Binary Weighted DAC with 2-ξ Resistor Ratio

In this paper we present a new digital analog converter (DAC) design, based on the binary weighted resistor network. The proposed design ensures high conversion accuracy using low precision resistors with ±1% ±2%, ±5%, ±10% and ±20% resistor tolerance. High accuracy is achieved due to better coverage of the analog domain of the transfer characteristic. In binary weighted converters the imprecision of resistors introduces positive and negative differential nonlinearities (DNL). Positive DNL causes gap in the analog domain of the transfer characteristic and negative DNL causes non-monotonicity. In the proposed solution we change the resistor ratio of the two consecutive DAC branches from 2 to 2-ξ, where ξ is small positive number. With this change, we intentionally introduce an additional negative DNL in order to entirely avoid the positive gap. Simulation results confirm that even with resistors tolerance of up to ±10%, we can achieve a converter with maximal gap in the transfer characteristic less than or around one LSB

Overnutrition and Scholastic Achievement: Is There a Relationship? An 8-Year Follow-Up Study

Objective: The aim of this study was to assess the association between overnutrition and scholastic achievement (SA). Methods: A representative and proportional sample of 477 children of the 5th elementary school grade of both genders was randomly chosen during 2010, in the Metropolitan Region of Chile. SA was measured through the 2009 Education Quality Measurement System (SIMCE) tests of language (LSA), mathematics (MSA) and understanding of the natural environment (UNESA). Current nutritional status was assessed through the body mass index Z-score (Z-BMI). Nutritional quality of diet, schedule exercise, socioeconomic status, family, and educational variables were also recorded. Four and 8 years later, SA was assessed through the 2013 SIMCE and the University Selection Test (2017 PSU), respectively. Results: Socioeconomic status, the number of repeated school years, and maternal schooling were strong predictors of 2009 SIMCE and the independent variables with the greatest explanatory power for LSA (Model R2 = 0.178; p 2 = 0.205; p2 = 0.272; p Conclusions: These results confirm that overnourished children did not achieve significantly lower SA

An overview of research activities and achievement in Geotechnics from the Scottish Universities Geotechnics Network (SUGN)

ABSTRACT: Design of geotechnical systems is often challenging as it requires the understanding of complex soil behaviour and its influence on field-scale performance of geo-structures. To advance the scientific knowledge and the technological development in geotechnical engineering, a Scottish academic community, named Scottish Universities Geotechnics Network (SUGN), was established in 2001, composing of eight higher education institutions. The network gathers geotechnics researchers, including experimentalists as well as centrifuge, constitutive, and numerical modellers, to generate multiple synergies for building larger collaboration and wider research dissemination in and beyond Scotland. The paper will highlight the research excellence and leading work undertaken in SUGN emphasising some of the contribution to the geotechnical research community and some of the significant research outcomes. RÉSUMÉ: Conception de systèmes géotechniques est souvent difficile car elle nécessite la compréhension du comportement des sols complexes et son influence sur la performance échelle du champ de géo-structures. Pour faire avancer la connaissance scientifique et le développement technologique en ingénierie géotechnique, une communauté universitaire écossais, nommé écossais universités Géotechnique réseau (SUGN), a été créé en 2001, la composition des huit établissements d'enseignement supérieur. Le réseau réunit géotechnique chercheurs, y compris les expérimentateurs ainsi que centrifugeuse, constitutif, et les modélisateurs numériques, de générer des synergies multiples pour la construction de plus grande collaboration et une plus large diffusion de la recherche en Ecosse et au-delà. Le document mettra l'accent sur l'excellence de la recherche et de diriger le travail entrepris dans SUGN soulignant certains de la contribution à la communauté de recherche en géotechnique et certains des résultats importants de la recherche

Transcriptional landscape of bone marrow-derived very small embryonic-like stem cells during hypoxia

<p>Abstract</p> <p>Background</p> <p>Hypoxia is a ubiquitous feature of many lung diseases and elicits cell-specific responses. While the effects of hypoxia on stem cells have been examined under <it>in vitro </it>conditions, the consequences of <it>in vivo </it>oxygen deprivation have not been studied.</p> <p>Methods</p> <p>We investigated the effects of <it>in vivo </it>hypoxia on a recently characterized population of pluripotent stem cells known as very small embryonic-like stem cells (VSELs) by whole-genome expression profiling and measuring peripheral blood stem cell chemokine levels.</p> <p>Results</p> <p>We found that exposure to hypoxia in mice mobilized VSELs from the bone marrow to peripheral blood, and induced a distinct genome-wide transcriptional signature. Applying a computationally-intensive methodology, we identified a hypoxia-induced gene interaction network that was functionally enriched in a diverse array of programs including organ-specific development, stress response, and wound repair. Topographic analysis of the network highlighted a number of densely connected hubs that may represent key controllers of stem cell response during hypoxia and, therefore, serve as putative targets for altering the pathophysiologic consequences of hypoxic burden.</p> <p>Conclusions</p> <p>A brief exposure to hypoxia recruits pluripotent stem cells to the peripheral circulation and actives diverse transcriptional programs that are orchestrated by a selective number of key genes.</p

Decoherence, einselection, and the quantum origins of the classical

Decoherence is caused by the interaction with the environment. Environment monitors certain observables of the system, destroying interference between the pointer states corresponding to their eigenvalues. This leads to environment-induced superselection or einselection, a quantum process associated with selective loss of information. Einselected pointer states are stable. They can retain correlations with the rest of the Universe in spite of the environment. Einselection enforces classicality by imposing an effective ban on the vast majority of the Hilbert space, eliminating especially the flagrantly non-local "Schr\"odinger cat" states. Classical structure of phase space emerges from the quantum Hilbert space in the appropriate macroscopic limit: Combination of einselection with dynamics leads to the idealizations of a point and of a classical trajectory. In measurements, einselection replaces quantum entanglement between the apparatus and the measured system with the classical correlation.Comment: Final version of the review, with brutally compressed figures. Apart from the changes introduced in the editorial process the text is identical with that in the Rev. Mod. Phys. July issue. Also available from http://www.vjquantuminfo.or

OXPHOS Supercomplexes as a Hallmark of the Mitochondrial Phenotype of Adipogenic Differentiated Human MSCs

Mitochondria are essential organelles with multiple functions, especially in energy metabolism. Recently, an increasing number of data has highlighted the role of mitochondria for cellular differentiation processes. Metabolic differences between stem cells and mature derivatives require an adaptation of mitochondrial function during differentiation. In this study we investigated alterations of the mitochondrial phenotype of human mesenchymal stem cells undergoing adipogenic differentiation. Maturation of adipocytes is accompanied by mitochondrial biogenesis and an increase of oxidative metabolism. Adaptation of the mt phenotype during differentiation is reflected by changes in the distribution of the mitochondrial network as well as marked alterations of gene expression and organization of the oxidative phosphorylation system (OXPHOS). Distinct differences in the supramolecular organization forms of cytochrome c oxidase (COX) were detected using 2D blue native (BN)-PAGE analysis. Most remarkably we observed a significant increase in the abundance of OXPHOS supercomplexes in mitochondria, emphasizing the change of the mitochondrial phenotype during adipogenic differentiation

Down-Regulation of HtrA1 Activates the Epithelial-Mesenchymal Transition and ATM DNA Damage Response Pathways

Expression of the serine protease HtrA1 is decreased or abrogated in a variety of human primary cancers, and higher levels of HtrA1 expression are directly related to better response to chemotherapeutics. However, the precise mechanisms leading to HtrA1 down regulation during malignant transformation are unclear. To investigate HtrA1 gene regulation in breast cancer, we characterized expression in primary breast tissues and seven human breast epithelial cell lines, including two non-tumorigenic cell lines. In human breast tissues, HtrA1 expression was prominent in normal ductal glands. In DCIS and in invasive cancers, HtrA1 expression was greatly reduced or lost entirely. HtrA1 staining was also reduced in all of the human breast cancer cell lines, compared with the normal tissue and non-tumorigenic cell line controls. Loss of HtrA1 gene expression was attributable primarily to epigenetic silencing mechanisms, with different mechanisms operative in the various cell lines. To mechanistically examine the functional consequences of HtrA1 loss, we stably reduced and/or overexpressed HtrA1 in the non-tumorigenic MCF10A cell line. Reduction of HtrA1 levels resulted in the epithelial-to-mesenchymal transition with acquisition of mesenchymal phenotypic characteristics, including increased growth rate, migration, and invasion, as well as expression of mesenchymal biomarkers. A concomitant decrease in expression of epithelial biomarkers and all microRNA 200 family members was also observed. Moreover, reduction of HtrA1 expression resulted in activation of the ATM and DNA damage response, whereas overexpression of HtrA1 prevented this activation. Collectively, these results suggest that HtrA1 may function as a tumor suppressor by controlling the epithelial-to-mesenchymal transition, and may function in chemotherapeutic responsiveness by mediating DNA damage response pathways

Acellular Bone Marrow Extracts Significantly Enhance Engraftment Levels of Human Hematopoietic Stem Cells in Mouse Xeno-Transplantation Models

Hematopoietic stem cells (HSC) derived from cord blood (CB), bone marrow (BM), or mobilized peripheral blood (PBSC) can differentiate into multiple lineages such as lymphoid, myeloid, erythroid cells and platelets. The local microenvironment is critical to the differentiation of HSCs and to the preservation of their phenotype in vivo. This microenvironment comprises a physical support supplied by the organ matrix as well as tissue specific cytokines, chemokines and growth factors. We investigated the effects of acellular bovine bone marrow extracts (BME) on HSC in vitro and in vivo. We observed a significant increase in the number of myeloid and erythroid colonies in CB mononuclear cells (MNC) or CB CD34+ cells cultured in methylcellulose media supplemented with BME. Similarly, in xeno-transplantation experiments, pretreatment with BME during ex-vivo culture of HSCs induced a significant increase in HSC engraftment in vivo. Indeed, we observed both an increase in the number of differentiated myeloid, lymphoid and erythroid cells and an acceleration of engraftment. These results were obtained using CB MNCs, BM MNCs or CD34+ cells, transplanted in immuno-compromised mice (NOD/SCID or NSG). These findings establish the basis for exploring the use of BME in the expansion of CB HSC prior to HSC Transplantation. This study stresses the importance of the mechanical structure and soluble mediators present in the surrounding niche for the proper activity and differentiation of stem cells

The Cytosolic Protein G0S2 Maintains Quiescence in Hematopoietic Stem Cells

Bone marrow hematopoietic stem cells (HSCs) balance proliferation and differentiation by integrating complex transcriptional and post-translational mechanisms regulated by cell intrinsic and extrinsic factors. We found that transcripts of G0/G1 switch gene 2 (G0S2) are enriched in lineage− Sca-1+ c-kit+ (LSK) CD150+ CD48− CD41− cells, a population highly enriched for quiescent HSCs, whereas G0S2 expression is suppressed in dividing LSK CD150+ CD48− cells. Gain-of-function analyses using retroviral expression vectors in bone marrow cells showed that G0S2 localizes to the mitochondria, endoplasmic reticulum, and early endosomes in hematopoietic cells. Co-transplantation of bone marrow cells transduced with the control or G0S2 retrovirus led to increased chimerism of G0S2-overexpressing cells in femurs, although their contribution to the blood was reduced. This finding was correlated with increased quiescence in G0S2-overexpressing HSCs (LSK CD150+ CD48−) and progenitor cells (LS−K). Conversely, silencing of endogenous G0S2 expression in bone marrow cells increased blood chimerism upon transplantation and promoted HSC cell division, supporting an inhibitory role for G0S2 in HSC proliferation. A proteomic study revealed that the hydrophobic domain of G0S2 interacts with a domain of nucleolin that is rich in arginine-glycine-glycine repeats, which results in the retention of nucleolin in the cytosol. We showed that this cytosolic retention of nucleolin occurs in resting, but not proliferating, wild-type LSK CD150+ CD48− cells. Collectively, we propose a novel model of HSC quiescence in which elevated G0S2 expression can sequester nucleolin in the cytosol, precluding its pro-proliferation functions in the nucleolus