Fast transport of cobalt in thorium

Three investigations associated with the fast transport behavior of cobalt in thorium have been conducted. These include (1) a study of a metastable ThCo[subscript] x phase and the solid solubility of cobalt in thorium in dilute thorium-cobalt alloys, (2) a study of the mechanism of fast diffusion of cobalt in thorium using diffusion and internal friction experiments and (3) a study of the thermotransport behavior of cobalt in thorium;A metastable plate phase, having a stoichiometry of about ThCo[subscript]0.08, forms in alloys containing greater than 0.004 at.% Co that are quenched from the single-phase field. Upon aging between 773 and 1073 K the plate phase transforms to rod-like precipitates of the equilibrium Th[subscript]7Co[subscript]3 phase. The solid solubility of cobalt in thorium increases from 0.05 at.% at 1120 K to 0.4 at.% at 1350 K according to the relation, c[subscript] s (at.%) = 7044 exp(-110.5 kJ mol[superscript]-1/RT). The terminal solid solubility at the eutectic temperature of 1373 K is 0.45 at.%;The activation energy for diffusion of cobalt in [alpha] thorium is 83.7 kJ/mol whereas that associated with the anelastic relaxation process for cobalt in thorium is 78.0 kJ/mol. The diffusion and internal friction results can be interpreted as supporting either the host-solute diplon mechanism or the interstitial mechanism of fast diffusion. The observed cobalt internal friction peak may be due to a host-solute diplon or a substitutional-interstitial pair;The heat of transport, Q*, for cobalt in thorium was determined by the single-phase steady-state technique and a new technique referred to as the two-phase nonsteady-state technique. Q* is temperature dependent, decreasing from about 20 kJ/mol at 1125 K to about -61 kJ/mol at 1458 K and is described by the relation, Q* = 274 - 0.24 T kJ/mol. The observed temperature dependence of Q* is consistent with a current model for the electronic contribution to Q*

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Excessive Biologic Response to IFNβ Is Associated with Poor Treatment Response in Patients with Multiple Sclerosis

Interferon-beta (IFNβ) is used to inhibit disease activity in multiple sclerosis (MS), but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified.he relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70) or poor response (n = 15). Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs).The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual ‘IFN response fingerprint’. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections.MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients

Tailoring of the magnetic properties of SmCo\u3csub\u3e5\u3c/sub\u3e:Nb\u3csub\u3e0.33\u3c/sub\u3eCr\u3csub\u3e0.67\u3c/sub\u3e nanocomposites using mechanical alloying

Nanocomposite structures composed of ferromagnetic particles dispersed in a matrix are systems in which the magnetic properties can be tailored by varying the size and spacing of the ferromagnetic particles. Nanocomposites of SmCo5 in a non-magnetic Nb0.33Cr0.67 matrix exhibit a wide variety of magnetic properties. SmCo5 powder is premilled prior to mechanical alloying. The premilliing results in a maximum coercivity of 16 kOe after 2 hours of milling, and an enhanced remanence ratio. Both features may be due to exchange anisotropy and/or exchange coupling between hard and soft ferromagnetic phases. The nanocomposite samples show that, when the SmCo5 particulates are small enough, the primary effect of alloying is to disperse them throughout the matrix with no further refinement of size

Adrenocorticotropic hormone methylprednisolone added to interferon β in patients with multiple sclerosis experiencing breakthrough disease: a randomized, rater-blinded trial

Background: The objective of this study was to evaluate monthly intramuscular adrenocorticotropic hormone (ACTH) gel versus intravenous methylprednisolone (IVMP) add-on therapy to interferon β for breakthrough disease in patients with relapsing forms of multiple sclerosis. Methods: This was a prospective, open-label, examiner-blinded, 15-month pilot study evaluating patients with Expanded Disability Status Scale (EDSS) score 3.0–6.5 and at least one clinical relapse or new T2 or gadolinium-enhanced lesion in the previous year. Twenty-three patients were randomized to ACTH ( n = 12) or IVMP ( n = 11) and completed the study. The primary outcome measure was the cumulative number of relapses. Secondary outcomes included EDSS, Mental Health Inventory (MHI), plasma cytokines, MS Functional Composite (MSFC), Quality-of-Life (MS-QOL) score, bone mineral density (BMD), and new or worsened psychiatric symptoms per month. Brain magnetic resonance imaging was analyzed post hoc . This was a preliminary and small-scale study. Results: Relapse rates differed significantly [ACTH 0.08, 95% confidence interval (CI) 0.01–0.54 versus IVMP 0.80, 95% CI 0.36–1.75; rate ratio, IVMP versus ACTH: 9.56, 95% CI 1.23–74.6; p = 0.03]. ACTH improved ( p = 0.03) MHI (slope 0.95 ± 0.38 points/month; p = 0.02 versus slope −0.38 ± 0.43 points/month; p = 0.39). On-study decreases (all p < 0.05) in eight cytokine levels occurred only in the ACTH group. However, on-study EDSS, MSFC, MS-QOL, BMD, and MRI lesion changes were not significant between groups. Psychiatric symptoms per patient were greater with IVMP than ACTH (0.55, 95% CI 0.12–2.6 versus 0; p < 0.0001). Other common adverse events were insomnia and urinary tract infections (IVMP, seven events each) and fatigue or flu symptoms (ACTH, five events each). Conclusions: This study provided class II evidence that ACTH produced better examiner-assessed cumulative rates of relapses per patient than IVMP in the adjunctive treatment of breakthrough disease in multiple sclerosis

mir-181a-1/b-1 Modulates Tolerance through Opposing Activities in Selection and Peripheral T Cell Function

Understanding the consequences of tuning TCR signaling on selection, peripheral T cell function, and tolerance in the context of native TCR repertoires may provide insight into the physiological control of tolerance. In this study, we show that genetic ablation of a natural tuner of TCR signaling, mir-181a-1/b-1, in double-positive thymocytes dampened TCR and Erk signaling and increased the threshold of positive selection. Whereas mir-181a-1/b-1 deletion in mice resulted in an increase in the intrinsic reactivity of naive T cells to self-antigens, it did not cause spontaneous autoimmunity. Loss of mir-181a-1/b-1 dampened the induction of experimental autoimmune encephalomyelitis and reduced basal TCR signaling in peripheral T cells and their migration from lymph nodes to pathogenic sites. Taken together, these results demonstrate that tolerance can be modulated by microRNA gene products through the control of opposing activities in T cell selection and peripheral T cell function

mir-181a-1/b-1

Understanding the consequences of tuning T cell receptor (TCR) signaling on selection, peripheral T cell function, and tolerance in the context of native TCR repertoires may provide insight into the physiological control of tolerance. Here we show that genetic ablation of a natural tuner of TCR signaling, mir-181a-1/b-1, in double-positive (DP) thymocytes dampened TCR and Erk signaling and increased the threshold of positive selection. Whereas mir-181a-1/b-1 deletion in mice resulted in an increase in the intrinsic reactivity of naive T cells to self-antigens, it did not cause spontaneous autoimmunity. Loss of mir-181a-1/b-1 dampened the induction of experimental autoimmune encephalomyelitis and reduced basal TCR signaling in peripheral T cells and their migration from lymph nodes to pathogenic sites. Together, these results demonstrate that tolerance can be modulated by miRNAs through the control of opposing activities in T cell selection and peripheral T cell function