Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.     

Less cyber,more café: Enhancing existing small businesses across the digital divide with ICTs

About 10% of the world has access to information and communication technologies (ICTs). Telecenters and cyber cafés are one prevalent way to increase access. This paper suggests increasing access through currently existing, local businesses where people already gather and where proprietors already posses existing business relationships with suppliers and customers. This paper questions the prevailing emphasis on the “cyber'' characteristics of access, e.g., computing and internet access as is currently known, and attempts to refocus the conversation by considering computing and access in the context of the “café,” e.g., as public life in the sense of Habermas, which permits an in situ evolution of relevant access. This analysis is based on extant literature and direct ethnographic research in several public places in six countries. We offer example design perspectives based on a reflection of “third places” as inspiration for appropriate innovation in the provision of computing and communications. © 2005 Wiley Periodicals, Inc.     

STATISTICAL LINGUISTIC LAWS IN ECOLOGICAL MODELS

This paper gives the theoretical setup so that an ecological model, as a particular mathematical model, can be considered a text written in a formal language (mathematics), and therefore, statistical linguistic laws can be applied to obtain information parameters in different semantic levels of the same model. The statistical laws will be useful to: a) compare semantic levels, submodels, and different models mutually; b) prove that information temperature parameter is an indirect measure of meaning: the significance or semantic component of information, opposed to significant, or comprehension, on the part of the observer (modeller) of the model text. We will apply these ideas in two practical examples.     

Physical aging in polymers: Comparison of two ways of determining narayanaswamy's parameter

In this work, we have investigated by differential scanning calorimetry the enthalpy relaxation of two poly[methyl(α-n-alkyl)acrylates] in which it is possible to change the length of the two alkyl chains. In particular, we have evaluated the Narayanaswamy parameter, which controls relative contribution of temperature and of structure to the relaxation times, by two methods: Grenet's method (GM) and the peak-shift method (PSM). The data obtained show that both methods lead to equivalent results. Nevertheless, PSM requires fewer experiments than GM, and PSM appears to be more practical. The results obtained on the two acrylates show that the parameter x increases with the lateral chain length, that is to say, that the temperature effects increase as the length of the alkyl chain is increased.     

Spatial and temporal distribution of ichthyoplankton during an unusual period of low flow in a tributary of the São Francisco River,Brazil

Flow‐dependent fish specialists require specific conditions for reproduction, so the success and reproductive intensity of these animals are determined by the flood regime. Thus, this study investigated the spatial and temporal reproductive patterns of fish, especially migratory Prochilodus species (flow‐dependent specialists) in an unusual period of low flow in the Pará River sub‐basin, one of the main tributaries of the upper São Francisco River. For this, ichthyoplankton collections were carried out between November 2013 and February 2014. Data were analysed considering the spatial and temporal variations in density of eggs and larvae for the upper, middle, and lower portions of the Pará River sub‐basin, and correlating this to some environmental variables. The results showed that the small headwater stretch of the Pará River is one relevant spawning area for migratory fish species. However, this area is isolated by the Cajuru reservoir, which makes it uncertain the recruitment of these embryos, due to interruption of natural drift between spawning/nursery areas caused for reservoirs. Larvae of newly hatched migratory species found in tributaries of the lower Pará River sub‐basin also indicate these species use these tributaries as spawning grounds and migratory routes. The period in which the research was conducted represented the most atypical low flow, one in the last 75 years, resulting in the low variability in the environmental parameters. Although few parameters increased briefly in this low flow period influenced by greater rainfall in December, this precipitation was possibly responsible for the final gonadal maturation and spawning of migratory species.     

FOS: a low-power cache organization for multicores

The Journal of Supercomputing - The cache hierarchy of current multicore processors typically consists of one or two levels of private caches per core and a large shared last-level cache. This...     

Higher-Order Adaptive Finite Difference Methods for Fully Nonlinear Elliptic Equations

We introduce generalised finite difference methods for solving fully nonlinear elliptic partial differential equations. Methods are based on piecewise Cartesian meshes augmented by additional points along the boundary. This allows for adaptive meshes and complicated geometries, while still ensuring consistency, monotonicity, and convergence. We describe an algorithm for efficiently computing the non-traditional finite difference stencils. We also present a strategy for computing formally higher-order convergent methods. Computational examples demonstrate the efficiency, accuracy, and flexibility of the methods.     

On the feasibility of ocean brine pool power stations

The demonstrated existence of vast brine pools in a number of places in the ocean basin around the world offers an interesting opportunity to the production of power from ocean, which has not been yet considered. The attractiveness of these vast deposits of brine lie in the fact that can be readily dissolved with the surrounding top waters extracting the spontaneous osmotic mixing energy released. In addition, osmotic engines can pumped out the brackish streams by buoyancy without the add of pressure exchangers (PEXs) as is required in current pressure retarded osmosis (PRO) technology and then simplifying significatively the overall process. Utilizing a simplified physical model, a first estimation for the density of power per unit of membrane area was calculated.     

Generalizing linguistic structures under high attention demands.

We explored whether the generalization of rules based on simple structures depends on attention. Participants were exposed to a stream of artificial words that followed a simple syllabic structure (ABA or AAB), overlaid on a sequence of familiar noises. After passively listening, participants successfully recognized the individual words present in the stream among foils, and they were able to generalize the underlying word structure to new exemplars. Yet, when attention was diverted from the speech stream (by requiring participants to monitor the sequence of noises), recognition of the individual words fell dramatically irrespective of word structure, whereas generalization depended on stimulus structure. For structures based on vowel repetitions across nonadjacent syllables (ABA; Experiment 1), generalization was affected by attention. In contrast, for structures based on adjacent repetitions (AAB; Experiment 2), generalization capacity was unaffected by attention. This pattern of results was replicated under favorable conditions for generalization, such as increased token variability and the implementation of the rule over whole syllables (Experiments 3 and 4). These results suggest a differential effect of attention on rule learning and generalization depending on stimulus structure. (PsycINFO Database Record (c) 2011 APA, all rights reserved)