White matter tract abnormalities are associated with cognitive dysfunction and secondary progressive multiple sclerosis

BACKGROUND: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. OBJECTIVE: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. METHODS: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). RESULTS: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance (R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. CONCLUSION: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patient

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

In Situ Imaging of the Conducting Filament in a Silicon Oxide Resistive Switch

The nature of the conducting filaments in many resistive switching systems has been elusive. Through in situ transmission electron microscopy, we image the real-time formation and evolution of the filament in a silicon oxide resistive switch. The electroforming process is revealed to involve the local enrichment of silicon from the silicon oxide matrix. Semi-metallic silicon nanocrystals with structural variations from the conventional diamond cubic form of silicon are observed, which likely accounts for the conduction in the filament. The growth and shrinkage of the silicon nanocrystals in response to different electrical stimuli show energetically viable transition processes in the silicon forms, offering evidence to the switching mechanism. The study here also provides insights into the electrical breakdown process in silicon oxide layers, which are ubiquitous in a host of electronic devices.Comment: 7 pages, 7 figure

Estimating Dynamic Gait Stability Using Data from Non-aligned Inertial Sensors

Recently, two methods for quantifying the stability of a dynamical system have been applied to human locomotion: local stability (quantified by finite time maximum Lyapunov exponents, λs and λL) and orbital stability (quantified by maximum Floquet multipliers, MaxFm). In most studies published to date, data from optoelectronic measurement systems were used to calculate these measures. However, using wireless inertial sensors may be more practical as they are easier to use, also in ambulatory applications. While inertial sensors have been employed in some studies, it is unknown whether they lead to similar stability estimates as obtained with optoelectronic measurement systems. In the present study, we compared stability measures of human walking estimated from an optoelectronic measurement system with those calculated from an inertial sensor measurement system. Subjects walked on a treadmill at three different speeds while kinematics were recorded using both measurement systems. From the angular velocities and linear accelerations, λs, λL, and MaxFm were calculated. Both measurement systems showed the same effects of walking speed for all variables. Estimates from both measurement systems correlated high for λs and λL, (R > 0.85) but less strongly for MaxFm (R = 0.66). These results indicate that inertial sensors constitute a valid alternative for an optoelectronic measurement system when assessing dynamic stability in human locomotion, and may thus be used instead, which paves the way to studying gait stability during natural, everyday walking

Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

The Association of AMPK with ULK1 Regulates Autophagy

Autophagy is a highly orchestrated intracellular bulk degradation process that is activated by various environmental stresses. The serine/threonine kinase ULK1, like its yeast homologue Atg1, is a key initiator of autophagy that is negatively regulated by the mTOR kinase. However, the molecular mechanism that controls the inhibitory effect of mTOR on ULK1-mediated autophagy is not fully understood. Here we identified AMPK, a central energy sensor, as a new ULK1-binding partner. We found that AMPK binds to the PS domain of ULK1 and this interaction is required for ULK1-mediated autophagy. Interestingly, activation of AMPK by AICAR induces 14-3-3 binding to the AMPK-ULK1-mTORC1 complex, which coincides with raptor Ser792 phosphorylation and mTOR inactivation. Consistently, AICAR induces autophagy in TSC2-deficient cells expressing wild-type raptor but not the mutant raptor that lacks the AMPK phosphorylation sites (Ser722 and Ser792). Taken together, these results suggest that AMPK association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory effect of mTOR on the ULK1 autophagic complex

Virtual environments as memory training devices in navigational tasks for older adults.

Cognitive training approaches using virtual environments (VEs) might counter age-related visuospatial memory decline and associated difficulties in wayfinding. However, the effects of the visual design of a VE in route learning are not fully understood. Therefore, we created a custom-designed VE optimized for route learning, with adjusted levels of realism and highlighted landmark locations (MixedVE). Herein we tested participants' route recall performance in identifying direction of turn at the intersection with this MixedVE against two baseline alternatives (AbstractVE, RealisticVE). An older vs. a younger group solved the tasks in two stages (immediate vs. delayed recall by one week). Our results demonstrate that the MixedVE facilitates better recall accuracy than the other two VEs for both age groups. Importantly, this pattern persists a week later. Additionally, our older participants were mostly overconfident in their route recall performance, but the MixedVE moderated this potentially detrimental overconfidence. Before the experiment, participants clearly preferred the RealisticVE, whereas after the experiment, most of the younger, and many of the older participants, preferred the MixedVE. Taken together, our findings provide insights into the importance of tailoring visualization design in route learning with VEs. Furthermore, we demonstrate the great potential of the MixedVE and by extension, of similar VEs as memory training devices for route learning, especially for older participants

Current status of haploidentical stem cell transplantation for leukemia

Haploidentical hematopoietic stem cell transplantation has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without a HLA identical sibling donor. The early complications of severe graft-versus-host disease (GVHD), graft failure and delayed engraftment, as well as disease recurrence have limited the use of this approach. Newer strategies have been applied and overcome some of the problems, including the use of T-cell depleted graft, "mega" dose of stem cells, intensive post-transplant immunosuppression and manipulation of the graft. These have decreased the transplant related mortality and GVHD associated with haploidentical transplantation, however, the major problems of disease relapse and infection, which related to late immune reconstitution, limit the development of haploidentical HSCT. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy