BackgroundThe Hand-Foot-Mouth Disease (HFMD) is the most common infectious disease in China, its total incidence being around 500,000 ~1,000,000 cases per year. The composite space-time disease variation is the result of underlining attribute mechanisms that could provide clues about the physiologic and demographic determinants of disease transmission and also guide the appropriate allocation of medical resources to control the disease.Methods and FindingsHFMD cases were aggregated into 1456 counties and during a period of 11 months. Suspected climate attributes to HFMD were recorded monthly at 674 stations throughout the country and subsequently interpolated within 1456 × 11 cells across space-time (same as the number of HFMD cases) using the Bayesian Maximum Entropy (BME) method while taking into consideration the relevant uncertainty sources. The dimensionalities of the two datasets together with the integrated dataset combining the two previous ones are very high when the topologies of the space-time relationships between cells are taken into account. Using a self-organizing map (SOM) algorithm the dataset dimensionality was effectively reduced into 2 dimensions, while the spatiotemporal attribute structure was maintained. 16 types of spatiotemporal HFMD transmission were identified, and 3-4 high spatial incidence clusters of the HFMD types were found throughout China, which are basically within the scope of the monthly climate (precipitation) types.ConclusionsHFMD propagates in a composite space-time domain rather than showing a purely spatial and purely temporal variation. There is a clear relationship between HFMD occurrence and climate. HFMD cases are geographically clustered and closely linked to the monthly precipitation types of the region. The occurrence of the former depends on the later.

Surface-enhanced Raman spectroscopy (SERS) has been shown to be able to detect low-concentration biofluids. Saliva SERS readings of 21 lung cancer patients and 20 normal people were measured and differentiated. Most of the Raman peak intensities decrease for lung cancer patients compared with that of normal people. Those peaks were assigned to proteins and nucleic acids, which indicate a corresponding decrease of those substances in saliva. Principal component analysis (PCA) and linear discriminant analysis (LDA) were used to reduce and discriminate between the two groups of data, and the study resulted in accuracy, sensitivity, and specificity being 80%, 78%, and 83%, respectively. In conclusion, SERS of saliva showed the ability to predict lung cancer in our experiment.

Network accountability, forensic analysis, and failure diagnosis are becoming increasingly important for network management and security. Such capabilities often utilize network provenance -the ability to issue queries over network meta-data. For example, network provenance may be used to trace the path a message traverses on the network as well as to determine how message data were derived and which parties were involved in its derivation. This paper presents the design and implementation of ExSPAN, a generic and extensible framework that achieves efficient network provenance in a distributed environment. We utilize the database notion of data provenance to "explain" the existence of any network state, providing a versatile mechanism for network provenance. To achieve such flexibility at Internet-scale, ExSPAN uses declarative networking in which network protocols can be modeled as continuous queries over distributed streams and specified concisely in a declarative query language. We extend existing data models for provenance developed in database literature to enable distribution at Internet-scale, and investigate numerous optimization techniques to maintain and query distributed network provenance efficiently. The ExSPAN prototype is developed using RapidNet, a declarative networking platform based on the emerging ns-3 toolkit. Experiments over a simulated network and an actual deployment in a testbed environment demonstrate that our system supports a wide range of distributed provenance computations efficiently, resulting in significant reductions in bandwidth costs compared to traditional approaches. ABSTRACTNetwork accountability, forensic analysis, and failure diagnosis are becoming increasingly important for network management and security. Such capabilities often utilize network provenance -the ability to issue queries over network meta-data. For example, network provenance may be used to trace the path a message traverses on the network as well as to determine how message data were derived and which parties were involved in its derivation. This paper presents the design and implementation of ExSPAN, a generic and extensible framework that achieves efficient network provenance in a distributed environment. We utilize the database notion of data provenance to "explain" the existence of any network state, providing a versatile mechanism for network provenance. To achieve such flexibility at Internet-scale, ExSPAN uses declarative networking in which network protocols can be modeled as continuous queries over distributed streams and specified concisely in a declarative query language. We extend existing data models for provenance developed in database literature to enable distribution at Internet-scale, and investigate numerous optimization techniques to maintain and query distributed network provenance efficiently. The ExSPAN prototype is developed using RapidNet, a declarative networking platform based on the emerging ns-3 toolkit. Experiments over a simulated network and an actual deployment in...

Fast concurrent hash tables are an increasingly important building block as we scale systems to greater numbers of cores and threads. This paper presents the design, implementation, and evaluation of a high-throughput and memory-efficient concurrent hash table that supports multiple readers and writers. The design arises from careful attention to systems-level optimizations such as minimizing critical section length and reducing interprocessor coherence traffic through algorithm re-engineering. As part of the architectural basis for this engineering, we include a discussion of our experience and results adopting Intel's recent hardware transactional memory (HTM) support to this critical building block. We find that naively allowing concurrent access using a coarse-grained lock on existing data structures reduces overall performance with more threads. While HTM mitigates this slowdown somewhat, it does not eliminate it. Algorithmic optimizations that benefit both HTM and designs for fine-grained locking are needed to achieve high performance.Our performance results demonstrate that our new hash table design-based around optimistic cuckoo hashingoutperforms other optimized concurrent hash tables by up to 2.5x for write-heavy workloads, even while using substantially less memory for small key-value items. On a 16-core machine, our hash table executes almost 40 million insert and more than 70 million lookup operations per second.

Motivated by the increasing popularity of eventually consistent keyvalue stores as a commercial service, we address two important problems related to the consistency properties in a history of operations on a read/write register (i.e., the start time, finish time, argument, and response of every operation). First, we consider how to detect a consistency violation as soon as one happens. To this end, we formulate a specification for online verification algorithms, and we present such algorithms for several well-known consistency properties. Second, we consider how to quantify the severity of the violations, if a history is found to contain consistency violations. We investigate two quantities: one is the staleness of the reads, and the other is the commonality of violations. For staleness, we further consider time-based staleness and operation-count-based staleness. We present efficient algorithms that compute these quantities. We believe that addressing these problems helps both key-value store providers and users adopt data consistency as an important aspect of key-value store offerings.

Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.

Objectives To reveal the role of circular RNA (circRNA) DOCK1 (circDOCK1) as a potential biomarker and therapeutic target and its competing endogenous RNA mechanism in bladder carcinoma (BC). Methods The next‐generation sequencing (NGS) technology was introduced to screen the circRNA expression profiles of BC using microarray. qPCR and Western blots assay were employed to measure the gene expression in different groups. Cell counting kit‐8, EdU and transwell assays were applied to detect the cell viability, proliferation and migration potential, respectively. Luciferase reporter assay was used to test the binds between hsa‐miR‐132‐3p/Sox5. Xenografted tumour growth of nude mice was performed to test the role of circDOCK1 in vivo. Results CircDOCK1 was upregulated in BC tissues and cell lines. Repression of circDOCK1 reduced cell viability, inhibited cell proliferation and curbed the cell migration potential of BC cell. CircDOCK1 played its role via regulation of circDOCK1/hsa‐miR‐132‐3p/Sox5 pathway in BC cells. Suppression circDOCK1 inhibited the tumour growth in vivo. Conclusion In this study, we revealed that circDOCK1 affected the progression of BC via modulation of circDOCK1/hsa‐miR‐132‐3p/Sox5 pathway both in vitro and in vivo and providing a potential biomarker and therapeutic targets for BC.

The molecular mechanism underlying the transition of acute kidney injury (AKI) to chronic kidney disease (CKD) induced by vancomycin (VAN) remains largely unknown. Methods : The mice model of VAN drives AKI to CKD was developed to investigate the role and molecular mechanism of epidermal growth factor receptor (EGFR). The EGF receptor mutant (Wa-2) mice and gefitinib were used to inactivation of EGFR. The homeodomain interacting protein kinase 2 (HIPK2) siRNA was applied to silence of HIPK2. Human proximal tubular epithelial cells (HK-2) were used to explore the molecular regulation methanism of EGFR. ChIp analysis was used to investigate if STAT3 interaction with the promoter of HIPK2. Results: A novel VAN-induced AKI mouse model was established for the first time. Moreover, the expression levels collagen I&IV, α-SMA, p-EGFR and the expression of HIPK2 proteins were upregulated in this model. Interestingly, AKI caused by VAN was markedly attenuated in waved-2 mice at the early stage, as evidenced by the suppression of renal dysfunction, renal cell apoptosis and caspase3 activation. In the latter stage, renal fibrosis and inflammation were significantly ameliorated in Wa-2 mice, accompanied by the downregulation of profibrotic molecules and F4/80. Besides, the expression levels of HIPK2 and p-STAT3 were suppressed in Wa-2 mice during VAN-induced transition of AKI to CKD. In addition, renal fibrosis and inflammation, profibrotic molecules, and EGFR/STAT3/HIPK2 signaling were ameliorated by gefitinib treatment after VAN-induced AKI. These results were consistent with the findings of Wa-2 mice. EGFR/STAT3 signaling mediated VAN-induced HIPK2 expression in HK-2 cells. ChIp analysis revealed that STAT3 directly bound to the promoter region of HIPK2. Finally, inhibition of HIPK2 attenuated the VAN drove the progression of AKI to CKD. Conclusion : These data suggest that EGFR plays an important role in VAN-driven progression of AKI to CKD.