Using web search query data to monitor dengue epidemics: a new model for neglected tropical disease surveillance

Background

A variety of obstacles including bureaucracy and lack of resources have interfered with timely detection and reporting of dengue cases in many endemic countries. Surveillance efforts have turned to modern data sources, such as Internet search queries, which have been shown to be effective for monitoring influenza-like illnesses. However, few have evaluated the utility of web search query data for other diseases, especially those of high morbidity and mortality or where a vaccine may not exist. In this study, we aimed to assess whether web search queries are a viable data source for the early detection and monitoring of dengue epidemics.

Methodology/Principal Findings

Bolivia, Brazil, India, Indonesia and Singapore were chosen for analysis based on available data and adequate search volume. For each country, a univariate linear model was then built by fitting a time series of the fraction of Google search query volume for specific dengue-related queries from that country against a time series of official dengue case counts for a time-frame within 2003–2010. The specific combination of queries used was chosen to maximize model fit. Spurious spikes in the data were also removed prior to model fitting. The final models, fit using a training subset of the data, were cross-validated against both the overall dataset and a holdout subset of the data. All models were found to fit the data quite well, with validation correlations ranging from 0.82 to 0.99.

Conclusions/Significance

Web search query data were found to be capable of tracking dengue activity in Bolivia, Brazil, India, Indonesia and Singapore. Whereas traditional dengue data from official sources are often not available until after some substantial delay, web search query data are available in near real-time. These data represent valuable complement to assist with traditional dengue surveillance.     

High-density spore production of Piriformospora indica, a plant growth-promoting endophyte, by optimization of nutritional and cultural parameters

Piriformospora indica is an axenically cultivable root endophytic fungus which exerts plant growth promoting effects on its host plants. To enable commercial production of its spores, the medium composition and culture conditions have been optimized in a 14 L bioreactor such that they result in maximum biomass during growth phase and in maximum spore yield during subsequent sporulation phase. Maximum spore yields were obtained with modified Kaefer medium using a glucose deprivation strategy. An enhancement of 100% in overall biomass productivity (0.18 g L(-1) h(-1)) and reduction of about 70% in the time (60 h) required to achieve the maximum spore yield (9.25×10(7) spores/mL) was achieved in comparison to the original Kaefer medium. The high spore yield obtained in the present study seems to be economical for commercial production of P. indica.     

Synthetic analogs of daidzein, having more potent osteoblast stimulating effect

A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of osteoblasts. Further, these three compounds did not show any estrogen agonistic activity, however had mild estrogen antagonistic effect. Out of the three compounds, 3c was found to maximally increase the mineralization of bone marrow osteoprogenitor cells. Compound 3c also robustly increased the mRNA levels of osteogenic genes including bone morphogenetic protein-2 and osteocalcin in osteoblasts. Unlike daidzein, 3c did not inhibit osteoclastogenesis. Collectively, we demonstrate osteogenic activity of daidzein analogs at significantly lower concentrations than daidzein.     

Melanoma invasion - current knowledge and future directions

The acquisition of invasive behaviour is the key transition in the progression of benign melanocyte hyperplasia to life threatening melanoma. Understanding this transition and the mechanisms of invasion are the key to understanding why malignant melanoma is such a devastating disease and will aid treatment strategies. Underlying the invasive behaviour is increased cell motility caused by changes in cytoskeletal organization and altered contacts with the extra-cellular matrix (ECM). In addition, changes in the interactions of melanoma cells with keratinocytes and fibroblasts enable them to survive and proliferate outside their normal epidermal location. Proteomic and genomic initiatives are greatly increasing our knowledge of which gene products are deregulated in invasive and metastatic melanoma; however, the next challenge is to understand how these genes promote the invasion of melanoma cells. In recent years new models have been developed that more closely recapitulate the conditions of melanoma invasion in vivo. It is hoped that these models will give us a better understanding of how the genes implicated in melanoma progression affect the motility of melanoma cells and their interactions with the ECM, stromal cells and blood vessels. This review will summarise our current understanding of melanoma invasion and focus on the new model systems that can be used to study melanoma.     

Immunomodulatory activity of hexapeptides related to proline rich peptide from colostrum

Twelve analogues of an immunomodulatory hexapeptide YVPGFP (I) derived from Proline rich peptide (from colostrum) have been synthesized with modifications at positions 2, 4 and 6. In MLR assay one of the analogues exhibited approx 50% inhibition at 0.1 microg/mL concentration in contrast to prednisolone and I which caused around 70 and 20% suppression respectively, at the same concentration.     

Translating Service Level Objectives to lower level policies for multi-tier services

Service providers and their customers agree on certain quality of service guarantees through Service Level Agreements (SLA). An SLA contains one or more Service Level Objectives (SLO)s that describe the agreed-upon quality requirements at the service level. Translating these SLOs into lower-level policies that can then be used for design and monitoring purposes is a difficult problem. Usually domain experts are involved in this translation that often necessitates application of domain knowledge to this problem. In this article, we propose an approach that combines performance modeling with regression analysis to solve this problem. We demonstrate that our approach is practical and that it can be applied to different n-tier services. Our experiments show that for a typical 3-tier e-commerce application in a virtualized environment, the SLA can be met while improving CPU utilization by up to 3 times.

Rac activation and inactivation control plasticity of tumor cell movement

Tumor cells exhibit two different modes of individual cell movement. Mesenchymal-type movement is characterized by an elongated cellular morphology and requires extracellular proteolysis. In amoeboid movement, cells have a rounded morphology, are less dependent on proteases, and require high Rho-kinase signaling to drive elevated levels of actomyosin contractility. These two modes of cell movement are interconvertible. We show that mesenchymal-type movement in melanoma cells is driven by activation of the GTPase Rac through a complex containing NEDD9, a recently identified melanoma metastasis gene, and DOCK3, a Rac guanine nucleotide exchange factor. Rac signals through WAVE2 to direct mesenchymal movement and suppress amoeboid movement through decreasing actomyosin contractility. Conversely, in amoeboid movement, Rho-kinase signaling activates a Rac GAP, ARHGAP22, that suppresses mesenchymal movement by inactivating Rac. We demonstrate tight interplay between Rho and Rac in determining different modes of tumor cell movement, revealing how tumor cells switch between different modes of movement.     

Mechanisms of cancer cell invasion

The movement of cancer cells into tissue surrounding the tumour and the vasculature is the first step in the spread of metastatic cancers. Recent advances in imaging, the use of 3D model systems and the application of microarray technologies have yielded new insights into these processes. This work has challenged our views about what causes cancer cells to become motile in the first place, and has demonstrated that cancer cells can move in many different ways.     

Comparison of growth and maintenance parameters for cellulase biosynthesis by Trichoderma reesei-C5 with some published data

Growth and maintenance parameters μ_max, K_s, m, and Y_m for cellulase biosynthesis on lactose by T. reesei-C5 were estimated and compared with published data on other soluble substrates and mutant strains of T. reesei in continuous culture. Growth was favored at higher feed lactose but cellulase productivities did not increase proportionally, suggesting that a degree of inhibition and/or catabolic repression within the strain is possible. The estimated values of growth kinetics and maintenance parameters varied little but were within a reasonable range of published data on other soluble substrates and mutant strains of T. reesei in continuous cultures.