Review—Organic Materials for Thermoelectric Energy Generation

Organic semiconductor materials have been promising alternatives to their inorganic counterparts in several electronic applications such as solar cells, light emitting diodes, field effect transistors as well as thermoelectric generators. Their low cost, light weight and flexibility make them appealing in future applications such as foldable electronics and wearable circuits using printing techniques. In this report, we present a mini-review on the organic materials that have been used for thermoelectric energy generation

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p  22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well-tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families

Public Health Emergency Preparedness and Response Communications with Health Care Providers: A Literature Review

<p>Abstract</p> <p>Background</p> <p>Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications.</p> <p>Methods</p> <p>A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs?</p> <p>Results</p> <p>We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience "message overload" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems.</p> <p>Conclusions</p> <p>We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.</p

Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair

Chemotactic activity of extracellular nucleotideson human immune cells.

Purinergic P2 receptors are a class of plasma membrane receptors that are express in many tissues and are ligated by extracellular nucleotides [such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), uridine 5–triphosphate (UTP) and uridine 5–diphosphate (UDP)], which are released as a consequence of cell damage, cell stress, bacterial infection or other noxious stimuli. According to the molecular structure, P2 receptors are divided into two subfamilies: P2X and P2Y receptors. The P2X receptors are ligand-gated channels, whereas P2Y receptors are G-protein-coupled seven-membrane-spanning receptors. Several studies indicate that nucleotides play an important role in immune response modulation through their action on multiple cell types, including monocytes, mast cells, dendritic cells, neutrophils, and eosinophils. Recent work by our group and others identified extracellular nucleotides as chemotaxins for various human immune cells, including eosinophils, neutrophils and dendritic cells. In this review, we summarise recent findings in this field and put forward a hypothesis on the role of P2 receptors in the early recruitment of human immune cells to the site of inflammation

Model-Derived Dispersal Pathways from Multiple Source Populations Explain Variability of Invertebrate Larval Supply

Background: Predicting the spatial and temporal patterns of marine larval dispersal and supply is a challenging task due to the small size of the larvae and the variability of oceanographic processes. Addressing this problem requires the use of novel approaches capable of capturing the inherent variability in the mechanisms involved. Methodology/Principal Findings: In this study we test whether dispersal and connectivity patterns generated from a biophysical model of larval dispersal of the crab Carcinus maenas, along the west coast of the Iberian Peninsula, can predict the highly variable daily pattern of wind-driven larval supply to an estuary observed during the peak reproductive season (March–June) in 2006 and 2007. Cross-correlations between observed and predicted supply were significant (p,0.05) and strong, ranging from 0.34 to 0.81 at time lags of 26 to+5 d. Importantly, the model correctly predicted observed cross-shelf distributions (Pearson r = 0.82, p,0.001, and r = 0.79, p,0.01, in 2006 and 2007) and indicated that all supply events were comprised of larvae that had been retained within the inner shelf; larvae transported to the outer shelf and beyond never recruited. Estimated average dispersal distances ranged from 57 to 198 km and were only marginally affected by mortality. Conclusions/Significance: The high degree of predicted demographic connectivity over relatively large geographic scales is consistent with the lack of genetic structuring in C. maenas along the Iberian Peninsula. These findings indicate that the dynamic nature of larval dispersal can be captured by mechanistic biophysical models, which can be used to provid

In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug

The anti-tumour effects and mechanism of action of combretastatin A-4 and its prodrug, combretastatin A-4 disodium phosphate, were examined in subcutaneous and orthotopically transplanted experimental colon tumour models. Additionally, the ability of these compounds to directly interfere with endothelial cell behaviour was also examined in HUVEC cultures. Combretastatin A-4 (150 mg kg–1, intraperitoneally (i.p.)) and its water-soluble prodrug (100 mg kg–1, i.p.) caused almost complete vascular shutdown (at 4 h), extensive haemorrhagic necrosis which started at 1 h after treatment and significant tumour growth delay in MAC 15A subcutaneous (s.c.) colon tumours. Similar vascular effects were obtained in MAC 15 orthotopic tumours and SW620 human colon tumour xenografts treated with the prodrug. More importantly, in the orthotopic models, necrosis was seen in vascularized metastatic deposits but not in avascular secondary deposits. The possible mechanism giving rise to these effects was examined in HUVEC cells. Here cellular networks formed in type I calf-skin collagen layers and these networks were completely disrupted when incubated with a non-cytotoxic concentration of combretastatin A-4 or its prodrug. This effect started at 4 h and was complete by 24 h. The same non-cytotoxic concentrations resulted in disorganization of F-actin and β-tubulin at 1 h after treatment. In conclusion, combretastatin A-4 and its prodrug caused extensive necrosis in MAC 15A s.c. and orthotopic colon cancer and metastases, resulting in anti-tumour effects. Necrosis was not seen in avascular tumour nodules, suggesting a vascular mechanism of action. © 1999 Cancer Research Campaig

Contrasting patterns of population structure and gene flow facilitate exploration of connectivity in two widely distributed temperate octocorals

This is the final version of the article. Available from Springer Nature via the DOI in this record.Connectivity is an important component of metapopulation dynamics in marine systems and can influence population persistence, migration rates and conservation decisions associated with Marine Protected Areas (MPAs). In this study, we compared the genetic diversity, gene flow and population structure of two octocoral species, Eunicella verrucosa and Alcyonium digitatum, in the northeast Atlantic (ranging from the northwest of Ireland and the southern North Sea, to southern Portugal), using two panels of thirteen and eight microsatellite loci, respectively. Our results identified regional genetic structure in E. verrucosa partitioned between populations from southern Portugal, northwest Ireland, and Britain/France; subsequent hierarchical analysis of population structure also indicated reduced gene flow between southwest Britain and northwest France. However, over a similar geographical area, A. digitatum showed little evidence of population structure, suggesting high gene flow and/or a large effective population size; indeed, the only significant genetic differentiation detected in A. digitatum occurred between North Sea samples and those from the English Channel/northeast Atlantic. In both species the vast majority of gene flow originated from sample sites within regions, with populations in southwest Britain being the predominant source of contemporary exogenous genetic variants for the populations studied. Unsurprisingly, historical patterns of gene flow appeared more complex, though again southwest Britain appeared an important source of genetic variation for both species. Our findings have major conservation implications, particularly for E. verrucosa, a protected species in UK waters and listed by the IUCN as ‘Vulnerable’, and for the designation and management of European MPAs.We thank Natural England (project No. RP0286, contract No. SAE 03-02-146), the NERC (grant No. NE/L002434/1) and the University of Exeter for funding this research. Additional funding for sample collection, travel and microsatellite development was provided by the EU Framework 7 ASSEMBLE programme, agreement no. 227799, and NERC grant No. NBAF-362

A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast

Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance