Current distribution in a parallel configuration superconducting strip-line detector

Superconducting detectors based on parallel microscopic strip-lines are promising candidates for single molecule detection in time-of-flight mass spectrometry. The device physics of this configuration is complex. In this letter, we employ nano-optical techniques to study the variation of current density, count rate, and pulse amplitude transversely across the parallel strip device. Using the phenomenological London theory, we are able to correlate our results to a non-uniform current distribution between the strips, governed by the London magnetic penetration depth. This fresh perspective convincingly explains anomalous behaviour in large area parallel superconducting strip-line detectors reported in previous studies

Transcriptome Analysis of Gene Expression Provides New Insights into the Effect of Mild Therapeutic Hypothermia on Primary Human Cortical Astrocytes Cultured under Hypoxia

Hypothermia is increasingly used as a therapeutic measure to treat brain injury. However, the cellular mechanisms underpinning its actions are complex and are not yet fully elucidated. Astrocytes are the most abundant cell type in the brain and are likely to play a critical role. In this study, transcriptional changes and the protein expression profile of human primary cortical astrocytes cultured under hypoxic conditions for 6 h were investigated. Cells were treated either with or without a mild hypothermic intervention 2 h post-insult to mimic the treatment of patients following traumatic brain injury (TBI) and/or stroke. Using human gene expression microarrays, 411 differentially expressed genes were identified following hypothermic treatment of astrocytes following a 2 h hypoxic insult. KEGG pathway analysis indicated that these genes were mainly enriched in the Wnt and p53 signaling pathways, which were inhibited following hypothermic intervention. The expression levels of 168 genes involved in Wnt signaling were validated by quantitative real-time-PCR (qPCR). Among these genes, 10 were up-regulated and 32 were down-regulated with the remainder unchanged. Two of the differentially expressed genes (DEGs), p38 and JNK, were selected for validation at the protein level using cell based ELISA. Hypothermic intervention significantly down-regulated total protein levels for the gene products of p38 and JNK. Moreover, hypothermia significantly up-regulated the phosphorylated (activated) forms of JNK protein, while downregulating phosphorylation of p38 protein. Within the p53 signaling pathway, 35 human apoptosis-related proteins closely associated with Wnt signaling were investigated using a Proteome Profiling Array. Hypothermic intervention significantly down-regulated 18 proteins, while upregulating one protein, survivin. Hypothermia is a complex intervention; this study provides the first detailed longitudinal investigation at the transcript and protein expression levels of the molecular effects of therapeutic hypothermic intervention on hypoxic human primary cortical astrocytes. The identified genes and proteins are targets for detailed functional studies, which may help to develop new treatments for brain injury based on an in-depth mechanistic understanding of the astrocytic response to hypoxia and/or hypothermia

B Cells Directly Tolerize CD8+ T Cells

This report investigates the response of CD8+ T cells to antigens presented by B cells. When C57BL/6 mice were injected with syngeneic B cells coated with the Kb-restricted ovalbumin (OVA) determinant OVA257–264, OVA-specific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate the mechanism of tolerance induction, in vitro–activated CD8+ T cells from the Kb-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survival was determined. Antigen recognition led to the killing of the B cells and, surprisingly, to the death of a large proportion of the OT-I CTLs. T cell death involved Fas (CD95), since OT-I cells deficient in CD95 molecules showed preferential survival after recognition of antigen on B cells. To investigate the tolerance mechanism in vivo, naive OT-I T cells were adoptively transferred into normal mice, and these mice were coinjected with antigen-bearing B cells. In this case, OT-I cells proliferated transiently and were then lost from the secondary lymphoid compartment. These data provide the first demonstration that B cells can directly tolerize CD8+ T cells, and suggest that this occurs via CD95-mediated, activation-induced deletion

Integrated Joule switches for the control of current dynamics in parallel superconducting strips

Understanding and harnessing the physics of the dynamic current distribution in parallel superconducting strips holds the key to creating next generation sensors for single molecule and single photon detection. Non-uniformity in the current distribution in parallel superconducting strips leads to low detection efficiency and unstable operation, preventing the scale up to large area sensors. Recent studies indicate that non-uniform current distributions occurring in parallel strips can be understood and modeled in the framework of the generalized London model. Here we build on this important physical insight, investigating an innovative design with integrated superconducting-to-resistive Joule switches to break the superconducting loops between the strips and thus control the current dynamics. Employing precision low temperature nano-optical techniques, we map the uniformity of the current distribution before- and after the resistive strip switching event, confirming the effectiveness of our design. These results provide important insights for the development of next generation large area superconducting strip-based sensors

EGIA–evolutionary optimisation of gene regulatory networks, an integrative approach

Quantitative modelling of gene regulatory networks (GRNs) is still limited by data issues such as noise and the restricted length of available time series, creating an under-determination problem. However, large amounts of other types of biological data and knowledge are available, such as knockout experiments, annotations and so on, and it has been postulated that integration of these can improve model quality. However, integration has not been fully explored, to date. Here, we present a novel integrative framework for different types of data that aims to enhance model inference. This is based on evolutionary computation and uses different types of knowledge to introduce a novel customised initialisation and mutation operator and complex evaluation criteria, used to distinguish between candidate models. Specifically, the algorithm uses information from (i) knockout experiments, (ii) annotations of transcription factors, (iii) binding site motifs (expressed as position weight matrices) and (iv) DNA sequence of gene promoters, to drive the algorithm towards more plausible network structures. Further, the evaluation basis is also extended to include structure information included in these additional data. This framework is applied to both synthetic and real gene expression data. Models obtained by data integration display both quantitative and qualitative improvement

Can sexual selection drive female life histories? A comparative study on Galliform birds

Sexual selection is an important driver of many of the most spectacular morphological traits that we find in the animal kingdom (for example see Andersson, 1994). As such, sexual selection is most often emphasized as

Effects of rapid prey evolution on predator-prey cycles

We study the qualitative properties of population cycles in a predator-prey system where genetic variability allows contemporary rapid evolution of the prey. Previous numerical studies have found that prey evolution in response to changing predation risk can have major quantitative and qualitative effects on predator-prey cycles, including: (i) large increases in cycle period, (ii) changes in phase relations (so that predator and prey are cycling exactly out of phase, rather than the classical quarter-period phase lag), and (iii) "cryptic" cycles in which total prey density remains nearly constant while predator density and prey traits cycle. Here we focus on a chemostat model motivated by our experimental system [Fussmann et al. 2000,Yoshida et al. 2003] with algae (prey) and rotifers (predators), in which the prey exhibit rapid evolution in their level of defense against predation. We show that the effects of rapid prey evolution are robust and general, and furthermore that they occur in a specific but biologically relevant region of parameter space: when traits that greatly reduce predation risk are relatively cheap (in terms of reductions in other fitness components), when there is coexistence between the two prey types and the predator, and when the interaction between predators and undefended prey alone would produce cycles. Because defense has been shown to be inexpensive, even cost-free, in a number of systems [Andersson and Levin 1999, Gagneux et al. 2006,Yoshida et al. 2004], our discoveries may well be reproduced in other model systems, and in nature. Finally, some of our key results are extended to a general model in which functional forms for the predation rate and prey birth rate are not specified.Comment: 35 pages, 8 figure

A novel length back-calculation approach accounting for ontogenetic changes in the fish length – otolith size relationship during the early life of sprat (Sprattus sprattus)

(Sprattus sprattus), accounting for ontogenetic changes in the relationship between fish length and otolith length. In sprat, metamorphosis from larvae to juveniles is characterized by the coincidence of low length growth, strong growth in body height, and maximal otolith growth. Consequently, the method identifies a point of metamorphosis for an individual as the otolith radius at maximum increment widths. By incorporating this information in our back-calculation method, estimated length growth for the early larval stage was more than 60% higher compared with the result of the biological intercept model. After minimal length growth during metamorphosis, we found the highest increase in length during the early juvenile stage. We thus located the strongest growth potential in the early juvenile stage, which is supposed to be critical in determining recruitment strength in Baltic sprat

Presenting a simplified assistant tool for breast cancer diagnosis in mammography to radiologists

This paper proposes a method to simplify a computational model from logistic regression for clinical use without computer. The model was built using human interpreted featrues including some BI-RADS standardized features for diagnosing the malignant masses. It was compared with the diagnosis using only assessment categorization from BI-RADS. The research aims at assisting radiologists to diagnose the malignancy of breast cancer in a way without using automated computer aided diagnosis system