Reductions of Hidden Information Sources

In all but special circumstances, measurements of time-dependent processes reflect internal structures and correlations only indirectly. Building predictive models of such hidden information sources requires discovering, in some way, the internal states and mechanisms. Unfortunately, there are often many possible models that are observationally equivalent. Here we show that the situation is not as arbitrary as one would think. We show that generators of hidden stochastic processes can be reduced to a minimal form and compare this reduced representation to that provided by computational mechanics--the epsilon-machine. On the way to developing deeper, measure-theoretic foundations for the latter, we introduce a new two-step reduction process. The first step (internal-event reduction) produces the smallest observationally equivalent sigma-algebra and the second (internal-state reduction) removes sigma-algebra components that are redundant for optimal prediction. For several classes of stochastic dynamical systems these reductions produce representations that are equivalent to epsilon-machines.Comment: 12 pages, 4 figures; 30 citations; Updates at http://www.santafe.edu/~cm

PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma

Background Many urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases. Methods We used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway. Results Specific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance. Conclusions Mutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer

Increased food production and reduced water use through optimized crop distribution

Growing demand for agricultural commodities for food, fuel and other uses is expected to be met through an intensification of production on lands that are currently under cultivation. Intensification typically entails investments in modern technology - such as irrigation or fertilizers - and increases in cropping frequency in regions suitable for multiple growing seasons. Here we combine a process-based crop water model with maps of spatially interpolated yields for 14 major food crops to identify potential differences in food production and water use between current and optimized crop distributions. We find that the current distribution of crops around the world neither attains maximum production nor minimum water use. We identify possible alternative configurations of the agricultural landscape that, by reshaping the global distribution of crops within current rainfed and irrigated croplands based on total water consumption, would feed an additional 825 million people while reducing the consumptive use of rainwater and irrigation water by 14% and 12%, respectively. Such an optimization process does not entail a loss of crop diversity, cropland expansion or impacts on nutrient and feed availability. It also does not necessarily invoke massive investments in modern technology that in many regions would require a switch from smallholder farming to large-scale commercial agriculture with important impacts on rural livelihoods

Parent-reported and clinician-observed autism spectrum disorder (ASD) symptoms in children with attention deficit/hyperactivity disorder (ADHD): implications for practice under DSM-5

BACKGROUND: Children with attention deficit/hyperactivity disorder (ADHD) often present with social difficulties, though the extent to which these clearly overlap with symptoms of autism spectrum disorder (ASD) is not well understood. METHODS: We explored parent-reported and directly-observed ASD symptoms on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in children referred to ASD-specialty clinics who received diagnoses of either ADHD (n = 48) or ASD (n = 164). RESULTS: Of the ADHD sample, 21 % met ASD cut-offs on the ADOS and 30 % met ASD cut-offs on all domains of the ADI-R. Four social communication ADOS items (Quality of Social Overtures, Unusual Eye Contact, Facial Expressions Directed to Examiner, and Amount of Reciprocal Social Communication) adequately differentiated the groups while none of the items on the ADI-R met the criteria for adequate discrimination. CONCLUSIONS: Results of this work highlight the challenges that clinicians and researchers face when distinguishing ASD from other disorders in verbally fluent, school-age children

Diffusion of MMPs on the Surface of Collagen Fibrils: The Mobile Cell Surface – Collagen Substratum Interface

Remodeling of the extracellular matrix catalyzed by MMPs is central to morphogenetic phenomena during development and wound healing as well as in numerous pathologic conditions such as fibrosis and cancer. We have previously demonstrated that secreted MMP-2 is tethered to the cell surface and activated by MT1-MMP/TIMP-2-dependent mechanism. The resulting cell-surface collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 can initiate (MT1-MMP) and complete (MMP-2) degradation of an underlying collagen fibril. The following question remained: What is the mechanism of substrate recognition involving the two structures of relatively restricted mobility, the cell surface enzymatic complex and a collagen fibril embedded in the ECM? Here we demonstrate that all the components of the complex are capable of processive movement on a surface of the collagen fibril. The mechanism of MT1-MMP movement is a biased diffusion with the bias component dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP) hydrolysis. It is similar to that of the MMP-1 Brownian ratchet we described earlier. In addition, both MMP-2 and MMP-9 as well as their respective complexes with TIMP-1 and -2 are capable of Brownian diffusion on the surface of native collagen fibrils without noticeable dissociation while the dimerization of MMP-9 renders the enzyme immobile. Most instructive is the finding that the inactivation of the enzymatic activity of MT1-MMP has a detectable negative effect on the cell force developed in miniaturized 3D tissue constructs. We propose that the collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 represents a Mobile Cell Surface – Collagen Substratum Interface. The biological implications of MT1-MMP acting as a molecular ratchet tethered to the cell surface in complex with MMP-2 suggest a new mechanism for the role of spatially regulated peri-cellular proteolysis in cell-matrix interactions

Amyloids - A functional coat for microorganisms

Amyloids are filamentous protein structures ~10 nm wide and 0.1–10 µm long that share a structural motif, the cross-β structure. These fibrils are usually associated with degenerative diseases in mammals. However, recent research has shown that these proteins are also expressed on bacterial and fungal cell surfaces. Microbial amyloids are important in mediating mechanical invasion of abiotic and biotic substrates. In animal hosts, evidence indicates that these protein structures also contribute to colonization by activating host proteases that are involved in haemostasis, inflammation and remodelling of the extracellular matrix. Activation of proteases by amyloids is also implicated in modulating blood coagulation, resulting in potentially life-threatening complications.

Malaria vector species in Colombia: a review

Here we present a comprehensive review of the literature on the vectorial importance of the major Anopheles malaria vectors in Colombia. We provide basic information on the geographical distribution, altitudinal range, immature habitats, adult behaviour, feeding preferences and anthropophily, endophily and infectivity rates. We additionally review information on the life cycle, longevity and population fluctuation of Colombian Anopheles species. Emphasis was placed on the primary vectors that have been epidemiologically incriminated in malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. The role of a selection of local, regional or secondary vectors (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We highlight the importance of combining biological, morphological and molecular data for the correct taxonomical determination of a given species, particularly for members of the species complexes. We likewise emphasise the importance of studying the bionomics of primary and secondary vectors along with an examination of the local conditions affecting the transmission of malaria. The presence and spread of the major vectors and the emergence of secondary species capable of transmitting human Plasmodia are of great interest. When selecting control measures, the anopheline diversity in the region must be considered. Variation in macroclimate conditions over a species' geographical range must be well understood and targeted to plan effective control measures based on the population dynamics of the local Anopheles species