A Crowdsourcing Approach for Finding Misidentifications of Bibliographic Records

Because there is no perfect technique for automatic identification of bibliographic records, cleaning the identification results manually is indispensable. However, to recruit human resources for the task is often difficult. This paper discusses a microtask-based crowdsourcing approach to the problem. An important issue is to design a good strategy for generating tasks to be assigned to workers, maintaining the quality and reducing the number of tasks. In this study, we explore a design space defined by two criteria to reduce the number of assigned microtasks for finding misidentifications caused by automatic identification techniques. We compare four task-generation strategies using bibliographic records of the National Diet Library. One of the strategies reduced 55.7% of tasks from the baseline strategy and statistic analysis showed that the quality of its result is comparable to those of the other three strategies.published or submitted for publicationis peer reviewe

Increased Nitric Oxide Production and GFAP Expression in the Brains of Influenza A/NWS Virus Infected Mice

The cause of influenza to the brain was investigated using the A/NWS/33 influenza virus infected BALB/c mouse model. NOS-2 mRNA levels in the infected mouse brain was greater than in control mice in all brain regions examined, particularly in the olfactory bulb and hippocampus by 1 day p.i. On the contrary, no differences in NOS-1 or NOS-3 mRNA levels were found between infected and control mice. There was also a marked increase in the levels of metabolites of nitric oxide in the olfactory bulb and hippocampus. Immunohistochemistry showed positive staining for anti-NOS-2 primarily in the hippocampus of infected mice. Further, anti-NOS-2 and GFAP staining was mostly found around capillary blood vessels of the hippocampus starting early in the course of the disease. These results indicate that the NWS enhances the activation of astrocytes and NOS-2 expression which in turn enhances NO production and the expansion of capillary blood vessels

Cytokine and chemokine response in children with the 2009 pandemic influenza A (H1N1) virus infection

We report the systemic cytokine and chemokine response in children with the 2009 pandemic influenza A (H1N1) virus infection. In patients with pneumonia, the serum levels of IFN-γ and IL-5 were significantly higher than those in patients without pneumonia. This tendency was also present for IL-6, IL-8, IL-10, IL-13, and MCP-1 in patients with pneumonia. Among patients with pneumonia, the levels of MCP-1 were significantly higher in the group of patients with pneumonia with severe respiratory failure than patients with mild pneumonia

Infantile exposure to lead and late-age cognitive decline: Relevance to AD

Background: Early-life lead (Pb) exposure induces overexpression of the amyloid beta precursor protein and its amyloid beta product in older rats and primates. We exposed rodents to Pb during different life span periods and examined cognitive function in old age and its impact on biomarkers associated with Alzheimer\u27s disease (AD). Methods: Morris, Y, and the elevated plus mazes were used. Western blot, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay were used to study the levels of AD biomarkers. Results: Cognitive impairment was observed in mice exposed as infants but not as adults. Overexpression of AD-related genes (amyloid beta precursor protein and β-site amyloid precursor protein cleaving enzyme 1) and their products, as well as their transcriptional regulator—specificity protein 1 (Sp1)—occurred only in older mice with developmental exposure to Pb. Conclusions: A window of vulnerability to Pb neurotoxicity exists in the developing brain that can influence AD pathogenesis and cognitive decline in old age

Cytoskeletal Polarization of T Cells Is Regulated by an Immunoreceptor Tyrosine-based Activation Motif–dependent Mechanism

Abstract. Binding of a T cell to an appropriate antigen-presenting cell (APC) induces the rapid reorientation of the T cell cytoskeleton and secretory apparatus towards the cell–cell contact site in a T cell antigen receptor (TCR) and peptide/major histocompatibility complex–dependent process. Such T cell polarization directs the delivery of cytokines and cytotoxic mediators towards the APC and contributes to the highly selective and specific action of effector T cells. To study the signaling pathways that regulate cytoskeletal rearrangements in T lymphocytes, we set up a conjugate formation assay using Jurkat T cells as effectors and cell-sized latex beads coated with various antibodies as artificial APCs. Here, we report that beads coated with antibodies specific for the TCR-CD3 complex were sufficient to induce T cell polarization towards the bead attachment site, as judged by reorientation of the microtubule-organizing center (MTOC) and localized actin polymerization. Thus, these cytoskeletal changes did not depend on activation of additional coreceptors. Moreover, single subunits of the TCR complex, namely TCR-ζ and CD3ε, were equally effective in inducing cytoskeletal polarization. However, mutagenesis of the immunoreceptor tyrosine-based activation motifs (ITAMs), present three times in TCR-ζ and once in CD3ε, revealed that the induction of cytoskeletal rearrangements required the presence of at least one intact ITAM. In agreement with this result, lack of functional Lck, the protein tyrosine kinase responsible for ITAM phosphorylation, abolished both MTOC reorientation and polarized actin polymerization. Both inhibitor and transient overexpression studies demonstrated that MTOC reorientation could occur in the absence of Ras activation. Our results suggest that APC-induced T cell polarization is a TCR-mediated event that is coupled to the TCR by the same signaling motif as TCR-induced gene activation, but diverges in its distal signaling requirements

Sferična kristalizacija zdravilnih učinkovin

Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such particles are spherical agglomeration and quasi-emulsion solvent diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are extensions of these techniques. By controlling process parameters during crystallization, such as temperature, stirring rate, type and amount of solvents, or excipient selection, it is possible to control the formation of agglomerates and obtain spherical particles of the desired size, porosity, or hardness. Researchers have reported that the particles produced have improved micromeritic, physical, and mechanical properties, which make them suitable for direct compression. In some cases, when additional excipients are incorporated during spherical crystallization, biopharmaceutical parameters including the bioavailability of drugs can also be tailored.Sferična kristalizacija je postopek izdelave večjih delcev z aglomeracijo manjših med samo kristalizacijo. Najpogosteje uporabljeni tehniki za izdelavo takšnih delcev sta sferična aglomeracija in kvaziemulzija z difuzijo topila. Sistem z difuzijo amoniaka in kristalo-ko-aglomeracija sta razširitvi teh dveh metod. Z nadzorovanjem procesnih parametrov med kristalizacijo, kot sta temperatura in hitrost mešanja, z izbiro lastnosti in množine topil ter z izbiro pomožnih snovi, lahko vplivamo na nastanek aglomeratov in izdelamo sferične delce želenih velikosti, primerne poroznosti ali trdote. Raziskovalci poročajo, da imajo izdelani delci izboljšane pretočne lastnosti, izboljšane druge fizikalne in mehanske lastnosti zaradi česar so primerni za direktno tabletiranje. V nekaterih primerih lahko ob vgradnji ustreznih pomožnih snovi, ki jih dodamo med procesom sferične kristalizacije, izboljšamo tudi biofarmacevtske lastnosti zdravilnih učinkovin vključno s povečanjem biološke uporabnosti

Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase C gamma 1, Grb2, and Src family kinases

The microtubule-associated protein tau can associate with various other proteins in addition to tubulin, including the SH3 domains of Src family tyrosine kinases. Tau is well known to aggregate to form hyperphosphorylated filamentous deposits in several neurodegenerative diseases (tauopathies) including Alzheimer disease. We now report that tau can bind to SH3 domains derived from the p85α subunit of phosphatidylinositol 3-kinase, phospholipase Cγ1, and the N-terminal (but not the C-terminal) SH3 of Grb2 as well as to the kinases Fyn, cSrc, and Fgr. However, the short inserts found in neuron-specific isoforms of Src prevented the binding of tau. The experimentally determined binding of tau peptides is well accounted for when modeled into the peptide binding cleft in the SH3 domain of Fyn. After phosphorylation in vitro or in transfected cells, tau showed reduced binding to SH3 domains; no binding was detected with hyperphosphorylated tau isolated from Alzheimer brain, but SH3 binding was restored by phosphatase treatment. Tau mutants with serines and threonines replaced by glutamate, to mimic phosphorylation, showed reduced SH3 binding. These results strongly suggest that tau has a potential role in cell signaling in addition to its accepted role in cytoskeletal assembly, with regulation by phosphorylation that may be disrupted in the tauopathies including Alzheimer disease