopy. However, the antiviral activity was fourfold lower for the preparation of CHO-derived IFN-gamma than for the E. coli-derived IFN-gamma. A different preparation or a natural IFN-gamma preparation with less extensive carboxy-terminal processing showed similar conformational properties and antiviral activity to the E. coli-derived IFN-gamma. These results indicate that the carboxyl terminus, but not glycosylation, plays an important role in the antiviral activity of IFN-gamma.
MitoNuc and MitoAln: two related databases of nuclear genes coding for mitochondrial proteins (2000)

Mitochondria, besides their central role in energy metabolism, have recently been found to be involved in a number of basic processes of cell life and to contribute to the pathogenesis of many degenerative diseases. All functions of mitochondria depend on the interaction of nuclear and organellar genomes. Mitochondrial genomes have been extensively sequenced and analysed and the data collected in several specialised databases. In order to collect information on nuclear coded mitochondrial proteins we developed MitoNuc and MitoAln, two related databases containing, respectively, detailed information on sequenced nuclear genes coding for mitochondrial proteins in Metazoa and yeast, and the multiple alignments of the relevant homologous protein coding regions. MitoNuc and MitoAln retrieval through SRS at http://bio-www.ba.cnr.it:8000/srs6/ can easily allow the extraction of sequence data, subsequences defined by specific features and nucleotide or amino acid multiple alignments.
Differential mode-locked cavity for measurements of minute displacements (2009)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text X. Luo, A. Braga, L. Arissian, and J. Diels, "Differential mode-locked cavity for measurements of minute displacements," in Conference on Lasers and Electro-Optics/International Quantum Electronics Conference, OSA Technical Digest (CD) (Optica Publishing Group, 2009), paper CTuZ2. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Self-Attention Generative Adversarial Networks (2018)

In this paper, we propose the Self-Attention Generative Adversarial Network (SAGAN) which allows attention-driven, long-range dependency modeling for image generation tasks. Traditional convolutional GANs generate high-resolution details as a function of only spatially local points in lower-resolution feature maps. In SAGAN, details can be generated using cues from all feature locations. Moreover, the discriminator can check that highly detailed features in distant portions of the image are consistent with each other. Furthermore, recent work has shown that generator conditioning affects GAN performance. Leveraging this insight, we apply spectral normalization to the GAN generator and find that this improves training dynamics. The proposed SAGAN achieves the state-of-the-art results, boosting the best published Inception score from 36.8 to 52.52 and reducing Frechet Inception distance from 27.62 to 18.65 on the challenging ImageNet dataset. Visualization of the attention layers shows that the generator leverages neighborhoods that correspond to object shapes rather than local regions of fixed shape.
Contribution of Astrocyte-Derived IL-15 to CD8 T Cell Effector Functions in Multiple Sclerosis (2010)

The contribution of local factors to the activation of immune cells infiltrating the CNS of patients with multiple sclerosis (MS) remains to be defined. The cytokine IL-15 is pivotal in the maintenance and activation of CD8 T lymphocytes, a prominent lymphocyte population found in MS lesions. We investigated whether astrocytes are a functional source of IL-15 sufficient to enhance CD8 T lymphocyte responses and whether they provide IL-15 in the inflamed CNS of patients with MS. We observed that human astrocytes in primary cultures increased surface IL-15 levels upon activation with combinations of proinflammatory cytokines. Expanded human myelin autoreactive CD8 T lymphocytes cultured with such activated astrocytes displayed elevated lytic enzyme content, NKG2D expression, and Ag-specific cytotoxicity. These functional enhancements were abrogated by anti-IL-15-blocking Abs. Immunohistochemical analysis of brain tissue sections obtained from patients with MS demonstrated colocalization for IL-15 and the astrocyte marker glial fibrillary acidic protein within white matter lesions. The majority of astrocytes (80-90%) present in demyelinating MS lesions expressed IL-15, whereas few astrocytes in normal control brain sections had detectable IL-15. IL-15 could be detected in the majority of Iba-1-expressing microglia in the control sections, albeit in lower numbers when compared with microglia/macrophages in MS lesions. Furthermore, infiltrating CD8 T lymphocytes in MS lesions were in close proximity to IL-15-expressing cells. Astrocyte production of IL-15 resulting in the activation of CD8 T lymphocytes ascribes a role for these cells as contributors to the exacerbation of tissue damage during MS pathogenesis.
Serotype distribution of invasive Streptococcus pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate vaccine, 2010–2012 (2013)

The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very effective in reducing invasive pneumococcal disease (IPD) in children; however, increases of non-PCV7 serotypes have subsequently offset some of these reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional serotypes was implemented between 2010 and 2011, and in 2012 changes in the incidence of disease and the distribution of IPD serotypes began to emerge. The incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per 100 000 population between 2010 and 2012; however, the incidence in ages ≥5 years remained relatively unchanged over the 3-year period, at about 9.7 cases per 100 000 population. From 2010 to 2012, PCV13 serotypes declined significantly from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children ≥5 years of age. Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from 14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727) to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to 10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates of antimicrobial resistance were observed with clarithromycin (23%), penicillin using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim-sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions in the incidence of disease suggest that current immunization programs in Canada are effective in reducing the burden of IPD in children. While we acknowledge the limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this study represents one of the first descriptions of the potential impact of the PCV13 vaccine in the Canadian population. Continued surveillance will be important to recognize replacement serotypes, to determine the extent of herd immunity effects in nonpaediatric populations, and to assess the overall effectiveness of PCV13 in reducing IPD in Canada.
Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays (2009)

All together we show parameters which are essential for measurement of cytokines in the context of clinical trials.
The β2-Adrenergic Receptor Mediates Extracellular Signal-regulated Kinase Activation via Assembly of a Multi-receptor Complex with the Epidermal Growth Factor Receptor (2000)

Many G protein-coupled receptors (GPCRs) activate MAP kinases by stimulating tyrosine kinase signaling cascades. In some systems, GPCRs stimulate tyrosine phosphorylation by inducing the "transactivation" of a receptor tyrosine kinase (RTK). The mechanisms underlying GPCR-induced RTK transactivation have not been clearly defined. Here we report that GPCR activation mimics growth factor-mediated stimulation of the epidermal growth factor receptor (EGFR) with respect to many facets of RTK function. beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization, tyrosine autophosphorylation, and EGFR internalization. Coincident with EGFR transactivation, isoproterenol exposure induces the formation of a multireceptor complex containing both the beta(2)AR and the "transactivated" EGFR. beta(2)AR-mediated EGFR phosphorylation and subsequent beta(2)AR stimulation of extracellular signal-regulated kinase (ERK) 1/2 are sensitive to selective inhibitors of both EGFR and Src kinases, indicating that both kinases are required for EGFR transactivation. beta(2)AR-dependent signaling to ERK1/2, like direct EGF stimulation of ERK1/2 activity, is sensitive to inhibitors of clathrin-mediated endocytosis, suggesting that signaling downstream of both the EGF-activated and the GPCR-transactivated EGFRs requires a productive engagement of the complex with the cellular endocytic machinery. Thus, RTK transactivation is revealed to be a process involving both association of receptors of distinct classes and the interaction of the transactivated RTK with the cells endocytic machinery.