Spectrum of an oscillator with jumping frequency and the interference of partial susceptibilities

We study an underdamped oscillator with shot-noise frequency fluctuations. The oscillator spectrum is determined by the interference of the susceptibilities for different eigenfrequencies. Depending on the parameters, it has a fine structure or displays a single asymmetric peak. For nano-mechanical resonators with a fluctuating number of attached molecules, the spectrum is found in a simple analytical form. The results bear on various types of systems where the reciprocal correlation time of frequency fluctuations can be comparable to the typical frequency jumps

Does malnutrition influence outcome in children undergoing congenital heart surgery in a developing country?

Background Most children undergoing cardiac surgery for congenital heart disease (CHD) in developing countries are malnourished. Malnutrition is known as a co-morbidity factor that might predict and influence outcomes after surgery. Objectives To evaluate the effect of malnutrition and other associated risk factors on post-operative outcomes in children with CHDs underwent cardiac surgery. Methods We conducted a retrospective cohort study in a single center tertiary pediatric cardiac intensive care unit (PCICU) in Indonesia. Our cohort included all children between 5 and 36 months of age undergoing congenital heart surgery with cardiopulmonary bypass from November 2011 until February 2014. Outcomes measured were the length of intubation and the length of ICU stay. Variables for potential influence investigated were the nutritional status, age, gender, type of cardiac anomaly (acyanotic vs. cyanotic), Aristotle score, cardiopulmonary bypass time, aortic cross-clamp time, and Pediatric Risk of Mortality (PRISM) III score. Results Out of 249 patients included, 147 (59%) showed malnourishment on admission. Malnourished patients were significantly younger in age, presented with an acyanotic heart defects, and had higher PRISM III score. Additionally, they also had a longer mechanical ventilation time and ICU stay than those with a normal nutritional status. After adjusting for various variables using a multiple logistic regression model it could be demonstrated that a higher Z-score for weight to age was a significant protective factor for the intubation time of more than 29 hours with an odds ratio of 0.66 (95% CI 0.48 to 0.92, P = 0.012). Non-malnourished patients had a 49% significantly higher chance for extubation with a hazard ratio of 1.49 (95% CI 1.12 to 1.99, P= 0.007). Conclusion Malnourishment is clearly associated in a linear fashion with longer mechanical ventilation and ICU stay. As one of significant and potentially treatable co-morbidity factors, prevention of malnourishment by early diagnosis and optimal timing for surgery is important

MuRF1 mono-ubiquitinates TRα to inhibit T3-induced cardiac hypertrophy in vivo

Thyroid hormone (TH) is recognized for its role in cellular metabolism and growth and participates in homeostasis of the heart. T3 activates pro-survival pathways including Akt and mTOR. Treatment with T3 after myocardial infarction is cardioprotective and promotes elements of physiological hypertrophic response after cardiac injury. Although T3 is known to benefit the heart, very little about its regulation at the molecular level has been described to date. The ubiquitin proteasome system (UPS) regulates nuclear hormone receptors such as estrogen, progesterone, androgen, and glucocorticoid receptors by both degradatory and non-degradatory mechanisms. However, how the UPS regulates T3-mediated activity is not well understood. In this study, we aim to determine the role of the muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) in regulating T3-induced cardiomyocyte growth. An increase in MuRF1 expression inhibits T3-induced physiological cardiac hypertrophy, whereas a decrease in MuRF1 expression enhances T3’s activity both in vitro and in cardiomyocytes in vivo. MuRF1 interacts directly with TRα to inhibit its activity by posttranslational ubiquitination in a non-canonical manner. We then demonstrated that a nuclear localization apparatus that regulates/inhibits nuclear receptors by sequestering them within a subcompartment of the nucleus was necessary for MuRF1 to inhibit T3 activity. This work implicates a novel mechanism that enhances the beneficial T3 activity specifically within the heart, thereby offering a potential target to enhance cardiac T3 activity in an organ-specific manner

Spin-Glass Model for Inverse Freezing

We analyze the Blume-Emery-Griffiths model with disordered magnetic interaction displaying the inverse freezing phenomenon. The behaviour of this spin-1 model in crystal field is studied throughout the phase diagram and the transition and spinodal lines for the model are computed using the Full Replica Symmetry Breaking Ansatz that always yelds a thermodynamically stable phase. We compare the results both with the quenched disordered model with Ising spins on lattice gas - where no reentrance takes place - and with the model with generalized spin variables recently introduced by Schupper and Shnerb [Phys. Rev. Lett. 93, 037202 (2004)]. The simplest version of all these models, known as Ghatak-Sherrington model, turns out to hold all the general features characterizing an inverse transition to an amorphous phase, including the right thermodynamic behavior.Comment: 6 pages, 4 figures, to appear in the Proceeding for the X International Workshop on Disordered Systems (2006), Molveno, Ital

Embedding a Native State into a Random Heteropolymer Model: The Dynamic Approach

We study a random heteropolymer model with Langevin dynamics, in the supersymmetric formulation. Employing a procedure similar to one that has been used in static calculations, we construct an ensemble in which the affinity of the system for a native state is controlled by a "selection temperature" T0. In the limit of high T0, the model reduces to a random heteropolymer, while for T0-->0 the system is forced into the native state. Within the Gaussian variational approach that we employed previously for the random heteropolymer, we explore the phases of the system for large and small T0. For large T0, the system exhibits a (dynamical) spin glass phase, like that found for the random heteropolymer, below a temperature Tg. For small T0, we find an ordered phase, characterized by a nonzero overlap with the native state, below a temperature Tn \propto 1/T0 > Tg. However, the random-globule phase remains locally stable below Tn, down to the dynamical glass transition at Tg. Thus, in this model, folding is rapid for temperatures between Tg and Tn, but below Tg the system can get trapped in conformations uncorrelated with the native state. At a lower temperature, the ordered phase can also undergo a dynamical glass transition, splitting into substates separated by large barriers.Comment: 19 pages, revtex, 6 figure

Decreased blood–brain barrier P-glycoprotein function in the progression of Parkinson’s disease, PSP and MSA

Decreased blood–brain barrier (BBB) efflux function of the P-glycoprotein (P-gp) transport system could facilitate the accumulation of toxic compounds in the brain, increasing the risk of neurodegenerative pathology such as Parkinson’s disease (PD). This study investigated in vivo BBB P-gp function in patients with parkinsonian neurodegenerative syndromes, using [11C]-verapamil PET in PD, PSP and MSA patients. Regional differences in distribution volume were studied using SPM with higher uptake interpreted as reduced P-gp function. Advanced PD patients and PSP patients had increased [11C]-verapamil uptake in frontal white matter regions compared to controls; while de novo PD patients showed lower uptake in midbrain and frontal regions. PSP and MSA patients had increased uptake in the basal ganglia. Decreased BBB P-gp function seems a late event in neurodegenerative disorders, and could enhance continuous neurodegeneration. Lower [11C]-verapamil uptake in midbrain and frontal regions of de novo PD patients could indicate a regional up-regulation of P-gp function

Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

The landscape of gifted and talented education in England and Wales: How are teachers implementing policy?

This is an Author's Accepted Manuscript of an article published in Research Papers in Education, 27(2), 167-186, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/02671522.2010.509514.This paper explores the evidence relating to how primary schools are responding to the ‘gifted and talented’ initiative in England and Wales. A questionnaire survey which invited both closed and open-ended responses was carried out with a national sample of primary schools. The survey indicated an increasing proportion of coordinators, compared with a survey carried out in 1996, were identifying their gifted and talented children as well as having associated school policies. However, the survey also highlighted a number of issues which need addressing if the initiative is to achieve its objective of providing the best possible educational opportunities for children. For example, it was found that a significant number of practitioners were not aware of the existence of the National Quality Standards for gifted and talented education, provided by the UK government in 2007, and the subject-specific criteria provided by the UK’s Curriculum Authority for identification and provision have been largely ignored. The process of identifying children to be placed on the ‘gifted and talented’ register seems haphazard and based on pragmatic reasons. Analysis of teachers’ responses also revealed a range of views and theoretical positioning held by them, which have implications for classroom practice. As the ‘gifted and talented’ initiative in the UK is entering a second decade, and yet more significant changes in policy are introduced, pertinent questions need to be raised and given consideration

A mesh reinforced pressure-sensitive adhesive for a linerless label design

A concept for an on-demand linerless pressure sensitive adhesive (PSA) label is shown. Containment of a PSA has been achieved by entrapment within a scaffolding 3D hard mesh structure. The label sticks upon instant application of heat and pressure, which softens and deforms the mesh allowing for PSA release. The design eliminates the need for a release liner and release coating in labels offering a more sustainable product. Herein, the mesh-reinforced PSA system was made by film formation of a binary polymer latex mixture consisting of ‘hard’ (high glass transition temperature, Tg,hard) polystyrene particles and a ‘soft’ (low glass transition temperature Tg,soft) poly(n-butyl acrylate)-based PSA latex of similar particle diameter, onto a model polyethylene terephthalate (PET) facestock. The system was annealed above Tg,hard to fuse the polystyrene colloids, creating a 3D interconnected open cellular network. The porous scaffold was shown by scanning electron microscopy, X-ray computed tomography, and confocal microscopy. The linerless PSA label is in a dormant, ‘non-stick’ state at room temperature l storage conditions. Adhesion is activated on demand with heat (T > Tg,hard) and light pressure. The adhesive behavior of the linerless PSA labels was probed using peel, shear strength and tack, its performance being promising

Temporal clustering of Kawasaki disease cases around the world

In a single-site study (San Diego, CA, USA), we previously showed that Kawasaki Disease (KD) cases cluster temporally in bursts of approximately 7 days. These clusters occurred more often than would be expected at random even after accounting for long-term trends and seasonality. This finding raised the question of whether other locations around the world experience similar temporal clusters of KD that might offer clues to disease etiology. Here we combine data from San Diego and nine additional sites around the world with hospitals that care for large numbers of KD patients, as well as two multi-hospital catchment regions. We found that across these sites, KD cases clustered at short time scales and there were anomalously long quiet periods with no cases. Both of these phenomena occurred more often than would be expected given local trends and seasonality. Additionally, we found unusually frequent temporal overlaps of KD clusters and quiet periods between pairs of sites. These findings suggest that regional and planetary range environmental influences create periods of higher or lower exposure to KD triggers that may offer clues to the etiology of KD