5-Fluorouracil-Loaded Transfersome as Theranostics in Dermal Tumor of Hypertrophic Scar Tissue

To investigate the ability of transfersomal gel carrying the antiscarring agent (5-FU) to permeate hypertrophic scars in vivo and in vitro, scar permeation studies were performed after the agent was labeled with the fluorescent agent, rhodamine 6GO. Laser confocal microscope was employed to dynamically observe the effects of transfersomal gel carrying 5-FU at different time points. High-performance liquid chromatography (HPLC) was used to analyze the contents of the agent in the scar tissues at different hours after administration. Scar elevation index (SEI) was used to evaluate the changes of the ear scar models in rabbits. Compared with the PBS gel of 5-FU, the transfersomal gel displayed greater permeation rate and depth, as well as a higher content retention of the agent in scar tissues. Local administrations of the agent for some certain periods effectively inhibited the hyperplasia of ear scars in rabbits. Transfersomes can be chosen as a potential transdermal drug delivery system

ScalaRDF: A Distributed, Elastic and Scalable In-Memory RDF Triple Store

The Resource Description Framework (RDF) andSPARQL query language are gaining increasing popularity andacceptance. The ever-increasing RDF data has reached a billionscale of triples, resulting in the proliferation of distributed RDFstore systems within the Semantic Web community. However, theelasticity and performance issues are still far from settled inface of data volume explosion and workload spike. In addition, providers face great pressures to provision uninterrupted reliablestorage service whilst reducing the operational costs due to avariety of system failures. Therefore, how to efficiently realizesystem fault tolerance remains an intractable problem. In this paper, we introduce ScalaRDF, a distributed and elastic in-memoryRDF triple store to provision a fault-tolerant and scalable RDFstore and query mechanism. Specifically, we describe a consistenthashing protocol that optimizes the RDF data placement, dataoperations (especially for online RDF triple update operations)and achieves an autonomously elastic data re-distribution in theevent of cluster node joining or departing, avoiding the holisticoscillation of data storage. In addition, the data store is ableto realize a rapid and transparent failover through replicationmechanism which stores in-memory data replica in the next hashhop. The experiments demonstrate that query time and updatetime are reduced by 87% and 90% respectively compared to otherapproaches. For an 18G source dataset, the data redistributiontakes at most 60 seconds when system scales out and at most 100seconds for recovery when nodes undergo crash-stop failures

Performance-Aware Speculative Resource Oversubscription for Large-Scale Clusters

It is a long-standing challenge to achieve a high degree of resource utilization in cluster scheduling. Resource oversubscription has become a common practice in improving resource utilization and cost reduction. However, current centralized approaches to oversubscription suffer from the issue with resource mismatch and fail to take into account other performance requirements, e.g., tail latency. In this article we present ROSE, a new resource management platform capable of conducting performance-aware resource oversubscription. ROSE allows latency-sensitive long-running applications (LRAs) to co-exist with computation-intensive batch jobs. Instead of waiting for resource allocation to be confirmed by the centralized scheduler, job managers in ROSE can independently request to launch speculative tasks within specific machines according to their suitability for oversubscription. Node agents of those machines can however, avoid any excessive resource oversubscription by means of a mechanism for admission control using multi-resource threshold control and performance-aware resource throttle. Experiments show that in case of mixed co-location of batch jobs and latency-sensitive LRAs, the CPU utilization and the disk utilization can reach 56.34 and 43.49 percent, respectively, but the 95th percentile of read latency in YCSB workloads only increases by 5.4 percent against the case of executing the LRAs alone

Testing the causal relationships of physical activity and sedentary behaviour with mental health and substance use disorders: a Mendelian randomisation study

Observational studies suggest that physical activity can reduce the risk of mental health and substance use disorders. However, it is unclear whether this relationship is causal or explained by confounding bias (e.g., common underlying causes or reverse causality). We investigated the bidirectional causal relationship of physical activity (PA) and sedentary behaviour (SB) with ten mental health and substance use disorders, applying two-sample Mendelian Randomisation (MR). Genetic instruments for the exposures and outcomes were derived from the largest available, non-overlapping genome-wide association studies (GWAS). Summary-level data for objectively assessed PA (accelerometer-based average activity, moderate activity, and walking) and SB and self-reported moderate-to-vigorous PA were obtained from the UK Biobank. Data for mental health/substance use disorders were obtained from the Psychiatric Genomics Consortium and the GWAS and Sequencing Consortium of Alcohol and Nicotine Use. MR estimates were combined using inverse variance weighted meta-analysis (IVW). Sensitivity analyses were conducted to assess the robustness of the results. Accelerometer-based average PA was associated with a lower risk of depression (b = -0.043, 95% CI: -0.071 to -0.016, effect size[OR] = 0.957) and cigarette smoking (b = -0.026; 95% CI: -0.035 to -0.017, effect size[β] = -0.022). Accelerometer-based SB decreased the risk of anorexia (b = -0.341, 95% CI: -0.530 to -0.152, effect size[OR] = 0.711) and schizophrenia (b = -0.230; 95% CI: -0.285 to -0.175, effect size[OR] = 0.795). However, we found evidence of reverse causality in the relationship between SB and schizophrenia. Further, PTSD, bipolar disorder, anorexia, and ADHD were all associated with increased PA. This study provides evidence consistent with a causal protective effect of objectively assessed but not self-reported PA on reduced depression and cigarette smoking. Objectively assessed SB had a protective relationship with anorexia. Enhancing PA may be an effective intervention strategy to reduce depressive symptoms and addictive behaviours, while promoting sedentary or light physical activities may help to reduce the risk of anorexia in at-risk individuals

Key rate available from mismatched mesurements in the BB84 protocol and the uncertainty principle

We consider the mismatched measurements in the BB84 quantum key distribution protocol, in which measuring bases are different from transmitting bases. We give a lower bound on the amount of a secret key that can be extracted from the mismatched measurements. Our lower bound shows that we can extract a secret key from the mismatched measurements with certain quantum channels, such as the channel over which the Hadamard matrix is applied to each qubit with high probability. Moreover, the entropic uncertainty principle implies that one cannot extract the secret key from both matched measurements and mismatched ones simultaneously, when we use the standard information reconciliation and privacy amplification procedure.Comment: 5 pages, no figure, ieice.cls. Title was changed from version 1. To appear in IEICE Trans. Fundamentals (http://ietfec.oxfordjournals.org/), vol. E91-A, no. 10, Oct. 200

Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination