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This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning.

We consider random metric instances for optimization problems obtained as follows: Every edge of a complete graph gets a weight drawn independently at random. And then the length of an edge is the length of a shortest path with respect to these weights that connects its two endpoints. We prove that the following algorithms achieve an approximation ratio of O(log log n) with high probability in this model: (1) a greedy heuristic for minimum-weight perfect matching, (2) the nearest-neighbor heuristic for the traveling salesman problem (TSP), and (3) any insertion heuristic for the TSP.

Stroke is a major cause of morbidity in developed countries and therefore finding adequate treatments to promote patient’s recovery is a priority task, requiring the elucidation of the molecular pathways influencing brain recovery. Few studies, however, have assessed the role of genes in stroke outcome. This study describes a pilot genome-wide association study (GWAS) to identify genetic factors contributing to patient’s outcome, using a DNA pooling design. Methods: Patient’s outcome was assessed using the modified Rankin Scale (mRS) three months after stroke. Using the 250K Affymetrix GeneChip Mapping Assay® – Nsp I, we compared SNP allele frequencies in a pool of non-disabled stroke patients (N=87, mRS=0), with a pool of severely disabled or deceased patients (N=100, mRS>=3). The 100 most interesting SNPs were selected for validation by individual genotyping. Results: 36 SNPs were validated, showing significant differences between patients with extremely good and extremely poor outcome at three months (1.7x10-4 ). This work was supported by the grant PTDC/SAU-GMG/64426/2006, Fundação para a Ciência e Tecnologia (FCT). Helena Manso and Tiago Krug were supported by FCT fellowships.

A complex interplay between genetic background, clinical and life-style factors and the environment is expected to ultimately regulate the onset, acute phase and outcome of stroke. There is substantial evidence that inflammation within the Central Nervous System contributes to stroke risk, and known clinical risk factors for stroke, like atherosclerosis, diabetes, obesity, hypertension, and peripheral infection, are associated with an elevated systemic inflammatory profile. The inflammatory response is equally of major importance in recovery and healing processes after stroke. In this study we tested the genetic association of major inflammatory players IL1B (2q14), IL6 (7p21), TNF (6p21.3) and MPO (17q23.1) with stroke susceptibility and with stroke outcome at three months, in a population sample of 672 patients and 530 controls, adjusting for demographic, clinical and life-style risk factors and/or stroke severity parameters. The apparent complexity of the inflammatory mechanisms in stroke, and the multiplicity of players involved suggest a concerted process, in which implicated molecules interact to tightly regulate each other. We therefore examined both independent gene effects and the occurrence of gene-gene interactions among the tested inflammatory genes in stroke risk and stroke recovery. Two IL6 and one MPO SNP were significantly associated with stroke risk after multiple testing correction (0.022 correctedP 0.042), highlighting gene variants of low to moderate effect in stroke risk. An epistatic interaction between the IL6 and MPO genes was also identified in association with stroke susceptibility (P=0.031 after 1000 permutations). In the subset of 546 patients assessed for stroke outcome at three months using the modified Rankin Scale (mRS), we found one IL6 haplotype associated with stroke outcome (correctedP=0.024). In the present study we present supporting evidence for a role of the IL6 and MPO inflammatory genes in stroke susceptibility, and show that stroke risk is modulated by main gene effects together with clinical and life-style factors as well as by gene-gene interactions. Our findings are compatible and strengthen previous genetic and biological observations, highlighting the need of further functional studies, particularly in view of the possible utility of IL-6 as a diagnostic and/or prognostic biomarker for stroke.

BACKGROUND: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. METHODS: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. RESULTS: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.

Due to the introduction of new broadband services, individual line data rates are expected to exceed 100 Gb/s in the near future. To operate at these high speeds, new optical signal processing techniques will have to be developed. This paper will demonstrate that two-photon absorption in a specially designed semiconductor microcavity is an ideal candidate for optical signal processing applications such as autocorrelation, sampling, and demultiplexing in high-speed wavelength-division-multiplexed (WDM) and hybrid WDM/optical time-division-multiplexed networks.

We show the potential use of a single photodetector for multichannel pulse monitoring. Two-photon absorption in a microcavity structure is used as the nonlinear optical technique for pulse monitoring. Angle tuning of the device allows the resonance to be tuned. For the device studied here that is optimized for 2-ps pulses, a possible tuning range of 55 nm is shown.

conference 5825A "Optoelectronics and Photonics Devices", poster session [5825-44], proceedings of SPIE (ISBN 0-8194-5810-4); International audience; Future high-speed optical communications networks operating at data rates in excess of 100Gbit/s per channel will require a sensitive and ultrafast technique for precise optical signal monitoring. The standard way of characterising high-speed optical signals to use a fast photodetector in conjunction with a high-speed oscilloscope. However, this method is limited to a maximum data rate of approximately 40Gbit/s. An alternative is to employ all-optical sampling techniques based on ultrafast optical nonlinearities present in optical fibres, optical crystals and semiconductors. One such nonlinearity is the optical-to-electrical process of Two-Photon Absorption (TPA) in a semiconductor. This paper presents an optical sampling technique based on TPA in a specially designed semiconductor microcavity. By incorporating the microcavity design, we are able to enhance the TPA efficiency to a level that can be used for high-speed optical sampling.

A highly-efficient optical sampling system based on Two-Photon Absorption in a semiconductor micro-cavity is presented. The sensitivity of the sampling system is calculated to be 0.1mW² with a temporal resolution of 2ps.

In this paper, we present a theoretical model of an all-optical demultiplexer based on two-photon absorption in a specially designed semiconductor micro-cavity for use in an optical time division multiplexed system. We show that it is possible to achieve error-free demultiplexing of a 250 Gbit/s OTDM signal (25 × 10 Gbit/s channels) using a control-to-signal peak pulse power ratios of around 30:1 with a device bandwidth of approximately 30 GHz.

Real-time TPA optical sampling is experimentally performed. Results demonstrate that the TPA efficiency is enhanced using the microcavity to a level that allows the successful real-time direct detection of a 100 Gbit/s data stream. The system sensitivity is calculated to be 0.35 mW2, with a signal peak power of 5.6 mW, and temporal resolution less than 500 fs. This higher temporal resolution, combined with the low sampling rate, allows the direct monitoring of high data rates (100 Gbit/s) without the need for high-speed electronics.