О взаимодействии карбазолилтиирана с карбоновыми кислотами

Изучено взаимодействие карбазолилтиирана с карбоновыми (уксусной, акриловой, метакриловой) и дикарбоновыми (адипиновой, себациновой, фталевой) кислотами. Показано, что основными продуктами взаимодействия являются олигомеры. С избытком уксусной кислоты, наряду с олигомером, выделен также продукт присоединения уксусной кислоты к карбазолилтиирану, идентифицированный как 2-меркапто-3-(9`-карбазолил)-1-ацетокси-пропан. Найдены условия получения всех олигомерных продуктов, изучены их свойства, показаны возможности применения

The effects of a plant proteinase inhibitor from Enterolobium contortisiliquum on human tumor cell lines

Supplementary to the efficient inhibition of trypsin, chymotrypsin, plasma kallikrein, and plasmin already described by the EcTI inhibitor from Enterolobium contortisiliquum, it also blocks human neutrophil elastase (K(iapp)=4.3 nM) and prevents phorbol ester (PMA)-stimulated activation of matrix metalloproteinase (MMP)-2 probably via interference with membrane-type 1 (MT1)-MMP. Moreover, plasminogen-induced activation of proMMP-9 and processing of active MMP-2 was also inhibited. Furthermore, the effect of EcTI on the human cancer cell lines HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), K562 and THP-1 (leukemia), as well as on human primary fibroblasts and human mesenchymal stem cells (hMSCs) was studied. EcTI inhibited in a concentration range of 1.0-2.5 mu M rather specifically tumor cell viability without targeting primary fibroblasts and hMSCs. Taken together, our data indicate that the polyspecific proteinase inhibitor EcTI prevents proMMP activation and is cytotoxic against tumor cells without affecting normal tissue remodeling fibroblasts or regenerative hMSCs being an important tool in the studies of tumor cell development and dissemination

Survey of Gravitationally lensed Objects in HSC Imaging (SuGOHI) −- X. Strong Lens Finding in The HSC-SSP using Convolutional Neural Networks

We apply a novel model based on convolutional neural networks (CNNs) to identify gravitationally-lensed galaxies in multi-band imaging of the Hyper Suprime Cam Subaru Strategic Program (HSC-SSP) Survey. The trained model is applied to a parent sample of 2 350 061 galaxies selected from the $\sim$ 800 deg$^2$ Wide area of the HSC-SSP Public Data Release 2. The galaxies in HSC Wide are selected based on stringent pre-selection criteria, such as multiband magnitudes, stellar mass, star formation rate, extendedness limit, photometric redshift range, etc. Initially, the CNNs provide a total of 20 241 cutouts with a score greater than 0.9, but this number is subsequently reduced to 1 522 cutouts by removing definite non-lenses for further inspection by human eyes. We discover 43 definite and 269 probable lenses, of which 97 are completely new. In addition, out of 880 potential lenses, we recovered 289 known systems in the literature. We identify 143 candidates from the known systems that had higher confidence in previous searches. Our model can also recover 285 candidate galaxy-scale lenses from the Survey of Gravitationally lensed Objects in HSC Imaging (SuGOHI), where a single foreground galaxy acts as the deflector. Even though group-scale and cluster-scale lens systems were not included in the training, a sample of 32 SuGOHI-c (i.e., group/cluster-scale systems) lens candidates was retrieved. Our discoveries will be useful for ongoing and planned spectroscopic surveys, such as the Subaru Prime Focus Spectrograph project, to measure lens and source redshifts in order to enable detailed lens modelling.Comment: Submitted to MNRAS, 16 pages, 13 figures. Comments welcom

Electrophysiological Phenotypes Of Mecp2 A140V Mutant Mouse Model

Aims: MeCP2 gene mutations are associated with Rett syndrome and X-linked mental retardation (XLMR), diseases characterized by abnormal brain development and function. Recently, we created a novel MeCP2 A140V mutation mouse model that exhibited abnormalities of cell packing density and dendritic branching consistent with that seen in Rett syndrome patients as well as other MeCP2 mutant mouse models. Therefore, we hypothesized that some deficits of neuronal and synaptic functions might also be present in the A140V mutant model. Methods: Here, we tested our hypothesis in hippocampal slices using electrophysiological recordings. Results: We found that in young A140V mutant mice (3- to 4-week-old), hippocampal CA1 pyramidal neurons exhibited more positive resting membrane potential, increased action potential (AP) firing frequency induced by injection of depolarizing current, wider AP duration, and smaller after hyperpolarization potential compared to neurons prepared from age-matched wild-type mice, suggesting a neuronal hyperexcitation. At the synaptic level, A140V mutant neurons exhibited a reduced frequency of spontaneous IPSCs (inhibitory postsynaptic potentials) and an enhanced probability of evoked glutamate release, both suggesting neuronal hyperexcitation. However, hippocampal CA1 long-term potentiation was not significantly different between A140V and WT mice. In adult mice (11- to 13-month-old), in addition to neuronal hyperexcitation, we also found significant deficits of both short-term and long-term potentiation of CA3-CA1 synapses in A140V mice compared to WT mice. Conclusions: These results clearly illustrate the age-dependent abnormalities of neuronal and synaptic function in the MeCP2 A140V mutant mouse model, which provides new insights into the understanding of the pathogenesis of Rett syndrome. © 2014 John Wiley & Sons Ltd

Lensed quasar search via time variability with the HSC transient survey

Gravitationally lensed quasars are useful for studying astrophysics and cosmology, and enlarging the sample size of lensed quasars is important for multiple studies. In this work, we develop a lens search algorithm for four-image (quad) lensed quasars based on their time variability. In the development of the lens search algorithm, we constructed a pipeline simulating multi-epoch images of lensed quasars in cadenced surveys, accounting for quasar variabilities, quasar hosts, lens galaxies, and the PSF variation. Applying the simulation pipeline to the Hyper Suprime-Cam (HSC) transient survey, we generated HSC-like difference images of the mock lensed quasars from Oguri & Marshall's lens catalog. We further developed a lens search algorithm that picks out variable objects as lensed quasar candidates based on their spatial extent in the difference images. We tested our lens search algorithm with the mock lensed quasars and variable objects from the HSC transient survey. Using difference images from multiple epochs, our lens search algorithm achieves a high true-positive rate (TPR) of 90.1% and a low false-positive rate (FPR) of 2.3% for the bright quads with wide separation. With a preselection of the number of blobs in the difference image, we obtain a TPR of 97.6% and a FPR of 2.6% for the bright quads with wide separation. Even when difference images are only available in one single epoch, our lens search algorithm can still detect the bright quads with wide separation at high TPR of 97.6% and low FPR of 2.4% in the optimal seeing scenario, and at TPR of $\sim94$ and FPR of $\sim5$ in typical scenarios. Therefore, our lens search algorithm is promising and is applicable to ongoing and upcoming cadenced surveys, particularly the HSC transient survey and the Rubin Observatory Legacy Survey of Space and Time, for finding new lensed quasar systems. [abridged]Comment: 15 pages, 11 figure

Hyper Suprime-Camera Survey of the Akari NEP Wide Field

The extragalactic background suggests half the energy generated by stars was reprocessed into the infrared (IR) by dust. At z ∼1.3, 90% of star formation is obscured by dust. To fully understand the cosmic star formation history, it is critical to investigate infrared emission. AKARI has made deep mid-IR observation using its continuous 9-band filters in the NEP field (5.4 deg2), using ∼10% of the entire pointed observations available throughout its lifetime. However, there remain 11,000 AKARI infrared sources undetected with the previous CFHT/Megacam imaging (r ∼25.9ABmag). Redshift and IR luminosity of these sources are unknown. These sources may contribute significantly to the cosmic star-formation rate density (CSFRD). For example, if they all lie at 1 z g, r, i, z, and y) using Hyper Suprime-Camera (HSC), which has 1.5 deg field of view in diameter on Subaru 8m telescope. This will provide photometric redshift information, and thereby IR luminosity for the previously-undetected 11,000 faint AKARI IR sources. Combined with AKARI's mid-IR AGN/SF diagnosis, and accurate mid-IR luminosity measurement, this will allow a complete census of cosmic star-formation/AGN accretion history obscured by dust

Beyond “yesterday’s tomorrow”: future-focused mobile interaction design by and for emergent users

Mobile and ubiquitous computing researchers have long envisioned future worlds for users in developed regions. Steered by such visions, they have innovated devices and services exploring the value of alternative propositions with and for individuals, groups and communities. Meanwhile, such radical and long-term explorations are uncommon for what have been termed emergent users; users, that is, for whom advanced technologies are just within grasp. Rather, a driving assumption is that today’s high-end mobile technologies will “trickle down” to these user groups in due course. In this paper, we open the debate about what mobile technologies might be like if emergent users were directly involved in creating their visions for the future 5–10 years from now. To do this, we report on a set of envisioning workshops in India, South Africa and Kenya that provide a roadmap for valued, effective devices and services for these regions in the next decade. © 2016, The Author(s)

Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons

Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons in vitro and in vivo. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system

Role of MeCP2, DNA methylation, and HDACs in regulating synapse function

Over the past several years there has been intense effort to delineate the role of epigenetic factors, including methyl-CpG-binding protein 2, histone deacetylases, and DNA methyltransferases, in synaptic function. Studies from our group as well as others have shown that these key epigenetic mechanisms are critical regulators of synapse formation, maturation, as well as function. Although most studies have identified selective deficits in excitatory neurotransmission, the latest work has also uncovered deficits in inhibitory neurotransmission as well. Despite the rapid pace of advances, the exact synaptic mechanisms and gene targets that mediate these effects on neurotransmission remain unclear. Nevertheless, these findings not only open new avenues for understanding neuronal circuit abnormalities associated with neurodevelopmental disorders but also elucidate potential targets for addressing the pathophysiology of several intractable neuropsychiatric disorders

Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus

A group of post-natal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased copy number of the gene causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however the gene expression changes observed in the hypothalamus of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression, given that the majority of genes are downregulated upon loss of MeCP2 and upregulated in its presence. To determine if this dual role of MeCP2 extends beyond the hypothalamus, we studied gene expression patterns in the cerebellum of Mecp2-null and MECP2-Tg mice, modeling RTT and MECP2 duplication syndrome, respectively. We found that abnormal MeCP2 dosage causes alterations in the expression of hundreds of genes in the cerebellum. The majority of genes were upregulated in MECP2-Tg mice and downregulated in Mecp2-null mice, consistent with a role for MeCP2 as a modulator that can both increase and decrease gene expression. Interestingly, many of the genes altered in the cerebellum, particularly those increased by the presence of MeCP2 and decreased in its absence, were similarly altered in the hypothalamus. Our data suggest that either gain or loss of MeCP2 results in gene expression changes in multiple brain regions and that some of these changes are global. Further delineation of the expression pattern of MeCP2 target genes throughout the brain might identify subsets of genes that are more amenable to manipulation, and can thus be used to modulate some of the disease phenotypes