Fault recovery in the reliable multicast protocol

The Reliable Multicast Protocol (RMP) provides a unique, group-based model for distributed programs that need to handle reconfiguration events at the application layer. This model, called membership views, provides an abstraction in which events such as site failures, network partitions, and normal join-leave events are viewed as group reformations. RMP provides access to this model through an application programming interface (API) that notifies an application when a group is reformed as the result of a some event. RMP provides applications with reliable delivery of messages using an underlying IP Multicast (12, 5) media to other group members in a distributed environment even in the case of reformations. A distributed application can use various Quality of Service (QoS) levels provided by RMP to tolerate group reformations. This paper explores the implementation details of the mechanisms in RMP that provide distributed applications with membership view information and fault recovery capabilities

Reliable multicast protocol specifications flow control and NACK policy

This appendix presents the flow and congestion control schemes recommended for RMP and a NACK policy based on the whiteboard tool. Because RMP uses a primarily NACK based error detection scheme, there is no direct feedback path through which receivers can signal losses through low buffer space or congestion. Reliable multicast protocols also suffer from the fact that throughput for a multicast group must be divided among the members of the group. This division is usually very dynamic in nature and therefore does not lend itself well to a priori determination. These facts have led the flow and congestion control schemes of RMP to be made completely orthogonal to the protocol specification. This allows several differing schemes to be used in different environments to produce the best results. As a default, a modified sliding window scheme based on previous algorithms are suggested and described below

Combining contact tracing with targeted indoor residual spraying significantly reduces dengue transmission

The widespread transmission of dengue viruses (DENV), coupled with the alarming increase of birth defects and neurological disorders associated with Zika virus, has put the world in dire need of more efficacious tools for Aedes aegypti–borne disease mitigation. We quantitatively investigated the epidemiological value of location-based contact tracing (identifying potential out-of-home exposure locations by phone interviews) to infer transmission foci where high-quality insecticide applications can be targeted. Space-time statistical modeling of data from a large epidemic affecting Cairns, Australia, in 2008–2009 revealed a complex pattern of transmission driven primarily by human mobility (Cairns accounted for ~60% of virus transmission to and from residents of satellite towns, and 57% of all potential exposure locations were nonresidential). Targeted indoor residual spraying with insecticides in potential exposure locations reduced the probability of future DENV transmission by 86 to 96%, compared to unsprayed premises. Our findings provide strong evidence for the effectiveness of combining contact tracing with residual spraying within a developed urban center, and should be directly applicable to areas with similar characteristics (for example, southern USA, Europe, or Caribbean countries) that need to control localized Aedes-borne virus transmission or to protect pregnant women’s homes in areas with active Zika transmission. Future theoretical and empirical research should focus on evaluation of the applicability and scalability of this approach to endemic areas with variable population size and force of DENV infection

Fine-Grain Parallelism

Computer hardware is at the beginning of the multi-core revolution. While hardware at the commodity level is capable of running concurrent software, most software does not take advantage of this fact because parallel software development is difficult. This project addressed potential remedies to these difficulties by investigating graphical programming and fine-grain parallelism. A prototype system taking advantage of both of these concepts was implemented and evaluated in terms of real-world applications

Cost‐effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144625/1/bju14151_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144625/2/bju14151.pd

A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy

<p>Abstract</p> <p>Background</p> <p>Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation.</p> <p>Methods</p> <p>The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a) that recognizes the N-terminus of micro-dystrophin. The degree of physiologic correction was assessed by measuring tetanic force and protection from eccentric contraction in the extensor digitorum longus muscle (EDL). The vascular delivery paradigm found successful in the mouse was carried to the non-human primate to test its potential translation to boys with DMD.</p> <p>Results</p> <p>Regional vascular delivery resulted in transduction by rAAV8.micro-dystrophin reaching 94.5 ± 0.9 (1 month), 91.3 ± 3.1 (2 months), and 89.6 ± 1.6% (3 months). rAAV6.micro-dystrophin treated animals demonstrated 87.7 ± 6.8 (1 month), 78.9 ± 7.4 (2 months), and 81.2 ± 6.2% (3 months) transduction. In striking contrast, rAAV1 demonstrated very low transduction efficiency [0.9 ± 0.3 (1 month), 2.1 ± 0.8 (2 months), and 2.1 ± 0.7% (3 months)] by vascular delivery. Micro-dystrophin delivered by rAAV8 and rAAV6 through the femoral artery significantly improved tetanic force and protected against eccentric contraction. Mouse studies translated to the hindlimb of cynamologous macaques using a similar vascular delivery paradigm. rAAV8 carrying eGFP in doses proportional to the mouse (5 × 10¹²vg/kg in mouse vs 2 × 10¹²vg/kg in monkey) demonstrated widespread gene expression [medial gastrocnemius – 63.8 ± 4.9%, lateral gastrocnemius – 66.0 ± 4.5%, EDL – 80.2 ± 3.1%, soleus – 86.4 ± 1.9%, TA – 72.2 ± 4.0%.</p> <p>Conclusion</p> <p>These studies demonstrate regional vascular gene delivery with AAV serotype(s) in mouse and non-human primate at doses, pressures and volumes applicable for clinical trials in children with DMD.</p

Geopolitical species revisited: genomic and morphological data indicate that the roundtail chub Gila robusta species complex (Teleostei, Cyprinidae) is a single species

The Gila robusta species complex in the Lower Colorado River Basin has a complicated taxonomic history. Recent authors have separated this group into three nominal taxa, G. robusta, G. intermedia, and G. nigra, however aside from location, no reliable method of distinguishing individuals of these species currently exists. To assess relationships within this group, we examined morphology of type specimens and fresh material, and used RADseq methods to assess phylogenetic relationship among these nominal species. Maximum likelihood and Bayesian inference tree building methods reveal high concordance between tree topologies based on the mitochondrial and nuclear datasets. Coalescent SNAPP analysis resolved a similar tree topology. Neither morphological nor molecular data reveal diagnostic differences between these species as currently defined. As such, G. intermedia and G. nigra should be considered synonyms of the senior G. robusta. We hypothesize that climate driven wet and dry cycles have led to periodic isolation of population subunits and subsequent local divergence followed by reestablished connectivity and mixing. Management plans should therefore focus on retaining genetic variability and viability of geographic populations to preserve adaptability to changing climate conditions

Establishment of wMel Wolbachia in Aedes aegypti mosquitoes and reduction of local dengue transmission in Cairns and surrounding locations in northern Queensland, Australia.

Background: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and subsequently shown in laboratory studies to reduce transmission of a range of viruses including dengue, Zika, chikungunya, yellow fever, and Mayaro viruses that cause human disease. Here we report the entomological and epidemiological outcomes of staged deployment of Wolbachia across nearly all significant dengue transmission risk areas in Australia. Methods: The  wMel strain of  Wolbachia was backcrossed into the local  Aedes aegypti genotype (Cairns and Townsville backgrounds) and mosquitoes were released in the field by staff or via community assisted methods. Mosquito monitoring was undertaken and mosquitoes were screened for the presence of  Wolbachia. Dengue case notifications were used to track dengue incidence in each location before and after releases. Results: Empirical analyses of the Wolbachia mosquito releases, including data on the density, frequency and duration of Wolbachia mosquito releases, indicate that Wolbachia can be readily established in local mosquito populations, using a variety of deployment options and over short release durations (mean release period 11 weeks, range 2-22 weeks). Importantly, Wolbachia frequencies have remained stable in mosquito populations since releases for up to 8 years. Analysis of dengue case notifications data demonstrates near-elimination of local dengue transmission for the past five years in locations where Wolbachia has been established. The regression model estimate of Wolbachia intervention effect from interrupted time series analyses of case notifications data prior to and after releases, indicated a 96% reduction in dengue incidence in Wolbachia treated populations (95% confidence interval: 84 - 99%). Conclusion: Deployment of the wMel strain of Wolbachia into local Ae. aegypti populations across the Australian regional cities of Cairns and most smaller regional communities with a past history of dengue has resulted in the reduction of local dengue transmission across all deployment areas