gebhart/patrepeval huggingface dataset:
Accumulation of Pathological Tau Species and Memory Loss in a Conditional Model of Tauopathy (2007)

Neurofibrillary tangles (NFTs) are a pathological hallmark of Alzheimer's disease and other tauopathies, but recent studies in a conditional mouse model of tauopathy (rTg4510) have suggested that NFT formation can be dissociated from memory loss and neurodegeneration. This suggests that NFTs are not the major neurotoxic tau species, at least during the early stages of pathogenesis. To identify other neurotoxic tau protein species, we performed biochemical analyses on brain tissues from the rTg4510 mouse model and then correlated the levels of these tau proteins with memory loss. We describe the identification and characterization of two forms of tau multimers (140 and 170 kDa), whose molecular weight suggests an oligomeric aggregate, that accumulate early in the pathogenic cascade in this mouse model. Similar tau multimers were detected in a second mouse model of tauopathy (JNPL3) and in tissue from patients with Alzheimer's disease and FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17). Moreover, levels of the tau multimers correlated consistently with memory loss at various ages in the rTg4510 mouse model. Our findings suggest that accumulation of early-stage aggregated tau species, before the formation of NFT, is associated with the development of functional deficits during the pathogenic progression of tauopathy.
Comparison of Nitric Oxide Removal by Cyanuric Acid and by Ammonia (1989)

Abstract Selective, non-catalytic techniques for removing nitric oxide (NO) from the exhaust gases of combustion processes include the addition of cyanuric acid, ammonia, or urea to the hot exhaust. This paper compares the effects of temperature and exhaust gas composition on the cyanuric acid (CA) and the ammonia (NH3) nitric oxide reduction processes and examines the decomposition of dry urea. The experiments were conducted in an electrically heated quartz flow reactor using mixtures of N2, 02, H2, H2, O, CO, and NO that simulated exhaust gases from overall lean hydrocarbon combustion processes Comparison of the CA and the NH3 nitric oxide reduction processes shows that the effects of the exhaust O2, H2, O, and CO concentrations on the NO reduction level and the temperature range over which the NO reduction occurs are different for each process. The comparison also shows that the by-products of each process are different for some conditions. These differences indicate that the detailed chemical mechanisms of the CA an the NH3, processes are not the same The examination of the decomposition of dry urea at high temperatures shows that dry urea decomposes into equal amounts of isocyanic acid (the decomposition product of CA) and NH3,. The decomposition products noted for urea suggest that the urea NO reduction process is a hybrid of the CA and the NH3, processes
Synthesis and Characterization of Conjugated Mono- and Dithiol Oligomers and Characterization of Their Self-Assembled Monolayers (2003)

The characterization of self-assembled monolayer molecular arrays, which serve as active layers in electronic devices, is an important step toward understanding molecular-scale electronics. To correlate the properties of self-assembled monolayers with their molecular structures, a series of π-conjugated mono- and dithiols and aromatic dithiols with an oxygen or sulfur atom between two aromatic units have been designed and synthesized. Their optical properties were determined by UV−vis spectroscopy. Their self-assembled monolayer films on gold surfaces were characterized by cyclic voltammetry, grazing incidence Fourier transform infrared spectroscopy (GI-FTIR), and contact angle and ellipsometry measurements. Increasing the chain length from two to four phenyl rings showed a more than linear increase of the intensity of the aromatic CC ring stretch modes in GI-FTIR, indicating that the longer p-phenylene system is oriented toward the surface normal. Similar to oligophenylenes, when the number of repeat units for oligothiophene is increased, a more than linear increase of the intensity of the CC stretch and C−H bend modes implies that the longest oligothiophenedithiol molecule is oriented close to the surface normal. Ellipsometry showed a smaller deviation from the calculated monolayer thickness with increasing number of thiophene or phenylene rings, corroborating the GI-FTIR data. We conclude that the conjugated phenylene- and thiophene-based dithiols demonstrate a less tilted molecular orientation with respect to the surface normal with increasing chain length.
Microscopic Understanding of the Anisotropic Conductivity of PEDOT:PSS Thin Films (2007)

The anisotropic conductivity of thin films of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is correlated to the film morphology as obtained from scanning tunneling and atomic force microscopy images. The material was found to consist of layers of flattened PEDOT-rich particles that are separated by quasi-continuous PSS lamella (see figure).
Isolated Limb Perfusion with Tumor Necrosis Factor and Melphalan for Limb Salvage in 186 Patients with Locally Advanced Soft Tissue Extremity Sarcomas (1996)

In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.
The destructive effect of botulinum neurotoxins on the SNARE protein: SNAP-25 and synaptic membrane fusion (2015)

Synaptic exocytosis requires the assembly of syntaxin 1A and SNAP-25 on the plasma membrane and synaptobrevin 2 (VAMP2) on the vesicular membrane to bridge the two opposite membranes. It is believed that the three SNARE proteins assemble in steps along the dynamic assembly pathway. The C-terminus of SNAP-25 is known to be the target of botulinum neurotoxins (BoNT/A and BoNT/E) that block neurotransmitters release in vivo. In this study, we employed electron paramagnetic resonance (EPR) spectroscopy to investigate the conformation of the SNAP-25 C-terminus in binary and ternary SNARE complexes. The fluorescence lipid mixing assay shows that the C-terminal of SNAP-25 is essential for membrane fusion, and that the truncated SNAP-25 mutants cleaved by BoNT/A and BoNT/E display different inhibition effects on membrane fusion: SNAP-25E (Δ26) abolishes the fusion activity of the SNARE complex, while SNAP-25A (Δ9) loses most of its function, although it can still form a SDS-resistant SNARE complex as the wild-type SNAP-25. CW-EPR spectra validate the unstable structures of the SNARE complex formed by SNAP-25 mutants. We propose that the truncated SNAP-25 mutants will disrupt the assembly of the SNARE core complex, and then inhibit the synaptic membrane fusion accordingly.
The wavelet transform, time-frequency localization and signal analysis (1990)

Two different procedures for effecting a frequency analysis of a time-dependent signal locally in time are studied. The first procedure is the short-time or windowed Fourier transform; the second is the wavelet transform, in which high-frequency components are studied with sharper time resolution than low-frequency components. The similarities and the differences between these two methods are discussed. For both schemes a detailed study is made of the reconstruction method and its stability as a function of the chosen time-frequency density. Finally, the notion of time-frequency localization is made precise, within this framework, by two localization theorems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An amino acid sequence shared by the herpes simplex virus 1 alpha regulatory proteins 0, 4, 22, and 27 predicts the nucleotidylylation of the UL21, UL31, UL47, and UL49 gene products (1994)

Earlier reports showed that at least 3 herpes simplex virus 1 proteins were adenylylated and guanylylated in addition to the infected cell proteins (ICPs) 0, 4, 22, and 27. ICP22 and 27 share the amino acid sequence R/PRAP/SR which is also predicted to be in ICPs 4 and 0 and in the products of the HSV-1 genes UL21, UL31, UL47, and UL49. ICPs 0, 4, 22, and 27 are regulatory proteins, UL21 is dispensable for growth in cultured cells, UL31 co-fractionates with the nuclear matrix, and UL47 may interact stoichiometrically with the alpha trans-inducing factor (VP16, the product of the UL48 gene). To avoid bias, the genes encoding the additional nucleotidylylated proteins were mapped, initially by analyses of intertypic recombinant viruses, and subsequently by analyses of the products encoded by the mapped genome domains. We conclude that (i) the products of UL21, UL31, UL47, and UL49 are nucleotidylylated by [alpha-32P]GTP or [alpha-32P]ATP in isolated nuclei, (ii) this modification does not involve the viral protein kinases encoded by the UL13 and US3 gene products and, (iii) UL49 is a virion protein which is labeled in cells with [32P]orthophosphate and also is ADP-ribosylated.
Antiangiogenic Activity of the Cleaved Conformation of the Serpin Antithrombin (1999)

Antithrombin, a member of the serpin family, functions as an inhibitor of thrombin and other enzymes. Cleavage of the carboxyl-terminal loop of antithrombin induces a conformational change in the molecule. Here it is shown that the cleaved conformation of antithrombin has potent antiangiogenic and antitumor activity in mouse models. The latent form of intact antithrombin, which is similar in conformation to the cleaved molecule, also inhibited angiogenesis and tumor growth. These data provide further evidence that the clotting and fibrinolytic pathways are directly involved in the regulation of angiogenesis.
Discovery and development of antimitotic agents that inhibit tubulin polymerisation for the treatment of cancer (2002)

Antimitotic agents have generated considerable interest among cytotoxic agents due to the tremendous success of the taxanes and the widespread use of the Vinca alkaloids in clinical oncology. Renewed interest in tubulin polymerisation inhibitors has been generated by the hope that non-multi-drug resistance (MDR) substrates that interact with tubulin at sites near to, overlapping with or different from those of the taxanes or Vinca alkaloids can be discovered. In this article, new antimitotic agents that inhibit tubulin polymerisation for the treatment of cancer are reviewed, with greater emphasis being focused on the small molecule colchicine site binders. Compounds that induce metaphase arrest, by other novel mechanisms, are summarised. Results of clinical trials of drug candidates that fall into these classes are also briefly discussed. The patent literature was surveyed from January 1998 through May 2002.
Repressor to activator switch by mutations in the first Zn finger of the glucocorticoid receptor: is direct DNA binding necessary? (1991)

Transfection of HeLa cells with cDNA vectors expressing the wild-type human glucocorticoid receptor (GR) enabled dexamethasone to strongly repress cytokine- and second messenger-induced expression of cotransfected chimeric reporter genes containing transcription regulatory DNA elements from the human interleukin 6 (IL-6) promoter. Deletion of the DNA-binding domain or of the second Zn finger or a point mutation in the Zn catenation site in the second finger blocked the ability of GR to mediate repression of the IL-6 promoter. Unexpectedly, deletion of the first Zn finger, a point mutation in the Zn-catenation site in the first finger, or one in the steroid-specificity domain at the base of the first finger converted GR into a dexamethasone-responsive activator that enhanced basal and interleukin 1-induced IL-6 promoter function. These first-finger mutants of GR also mediated dexamethasone-responsive enhancement of expression of the herpesvirus thymidine kinase-chloramphenicol acetyltransferase (TK-105-CAT and TK-80-CAT) reporter genes but not of the murine mammary tumor virus long terminal repeat-CAT or the c-fos-CAT (pFC700) reporter genes. Wild-type GR was able to specifically bind to DNA fragments containing glucocorticoid response element sequences in both the murine mammary tumor virus and IL-6 promoters, albeit weakly to the latter, in a sequential DNA-binding immunoprecipitation assay. The first-finger mutants of GR, however, were inactive in this assay. Thus, mutations in the first Zn finger unmask unusual promoter-specific activation properties of GR that may not require direct high-affinity binding of the mutant GR to target DNA.
Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated T regs (2017)

Major barriers to cancer therapy include the lack of selective inhibitors of regulatory T cells (T<sub>regs</sub>) and the lack of broadly applicable ways to directly target tumors through frequently expressed surface oncogenes. Tumor necrosis factor receptor 2 (TNFR2) is an attractive target protein because of its restricted abundance to highly immunosuppressive T<sub>regs</sub> and oncogenic presence on human tumors. We characterized the effect of TNFR2 inhibition using antagonistic antibodies. In culture-based assays, we found that two TNFR2 antagonists inhibited T<sub>reg</sub> proliferation, reduced soluble TNFR2 secretion from normal cells, and enabled T effector cell expansion. The antagonistic activity occurred in the presence of added TNF, a natural TNFR2 agonist. These TNFR2 antibodies killed T<sub>regs</sub> isolated from ovarian cancer ascites more potently than it killed T<sub>regs</sub> from healthy donor samples, suggesting that these antibodies may have specificity for the tumor microenvironment. The TNFR2 antagonists also killed OVCAR3 ovarian cancer cells, which have abundant surface TNFR2. The antibodies stabilized antiparallel dimers in cell surface TNFR2 that rendered the receptor unable to activate the nuclear factor κB pathway and trigger cell proliferation. Our data suggest that, by targeting tumor cells and immunosuppressive tumor-associated T<sub>regs</sub>, antagonistic TNFR2 antibodies may be an effective treatment for cancers positive for TNFR2.
Bioactive paper and fibre products Patent and literary survey (2006)

In this patent and literary survey bioactive papers and fibre products, i.e. paper-like products, cardboard, fabrics and their combinations, etc., with active recognition and/or functional material capabilities are reviewed. The focus is on materials that specifically react with the target entity or environmental condition, and this reaction initializes different events, like a discharge of molecules or signalling function, in the product. The aim of this publication is to review and provide basic information on biomolecules and their potential utilisation for functional purposes, embedded signalling  concentrating especially on conducting polymers and optics  low-cost manufacturing on a large scale, modification of fibres and grafting or immobilisation of bioactive components. In addition, some application scenarios for bioactive paper products are presented.
Reconstitution of pyruvate dehydrogenase multienzyme complexes based on chimeric core structures from Azotobacter vinelandii and Escherichia coli (1992)

Two unique restriction sites were introduced by site-directed mutagenesis at identical positions in the DNA encoding the dihydrolipoyltransacetylase (E2p) components of the pyruvate dehydrogenase complex from Azotobacter vinelandii and from Escherichia coli. In this manner each DNA chain could be cut into three parts, coding for the lipoyl domain, which consists of three lipoyl subdomains, the binding domain and the core-forming catalytic domain, respectively. Chimeric E2p components were constructed by exchanging the three domains between E2p from A. vinelandii and E. coli on gene level. The six chimeric E2p proteins were expressed and purified from E. coli TG2. All chimeras were catalytically active, 24-subunit E2p proteins. Interactions of the peripheral components E1p and E3 with the wild-type enzymes from A. vinelandii and E. coli and with the chimeric proteins were studied by gel-filtration experiments, analytical ultracentrifugation and reconstitution of the overall activity of the complex. A. vinelandii E3 interacts only with those chimeras that contain the A. vinelandii binding domain, whereas E. coli E3 interacts with all chimeras. Exchange of the lipoyl or catalytic domain did not influence the binding properties of E3. Recognition of E1p depends on the origin of both the binding domain and the catalytic domain. E. coli E1p interacts strongly with those chimeras in which both the binding domain and the catalytic domain were derived from E. coli E2p and weakly with chimeras that contained either the binding domain or the catalytic domain from E. coli E2p. No binding of E. coli E1p was observed when both domains were of A. vinelandii origin. A. vinelandii E1p recognizes E2p from A. vinelandii and E. coli, but strong interaction required that the binding and catalytic domain were of the same origin. Exchange of lipoyl domains had no effect on the binding properties of the E1p component. These observations confirm previous conclusions, based on site-directed mutagenesis of A. vinelandii E2p [Schulze, E., Westphal, A. H., Boumans, H., and de Kok, A. (1991) Eur. J. Biochem. 202, 841-848], that the binding site for E1p consists of amino acid residues derived from both the binding and the catalytic domain and extend these conclusions to E. coli E2p. Dissociation of the 24 subunit E2p core was only detected when the chimeric E2p proteins contained the catalytic domain from A. vinelandii E2p. Dissociation depends on the binding of peripheral components to the E1p-binding sites, pointing to differences in the inter-trimer contacts between the E2p proteins from both species.(ABSTRACT TRUNCATED AT 400 WORDS)
The Epidemiology of Acute Respiratory Tract Infection in Young Children: Comparison of Findings from Several Developing Countries (1990)

Investigators from 10 countries studied the epidemiology of acute respiratory tract infection (ARI) among children 0-59 months old. Data on incidence rates, by age, gender, and season; on pathogenic agents; on case-fatality rates; and on selected risk factor findings are presented. Incidence rates from six of the community-based studies ranged from 12.7 to 16.8 new episodes of ARI per 100 child-weeks at risk, and rates of lower respiratory tract infection (LRI) ranged from 0.2 to 3.4 new episodes per 100 child-weeks at risk. Children spend from 21.7% to 40.1% of observed weeks with ARI and from 1% to 14.4% of observed weeks with LRI. The incidence rates for ARI are highest in younger children. Viruses, especially respiratory syncytial virus, are isolated more frequently than bacteria from children with episodes of LRI. Risk factors exhibited different patterns of association with ARI in different studies. Interventions could have great impact on high-risk levels common in the study populations. These studies provide interesting and useful data on the epidemiologic dynamics of ARI.
Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. (1993)

The mitogen-activated protein kinases (MAP kinases) p42mapk and p44mapk are serine/threonine kinases rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in integrating and transmitting transmembrane signals required for growth and differentiation. Here we demonstrate that activation of these ubiquitously expressed MAP kinases is essential for growth. To specifically suppress MAP kinase activation in fibroblasts, we transiently expressed either the entire p44mapk antisense RNA or p44mapk kinase-deficient mutants (T192A or Y194F). As expected, and through independent mechanisms, both approaches strongly inhibited MAP kinase activation. The antisense reduced the expression of endogenous p42mapk and p44mapk by 90%, whereas overexpression of the T192A mutant inhibited growth factor activation of both endogenous MAP kinases by up to 70%. As a consequence, we found that the antisense as well as the T192A mutant of p44mapk inhibited growth factor-stimulated gene transcription (collagenase promoter assay with chloramphenicol acetyltransferase reporter) and cell growth. These effects were proportional to the extent of MAP kinase inhibition and reversed by coexpression of the wild-type p44mapk. Therefore we conclude that growth factor activation of p42mapk and p44mapk is an absolute requirement for triggering the proliferative response.
Mini-Mental State Examination. Norms, normals, and numbers (1993)

The Mini-Mental State Examination (MMSE), first introduced by Folstein and colleagues in 1975,<sup>1</sup>has become a standard tool for cognitive assessment in the clinical setting. The MMSE facilitates the detection of mental status changes, particularly in the elderly, and thereby enhances patient care. Bedside mental status testing without a standardized approach is subject to considerable interpretive bias, dependent on the skill and experience of the examiner, and often completely neglected. The MMSE provides a structured approach to mental status testing that screens for intellectual impairment and allows comparison of performance across time and among patients or studies.<sup>2</sup>The publication in this issue of<i>JAMA</i>of new data from Crum et al<sup>3</sup>regarding the influence of age and education on the interpretation of the MMSE is welcome and further improves the utility of this instrument. See also p 2386. <h3>MMSE Elements</h3> The MMSE comprises 30 questions with 10
The METEOR-S framework for semantic Web process composition (2003)

Web services have been recognized to have the potential to revolutionize e-commerce. The potential for businesses to be able to interact with each other on the fly is very appealing. To date, however, the activity of creating Web processes using Web services has been handled mostly at the syntactic level. Current composition standards focus on building the processes based on the interface description of the participating services. The limitation of such a rigid approach is that it does not allow businesses to dynamically change partners and services. We enhance the current Web process composition techniques by using Semantic Process Templates to capture the semantic requirements of the process. The semantic process templates can act as configurable modules for common industry processes maintaining the semantics of the participating activities, control flow, intermediate calculations, conditional branches and exposing it in an industry accepted interface. The templates are instantiated to form executable processes according to the semantics of the activities in the templates. The use of ontologies in template definition allows much richer description of activity requirements and more effective way of locating services to carry out the activities in the executable Web process. During discovery of services, we consider not only functionality, but also the QoS of the corresponding activities. Our unique approach combines the expressive power of the present Web service composition standards and the advantages of the semantic Web techniques for process template definition and Web service discovery. The prototype implementation of the framework for building the templates, carrying out semantic Web service discovery and generating the processes is discussed.
Derivation of Endothelial Cells From Human Embryonic Stem Cells by Directed Differentiation (2010)

The directed differentiation of hESCs is efficient and effective for the differentiation of functional endothelial cells from hESCs.