Global function approach in structural analysis: Basic approach, numerical results

The structural response to a given environment is described by the differential equations of motion of deformable bodies. Analytic solutions of such problems for a reasonably large class of structural configurations are not within the realm of the possible. Consequently, the mathematical problem is recast into a numerical problem for solution on the computer. New technology in the space and energy fields led to a growing demand for accurate analysis which at times cannot be met due to the limits set by available budgets for computer time. In response to this need for more efficient numerical analysis, the possibilities of reducing the number of freedoms in the system through a revival of the global function approach were explored

Characterizing cross‐linking within polymeric biomaterials in the SEM by secondary electron hyperspectral imaging

A novel capability built upon secondary electron (SE) spectroscopy provides an enhanced cross‐linking characterization toolset for polymeric biomaterials, with cross‐linking density and variation captured at a multiscale level. The potential of SE spectroscopy for material characterization has been investigated since 1947. The absence of suitable instrumentation and signal processing proved insurmountable barriers to applying SE spectroscopy to biomaterials, and consequently, capturing SE spectra containing cross‐linking information is a new concept. To date, cross‐linking extent is inferred from analytical techniques such as nuclear magnetic resonance (NMR), differential scanning calorimetry, and Raman spectroscopy (RS). NMR provides extremely localized information on the atomic scale and molecular scale, while RS information volume is on the microscale. Other methods for the indirect study of cross‐linking are bulk mechanical averaging methods, such as tensile and compression modulus testing. However, these established averaging methods for the estimation of polymer cross‐linking density are incomplete because they fail to provide information of spatial distributions within the biomaterial morphology across all relevant length scales. The efficacy of the SE spectroscopy capability is demonstrated in this paper by the analysis of poly(glycerol sebacate)‐methacrylate (PGS‐M) at different degrees of methacrylation delivering new insights into PGS‐M morphology

Tensegrity modelling and the high toughness of spider dragline silk

This work establishes a tensegrity model of spider dragline silk. Tensegrity systems are ubiquitous in nature, being able to capture the mechanics of biological shapes through simple and effective modes of deformation via extension and contraction. Guided by quantitative microstructural characterization via air plasma etching and low voltage scanning electron microscopy, we report that this model is able to capture experimentally observed phenomena such as the Poisson effect, tensile stress-strain response, and fibre toughness. This is achieved by accounting for spider silks’ hierarchical organization into microfibrils with radially variable properties. Each fibril is described as a chain of polypeptide tensegrity units formed by crystalline granules operating under compression, which are connected to each other by amorphous links acting under tension. Our results demonstrate, for the first time, that a radial variability in the ductility of tensegrity chains is responsible for high fibre toughness, a defining and desirable feature of spider silk. Based on this model, a discussion about the use of graded tensegrity structures for the optimal design of next-generation biomimetic fibres is presented

The American Preparedness Project: Where the US Public Stands in 2007 on Terrorism, Security, and Disaster Preparedness

Since 2002, the National Center for Disaster Preparedness (NCDP) at Columbia University's Mailman School of Public Health and The Children's Health Fund (CHF), have conducted annual surveys of public attitudes and personal preparedness in the aftermath of the terror attacks of September 11, 2001. Produced in collaboration with the Marist College Institute for Public Opinion (MIPO), each is a random-dial telephone survey of a representative random sample of the US population (selected consistent with demographic characteristics of the most recent available update of the 2000 census). Each survey, including the current, has included a set of questions repeated every year, which generate trend data, as well as questions specific to events current to each study period. Repeated questions ask about confidence in government; willingness and ability to evacuate; extent of personal and family preparedness; and perceptions of community preparedness. All questions are compared across a variety of demographic characteristics including race, age, gender, income, and region, size of community, political affiliation, and education. Further, the responses to select questions, such as awareness of community preparedness plans, are compared across certain groups of respondents (e.g. those having personal and family preparedness plans vs. those who do not). The surveys are developed by NCDP and CHF investigators in conjunction with MIPO, who administers the survey, codes the data, and produces the frequency tables

2P15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment

Elevated fetal hemoglobin (HbF) ameliorates the clinical severity of hemoglobinopathies such as β-thalassemia and sickle cell anemia. Currently, the only curative approach for individuals under chronic transfusion/chelation support therapy is allogeneic stem cell transplantation. However, recent analyses of heritable variations in HbF levels have provided a new therapeutic target for HbF reactivation: the transcriptional repressor BCL11A. Erythroid-specific BCL11A abrogation is now actively being sought as a therapeutic avenue, but the specific impact of such disruption in humans remains to be determined. Although single nucleotide polymorphisms in BCL11A erythroid regulatory elements have been reported, coding mutations are scarcer. It is thus of great interest that patients have recently been described with microdeletions encompassing BCL11A. These patients display neurodevelopmental abnormalities, but whether they show increased HbF has not been reported. We have examined the hematological phenotype, HbF levels, and erythroid BCL11A expression in 3 such patients. Haploinsufficiency of BCL11A induces only partial developmental g-globin silencing. Of greater interest is that a patient with a downstream deletion exhibits reduced BCL11A expression and increased HbF. Novel erythroid-specific regulatory elements in this region may be required for normal erythroid BCL11A expression, whereas loss of separate elements in the developing brain may explain the neurological phenotype

Qualidade de silagens de sorgo com aditivos.

Um delineamento inteiramente ao acaso, com três repetições, foi utilizado para avaliar os efeitos da adição de 0,5% de uréia, de 0,5% de carbonato de cálcio (CaCO3), de 0,5% de uréia mais 0,5% de CaCO3 e de inoculante bacteriano sobre o pH, teores de matéria seca (MS), proteína bruta (PB), fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), hemicelulose, celulose, lignina, carboidratos solúveis, ácido lático e ácido acético sobre a digestibilidade in vitro da matéria seca (DIVMS) de silagens de quatro híbridos de sorgo (BR700, BR701, BR601 e AG2002). Os híbridos ensilados sem a adição de aditivos constituíram o grupo-controle. De cada genótipo foram coletadas três amostras do material original (MOR). Foram utilizados 60 silos de PVC com 10cm de diâmetro interno e 50cm de comprimento, sendo três por tratamento. A abertura dos silos ocorreu depois de 56 dias de fermentação. As silagens contendo CaCO3 e inoculante bacteriano apresentaram, em geral, características muito semelhantes às do controle. A adição de uréia e de uréia mais CaCO3 às silagens resultou em aumento (P<0,05) nos teores de PB. A adição conjunta de uréia e CaCO3 não propiciou aumento (P<0,05) superior ao obtido nas silagens contendo apenas uréia. Uréia pura, como aditivo, pode ser recomendada na ensilagem dos híbridos BR700, BR601 e AG2002

Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1

Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1−/− bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1−/− in MLL—AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia

Specific fibroblast subpopulations and neuronal structures provide local sources of Vegfc-processing components during zebrafish lymphangiogenesis

Proteolytical processing of the growth factor VEGFC through the concerted activity of CCBE1 and ADAMTS3 is required for lymphatic development to occur. How these factors act together in time and space, and which cell types produce these factors is not understood. Here we assess the function of Adamts3 and the related protease Adamts14 during zebrafish lymphangiogenesis and show both proteins to be able to process Vegfc. Only the simultaneous loss of both protein functions results in lymphatic defects identical to vegfc loss-of-function situations. Cell transplantation experiments demonstrate neuronal structures and/or fibroblasts to constitute cellular sources not only for both proteases but also for Ccbe1 and Vegfc. We further show that this locally restricted Vegfc maturation is needed to trigger normal lymphatic sprouting and directional migration. Our data provide a single-cell resolution model for establishing secretion and processing hubs for Vegfc during developmental lymphangiogenesis