Tests of electron flavor conservation with the Sudbury Neutrino Observatory

We analyze tests of electron flavor conservation that can be performed at the Sudbury Neutrino Observatory (SNO). These tests, which utilize $^8$B solar neutrinos interacting with deuterium, measure: 1) the shape of the recoil electron spectrum in charged-current (CC) interactions (the CC spectrum shape); and 2) the ratio of the number of charged current to neutral current (NC) events (the CC/NC ratio). We determine standard model predictions for the CC spectral shape and for the CC/NC ratio, together with realistic estimates of their errors and the correlations between errors. We consider systematic uncertainties in the standard neutrino spectrum and in the charged-current and neutral current cross-sections, the SNO energy resolution and absolute energy scale, and the SNO detection efficiencies. Assuming that either matter-enhanced or vacuum neutrino oscillations solve the solar neutrino problems, we calculate the confidence levels with which electron flavor non-conservation can be detected using either the CC spectrum shape or the CC/NC ratio, or both. If the SNO detector works as expected, the neutrino oscillation solutions that best-fit the results of the four operating solar neutrino experiments can be distinguished unambiguously from the standard predictions of electron flavor conservation.Comment: 31 pages (RevTeX) + 10 figures (postscript). Requires epsfig.sty. Gzipped figures also available at ftp://ftp.sns.ias.edu/pub/lisi/snopaper . To appear in Phys. Rev.

Is poetry therapy an appropriate intervention for clients recovering from anorexia? A critical review of the literature and client report

© 2017 Informa UK Limited, trading as Taylor & Francis Group. Poetry therapy is an arts-based psychotherapeutic intervention, often delivered in groups. This paper argues that the process and benefits of poetry therapy may be particularly suited to clients recovering from anorexia, as an adjunct to other treatments. Poetry therapy and its history are described briefly, and the relevance of poetry therapy for clients recovering from anorexia is outlined. After one client contributes her experience of this treatment for illustration, the paper offers a review of the evidence base for poetry therapy for eating disorders, and argues that, while research is limited, further research is warranted. Finally, a description of one form of clinical application is offered, to enable replication

Effects of aging and type 2 diabetes on resting and post occlusive hyperemia of the forearm; the impact of rosiglitazone

BACKGROUND: Both Diabetes and ageing are associated with reduced vascular endothelial function. The exact relationship between the 2 and any improvements from the insulin sensitizer rosiglitazone have not been explored. METHODS: Thirty controls and sixteen subjects with type 2 diabetes participated in a series of experiments to examine the interrelationships between age, diabetes and endothelial cell function. In subjects with diabetes, the insulin sensitizer rosiglitazone (RSG), a drug also known to improve vascular function, was administered for 3 months to see how it altered these relationships. Resting forearm flows (RF) and blood flows after 4 min of vascular occlusion (PF) were measured as an index of endothelial cell function. RESULTS: RF, measured by venous occlusion plethysmography, was negatively correlated to both age and diabetes. Administration of RSG for 3 months was associated with an increase in the blood flow response to venous occlusion so that it was not significantly different than that of age matched controls. Total PF in control subjects, compared to subjects with diabetes, averaged 56.58 +/- 12.57 and 13.6 +/- 8.01 cc/100 cc tissue per min respectively, and were significantly different (p < 0.01). After 3 months on RSG, differences between PF in the two groups were no longer evident. CONCLUSION: These studies suggest a different mechanism causing a reduction in vascular reactivity with aging and diabetes

MiTF links Erk1/2 kinase and p21CIP1/WAF1 activation after UVC radiation in normal human melanocytes and melanoma cells

As a survival factor for melanocytes lineage cells, MiTF plays multiple roles in development and melanomagenesis. What role MiTF plays in the DNA damage response is currently unknown. In this report we observed that MiTF was phosphorylated at serine 73 after UVC radiation, which was followed by proteasome-mediated degradation. Unlike after c-Kit stimulation, inhibiting p90RSK-1 did not abolish the band shift of MiTF protein, nor did it abolish the UVC-mediated MiTF degradation, suggesting that phosphorylation on serine 73 by Erk1/2 is a key event after UVC. Furthermore, the MiTF-S73A mutant (Serine 73 changed to Alanine via site-directed mutagenesis) was unable to degrade and was continuously expressed after UVC exposure. Compared to A375 melanoma cells expressing wild-type MiTF (MiTF-WT), cells expressing MiTF-S73A mutant showed less p21WAF1/CIP1 accumulation and a delayed p21WAF1/CIP1 recovery after UVC. Consequently, cells expressing MiTF-WT showed a temporary G1 arrest after UVC, but cells expressing MiTF-S73A mutant or lack of MiTF expression did not. Finally, cell lines with high levels of MiTF expression showed higher resistance to UVC-induced cell death than those with low-level MiTF. These data suggest that MiTF mediates a survival signal linking Erk1/2 activation and p21WAF1/CIP1 regulation via phosphorylation on serine 73, which facilitates cell cycle arrest. In addition, our data also showed that exposure to different wavelengths of UV light elicited different signal pathways involving MiTF

Chaotic Signatures of Heart Rate Variability and Its Power Spectrum in Health, Aging and Heart Failure

A paradox regarding the classic power spectral analysis of heart rate variability (HRV) is whether the characteristic high- (HF) and low-frequency (LF) spectral peaks represent stochastic or chaotic phenomena. Resolution of this fundamental issue is key to unraveling the mechanisms of HRV, which is critical to its proper use as a noninvasive marker for cardiac mortality risk assessment and stratification in congestive heart failure (CHF) and other cardiac dysfunctions. However, conventional techniques of nonlinear time series analysis generally lack sufficient sensitivity, specificity and robustness to discriminate chaos from random noise, much less quantify the chaos level. Here, we apply a ‘litmus test’ for heartbeat chaos based on a novel noise titration assay which affords a robust, specific, time-resolved and quantitative measure of the relative chaos level. Noise titration of running short-segment Holter tachograms from healthy subjects revealed circadian-dependent (or sleep/wake-dependent) heartbeat chaos that was linked to the HF component (respiratory sinus arrhythmia). The relative ‘HF chaos’ levels were similar in young and elderly subjects despite proportional age-related decreases in HF and LF power. In contrast, the near-regular heartbeat in CHF patients was primarily nonchaotic except punctuated by undetected ectopic beats and other abnormal beats, causing transient chaos. Such profound circadian-, age- and CHF-dependent changes in the chaotic and spectral characteristics of HRV were accompanied by little changes in approximate entropy, a measure of signal irregularity. The salient chaotic signatures of HRV in these subject groups reveal distinct autonomic, cardiac, respiratory and circadian/sleep-wake mechanisms that distinguish health and aging from CHF

Assessing Walking Ability in People with HTLV-1-Associated Myelopathy Using the 10 Meter Timed Walk and the 6 Minute Walk Test

Five to ten million persons, are infected by HTLV-1 of which 3% will develop HTLV-1-associated myelopathy (HAM) a chronic, disabling inflammation of the spinal cord. Walking, a fundamental, complex, multi-functional task is demanding of multiple body systems. Restricted walking ability compromises activity and participation levels in people with HAM (pwHAM). Therapy aims to improve mobility but validated measures are required to assess change.Prospective observational study.To explore walking capacity in pwHAM, walking endurance using the 6 minute walk (6MW), and gait speed, using the timed 10m walk (10mTW).Out-patient setting in an inner London Teaching hospital.Prospective documentation of 10mTW and 6MW distance; walking aid usage and pain scores measured twice, a median of 18 months apart.Data analysis was completed for twenty-six pwHAM, (8♂; 18♀; median age: 57.8 years; median disease duration: 8 years). Median time at baseline to: complete 10m was 17.5 seconds, versus 21.4 seconds at follow up; 23% completed the 6MW compared to 42% at follow up and a median distance of 55m was covered compared to 71m at follow up. Using the 10mTW velocity to predict the 6MW distance, overestimated the distance walked in 6 minutes (p<0.01). Functional decline over time was captured using the functional ambulation categories.The 10mTW velocity underestimated the degree of disability. Gait speed usefully predicts functional domains, shows direction of functional change and comparison with published healthy age matched controls show that these patients have significantly slower gait speeds. The measured differences over 18 months were sufficient to reliably detect change and therefore these assessments can be useful to detect improvement or deterioration within broader disability grades. Walking capacity in pwHAM should be measured using the 10mTW for gait speed and the 6MW for endurance

PAX3 Expression in Normal Skin Melanocytes and Melanocytic Lesions (Naevi and Melanomas)

Background Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanoma staging and detection. In this study we analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions to better assess its function in these various tissues. Pax3 and PAX3 (italicized) refer to the mouse and human gene, respectively; whereas Pax3 and PAX3 (non-italicized) refer to the corresponding mouse and human protein. Methodology and Principal Findings PAX3 expression was analysed by immunohistochemistry and qRT-PCR. Immunofluorescence was used for co-expression with differentiation, migration and survival markers. As expected PAX3 expression was observed in naevi and melanoma cells. It was also found in melanocytes of normal skin where it co-expressed with melanocyte markers, MITF and MLANA. Co-expression with its downstream target, antiapoptotic factor BCL2L1 confirms PAX3 as a cell survival regulator. PAX3 was also co-expressed with melanoma cell migration marker MCAM in dermal naevi and melanoma cell nests, but this downstream target of PAX3 was not present in normal epidermal melanocytes, suggesting differential roles for PAX3 in normal epidermal melanocytes and melanoma cells. Most interestingly, a proportion of PAX3-positive epidermal melanocytes in normal skin show HES1 and Ki67 co-expression, indicating their less differentiated proliferative phenotype. Conclusions and Significance Our results suggest that a previously identified role for PAX3, that of regulator of an undifferentiated plastic state, may operate in melanocytes of normal skin. This role, possibly required for cellular response to environmental stimuli, may contribute to formation and development of melanocytic lesions in which PAX3 expression is prominent

The Secreted Metalloprotease ADAMTS20 Is Required for Melanoblast Survival

ADAMTS20 (A disintegrin-like and metalloprotease domain with thrombospondin type-1 motifs) is a member of a family of secreted metalloproteases that can process a variety of extracellular matrix (ECM) components and secreted molecules. Adamts20 mutations in belted (bt) mice cause white spotting of the dorsal and ventral torso, indicative of defective neural crest (NC)-derived melanoblast development. The expression pattern of Adamts20 in dermal mesenchymal cells adjacent to migrating melanoblasts led us to initially propose that Adamts20 regulated melanoblast migration. However, using a Dct-LacZ transgene to track melanoblast development, we determined that melanoblasts were distributed normally in whole mount E12.5 bt/bt embryos, but were specifically reduced in the trunk of E13.5 bt/bt embryos due to a seven-fold higher rate of apoptosis. The melanoblast defect was exacerbated in newborn skin and embryos from bt/bt animals that were also haploinsufficient for Adamts9, a close homolog of Adamts20, indicating that these metalloproteases functionally overlap in melanoblast development. We identified two potential mechanisms by which Adamts20 may regulate melanoblast survival. First, skin explant cultures demonstrated that Adamts20 was required for melanoblasts to respond to soluble Kit ligand (sKitl). In support of this requirement, bt/bt;Kittm1Alf/+ and bt/bt;KitlSl/+ mice exhibited synergistically increased spotting. Second, ADAMTS20 cleaved the aggregating proteoglycan versican in vitro and was necessary for versican processing in vivo, raising the possibility that versican can participate in melanoblast development. These findings reveal previously unrecognized roles for Adamts proteases in cell survival and in mediating Kit signaling during melanoblast colonization of the skin. Our results have implications not only for understanding mechanisms of NC-derived melanoblast development but also provide insights on novel biological functions of secreted metalloproteases