The Effect of Neutral Atoms on Capillary Discharge Z-pinch

We study the effect of neutral atoms on the dynamics of a capillary discharge Z-pinch, in a regime for which a large soft-x-ray amplification has been demonstrated. We extended the commonly used one-fluid magneto-hydrodynamics (MHD) model by separating out the neutral atoms as a second fluid. Numerical calculations using this extended model yield new predictions for the dynamics of the pinch collapse, and better agreement with known measured data.Comment: 4 pages, 4 postscript figures, to be published in Phys. Rev. Let

Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats

Slow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development and further our understanding, implementation of the method in animal models is indispensable. Here, we report the successful employment of slow waves' phase-targeted closed-loop auditory stimulation (CLAS) in rats. To validate this new tool both conceptually and functionally, we tested the effects of up- and down-phase CLAS on proportions and spectral characteristics of sleep, and on learning performance in the single-pellet reaching task, respectively. Without affecting 24 hr sleep-wake behavior, CLAS specifically altered delta (slow waves) and sigma (sleep spindles) power persistently over chronic periods of stimulation. While up-phase CLAS does not elicit a significant change in behavioral performance, down-phase CLAS exerted a detrimental effect on overall engagement and success rate in the behavioral test. Overall CLAS-dependent spectral changes were positively correlated with learning performance. Altogether, our results provide proof-of-principle evidence that phase-targeted CLAS of slow waves in rodents is efficient, safe, and stable over chronic experimental periods, enabling the use of this high-specificity tool for basic and preclinical translational sleep research

Scaling of Self-Avoiding Walks in High Dimensions

We examine self-avoiding walks in dimensions 4 to 8 using high-precision Monte-Carlo simulations up to length N=16384, providing the first such results in dimensions $d > 4$ on which we concentrate our analysis. We analyse the scaling behaviour of the partition function and the statistics of nearest-neighbour contacts, as well as the average geometric size of the walks, and compare our results to $1/d$-expansions and to excellent rigorous bounds that exist. In particular, we obtain precise values for the connective constants, $\mu_5=8.838544(3)$, $\mu_6=10.878094(4)$, $\mu_7=12.902817(3)$, $\mu_8=14.919257(2)$ and give a revised estimate of $\mu_4=6.774043(5)$. All of these are by at least one order of magnitude more accurate than those previously given (from other approaches in $d>4$ and all approaches in $d=4$). Our results are consistent with most theoretical predictions, though in $d=5$ we find clear evidence of anomalous $N^{-1/2}$-corrections for the scaling of the geometric size of the walks, which we understand as a non-analytic correction to scaling of the general form $N^{(4-d)/2}$ (not present in pure Gaussian random walks).Comment: 14 pages, 2 figure

Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer: association of marker changes after two chemotherapy cycles with different measures of clinical response and survival

Prognostic implication of serum cytokeratin 19 fragments (CYFRA 21-1) was explored in 60 advanced NSCLC patients, whereas in 45 patients assessable for serological response a ⩾35% CYFRA 21-1 decline after two chemotherapy cycles was strongly associated with non-progression (NP), defined as a sum of objective response (OR)+stable disease (P<0.0001) and survival (P=0.0002). Association of OR with survival was not significant. In multivariate survival analysis, ⩾35% marker decline and radiological NP status were found as major determinants of prolonged survival with RR: 0.37 (P=0.01) and 0.63 (P=0.01), respectively. In advanced NSCLC patients, NP reflects therapeutic efficacy better than traditional OR. CYFRA 21-1 ⩾35% decline seems to be a reliable surrogate marker of treatment efficacy in terms of survival

Towards Machine Wald

The past century has seen a steady increase in the need of estimating and predicting complex systems and making (possibly critical) decisions with limited information. Although computers have made possible the numerical evaluation of sophisticated statistical models, these models are still designed \emph{by humans} because there is currently no known recipe or algorithm for dividing the design of a statistical model into a sequence of arithmetic operations. Indeed enabling computers to \emph{think} as \emph{humans} have the ability to do when faced with uncertainty is challenging in several major ways: (1) Finding optimal statistical models remains to be formulated as a well posed problem when information on the system of interest is incomplete and comes in the form of a complex combination of sample data, partial knowledge of constitutive relations and a limited description of the distribution of input random variables. (2) The space of admissible scenarios along with the space of relevant information, assumptions, and/or beliefs, tend to be infinite dimensional, whereas calculus on a computer is necessarily discrete and finite. With this purpose, this paper explores the foundations of a rigorous framework for the scientific computation of optimal statistical estimators/models and reviews their connections with Decision Theory, Machine Learning, Bayesian Inference, Stochastic Optimization, Robust Optimization, Optimal Uncertainty Quantification and Information Based Complexity.Comment: 37 page

Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder

International audienceAbstractBackgroundDeletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD).Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.Case presentationHere, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3.The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.ConclusionOur present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years

T Cells Specifically Targeted to Amyloid Plaques Enhance Plaque Clearance in a Mouse Model of Alzheimer's Disease

Patients with Alzheimer's disease (AD) exhibit substantial accumulation of amyloid-β (Aβ) plaques in the brain. Here, we examine whether Aβ vaccination can facilitate the migration of T lymphocytes to specifically target Aβ plaques and consequently enhance their removal. Using a new mouse model of AD, we show that immunization with Aβ, but not with the encephalitogenic proteolipid protein (PLP), results in the accumulation of T cells at Aβ plaques in the brain. Although both Aβ-reactive and PLP-reactive T cells have a similar phenotype of Th1 cells secreting primarily IFN-γ, the encephalitogenic T cells penetrated the spinal cord and caused experimental autoimmune encephalomyelitis (EAE), whereas Aβ T cells accumulated primarily at Aβ plaques in the brain but not the spinal cord and induced almost complete clearance of Aβ. Furthermore, while a single vaccination with Aβ resulted in upregulation of the phagocytic markers triggering receptors expressed on myeloid cells-2 (TREM2) and signal regulatory protein-β1 (SIRPβ1) in the brain, it caused downregulation of the proinflammatory cytokines TNF-α and IL-6. We thus suggest that Aβ deposits in the hippocampus area prioritize the targeting of Aβ-reactive but not PLP-reactive T cells upon vaccination. The stimulation of Aβ-reactive T cells at sites of Aβ plaques resulted in IFN-γ-induced chemotaxis of leukocytes and therapeutic clearance of Aβ

The Development of a Conceptual Framework and Tools to Assess Undergraduates' Principled Use of Models in Cellular Biology

Recent science education reform has been marked by a shift away from a focus on facts toward deep, rich, conceptual understanding. This requires assessment that also focuses on conceptual understanding rather than recall of facts. This study outlines our development of a new assessment framework and tool—a taxonomy— which, unlike existing frameworks and tools, is grounded firmly in a framework that considers the critical role that models play in science. It also provides instructors a resource for assessing students' ability to reason about models that are central to the organization of key scientific concepts. We describe preliminary data arising from the application of our tool to exam questions used by instructors of a large-enrollment cell and molecular biology course over a 5-yr period during which time our framework and the assessment tool were increasingly used. Students were increasingly able to describe and manipulate models of the processes and systems being studied in this course as measured by assessment items. However, their ability to apply these models in new contexts did not improve. Finally, we discuss the implications of our results and the future directions for our research