A fast time-domain EM-TCAD coupled simulation framework via matrix exponential

We present a fast time-domain multiphysics simulation framework that combines full-wave electromagnetism (EM) and carrier transport in semiconductor devices (TCAD). The proposed framework features a division of linear and nonlinear components in the EM-TCAD coupled system. The former is extracted and handled independently with high efficiency by a matrix exponential approach assisted with Krylov subspace method. The latter is treated by ordinary Newton's method yet with a much sparser Jacobian matrix that leads to substantial speedup in solving the linear system of equations. More convenient error management and adaptive control are also available through the linear and nonlinear decoupling. © 2012 ACM.published_or_final_versio

Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells.

The Notch ligand, Dll4, is essential for angiogenesis during embryonic vascular development and is involved in tumour angiogenesis. Several recent publications demonstrated that blockade of Dll4 signalling inhibits tumour growth, suggesting that it may constitute a good candidate for anti-cancer therapy. In order to understand the role of Dll4 at the cellular level, we performed an analysis of Dll4-regulated genes in HUVECs. The genes identified included several angiogenic signalling pathways, such as VEGF, FGF and HGF. In particular we identified downregulation (VEGFR2, placenta growth factor PlGF) of VEGF pathway components resulting in the overall effect of limiting the response of HUVEC to VEGF. However extensive upregulation of VEGFR1 was observed allowing continued response to its ligand PlGF but the soluble form of the VEGFR1, sVEGFR1 was also upregulated. PlGF enhanced tubulogenesis of HUVEC suggesting that downregulation of PlGF and upregulation of VEGFR1 including sVEGFR1 are important mechanisms by which Dll4 attenuates PlGF and VEGF signalling. Dll4-stimulated HUVECs had impaired ERK activation in response to VEGF and HGF indicating that Dll4 signalling negatively regulates these pathways. Dll4 expression reduced vessel sprout length in a 3D tubulogenesis assay confirming that Dll4 signalling inhibits angiogenesis. Altogether, our data suggest that Dll4 expression acts as a switch from the proliferative phase of angiogenesis to the maturation and stabilisation phase by blocking endothelial cell proliferation and allowing induction of a more mature, differentiated phenotype. The regulation of sVEGFR1 provides a novel mechanism for Dll4 signalling to regulate cells at distance, not just in adjacent cells

Change in Negative Affective Bias following a Single Ketamine Treatment for Treatment-Resistant Depression

Ketamine has recently emerged as a highly effective new treatment for people with treatment-resistant depression with rapid antidepressant effects. However, these effects are often short lasting, and the potential cognitive mechanisms underlying the therapeutic effects, such as effects on emotional processing bias, remain poorly understood. In the present study, we explored potential changes in emotional and cognitive processing following a single treatment of subcutaneous ketamine in a randomised double-blind controlled study with an active control. Participants with treatment-resistant major depressive disorder (MDD) were recruited from a single site from the Ketamine for Adult Depression Study (KADS Trial) and were randomly assigned to receive racemic ketamine hydrochloride (n=10) or midazolam hydrochloride (n=11) in a 1: 1 ratio. A healthy control sample (n=23) was recruited to attend a single experimental session without any treatment. All MDD participants completed mood ratings and cognitive assessments prior to and one day after a single randomised treatment. The results showed no significant differences in performance changes after treatment across the majority of emotion-related (i.e., Emotional Stroop Task, Affective Go/No-Go Task) and cognitive (Ruff 2 and 7 Selective Attention Test, Controlled Word Association Test) outcome measures. Participants who received ketamine showed a significant improvement in a negative processing bias test (i.e., The Scrambled Sentence Task; Cohen's d=.67, p=.016), which was not significantly associated with improvement in psychological symptoms (r=-.662, p=.074). The results from this exploratory study suggest that a single ketamine treatment may modulate negative affective bias. Limitations to this study included the small sample size and lack of follow-up. Future larger trials are required to confirm this finding

Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries

Shifting Attention From Theory to Practice in Philosophy of Biology

Traditional approaches in philosophy of biology focus attention on biological concepts, explanations, and theories, on evidential support and inter-theoretical relations. Newer approaches shift attention from concepts to conceptual practices, from theories to practices of theorizing, and from theoretical reduction to reductive retooling. In this article, I describe the shift from theory-focused to practice-centered philosophy of science and explain how it is leading philosophers to abandon fundamentalist assumptions associated with traditional approaches in philosophy of science and to embrace scientific pluralism. This article comes in three parts, each illustrating the shift from theory-focused to practice-centered epistemology. The first illustration shows how shifting philosophical attention to conceptual practice reveals how molecular biologists succeed in identifying coherent causal strands within systems of bewildering complexity. The second illustration suggests that analyzing how a multiplicity of alternative models function in practice provides an illuminating approach for understanding the nature of theoretical knowledge in evolutionary biology. The third illustration demonstrates how framing reductionism in terms of the reductive retooling of practice offers an informative perspective for understanding why putting DNA at the center of biological research has been incredibly productive throughout much of biology. Each illustration begins by describing how traditional theory-focused philosophical approaches are laden with fundamentalist assumptions and then proceeds to show that shifting attention to practice undermines these assumptions and motivates a philosophy of scientific pluralism

Structure of a seeded palladium nanoparticle and its dynamics during the hydride phase transformation

Palladium absorbs large volumetric quantities of hydrogen at room temperature and ambient pressure, making the palladium hydride system a promising candidate for hydrogen storage. Here, we use Bragg coherent diffraction imaging to map the strain associated with defects in three dimensions before and during the hydride phase transformation of an individual octahedral palladium nanoparticle, synthesized using a seed-mediated approach. The displacement distribution imaging unveils the location of the seed nanoparticle in the final nanocrystal. By comparing our experimental results with a finite-element model, we verify that the seed nanoparticle causes a characteristic displacement distribution of the larger nanocrystal. During the hydrogen exposure, the hydride phase is predominantly formed on one tip of the octahedra, where there is a high number of lower coordinated Pd atoms. Our experimental and theoretical results provide an unambiguous method for future structure optimization of seed-mediated nanoparticle growth and in the design of palladium-based hydrogen storage systems

Inclusive Prompt Photon Production in Hadronic Final States of e+e−e^+e^- Annihilation

We provide complete analytic expressions for the inclusive prompt photon production cross section in hadronic final states of $e^+e^-$ annihilation reactions through one-loop order in quantum chromodynamics perturbation theory. Computed explicitly are direct photon production through first order in the electromagnetic strength $\alpha_{em}$ and the quark-to-photon and gluon-to-photon fragmentation contributions through first order in the strong coupling $\alpha_s$. The full angular dependence of the cross sections is displayed, separated into transverse $(1 +\cos ^2\theta _\gamma)$ and longitudinal $(\sin ^2\theta_\gamma)$ components, where $\theta_\gamma$ specifies the direction of the photon with respect to the $e^+e^-$ collision axis. We discuss extraction of fragmentation functions from $e^+e^-$ data.Comment: 40 pages, RevTex, 30 figures in postscript available in a separate fil

EQ-5D-3L Derived Population Norms for Health Related Quality of Life in Sri Lanka

Background Health Related Quality of Life (HRQoL) is an important outcome measure in health economic evaluation that guides health resource allocations. Population norms for HRQoL are an essential ingredient in health economics and in the evaluation of population health. The aim of this study was to produce EQ-5D-3L-derived population norms for Sri Lanka. Method A population sample (n =  780) was selected from four districts of Sri Lanka. A stratified cluster sampling approach with probability proportionate to size was employed. Twenty six clusters of 30 participants each were selected; each participant completed the EQ-5D-3L in a face-to-face interview. Utility weights for their EQ-5D-3L health states were assigned using the Sri Lankan EQ-5D-3L algorithm. The population norms are reported by age and socio-economic variables. Results The EQ-5D-3L was completed by 736 people, representing a 94% response rate. Sixty per cent of the sample reported being in full health. The percentage of people responding to any problems in the five EQ-5D-3L dimensions increased with age. The mean EQ-5D-3L weight was 0.85 (SD 0.008; 95%CI 0.84-0.87). The mean EQ-5D-3L weight was significantly associated with age, housing type, disease experience and religiosity. People above 70 years of age were 7.5 times more likely to report mobility problems and 3.7 times more likely to report pain/discomfort than those aged 18-29 years. Those with a tertiary education were five times less likely to report any HRQoL problems than those without a tertiary education. A person living in a shanty was 4.3 more likely to have problems in usual activities than a person living in a single house. Conclusion The population norms in Sri Lanka vary with socio-demographic characteristics. The socioeconomically disadvantaged have a lower HRQoL. The trends of population norms observed in this lower middle income country were generally similar to those previously reported in high income countries

Selection of diagnostic features on breast MRI to differentiate between malignant and benign lesions using computer-aided diagnosis: differences in lesions presenting as mass and non-mass-like enhancement

Purpose: To investigate methods developed for the characterisation of the morphology and enhancement kinetic features of both mass and non-mass lesions, and to determine their diagnostic performance to differentiate between malignant and benign lesions that present as mass versus non-mass types. Methods: Quantitative analysis of morphological features and enhancement kinetic parameters of breast lesions were used to differentiate among four groups of lesions: 88 malignant (43 mass, 45 non-mass) and 28 benign (19 mass, 9 non-mass). The enhancement kinetics was measured and analysed to obtain transfer constant (Ktrans) and rate constant (kep). For each mass eight shape/margin parameters and 10 enhancement texture features were obtained. For the lesions presenting as nonmass-like enhancement, only the texture parameters were obtained. An artificial neural network (ANN) was used to build the diagnostic model. Results: For lesions presenting as mass, the four selected morphological features could reach an area under the ROC curve (AUC) of 0.87 in differentiating between malignant and benign lesions. The kinetic parameter (kep) analysed from the hot spot of the tumour reached a comparable AUC of 0.88. The combined morphological and kinetic features improved the AUC to 0.93, with a sensitivity of 0.97 and a specificity of 0.80. For lesions presenting as non-mass-like enhancement, four texture features were selected by the ANN and achieved an AUC of 0.76. The kinetic parameter kepfrom the hot spot only achieved an AUC of 0.59, with a low added diagnostic value. Conclusion: The results suggest that the quantitative diagnostic features can be used for developing automated breast CAD (computer-aided diagnosis) for mass lesions to achieve a high diagnostic performance, but more advanced algorithms are needed for diagnosis of lesions presenting as non-mass-like enhancement. © The Author(s) 2009