Wavelet packets based denoising method for measurement domain repeat-time multipath filtering in GPS static high-precision positioning

Repeatable satellite orbits can be used for multipath mitigation in GPS-based deformation monitoring and other high-precision GPS applications that involve continuous observation with static antennas. Multipath signals at a static station repeat when the GPS constellation repeats given the same site environment. Repeat-time multipath filtering techniques need noise reduction methods to remove the white noise in carrier phase measurement residuals in order to retrieve the carrier phase multipath corrections for the next day. We propose a generic and robust three-level wavelet packets based denoising method for repeat-time-based carrier phase multipath filtering in relative positioning; the method does not need tuning to work with different data sets. The proposed denoising method is tested rigorously and compared with two other denoising methods. Three rooftop data sets collected at the University of Nottingham Ningbo China and two data sets collected at three Southern California Integrated GPS Network high-rate stations are used in the performance assessment. Test results of the wavelet packets denoising method are compared with the results of the resistor–capacitor (RC) low-pass filter and the single-level discrete wavelet transform (DWT) denoising method. Multipath mitigation efficiency in carrier phase measurement domain is shown by spectrum analysis of two selected satellites in two data sets. The positioning performance of the repeat-time-based multipath filtering techniques is assessed. The results show that the performance of the three noise reduction techniques is about 1–46 % improvement on positioning accuracy when compared with no multipath filtering. The statistical results show that the wavelet packets based denoising method is always better than the RC filter by 2–4 %, and better than the DWT method by 6–15 %. These results suggest that the proposed wavelet packets based denoising method is better than both the DWT method and the relatively simple RC low-pass filter for noise reduction in multipath filtering. However, the wavelet packets based denoising method is not significantly better than the RC filter

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study

Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Internet-based medical education: a realist review of what works, for whom and in what circumstances

http://creativecommons.org/licenses/by/2.0

Characterization of a Large Group of Individuals with Huntington Disease and Their Relatives Enrolled in the COHORT Study

Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.We conducted a cohort study in the United States, Canada, and Australia of members of families affected by HD. We collected demographic and clinical data, conducted the Unified Huntington's Disease Rating Scale and Mini-Mental State Examination, and determined Huntingtin trinucleotide CAG repeat length. We report primarily on cross-sectional baseline data from this recently completed prospective, longitudinal, observational study.As of December 31, 2009, 2,318 individuals enrolled; of these, 1,985 (85.6%) were classified into six analysis groups. Three groups had expanded CAG alleles (36 repeats or more): individuals with clinically diagnosed HD [n = 930], and clinically unaffected first-degree relatives who had previously pursued [n = 248] or not pursued [n = 112] predictive DNA testing. Three groups lacked expanded alleles: first-degree relatives who had previously pursued [n = 41] or not pursued [n = 224] genetic testing, and spouses and caregivers [n = 430]. Baseline mean performance differed across groups in all motor, behavioral, cognitive, and functional measures (p<0.001). Clinically unaffected individuals with expanded alleles weighed less (76.0 vs. 79.6 kg; p = 0.01) and had lower cognitive scores (28.5 vs. 29.1 on the Mini Mental State Examination; p = 0.008) than individuals without expanded alleles. The frequency of "high normal" repeat lengths (27 to 35) was 2.5% and repeat lengths associated with reduced penetrance (36 to 39) was 2.7%.Baseline analysis of COHORT study participants revealed differences that emerge prior to clinical diagnosis. Longitudinal investigation of this cohort will further characterize the natural history of HD and genetic and biological modifiers.Clinicaltrials.gov NCT00313495

Control of Gastric H,K-ATPase Activity by Cations, Voltage and Intracellular pH Analyzed by Voltage Clamp Fluorometry in Xenopus Oocytes

Whereas electrogenic partial reactions of the Na,K-ATPase have been studied in depth, much less is known about the influence of the membrane potential on the electroneutrally operating gastric H,K-ATPase. In this work, we investigated site-specifically fluorescence-labeled H,K-ATPase expressed in Xenopus oocytes by voltage clamp fluorometry to monitor the voltage-dependent distribution between E1P and E2P states and measured Rb+ uptake under various ionic and pH conditions. The steady-state E1P/E2P distribution, as indicated by the voltage-dependent fluorescence amplitudes and the Rb+ uptake activity were highly sensitive to small changes in intracellular pH, whereas even large extracellular pH changes affected neither the E1P/E2P distribution nor transport activity. Notably, intracellular acidification by approximately 0.5 pH units shifted V0.5, the voltage, at which the E1P/E2P ratio is 50∶50, by −100 mV. This was paralleled by an approximately two-fold acceleration of the forward rate constant of the E1P→E2P transition and a similar increase in the rate of steady-state cation transport. The temperature dependence of Rb+ uptake yielded an activation energy of ∼90 kJ/mol, suggesting that ion transport is rate-limited by a major conformational transition. The pronounced sensitivity towards intracellular pH suggests that proton uptake from the cytoplasmic side controls the level of phosphoenzyme entering the E1P→E2P conformational transition, thus limiting ion transport of the gastric H,K-ATPase. These findings highlight the significance of cellular mechanisms contributing to increased proton availability in the cytoplasm of gastric parietal cells. Furthermore, we show that extracellular Na+ profoundly alters the voltage-dependent E1P/E2P distribution indicating that Na+ ions can act as surrogates for protons regarding the E2P→E1P transition. The complexity of the intra- and extracellular cation effects can be rationalized by a kinetic model suggesting that cations reach the binding sites through a rather high-field intra- and a rather low-field extracellular access channel, with fractional electrical distances of ∼0.5 and ∼0.2, respectively

When Can Antibiotic Treatments for Trachoma Be Discontinued? Graduating Communities in Three African Countries

Trachoma, the major cause of infectious blindness in the world, occurs when repeated infections of the ocular strains of Chlamydia trachomatis lead to a cascade of conjunctival scarring, in-turned eyelids and eyelashes, and eventually blindness due to corneal opacity. To reduce the prevalence of infection, the World Health Organization (WHO) advocates at least three annual community-wide distributions of oral antibiotics in affected areas. This approach has proven effective, but there is room to explore other treatment strategies which reduce the use of antibiotics. Here, we used mathematical models and data from three trachoma-endemic countries (Tanzania, The Gambia, and Ethiopia) to analyze different treatment strategies. In the simulations, we show that a graduation strategy can reduce antibiotic distributions more than 2-fold in moderately affected areas. Both treatment strategies provide favorable results in reducing the prevalence of ocular chlamydia, but high costs and the potential for resistance are important issues to consider when administering mass doses of antibiotics

The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production of inflammatory mediators in the synovium mediated, in part, by the transcription factor NF-κB. We have identified a non-steroidal estrogen receptor ligand, WAY-169916, that selectively inhibits NF-κB transcriptional activity but is devoid of conventional estrogenic activity. The activity of WAY-169916 was monitored in two models of arthritis, the HLA-B27 transgenic rat and the Lewis rat adjuvant-induced model, after daily oral administration. In both models, a near complete reversal in hindpaw scores was observed as well as marked improvements in the histological scores. In the Lewis rat adjuvant model, WAY-169916 markedly suppresses the adjuvant induction of three serum acute phase proteins: haptoglobin, α1-acid glycoprotein (α1-AGP), and C-reactive protein (CRP). Gene expression experiments also demonstrate a global suppression of adjuvant-induced gene expression in the spleen, liver, and popliteal lymph nodes. Finally, WAY-169916 was effective in suppressing tumor necrosis factor-α-mediated inflammatory gene expression in fibroblast-like synoviocytes isolated from patients with RA. Together, these data suggest the utility of WAY-169916, and other compounds in its class, in treating RA through global suppression of inflammation via selective blockade of NF-κB transcriptional activity