Management and Service-aware Networking Architectures (MANA) for Future Internet Position Paper: System Functions, Capabilities and Requirements

Future Internet (FI) research and development threads have recently been gaining momentum all over the world and as such the international race to create a new generation Internet is in full swing: GENI, Asia Future Internet, Future Internet Forum Korea, European Union Future Internet Assembly (FIA). This is a position paper identifying the research orientation with a time horizon of 10 years, together with the key challenges for the capabilities in the Management and Service-aware Networking Architectures (MANA) part of the Future Internet (FI) allowing for parallel and federated Internet(s)

Self-management of context-aware overlay ambient networks

Ambient Networks (ANs) are dynamically changing and heterogeneous as they consist of potentially large numbers of independent, heterogeneous mobile nodes, with spontaneous topologies that can logically interact with each other to share a common control space, known as the Ambient Control Space. ANs are also flexible i.e. they can compose and decompose dynamically and automatically, for supporting the deployment of cross-domain (new) services. Thus, the AN architecture must be sophisticatedly designed to support such high level of dynamicity, heterogeneity and flexibility. We advocate the use of service specific overlay networks in ANs, that are created on-demand according to specific service requirements, to deliver, and to automatically adapt services to the dynamically changing user and network context. This paper presents a self-management approach to create, configure, adapt, contextualise, and finally teardown service specific overlay networks

Hox Genes, Digit Identities and the Theropod/Bird Transition

Vargas and Fallon (2005) propose that Hox gene expression patterns indicate that the most anterior digit in bird wings is homologous to digit 1 rather than to digit 2 in other amniotes. This interpretation is based on the presence of Hoxd13 expression in combination with the absence of Hoxd12 expression in the second digit condensation from which this digit develops (the first condensation is transiently present). This is a pattern that is similar to that in the developing digit 1 of the chicken foot and the mouse hand and foot. They have tested this new hypothesis by analysing Hoxd12 and Hoxd13 expression patterns in two polydactylous chicken mutants, Silkie and talpid2. They conclude that the data supports the notion that the most anterior remaining digit of the bird wing is homologous to digit 1 in other amniotes either in a standard phylogenetic sense, or alternatively in a (limited) developmental sense in agreement with the Frameshift Hypothesis of Wagner and Gautier (1997, i.e. that the developmental pathway is homologous to the one that leads to a digit 1 identity in other amniotes, albeit that it occurs in the second instead of the first digit condensation). We argue that the Hoxd12 and Hoxd13 expression patterns found for these and other limb mutants do not allow distinguishing between the hypothesis of Vargas and Fallon (2005) and the alternative one, i.e. the most anterior digit in bird wings is homologous to digit 2 in other amniotes, in a phylogenetic, or developmental sense. Therefore, at the moment the data on limb mutants does not present a challenge to the hypothesis, based on other developmental data (Holmgren 55, Hinchliffe 484, Burke and Feduccia 497, Kundrat et al. 2002, Larsson and Wagner 2002, Feduccia and Nowicki 2002), that the digits of bird wings are homologous to digits 2,3,4 in amniotes. We recommend further testing of the hypothesis by comparing Hoxd expression patterns in different taxa

Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques

Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We investigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components in human atherosclerotic plaques (n = 30) and in uninvolved arterial specimens (n = 11). We studied members of all three MMP classes (interstitial collagenase, MMP-1; gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immunocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD gelatinase, stromelysin, and interstitial collagenase. However, the mere presence of MMP does not establish their catalytic capacity, as the zymogens lack activity, and TIMPs may block activated MMPs. All plaque extracts contained activated forms of gelatinases determined zymographically and by degradation of 3H-collagen type IV. To test directly whether atheromata actually contain active matrix-degrading enzymes in situ, we devised a method which allows the detection and microscopic localization of MMP enzymatic activity directly in tissue sections. In situ zymography revealed gelatinolytic and caseinolytic activity in frozen sections of atherosclerotic but not of uninvolved arterial tissues. The MMP inhibitors, EDTA and 1,10-phenanthroline, as well as recombinant TIMP-1, reduced these activities which colocalized with regions of increased immunoreactive MMP expression, i.e., the shoulders, core, and microvasculature of the plaques. Focal overexpression of activated MMP may promote destabilization and complication of atherosclerotic plaques and provide novel targets for therapeutic intervention

On the initiation of sustained slip-weakening ruptures by localized stresses

Numerical simulations of dynamic earthquake rupture require an artificial initiation procedure, if they are not integrated in long-term earthquake cycle simulations. A widely applied procedure involves an ‘overstressed asperity’, a localized region stressed beyond the static frictional strength. The physical properties of the asperity (size, shape and overstress) may significantly impact rupture propagation. In particular, to induce a sustained rupture the asperity size needs to exceed a critical value. Although criteria for estimating the critical nucleation size under linear slip-weakening friction have been proposed for 2-D and 3-D problems based on simplifying assumptions, they do not provide general rules for designing 3-D numerical simulations. We conduct a parametric study to estimate parameters of the asperity that minimize numerical artefacts (e.g. changes of rupture shape and speed, artificial supershear transition, higher slip-rate amplitudes). We examine the critical size of square, circular and elliptical asperities as a function of asperity overstress and background (off-asperity) stress. For a given overstress, we find that asperity area controls rupture initiation while asperity shape is of lesser importance. The critical area obtained from our numerical results contrasts with published theoretical estimates when background stress is low. Therefore, we derive two new theoretical estimates of the critical size under low background stress while also accounting for overstress. Our numerical results suggest that setting the asperity overstress and area close to their critical values eliminates strong numerical artefacts even when the overstress is large. We also find that properly chosen asperity size or overstress may significantly shorten the duration of the initiation. Overall, our results provide guidelines for determining the size of the asperity and overstress to minimize the effects of the forced initiation on the subsequent spontaneous rupture propagation

Sexual Dimorphism in the Prenatal Digit Ratio (2D:4D)

The second to fourth digit ratio (2D:4D) is smaller in human males than in females and hence this trait is sexually dimorphic. The digit ratio is thought to be established during early prenatal development under the influence of prenatal sex hormones. However, the general assumption of early establishment has hardly been studied. In our study, we analyzed the 2D:4D ratio in 327 deceased human fetuses. We measured digit lengths in 169 male and 158 female fetuses ranging from 14 to 42 weeks old. Our results showed a slight, but significant, sexual dimorphism in the expected direction, i.e., females had, on average, a ratio of 0.924 and males a ratio of 0.916. There was no significant relationship with the presence or absence of minor and major or single and multiple congenital abnormalities. There was a minimal, but significant difference between digit ratios based on digit lengths including and excluding the non-bony fingertip with the values being strongly correlated (r = .98). The prenatal 2D:4D ratio was lower than has thus far been reported for children and adults both for males and females. The extent of the sexual dimorphism in fetuses was similar to that found for children, but lower than for adults. The 2D:4D ratio, thus, seems to increase after birth in both men and women, with the second digit growing faster than the fourth digit (positive allometric growth of digit two) and perhaps more so in women than in men. Therefore, the sexual dimorphism is probably determined by prenatal as well as by postnatal developmental processes

Exogenously added GPI-anchored tissue inhibitor of matrix metal loproteinase-1 (TIMP-1) displays enhanced and novel biological activities

The family of tissue inhibitors of metalloproteinases (TIMPs) exhibits diverse physiological/biological functions including the inhibition of active matrix metalloproteinases, regulation of proMMP activation, cell growth, and the modulation of angiogenesis. TIMP-1 is a secreted protein that can be detected on the cell surface through its interaction with surface proteins. The diverse biological functions of TIMP-1 are thought to lie, in part, in the kinetics of TIMP-1/MMP/surface protein interactions. Proteins anchored by glycoinositol phospholipids (GPIs), when purified and added to cells in vitro, are incorporated into their surface membranes. A GPI anchor was fused to TIMP-1 to generate a reagent that could be added directly to cell membranes and thus focus defined concentrations of TIMP-1 protein on any cell surface independent of protein-protein interaction. Unlike native TIMP-1, exogenously added GPI-anchored TIMP-1 protein effectively blocked release of MMP-2 and MMP-9 from osteosarcoma cells. TIMP-1-GP1 was a more effective modulator of migration and proliferation than TIMP-1. While control hTIMP-1 protein did not significantly affect migration of primary microvascular endothelial cells at the concentrations tested, the GPI-anchored TIMP-1 protein showed a pronounced suppression of endothelial cell migration in response to bFGF. In addition, TIMP-1-GPI was more effective at inducing microvascular endothelial proliferation. In contrast, fibroblast proliferation was suppressed by the agent. Reagents based on this method should assist in the dissection of the protease cascades and activities involved in TIMP biology. Membrane-fixed TIMP-1 may represent a more effective version of the protein for use in therapeutic expression

Increased prevalence of abnormal vertebral patterning in fetuses and neonates with trisomy 21

Purpose: To assess the prevalence of an abnormal number of ribs in a cohort of fetuses and neonates with trisomy 21 and compare this with a subgroup of fetuses without anomalies. Materials and methods: Radiographs of 67 deceased fetuses, neonates, and infants that were diagnosed with trisomy 21 were reviewed. Terminations of pregnancy were included. The control group was composed of 107 deceased fetuses, neonates, and infants without known chromosomal abnormalities, structural malformations, infections or placental pathology. Cases in which the number of thoracic ribs or presence of cervical ribs could not be reliably assessed were excluded. The literature concerning vertebral patterning in trisomy 21 cases and healthy subjects was reviewed. Results: Absent or rudimentary 12th thoracic ribs were found in 26/54 (48.1%) cases with trisomy 21 and cervical ribs were present in 27/47 (57.4%) cases. This prevalence was significantly higher compared to controls (28/100, 28.0%, Χ2(1) = 6.252, p = .012 and 28/97, 28.9%, Χ2(1) = 10.955, p < .001, respectively). Conclusions: Rudimentary or absent 12th thoracic ribs and cervical ribs are significantly more prevalent in deceased fetuses and infants with trisomy 21

Containing COVID: the establishment and management of a COVID-19 ward in an adult psychiatric hospital

BACKGROUND: As the coronavirus disease 2019 (COVID-19) epidemic in the UK emerged and escalated, clinicians working in mental health in-patient facilities faced unique medical, psychiatric and staffing challenges in managing and containing the impact of the virus and, in the context of legislation, enforcing social distancing. AIMS: To describe (a) the steps taken by one mental health hospital to establish a COVID-19 isolation ward for adult psychiatric in-patients and (b) how staff addressed the challenges that emerged over the period March to June 2020. METHOD: A descriptive study detailing the processes involved in changing the role of the ward and the measures taken to address the various challenges that arose. Brief clinical cases of two patients are included for illustrative purposes. RESULTS: We describe the achievements, lessons learned and outcomes of the process of repurposing a mental health triage ward into a COVID-19 isolation facility, including the impact on staff. Flexibility, rapid problem-solving and close teamwork were essential. Some of the changes made will be sustained on the ward in our primary role as a triage ward. CONCLUSIONS: Although the challenges faced were difficult, the legacy they have left is that of a range of improvements in patient care and the working environment