Developmental components of resting ventilation among high- and low-altitude Andean children and adults

This paper evaluates the age-associated changes of resting ventilation of 115 high- and low-altitude Aymara subjects, of whom 61 were from the rural Aymara village of Ventilla situated at an average altitude of 4,200 m and 54 from the rural village of Caranavi situated at an average altitude of 900 m. Comparison of the age patterns of resting ventilation suggests the following conclusions: 1) the resting ventilation (ml/kg/min) of high-altitude natives is markedly higher than that of low-altitude natives; 2) the age decline of ventilation is similar in both lowlanders and highlanders, but the starting point and therefore the age decline are much higher at high altitude; 3) the resting ventilation that characterizes high-altitude Andean natives is developmentally expressed in the same manner as it is at low altitude; and 4) the resting ventilation (ml/kg/min) of Aymara high-altitude natives is between 40–80% lower than that of Tibetans. Am J Phys Anthropol 109:295–301, 1999. © 1999 Wiley-Liss, Inc.

Bone tissue engineering : from bench to bedside - Review article

The drive to develop bone grafts for the filling of major gaps in the skeletal structure has led to a major research thrust towards developing biomaterials for bone engineering. Unfortunately, from a clinical perspective, the promise of bone tissue engineering which was so vibrant a decade ago has so far failed to deliver the anticipated results of becoming a routine therapeutic application in reconstructive surgery. Here we describe the analysis of long-term bone regeneration studies in preclinical animal models, exploiting methods of micro- and nano analysis of biodegradable composite scaffolds.

Bone tissue engineering

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. These standard techniques face significant disadvantages. As a result, research has focused on the development of alternative therapeutic concepts aiming to design and engineer unparalleled structural and functional bone grafts. Substantial academic and commercial interest has been sparked in bone engineering methods to stimulate, control and eventually replicate key events of bone regeneration ex vivo. Over the years, this interest has further increased and bone tissue engineering has now become a well-recognized research discipline in the area of regenerative medicine. The following chapter gives an overview of bone tissue engineering principles. It focuses on research related to the combination of scaffolds with multipotent precursor cells, such as bone marrow-derived mesenchymal stem cells or human umbilical cord perivascular cells, and the clinical applications of these tissue engineered bone constructs.

FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer

Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.

Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical-sized segmental tibial bone defects in aged sheep

Mesenchymal progenitor cells (MPCs) represent an attractive cell population for bone tissue engineering. Their special immunological characteristics suggest that MPCs may be used in an allogenic application. The objective of this study was to compare the regenerative potential of autologous vs. allogenic MPCs in an ovine critical-sized segmental defect model. Ovine MPCs were isolated from bone marrow aspirates, expanded and cultured with osteogenic media for two weeks before implantation. Autologous and allogenic transplantation was performed by using the cell-seeded scaffolds, unloaded scaffolds and the application of autologous bone grafts served as control groups (n=6). Bone healing was assessed twelve weeks after surgery by radiology, micro computed tomography, biomechanical testing and histology. Radiology, biomechanical testing and histology revealed no significant difference in bone formation between the autologous and allogenic group. Both cell groups showed more bone formation than the scaffold alone, whereas the biomechanical data showed no significant differences between the cell-groups and the unloaded scaffolds. The results of the study suggest that scaffold based bone tissue engineering using allogenic cells offers the potential for an off the shelf product. Therefore, the results of this study serve as an important baseline for the translation of the assessed concepts into clinical application.

Mechanism based emulation of dynamic simulation models : concept and application in hydrology

Many model-based investigation techniques, such as sensitivity analysis, optimization, and statistical inference, require a large number of model evaluations to be performed at different input and/or parameter values. This limits the application of these techniques to models that can be implemented in computationally efficient computer codes. Emulators, by providing efficient interpolation between outputs of deterministic simulation models, can considerably extend the field of applicability of such computationally demanding techniques. So far, the dominant techniques for developing emulators have been priors in the form of Gaussian stochastic processes (GASP) that were conditioned with a design data set of inputs and corresponding model outputs. In the context of dynamic models, this approach has two essential disadvantages: (i) these emulators do not consider our knowledge of the structure of the model, and (ii) they run into numerical difficulties if there are a large number of closely spaced input points as is often the case in the time dimension of dynamic models. To address both of these problems, a new concept of developing emulators for dynamic models is proposed. This concept is based on a prior that combines a simplified linear state space model of the temporal evolution of the dynamic model with Gaussian stochastic processes for the innovation terms as functions of model parameters and/or inputs. These innovation terms are intended to correct the error of the linear model at each output step. Conditioning this prior to the design data set is done by Kalman smoothing. This leads to an efficient emulator that, due to the consideration of our knowledge about dominant mechanisms built into the simulation model, can be expected to outperform purely statistical emulators at least in cases in which the design data set is small. The feasibility and potential difficulties of the proposed approach are demonstrated by the application to a simple hydrological model.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.

Twitter-archive und die Herausforderungen von "Big Social Data" für die Medien- und Kommunikationswissenschaft

Twitter ist eine besonders nützliche Quelle für Social-Media-Daten: mit dem Twitter-API (dem Application Programming Interface, das einen strukturierten Zugang zu Kommunikationsdaten in standardisierten Formaten bietet) ist es Forschern möglich, mit ein wenig Mühe und ausreichenden technische Ressourcen sehr große Archive öffentlich verbreiteter Tweets zu bestimmten Themen, Interessenbereichen, oder Veranstaltungen aufzubauen. Grundsätzlich liefert das API sehr langen Listen von Hunderten, Tausenden oder Millionen von Tweets und den Metadaten zu diesen Tweets; diese Daten können dann auf verschiedentlichste Weise extrahiert, kombiniert, und visualisiert werden, um die Dynamik der Social-Media-Kommunikation zu verstehen. Diese Forschung ist häufig um althergebrachte Fragestellungen herum aufgebaut, wird aber in der Regel in einem bislang unbekannt großen Maßstab durchgeführt. Die Projekte von Medien- und Kommunikationswissenschaftlern wie Papacharissi und de Fatima Oliveira (2012), Wood und Baughman (2012) oder Lotan et al. (2011) – um nur eine Handvoll der letzten Beispiele zu nennen – sind grundlegend auf Twitterdatensätze aufgebaut, die jetzt routinemäßig Millionen von Tweets und zugehörigen Metadaten umfassen, erfaßt nach einer Vielzahl von Kriterien. Was allen diesen Fällen gemein ist, ist jedoch die Notwendigkeit, neue methodische Wege in der Verarbeitung und Analyse derart großer Datensätze zur medienvermittelten sozialen Interaktion zu gehen.

Graenum Berger papers, undated, (1825)-2002

Contains correspondence, minutes, reports, clippings, manuscripts, research materials, journal articles, photographs and publications; primarily relating to Berger's involvement with Ethiopian Jewry and his efforts to bring about their rescue through the organization he formed, the American Association for Ethiopian Jews. Also contains material from Berger's other interests- his writings, travels through the world and to Israel and Ethiopia, community affiliations, research in Black American Jews, profession as a Jewish social work executive, his commitment to Jewish causes and to Israel. There are also many personal and biographical materials from the numerous long-term friendships and associations he established.

Spiral-Wave Turbulence and Its Control in the Presence of Inhomogeneities in Four Mathematical Models of Cardiac Tissue

Regular electrical activation waves in cardiac tissue lead to the rhythmic contraction and expansion of the heart that ensures blood supply to the whole body. Irregularities in the propagation of these activation waves can result in cardiac arrhythmias, like ventricular tachycardia (VT) and ventricular fibrillation (VF), which are major causes of death in the industrialised world. Indeed there is growing consensus that spiral or scroll waves of electrical activation in cardiac tissue are associated with VT, whereas, when these waves break to yield spiral- or scroll-wave turbulence, VT develops into life-threatening VF: in the absence of medical intervention, this makes the heart incapable of pumping blood and a patient dies in roughly two-and-a-half minutes after the initiation of VF. Thus studies of spiral- and scroll-wave dynamics in cardiac tissue pose important challenges for in vivo and in vitro experimental studies and for in silico numerical studies of mathematical models for cardiac tissue. A major goal here is to develop low-amplitude defibrillation schemes for the elimination of VT and VF, especially in the presence of inhomogeneities that occur commonly in cardiac tissue. We present a detailed and systematic study of spiral- and scroll-wave turbulence and spatiotemporal chaos in four mathematical models for cardiac tissue, namely, the Panfilov, Luo-Rudy phase 1 (LRI), reduced Priebe-Beuckelmann (RPB) models, and the model of ten Tusscher, Noble, Noble, and Panfilov (TNNP). In particular, we use extensive numerical simulations to elucidate the interaction of spiral and scroll waves in these models with conduction and ionic inhomogeneities; we also examine the suppression of spiral- and scroll-wave turbulence by low-amplitude control pulses. Our central qualitative result is that, in all these models, the dynamics of such spiral waves depends very sensitively on such inhomogeneities. We also study two types of control chemes that have been suggested for the control of spiral turbulence, via low amplitude current pulses, in such mathematical models for cardiac tissue; our investigations here are designed to examine the efficacy of such control schemes in the presence of inhomogeneities. We find that a local pulsing scheme does not suppress spiral turbulence in the presence of inhomogeneities; but a scheme that uses control pulses on a spatially extended mesh is more successful in the elimination of spiral turbulence. We discuss the theoretical and experimental implications of our study that have a direct bearing on defibrillation, the control of life-threatening cardiac arrhythmias such as ventricular fibrillation.

The top 100 questions of importance to the future of global agriculture

Despite a significant growth in food production over the past half-century, one of the most important challenges facing society today is how to feed an expected population of some nine billion by the middle of the 20th century. To meet the expected demand for food without significant increases in prices, it has been estimated that we need to produce 70-100 per cent more food, in light of the growing impacts of climate change, concerns over energy security, regional dietary shifts and the Millennium Development target of halving world poverty and hunger by 2015. The goal for the agricultural sector is no longer simply to maximize productivity, but to optimize across a far more complex landscape of production, rural development, environmental, social justice and food consumption outcomes. However, there remain significant challenges to developing national and international policies that support the wide emergence of more sustainable forms of land use and efficient agricultural production. The lack of information flow between scientists, practitioners and policy makers is known to exacerbate the difficulties, despite increased emphasis upon evidence-based policy. In this paper, we seek to improve dialogue and understanding between agricultural research and policy by identifying the 100 most important questions for global agriculture. These have been compiled using a horizon-scanning approach with leading experts and representatives of major agricultural organizations worldwide. The aim is to use sound scientific evidence to inform decision making and guide policy makers in the future direction of agricultural research priorities and policy support. If addressed, we anticipate that these questions will have a significant impact on global agricultural practices worldwide, while improving the synergy between agricultural policy, practice and research. This research forms part of the UK Government's Foresight Global Food and Farming Futures project.