269 research outputs found
Progressive ShallowNet for large scale dynamic and spontaneous facial behaviour analysis in children
COVID-19 has severely disrupted every aspect of society and left negative impact on our life. Resisting the temptation in engaging face-to-face social connection is not as easy as we imagine. Breaking ties within social circle makes us lonely and isolated, that in turns increase the likelihood of depression related disease and even can leads to death by increasing the chance of heart disease. Not only adults, children's are equally impacted where the contribution of emotional competence to social competence has long term implications. Early identification skill for facial behaviour emotions, deficits, and expression may help to prevent the low social functioning. Deficits in young children's ability to differentiate human emotions can leads to social functioning impairment. However, the existing work focus on adult emotions recognition mostly and ignores emotion recognition in children. By considering the working of pyramidal cells in the cerebral cortex, in this paper, we present progressive lightweight shallow learning for the classification by efficiently utilizing the skip-connection for spontaneous facial behaviour recognition in children. Unlike earlier deep neural networks, we limit the alternative path for the gradient at the earlier part of the network by increase gradually with the depth of the network. Progressive ShallowNet is not only able to explore more feature space but also resolve the over-fitting issue for smaller data, due to limiting the residual path locally, making the network vulnerable to perturbations. We have conducted extensive experiments on benchmark facial behaviour analysis in children that showed significant performance gain comparatively
Nuclear expression of Lyn, a Src family kinase member, is associated with poor prognosis in renal cancer patients
Background: 8000 cases of renal cancer are diagnosed each year in the UK, with a five-year survival rate of 50 %.
Treatment options are limited; a potential therapeutic target is the Src family kinases (SFKs). SFKs have roles in
multiple oncogenic processes and promote metastases in solid tumours. The aim of this study was to investigate
SFKs as potential therapeutic targets for clear cell renal cell carcinoma (ccRCC).
Methods: SFKs expression was assessed in a tissue microarray consisting of 192 ccRCC patients with full clinical
follow-up. SFK inhibitors, dasatinib and saracatinib, were assessed in early ccRCC cell lines, 786-O and 769-P and a
metastatic ccRCC cell line, ACHN (± Src) for effects on protein expression, apoptosis, proliferation and wound
healing.
Results: High nuclear expression of Lyn and the downstream marker of activation, paxillin, were associated with
decreased patient survival. Conversely, high cytoplasmic expression of other SFK members and downstream marker
of activation, focal adhesion kinase (FAK) were associated with increased patient survival. Treatment of non-metastatic
786-O and 769-P cells with dasatinib, dose dependently reduced SFK activation, shown via SFK (Y419) and FAK (Y861)
phosphorylation, with no effect in metastatic ACHN cells. Dasatinib also increased apoptosis, while decreasing
proliferation and migration in 786-O and 769-P cell lines, both in the presence and absence of Src protein.
Conclusions: Our data suggests that nuclear Lyn is a potential therapeutic target for ccRCC and dasatinib
affects cellular functions associated with cancer progression via a Src kinase independent mechanism
Attitudes and practices of postgraduate medical trainees towards research--a snapshot from Faisalabad
Objective: To assess the attitudes and practices of postgraduate medical trainees towards research.Methods: It was a self-administered questionnaire based cross-sectional survey conducted on 55 conveniently selected trainees in Allied Hospital, Faisalabad.Results: Only 11 trainees read journals monthly, seven had written an article for a journal, 51 regarded reading literature important, 39 intended to engage in future research and 37 said they received inappropriate research training. The major reasons cited for poor research activity in Pakistan were poor research training and awareness.CONCLUSION: Though the attitudes towards research were positive, they were deficient practically in terms of reading and writing literature. There is an immediate need to improve research training in our educational institutes to facilitate the development of the local literature both in terms of research utilization and productio
Spectroscopic and Theoretical Study of CuI Binding to His111 in the Human Prion Protein Fragment 106-115
The ability of the cellular prion protein (PrPC) to bind copper in vivo points to a physiological role for PrPC in copper transport. Six copper binding sites have been identified in the nonstructured N-terminal region of human PrPC. Among these sites, the His111 site is unique in that it contains a MKHM motif that would confer interesting CuI and CuII binding properties. We have evaluated CuI coordination to the PrP(106-115) fragment of the human PrP protein, using NMR and X-ray absorption spectroscopies and electronic structure calculations. We find that Met109 and Met112 play an important role in anchoring this metal ion. CuI coordination to His111 is pH-dependent: at pH >8, 2N1O1S species are formed with one Met ligand; in the range of pH 5-8, both methionine (Met) residues bind to CuI, forming a 1N1O2S species, where N is from His111 and O is from a backbone carbonyl or a water molecule; at pH <5, only the two Met residues remain coordinated. Thus, even upon drastic changes in the chemical environment, such as those occurring during endocytosis of PrPC (decreased pH and a reducing potential), the two Met residues in the MKHM motif enable PrPC to maintain the bound CuI ions, consistent with a copper transport function for this protein. We also find that the physiologically relevant CuI-1N1O2S species activates dioxygen via an inner-sphere mechanism, likely involving the formation of a copper(II) superoxide complex. In this process, the Met residues are partially oxidized to sulfoxide; this ability to scavenge superoxide may play a role in the proposed antioxidant properties of PrPC. This study provides further insight into the CuI coordination properties of His111 in human PrPC and the molecular mechanism of oxygen activation by this site.Fil: Arcos López, Trinidad. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Qayyum, Munzarin. University of Stanford; Estados UnidosFil: Rivillas Acevedo, Lina. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Miotto, Marco César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Grande Aztatzi, Rafael. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Hedman, Britt. University of Stanford; Estados UnidosFil: Hodgson, Keith O.. University of Stanford; Estados UnidosFil: Vela, Alberto. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Solomon, Edward I.. University of Stanford; Estados UnidosFil: Quintanar, Liliana. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; Méxic
A Comparison and Error Analysis of Error Bounds
In this paper, we present an error analysis with the help of Ostrowski type inequalities for n-times differentiable mappings by using n-times peano kernel. A comparison is also presented which shows that obtained error bounds are better than the previous error bounds
Structure of the Reduced Copper Active Site in Pre-Processed Galactose Oxidase: Ligand Tuning for One-Electron O2 Activation in Cofactor Biogenesis
Galactose oxidase (GO) is a copper-dependent enzyme that accomplishes 2e- substrate oxidation by pairing a single copper with an unusual cysteinylated tyrosine (Cys-Tyr) redox cofactor. Previous studies have demonstrated that the post-translational biogenesis of Cys-Tyr is copper- and O2-dependent, resulting in a self-processing enzyme system. To investigate the mechanism of cofactor biogenesis in GO, the active-site structure of Cu(I)-loaded GO was determined using X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy, and density-functional theory (DFT) calculations were performed on this model. Our results show that the active-site tyrosine lowers the Cu potential to enable the thermodynamically unfavorable 1e- reduction of O2, and the resulting Cu(II)-O2¿- is activated toward H atom abstraction from cysteine. The final step of biogenesis is a concerted reaction involving coordinated Tyr ring deprotonation where Cu(II) coordination enables formation of the Cys-Tyr cross-link. These spectroscopic and computational results highlight the role of the Cu(I) in enabling O2 activation by 1e- and the role of the resulting Cu(II) in enabling substrate activation for biogenesis
Keberkesanan ruangan lebuh medan pasar dalam mempengaruhi aktiviti masyarakat setempat
Kajian ini dijalankan bertujuan mengenalpasti dan memahami sejauh manakah kepenggunaan sesebuah ruangan awam serta mengkaji karakter fizikal dan aktiviti-aktiviti yang dilaksanakan oleh masyarakat sekeliling yang mempengaruhi aktiviti tersebut. Ruangan awam yang telah dipilih ialah ruangan Lebuh Medan Pasar yang terletak di tengah kawasan Kuala Lumpur Lama. Ruang awam tersebut dipilih kerana menjadi tumpuan masyarakat di ibu kota serta mempunyai kepentingan dan keistimewaan sejarah yang tersendiri. Kajian ini mengaplikasikan kaedah metodologi kualitatif dimana ia melibatkan dua teknik pengumpulan data iaitu kajian kes, pemerhatian di tapak kajian serta kajian literatur. Teknik pemerhatian akan dianalisa secara kualitatif di mana pendekatan pemerhatian berstruktur digunakan. Oleh itu, hasil penemuan dan dapatan kajian ini akan membantu dalam membangunkan kawasan kajian serta mengekalkan elemen penting sebagai identiti setempat terhadap ruangan awam tersebut
Fluctuations and differential contraction during regeneration of Hydra vulgaris tissue toroids
We studied regenerating bilayered tissue toroids dissected from Hydra
vulgaris polyps and relate our macroscopic observations to the dynamics of
force-generating mesoscopic cytoskeletal structures. Tissue fragments undergo a
specific toroid-spheroid folding process leading to complete regeneration
towards a new organism. The time scale of folding is too fast for biochemical
signalling or morphogenetic gradients which forced us to assume purely
mechanical self-organization. The initial pattern selection dynamics was
studied by embedding toroids into hydro-gels allowing us to observe the
deformation modes over longer periods of time. We found increasing mechanical
fluctuations which break the toroidal symmetry and discuss the evolution of
their power spectra for various gel stiffnesses. Our observations are related
to single cell studies which explain the mechanical feasibility of the folding
process. In addition, we observed switching of cells from a tissue bound to a
migrating state after folding failure as well as in tissue injury.
We found a supra-cellular actin ring assembled along the toroid's inner edge.
Its contraction can lead to the observed folding dynamics as we could confirm
by finite element simulations. This actin ring in the inner cell layer is
assembled by myosin- driven length fluctuations of supra-cellular
{\alpha}-actin structures (myonemes) in the outer cell-layer.Comment: 19 pages and 8 figures, submitted to New Journal of Physic
Development of indirect elisa for the diagnosis of bovine hypodermosis (hypoderma lineatum) in the cattle of subtropical region of pakistan
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