409 research outputs found

    Recommender Thermometer for Measuring the Preparedness for Flood Resilience Management

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    A range of various thermometers and similar scales are employed in different human and resilience management activities: Distress Thermometer, Panic Thermometer, Fear Thermometer, fire danger rating, hurricane scales, earthquake scales (Richter Magnitude Scale, Mercalli Scale), Anxiety Thermometer, Help Thermometer, Problem Thermometer, Emotion Thermometer, Depression Thermometer, the Torino scale (assessing asteroid/comet impact prediction), Excessive Heat Watch, etc. Extensive financing of the preparedness for flood resilience management with overheated full-scale resilience management might be compared to someone ill running a fever of 41°C. As the financial crisis hits and resilience management financing cools down it reminds a sick person whose body temperature is too low. The degree indicated by the Recommender Thermometer for Measuring the Preparedness for Flood Resilience Management with a scale between Tmin=34,0° and Tmax=42,0° shows either cool or overheated preparedness for flood resilience management. The formalized presentation of this research shows how changes in the micro, meso and macro environment of resilience management and the extent to which the goals pursued by various interested parties are met cause corresponding changes in the “temperature” of the preparedness for resilience management. Global innovative aspects of the Recommender Thermometer developed by the authors of this paper are, primarily, its capacity to measure the “temperature” of the preparedness for flood resilience management automatically, to compile multiple alternative recommendations (preparedness for floods, including preparing your home for floods, taking precautions against a threat of floods, retrofitting for flood-prone areas, checking your house insurance; preparedness for bushfires, preparedness for cyclones, preparedness for severe storms, preparedness for heat waves, etc.) customised for a specific user, to perform multiple criteria analysis of the recommendations, and to select the ten most rational ones for that user. Across the world, no other system offers these functions yet. The Recommender Thermometer was developed and fine-tuned in the course of the Android (Academic Network for Disaster Resilience to Optimise educational Development) project

    Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

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    Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

    Fiber Mediated Receptor Masking in Non-Infected Bystander Cells Restricts Adenovirus Cell Killing Effect but Promotes Adenovirus Host Co-Existence

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    The basic concept of conditionally replicating adenoviruses (CRAD) as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI), and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses

    Linear Streptomyces plasmids form superhelical circles through interactions between their terminal proteins

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    Linear chromosomes and linear plasmids of Streptomyces possess covalently bound terminal proteins (TPs) at the 5′ ends of their telomeres. These TPs are proposed to act as primers for DNA synthesis that patches the single-stranded gaps at the 3′ ends during replication. Most (‘archetypal’) Streptomyces TPs (designated Tpg) are highly conserved in size and sequence. In addition, there are a number of atypical TPs with heterologous sequences and sizes, one of which is Tpc that caps SCP1 plasmid of Streptomyces coelicolor. Interactions between the TPs on the linear Streptomyces replicons have been suggested by electrophoretic behaviors of TP-capped DNA and circular genetic maps of Streptomyces chromosomes. Using chemical cross-linking, we demonstrated intramolecular and intermolecular interactions in vivo between Tpgs, between Tpcs and between Tpg and Tpc. Interactions between the chromosomal and plasmid telomeres were also detected in vivo. The intramolecular telomere interactions produced negative superhelicity in the linear DNA, which was relaxed by topoisomerase I. Such intramolecular association between the TPs poses a post-replicational complication in the formation of a pseudo-dimeric structure that requires resolution by exchanging TPs or DNA

    Enteric Species F Human Adenoviruses use Laminin-Binding Integrins as Co-Receptors for Infection of Ht-29 Cells

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    The enteric species F human adenovirus types 40 and 41 (HAdV-40 and -41) are the third most common cause of infantile gastroenteritis in the world. Knowledge about HAdV-40 and -41 cellular infection is assumed to be fundamentally different from that of other HAdVs since HAdV-40 and -41 penton bases lack the aV-integrin-interacting RGD motif. This motif is used by other HAdVs mainly for internalization and endosomal escape. We hypothesised that the penton bases of HAdV-40 and -41 interact with integrins independently of the RGD motif. HAdV-41 transduction of a library of rodent cells expressing specific human integrin subunits pointed to the use of laminin-binding alpha 2-, alpha 3- and alpha 6- containing integrins as well as other integrins as candidate co-receptors. Specific laminins prevented internalisation and infection, and recombinant, soluble HAdV-41 penton base proteins prevented infection of human intestinal HT-29 cells. Surface plasmon resonance analysis demonstrated that HAdV-40 and -41 penton base proteins bind to alpha 6-containing integrins with an affinity similar to that of previously characterised penton base:integrin interactions. With these results, we propose that laminin-binding integrins are co-receptors for HAdV-40 and -41

    Prescribing where there is a comorbid presentation of anxiety and depression: a case study

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    This case study considers a complex presentation of anxiety with associated depression, and describes a stepped approach to care and treatment, as advocated by the National Institute for Health and Clinical Excellence. The classification of mental disorders is referred to in the case study. Mixed anxiety and depression is a common presentation in primary care, characterised by a mix of anxiety and depressive symptoms without clear prominence of any one type and the presence of one or more physical symptoms that are present for more than six months. Anxiolytic medication is often used as a first aid measure in anxiety, and is very useful and appropriate for this. However, it is quite difficult to assess the longer-term effectiveness of these drugs, as anxiety tends to vary for reasons other than drug treatment, such as external pressures. There is good evidence to support the efficacy of psychological interventions in anxiety spectrum disorders. Consequently, self help and cognitive behaviour therapy may be the first line of treatment for less severe cases and can be used in conjunction with medication

    4D synchrotron X-ray tomographic quantification of the transition from cellular to dendrite growth during directional solidification

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    Solidification morphology directly impacts the mechanical properties of materials; hence many models of the morphological evolution of dendritic structures have been formulated. However, there is a paucity of validation data for directional solidification models, especially the direct observations of metallic alloys, both for cellular and dendritic structures. In this study, we performed 4D synchrotron X-ray tomographic imaging (three spatial directions plus time), to study the transition from cellular to a columnar dendritic morphology and the subsequent growth of columnar dendrite in a temperature gradient stage. The cellular morphology was found to be highly complex, with frequent lateral bridging. Protrusions growing out of the cellular front with the onset of morphological instabilities were captured, together with the subsequent development of these protrusions into established dendrites. Other mechanisms affecting the solidification microstructure, including dendrite fragmentation/pinch-off were also captured and the quantitative results were compared to proposed mechanisms. The results demonstrate that 4D imaging can provide new data to both inform and validate solidification models

    Effects of oil and global environmental drivers on two keystone marine invertebrates

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    Ocean warming (OW) and acidification (OA) are key features of global change and are predicted to have negative consequences for marine species and ecosystems. At a smaller scale increasing oil and gas activities at northern high latitudes could lead to greater risk of petroleum pollution, potentially exacerbating the effects of such global stressors. However, knowledge of combined effects is limited. This study employed a scenario-based, collapsed design to investigate the impact of one local acute stressor (North Sea crude oil) and two chronic global drivers (pH for OA and temperature for OW), alone or in combination on aspects of the biology of larval stages of two key invertebrates: the northern shrimp (Pandalus borealis) and the green sea urchin (Strongylocentrotus droebachiensis). Both local and global drivers had negative effects on survival, development and growth of the larval stages. These effects were species- and stage-dependent. No statistical interactions were observed between local and global drivers and the combined effects of the two drivers were approximately equal to the sum of their separate effects. This study highlights the importance of adjusting regulation associated with oil spill prevention to maximize the resilience of marine organisms to predicted future global conditions
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