Development of the object concept in infancy

Piaget first observed and described the problems which young infants have in understanding the nature of objects forty years ago. Both his description and his analysis of the development of the object concept are still widely supported today. This thesis, while accepting the Piagetian description of the behaviours involved, suggests that Piaget's account of the underlying cognitive processes is no longer tenable. Alternative theories of object concept development which have been put forward in recent years are also examined and rejected. An identity theory of object concept development is proposed and a series of six interlinked experiments presented in an attempt to provide support for this theory. On the basis of these and the many other experiments reported in the literature, it is suggested that an identity theory alone can adequately cover the variety of appropriate and inappropriate object-related behaviours seen in the first two years of life

Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations in the survival motor neuron 1 (SMN1) gene. Recent breakthroughs in preclinical research have highlighted several potential novel therapies for SMA, increasing the need for robust and sensitive clinical trial platforms for evaluating their effectiveness in human patient cohorts. Given that most clinical trials for SMA are likely to involve young children, there is a need for validated molecular biomarkers to assist with monitoring disease progression and establishing the effectiveness of therapies being tested. Proteomics technologies have recently been highlighted as a potentially powerful tool for such biomarker discovery. METHODS: We utilized label-free proteomics to identify individual proteins in pathologically-affected skeletal muscle from SMA mice that report directly on disease status. Quantitative fluorescent western blotting was then used to assess whether protein biomarkers were robustly changed in muscle, skin and blood from another mouse model of SMA, as well as in a small cohort of human SMA patient muscle biopsies. RESULTS: By comparing the protein composition of skeletal muscle in SMA mice at a pre-symptomatic time-point with the muscle proteome at a late-symptomatic time-point we identified increased expression of both Calreticulin and GRP75/Mortalin as robust indicators of disease progression in SMA mice. We report that these protein biomarkers were consistently modified in different mouse models of SMA, as well as across multiple skeletal muscles, and were also measurable in skin biopsies. Furthermore, Calreticulin and GRP75/Mortalin were measurable in muscle biopsy samples from human SMA patients. CONCLUSIONS: We conclude that label-free proteomics technology provides a powerful platform for biomarker identification in SMA, revealing Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers capable of reporting on disease progression in samples of muscle and skin

Farm Adjustment Possibilities to Increase Income in the Wellton-Mohawk District of Yuma County

This item is part of the Agricultural Experiment Station archive. It was digitized from a physical copy provided by the University Libraries at the University of Arizona. For more information, please email CALS Publications at [email protected]

Novel anticancer and treatment sensitizing compounds against pancreatic cancer

The isolation of chemical compounds from natural origins for medical application has played an important role in modern medicine with a range of novel treatments having emerged from various natural forms over the past decades. Natural compounds have been exploited for their antioxidant, antimicrobial and antitumor capabilities. Specifically, 60% of today’s anticancer drugs originate from natural sources. Moreover, the combination of synthetic and natural treatments has shown applications for (i) reduced side effects, (ii) treatment sensitization and (iii) reduction in treatment resistance. This review aims to collate novel and natural compounds that are being explored for their preclinical anticancer, chemosensitizing and radiosensitizing effects on Pancreatic Ductal Adenocarcinoma (PDAC), which is a lethal disease with current treatments being inefficient and causing serve side effects. Two key points are highlighted by this work: (i) the availability of a range of natural compounds for potentially new therapeutic approaches for PDAC, (ii) potential synergetic impact of natural compounds with advanced chemo-and radio-therapeutic modalities for PDAC

On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening

Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment

Spectral Density of Sparse Sample Covariance Matrices

Applying the replica method of statistical mechanics, we evaluate the eigenvalue density of the large random matrix (sample covariance matrix) of the form $J = A^{\rm T} A$, where $A$ is an $M \times N$ real sparse random matrix. The difference from a dense random matrix is the most significant in the tail region of the spectrum. We compare the results of several approximation schemes, focusing on the behavior in the tail region.Comment: 22 pages, 4 figures, minor corrections mad

Star formation in disk galaxies driven by primordial H_2

We show that gaseous \HI disks of primordial composition irradiated by an external radiation field can develop a multiphase medium with temperatures between 10^2 and 10^4 K due to the formation of molecular hydrogen. For a given \HI column density there is a critical value of the radiation field below which only the cold \HI phase can exist. Due to a time decreasing quasar background, the gas starts cooling slowly after recombination until the lowest stable temperature in the warm phase is reached at a critical redshift $z=z_{cr}$. Below this redshift the formation of molecular hydrogen promotes a rapid transition towards the cold \HI phase. We find that disks of protogalaxies with 10^{20}\simlt N_{HI}\simlt 10^{21} cm^{-2} are gravitationally stable at $T\sim 10^4$ K and can start their star formation history only at z \simlt z_{cr}\sim 2, after the gas in the central portion of the disk has cooled to temperatures T\simlt 300 K. Such a delayed starbust phase in galaxies of low gas surface density and low dynamical mass can disrupt the disks and cause them to fade away. These objects could contribute significantly to the faint blue galaxy population.Comment: 16 pages (LaTeX), 2 Figures to be published in Astrophysical Journal Letter

Architectures of domestication : on emplacing human-animal relations in the North

Acknowledgements. This fieldwork and discussions which led to this article was sponsored by ERC Advanced Grant 295458 Arctic Domus and ESRC grant ES‐MO110548‐1 JPI Climate Humanor. We would like to thank Rob Losey, Bente Sundsvold, and Konstantin Klokov for their comments on the manuscript. We would also like to thank that particularly engaging and constructive comments from three anonymous reviewers.Peer reviewedPublisher PD

FUSE observations of G226-29: First detection of the H_2 quasi-molecular satellite at 1150A

We present new FUV observations of the pulsating DA white dwarf G226-29 obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE). This ZZ Ceti star is the brightest one of its class and the coolest white dwarf observed by FUSE. We report the first detection of the broad quasi-molecular collision-induced satellite of Ly-beta at 1150 A, an absorption feature that is due to transitions which take place during close collisions of hydrogen atoms. The physical interpretation of this feature is based on recent progress of the line broadening theory of the far wing of Ly-beta. This predicted feature had never been observed before, even in laboratory spectra.Comment: Accepted for publication in ApJ Letters; 6 pages, 3 figure

Compact smallest eigenvalue expressions in Wishart-Laguerre ensembles with or without fixed-trace

The degree of entanglement of random pure states in bipartite quantum systems can be estimated from the distribution of the extreme Schmidt eigenvalues. For a bipartition of size M\geq N, these are distributed according to a Wishart-Laguerre ensemble (WL) of random matrices of size N x M, with a fixed-trace constraint. We first compute the distribution and moments of the smallest eigenvalue in the fixed trace orthogonal WL ensemble for arbitrary M\geq N. Our method is based on a Laplace inversion of the recursive results for the corresponding orthogonal WL ensemble by Edelman. Explicit examples are given for fixed N and M, generalizing and simplifying earlier results. In the microscopic large-N limit with M-N fixed, the orthogonal and unitary WL distributions exhibit universality after a suitable rescaling and are therefore independent of the constraint. We prove that very recent results given in terms of hypergeometric functions of matrix argument are equivalent to more explicit expressions in terms of a Pfaffian or determinant of Bessel functions. While the latter were mostly known from the random matrix literature on the QCD Dirac operator spectrum, we also derive some new results in the orthogonal symmetry class.Comment: 25 pag., 4 fig - minor changes, typos fixed. To appear in JSTA