Impaired Hyperemic Response to Exercise Post Stroke

Individuals with chronic stroke have reduced perfusion of the paretic lower limb at rest; however, the hyperemic response to graded muscle contractions in this patient population has not been examined. This study quantified blood flow to the paretic and non-paretic lower limbs of subjects with chronic stroke after submaximal contractions of the knee extensor muscles and correlated those measures with limb function and activity. Ten subjects with chronic stroke and ten controls had blood flow through the superficial femoral artery quantified with ultrasonography before and immediately after 10 second contractions of the knee extensor muscles at 20, 40, 60, and 80% of the maximal voluntary contraction (MVC) of the test limb. Blood flow to the paretic and non-paretic limb of stroke subjects was significantly reduced at all load levels compared to control subjects even after normalization to lean muscle mass. Of variables measured, increased blood flow after an 80% MVC was the single best predictor of paretic limb strength, the symmetry of strength between the paretic and non-paretic limbs, coordination of the paretic limb, and physical activity. The impaired hemodynamic response to high intensity contractions was a better predictor of lower limb function than resting perfusion measures. Stroke-dependent weakness and atrophy of the paretic limb do not explain the reduced hyperemic response to muscle contraction alone as the response is similarly reduced in the non-paretic limb when compared to controls. These data may suggest a role for perfusion therapies to optimize rehabilitation post stroke

Rapid enhancement of touch from non-informative vision of the hand

Processing in one sensory modality may modulate processing in another. Here we investigate how simply viewing the hand can influence the sense of touch. Previous studies showed that non-informative vision of the hand enhances tactile acuity, relative to viewing an object at the same location. However, it remains unclear whether this Visual Enhancement of Touch (VET) involves a phasic enhancement of tactile processing circuits triggered by the visual event of seeing the hand, or more prolonged, tonic neuroplastic changes, such as recruitment of additional cortical areas for tactile processing. We recorded somatosensory evoked potentials (SEPs) evoked by electrical stimulation of the right middle finger, both before and shortly after viewing either the right hand, or a neutral object presented via a mirror. Crucially, and unlike prior studies, our visual exposures were unpredictable and brief, in addition to being non-informative about touch. Viewing the hand, as opposed to viewing an object, enhanced tactile spatial discrimination measured using grating orientation judgements, and also the P50 SEP component, which has been linked to early somatosensory cortical processing. This was a trial-specific, phasic effect, occurring within a few seconds of each visual onset, rather than an accumulating, tonic effect. Thus, somatosensory cortical modulation can be triggered even by a brief, non-informative glimpse of one’s hand. Such rapid multisensory modulation reveals novel aspects of the specialised brain systems for functionally representing the body

Assessment of Stellar Stratification in Three Young Star Clusters in the Large Magellanic Cloud

(abridged) We present a comprehensive study of stellar stratification in young star clusters in the Large Magellanic Cloud (LMC). We apply our recently developed effective radius method for the assessment of stellar stratification on imaging data obtained with the Advanced Camera for Surveys of three young LMC clusters to characterize the phenomenon and develop a comparative scheme for its assessment in such clusters. The clusters of our sample, NGC 1983, NGC 2002 and NGC 2010, are selected on the basis of their youthfulness, and their variety in appearance, structure, stellar content, and surrounding stellar ambient. Our photometry is complete for magnitudes down to m_814 ~ 23 mag, allowing the calculation of the structural parameters of the clusters, the estimation of their ages and the determination of their stellar content. Our study shows that each cluster in our sample demonstrates stellar stratification in a quite different manner and at different degree from the others. Specifically, NGC 1983 shows to be partially segregated only for the faintest stars of the cluster, NGC 2002 shows evidence of strong stellar stratification for both bright and faint stars, and NGC 2010 is found not to be segregated. For the parametrization of the phenomenon of stellar stratification and its quantitative comparison among these clusters, we propose the slope derived from the change in the effective radius over the corresponding magnitude range as indicative parameter of the degree of stratification in the clusters. A positive value of this slope indicates mass segregation in the cluster, while a negative or zero value signifies the lack of the phenomenon.Comment: To appear in the Astrophysical Journal Vol. 709 (2010), pp. 263-277 Version with low-Resolution gray-scaled figures. Version with full resolution color figures available from http://rapidshare.com/files/328406139/Gouliermis_2010.ApJ.709.pd

Clinically relevant dual probe difference specimen imaging (DDSI) protocol for freshly resected breast cancer specimen staining

Background: Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow. Methods: In previous work, we have developed and validated a fluorescence imaging method termed dual probe difference specimen imaging (DDSI) to accurately detect benign and malignant tissue with direct correlation to the targeted biomarker expression levels intraoperatively. The DDSI method is currently on par with touch prep cytology in execution time (~ 15-min). In this study, the main goal was to shorten the DDSI protocol by decreasing tissue blocking and washing times to optimize the DDSI protocol to \u3c 10-min whilst maintaining robust benign and malignant tissue differentiation. Results: We evaluated the utility of the shortened DDSI staining methodology using xenografts grown from cell lines with varied epidermal growth factor receptor (EGFR) expression levels, comparing accuracy through receiver operator characteristic (ROC) curve analyses across varied tissue blocking and washing times. An optimized 8-min DDSI methodology was developed for future clinical translation. Conclusions: Successful completion of this work resulted in substantial shortening of the DDSI methodology for use in the operating room, that provided robust, highly receptor specific, sensitive diagnostic capabilities between benign and malignant tissues

Vector Correlators in Lattice QCD: methods and applications

We discuss the calculation of the leading hadronic vacuum polarization in lattice QCD. Exploiting the excellent quality of the compiled experimental data for the e^+e^- --> hadrons cross-section, we predict the outcome of large-volume lattice calculations at the physical pion mass, and design computational strategies for the lattice to have an impact on important phenomenological quantities such as the leading hadronic contribution to (g-2)mu and the running of the electromagnetic coupling constant. First, the R(s) ratio can be calculated directly on the lattice in the threshold region, and we provide the formulae to do so with twisted boundary conditions. Second, the current correlator projected onto zero spatial momentum, in a Euclidean time interval where it can be calculated accurately, provides a potentially critical test of the experimental R(s) ratio in the region that is most relevant for (g-2)mu. This observation can also be turned around: the vector correlator at intermediate distances can be used to determine the lattice spacing in fm, and we make a concrete proposal in this direction. Finally, we quantify the finite-size effects on the current correlator coming from low-energy two-pion states and provide a general parametrization of the vacuum polarization on the torus.Comment: 16 pages, 9 figure files; corrected a factor 2 in Eq. (7) over the published versio

Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses

Purpose: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments. Methods: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions. Results: Most CAPN5 genetic variation occurs outside its protease core; and searches of cancer and epilepsy/autism genetic databases found no variants similar to hyperactivating retinal disease alleles. The mouse retina expressed one transcript for CAPN5 plus those of nine other calpains, similar to the human retina. In Y79 retinoblastoma cells, the level of CAPN5 transcript was very low. Immunohistochemistry detected CAPN5 expression in the inner and outer nuclear layers and at synapses in the outer plexiform layer. Western analysis of fractionated retinal extracts confirmed CAPN5 synapse localization. Western blots of fractionated brain neuronal extracts revealed distinct subcellular patterns and the potential presence of autoproteolytic CAPN5 domains. Conclusions: CAPN5 is moderately expressed in the retina and, despite higher expression in other tissues, hyperactive disease mutants of CAPN5 only manifest as eye disease. At the cellular level, CAPN5 is expressed in several different functional compartments. CAPN5 localization at the photoreceptor synapse and with mitochondria explains the neural circuitry phenotype in human CAPN5 disease alleles

A necroptosis-independent function of RIPK3 promotes immune dysfunction and prevents control of chronic LCMV infection

Necroptosis is a lytic and inflammatory form of cell death that is highly constrained to mitigate detrimental collateral tissue damageand impaired immunity. These constraints make it difficult to define the relevance of necroptosis in diseases such as chronic andpersistent viral infections and within individual organ systems. The role of necroptotic signalling is further complicated becauseproteins essential to this pathway, such as receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like(MLKL), have been implicated in roles outside of necroptotic signalling. We sought to address this issue by individually defining therole of RIPK3 and MLKL in chronic lymphocytic choriomeningitis virus (LCMV) infection. We investigated if necroptosis contributesto the death of LCMV-specific CD8+ T cells or virally infected target cells during infection. We provide evidence showing thatnecroptosis was redundant in the pathogenesis of acute forms of LCMV (Armstrong strain) and the early stages of chronic (Docilestrain) LCMV infection in vivo. The number of immune cells, their specificity and reactivity towards viral antigens and viral loads arenot altered in the absence of either MLKL or RIPK3 during acute and during the early stages of chronic LCMV infection. However, weidentified that RIPK3 promotes immune dysfunction and prevents control of infection at later stages of chronic LCMV disease. Thiswas not phenocopied by the loss of MLKL indicating that the phenotype was driven by a necroptosis-independent function ofRIPK3. We provide evidence that RIPK3 signaling evoked a dysregulated type 1 interferone response which we linked to animpaired antiviral immune response and abrogated clearance of chronic LCMV infectio

Comparing Internalization of Appearance Ideals and Appearance-Related Pressures Among Women from the United States, Italy, England, and Australia

Researchers have observed variation in levels of body image disturbance and eating pathology among women from different Western countries. Examination of cross-cultural differences in the established risk factors (i.e., thin-ideal internalization, muscular-ideal internalization, and appearance pressures from family, peers, and media) for negative outcomes may help to elucidate the prominence of specific risk factors within a given Western society and guide associated interventions. Women from the United States (US), Italy, England, and Australia completed the Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4). Analysis of covariance controlling for age and BMI indicated significant cross-country differences for all SATAQ-4 subscales. Results typically indicated higher levels of appearance-ideal internalization and appearance pressures in the US and lower levels in Italy; however, associated effect sizes were generally small. A medium effect of country was observed for peer-appearance pressures, which were highest in the US compared with all other countries. Repeated-measures analysis of variance and paired samples t tests conducted within each country identified thin-ideal internalization and media appearance pressures as the predominant risk factors for all four countries. Overall, findings suggest more cross-country similarities than differences, and highlight the importance of delivering interventions to address thin-ideal internalization and media appearance pressures among women from Western backgrounds

Implications of mirror neutrinos for early universe cosmology

The Exact Parity Model (EPM) is, in part, a theory of neutrino mass and mixing that can solve the atmospheric, solar and LSND anomalies. The central feature of the neutrino sector is three pairs of maximally mixed ordinary and mirror neutrinos. It has been shown that ordinary-mirror neutrino oscillations can generate large neutrino asymmetries in the epoch of the early universe immediately prior to Big Bang Nucleosynthesis (BBN). The large neutrino asymmetries generically suppress the production of mirror neutrinos, and a sufficiently large $\nu_e$ asymmetry can directly affect light element synthesis through nuclear reaction rates. In this paper we present a detailed calculation of neutrino asymmetry evolution driven by the six-flavour EPM neutrino sector, focusing on implications for BBN.Comment: Latex, about 55 pages long with some figure