233 research outputs found
Corporate sustainability reporting index and baseline data for the cruise industry
Sustainability policies and corporate reports demonstrate the impacts cruise companies acknowledge as their responsibility, and the actions put in place to address them. This paper develops a corporate social responsibility index based on the Global Reporting Initiative, with industry specific additions including labor and human rights, health and safety, and environmental and economic aspects. Companies disclose more management than performance data, which is typical of early stages of development. Companies disclosing less information focus on soft indicators which are easy to mimic and demonstrate posturing. Items disclosed tend to be marginal to the core of the business, have a positive economic impact or pre-empt sector regulation. Reports echo the voice of the corporations and not the demands of stakeholders. Institutional isomorphism has not influenced a homogenization in reporting, with only the largest firms reporting at this stage
Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes
Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans
Hierarchy measure for complex networks
Nature, technology and society are full of complexity arising from the
intricate web of the interactions among the units of the related systems (e.g.,
proteins, computers, people). Consequently, one of the most successful recent
approaches to capturing the fundamental features of the structure and dynamics
of complex systems has been the investigation of the networks associated with
the above units (nodes) together with their relations (edges). Most complex
systems have an inherently hierarchical organization and, correspondingly, the
networks behind them also exhibit hierarchical features. Indeed, several papers
have been devoted to describing this essential aspect of networks, however,
without resulting in a widely accepted, converging concept concerning the
quantitative characterization of the level of their hierarchy. Here we develop
an approach and propose a quantity (measure) which is simple enough to be
widely applicable, reveals a number of universal features of the organization
of real-world networks and, as we demonstrate, is capable of capturing the
essential features of the structure and the degree of hierarchy in a complex
network. The measure we introduce is based on a generalization of the m-reach
centrality, which we first extend to directed/partially directed graphs. Then,
we define the global reaching centrality (GRC), which is the difference between
the maximum and the average value of the generalized reach centralities over
the network. We investigate the behavior of the GRC considering both a
synthetic model with an adjustable level of hierarchy and real networks.
Results for real networks show that our hierarchy measure is related to the
controllability of the given system. We also propose a visualization procedure
for large complex networks that can be used to obtain an overall qualitative
picture about the nature of their hierarchical structure.Comment: 29 pages, 9 figures, 4 table
Medical countermeasures for national security: a new government role in the pharmaceuticalization of society
How do governments contribute to the pharmaceuticalization of society? Whilst the pivotal role of industry is extensively documented, this article shows that governments too are accelerating, intensifying and opening up new trajectories of pharmaceuticalization in society. Governments are becoming more deeply invested in pharmaceuticals because their national security strategies now aspire to defend populations against health-based threats like bioterrorism and pandemics. To counter those threats, governments are acquiring and stockpiling a panoply of ‘medical countermeasures’ such as antivirals, next-generation vaccines, antibiotics and anti-toxins. More than that, governments are actively incentivizing the development of many new medical countermeasures – principally by marshaling the state's unique powers to introduce exceptional measures in the name of protecting national security. At least five extraordinary policy interventions have been introduced by governments with the aim of stimulating the commercial development of novel medical countermeasures: (1) allocating earmarked public funds, (2) granting comprehensive legal protections to pharmaceutical companies against injury compensation claims, (3) introducing bespoke pathways for regulatory approval, (4) instantiating extraordinary emergency use procedures allowing for the use of unapproved medicines, and (5) designing innovative logistical distribution systems for mass drug administration outside of clinical settings. Those combined efforts, the article argues, are spawning a new, government-led and quite exceptional medical countermeasure regime operating beyond the conventional boundaries of pharmaceutical development and regulation. In the first comprehensive analysis of the pharmaceuticalization dynamics at play in national security policy, this article unearths the detailed array of policy interventions through which governments too are becoming more deeply imbricated in the pharmaceuticalization of society
Medical countermeasures for national security: a new government role in the pharmaceuticalization of society
How do governments contribute to the pharmaceuticalization of society? Whilst the pivotal role of industry is extensively documented, this article shows that governments too are accelerating, intensifying and opening up new trajectories of pharmaceuticalization in society. Governments are becoming more deeply invested in pharmaceuticals because their national security strategies now aspire to defend populations against health-based threats like bioterrorism and pandemics. To counter those threats, governments are acquiring and stockpiling a panoply of ‘medical countermeasures’ such as antivirals, next-generation vaccines, antibiotics and anti-toxins. More than that, governments are actively incentivizing the development of many new medical countermeasures – principally by marshaling the state's unique powers to introduce exceptional measures in the name of protecting national security. At least five extraordinary policy interventions have been introduced by governments with the aim of stimulating the commercial development of novel medical countermeasures: (1) allocating earmarked public funds, (2) granting comprehensive legal protections to pharmaceutical companies against injury compensation claims, (3) introducing bespoke pathways for regulatory approval, (4) instantiating extraordinary emergency use procedures allowing for the use of unapproved medicines, and (5) designing innovative logistical distribution systems for mass drug administration outside of clinical settings. Those combined efforts, the article argues, are spawning a new, government-led and quite exceptional medical countermeasure regime operating beyond the conventional boundaries of pharmaceutical development and regulation. In the first comprehensive analysis of the pharmaceuticalization dynamics at play in national security policy, this article unearths the detailed array of policy interventions through which governments too are becoming more deeply imbricated in the pharmaceuticalization of society
ReRep: Computational detection of repetitive sequences in genome survey sequences (GSS)
<p>Abstract</p> <p>Background</p> <p>Genome survey sequences (GSS) offer a preliminary global view of a genome since, unlike ESTs, they cover coding as well as non-coding DNA and include repetitive regions of the genome. A more precise estimation of the nature, quantity and variability of repetitive sequences very early in a genome sequencing project is of considerable importance, as such data strongly influence the estimation of genome coverage, library quality and progress in scaffold construction. Also, the elimination of repetitive sequences from the initial assembly process is important to avoid errors and unnecessary complexity. Repetitive sequences are also of interest in a variety of other studies, for instance as molecular markers.</p> <p>Results</p> <p>We designed and implemented a straightforward pipeline called ReRep, which combines bioinformatics tools for identifying repetitive structures in a GSS dataset. In a case study, we first applied the pipeline to a set of 970 GSSs, sequenced in our laboratory from the human pathogen <it>Leishmania braziliensis</it>, the causative agent of leishmaniosis, an important public health problem in Brazil. We also verified the applicability of ReRep to new sequencing technologies using a set of 454-reads of an <it>Escheria coli</it>. The behaviour of several parameters in the algorithm is evaluated and suggestions are made for tuning of the analysis.</p> <p>Conclusion</p> <p>The ReRep approach for identification of repetitive elements in GSS datasets proved to be straightforward and efficient. Several potential repetitive sequences were found in a <it>L. braziliensis </it>GSS dataset generated in our laboratory, and further validated by the analysis of a more complete genomic dataset from the EMBL and Sanger Centre databases. ReRep also identified most of the <it>E. coli </it>K12 repeats prior to assembly in an example dataset obtained by automated sequencing using 454 technology. The parameters controlling the algorithm behaved consistently and may be tuned to the properties of the dataset, in particular to the length of sequencing reads and the genome coverage. ReRep is freely available for academic use at <url>http://bioinfo.pdtis.fiocruz.br/ReRep/</url>.</p
A selective cyclic integrin antagonist blocks the integrin receptors α(v)β(3 )and α(v)β(5 )and inhibits retinal pigment epithelium cell attachment, migration and invasion
BACKGROUND: Proliferative vitreoretinopathy (PVR) is a leading cause of blindness after failed retinal reattachment surgery. PVR is characterized by the proliferation, migration and contraction of retinal pigmented epithelial cells (RPE), and these cellular responses are influenced by the expression and function of integrin receptors. The effect of a cyclic integrin antagonist containing the amino acid sequence Arg-Gly-Asp-D-Phe-Val (RGDfV), specific for the integrin receptors α(v)β(3 )and α(v)β(5), was investigated on basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), and serum induced human RPE proliferation, migration, invasion and attachment to the extracellular matrix. Furthermore, the effects of bFGF and PDGF-BB regulated expression of integrins α(v)β(3 )and α(v)β(5 )on RPE cells was examined. METHODS: The effect of a cyclic integrin antagonist and a control peptide (0.01 μg/ml to 300 μg/ml) was investigated on serum or cytokine (bFGF or PDGF-BB pretreatment) induced human fetal RPE cell proliferation by H(3)-thymidine uptake. The effect of the cyclic integrin antagonist on RPE cell attachment onto different extracellular matrices (laminin, collagen IV, fibronectin), RPE cell invasion stimulated by PDGF-BB or serum, and migration stimulated by PDGF-BB, vascular endothelial growth factor (VEGF) or serum was explored. PDGF-BB and bFGF modulation of the integrin receptors α(v)β(3 )and α(v)β(5 )was evaluated by flow cytometry. RESULTS: The integrin antagonist did not inhibit DNA synthesis stimulated by serum, bFGF, or PDGF-BB treatment. RPE attachment onto fibronectin was inhibited in a concentration range of 1–10 μg/ml (p < 0.05). Attachment of the RPE cells onto collagen IV and laminin was inhibited in a range of 3–10 μg/ml (p < 0.05). Serum and PDGF-BB stimulated migration was inhibited by the cyclic integrin antagonist in a concentration range of 1–10 μg/ml (p < 0.05). Furthermore, the cyclic integrin antagonist inhibited PDGF-BB stimulated RPE cell invasion through fibronectin (3μg/ml: 66% inhibition, p < 0.001). In each of these experiments, the control peptides had no significant effects. PDGF-BB and bFGF pretreatment of RPE cells increased the expression of integrin receptors α(v)β(3 )(bFGF: 1.9 fold, PDGF-BB: 2.3 fold) and α(v)β(5 )(bFGF: 2.9 fold, PDGF-BB: 1.5 fold). CONCLUSION: A selective inhibition of the integrin receptors α(v)β(3 )and α(v)β(5 )through a cyclic integrin antagonist is able to inhibit RPE cell attachment, migration and invasion. Since these steps are of importance for the progression of PVR, a cyclic integrin antagonist should be further evaluated for the treatment of this disease
The α-Hemolysin nanopore transduction detector – single-molecule binding studies and immunological screening of antibodies and aptamers
Retention of Memory through Metamorphosis: Can a Moth Remember What It Learned As a Caterpillar?
Insects that undergo complete metamorphosis experience enormous changes in both morphology and lifestyle. The current study examines whether larval experience can persist through pupation into adulthood in Lepidoptera, and assesses two possible mechanisms that could underlie such behavior: exposure of emerging adults to chemicals from the larval environment, or associative learning transferred to adulthood via maintenance of intact synaptic connections. Fifth instar Manduca sexta caterpillars received an electrical shock associatively paired with a specific odor in order to create a conditioned odor aversion, and were assayed for learning in a Y choice apparatus as larvae and again as adult moths. We show that larvae learned to avoid the training odor, and that this aversion was still present in the adults. The adult aversion did not result from carryover of chemicals from the larval environment, as neither applying odorants to naïve pupae nor washing the pupae of trained caterpillars resulted in a change in behavior. In addition, we report that larvae trained at third instar still showed odor aversion after two molts, as fifth instars, but did not avoid the odor as adults, consistent with the idea that post-metamorphic recall involves regions of the brain that are not produced until later in larval development. The present study, the first to demonstrate conclusively that associative memory survives metamorphosis in Lepidoptera, provokes intriguing new questions about the organization and persistence of the central nervous system during metamorphosis. Our results have both ecological and evolutionary implications, as retention of memory through metamorphosis could influence host choice by polyphagous insects, shape habitat selection, and lead to eventual sympatric speciation
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