Room acoustics simulation using 3-D compact explicit FDTD schemes

This paper presents methods for simulating room acoustics using the finite-difference time-domain (FDTD) technique, focusing on boundary and medium modeling. A family of nonstaggered 3-D compact explicit FDTD schemes is analyzed in terms of stability, accuracy, and computational efficiency, and the most accurate and isotropic schemes based on a rectilinear grid are identified. A frequency-dependent boundary model that is consistent with locally reacting surface theory is also presented, in which the wall impedance is represented with a digital filter. For boundaries, accuracy in numerical reflection is analyzed and a stability proof is provided. The results indicate that the proposed 3-D interpolated wideband and isotropic schemes outperform directly related techniques based on Yee's staggered grid and standard digital waveguide mesh, and that the boundary formulations generally have properties that are similar to that of the basic scheme used.

Quasi-classical model of non-destructive wavepacket manipulation by intense ultrashort nonresonant laser pulses

A quasi-classical model (QCM) of nuclear wavepacket generation, modification and imaging by three intense ultrafast near-infrared laser pulses has been developed. Intensities in excess of 10(13) W cm(-2) are studied, the laser radiation is non-resonant and pulse durations are in the few-cycle regime, hence significantly removed from the conditions typical of coherent control and femtochemistry. The 1s sigma ground state of the D-2 precursor is projected onto the available electronic states in D-2(+) (1s sigma(g) ground and 2p sigma(u) dissociative) and D+ + D+ (Coulomb explosion) by tunnel ionization by an ultrashort 'pump' pulse, and relative populations are found numerically. A generalized non-adiabatic treatment allows the dependence of the initial vibrational population distribution on laser intensity to be calculated. The wavepacket is approximated as a classical ensemble of particles moving on the 1s sigma(g) potential energy surface (PES), and hence follow trajectories of different amplitudes and frequencies depending on the initial vibrational state. The 'control' pulse introduces a time-dependent polarization of the molecular orbital, causing the PES to be modified according to the dynamic Stark effect and the transition dipole. The trajectories adjust in amplitude, frequency and phase-offset as work is done on or by the resulting force; comparing the perturbed and unperturbed trajectories allows the final vibrational state populations and phases to be determined. The action of the 'probe' pulse is represented by a discrete internuclear boundary, such that elements of the ensemble at a larger internuclear separation are assumed to be photodissociated. The vibrational populations predicted by the QCM are compared to recent quantum simulations (Niederhausen and Thumm 2008 Phys. Rev. A 77 013404), and a remarkable agreement has been found. The applicability of this model to femtosecond and attosecond time-scale experiments is discussed and the relation to established femtochemistry and coherent control techniques are explored.

Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy

Background: Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models.

Methodology/Principal Findings: The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNF alpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001).

Conclusions: This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs.

Strong-field approximation for Coulomb explosion of H-2(+) and D-2(+) by short intense laser pulses

We present a simple quantum mechanical model to describe Coulomb explosion of H-2(+) and D-2(+) by short, intense infrared laser pulses. The model is based on the length gauge version of the molecular strong-field approximation and is valid when the process of dissociation prior to ionization is negligible. The results are compared with recent experimental data for the proton kinetic energy spectrum [Th. Ergler , Phys. Rev. Lett. 95, 093001 (2005); D. S. Murphy , J. Phys. B 40, S359 (2007)]. Using a Franck-Condon distribution over initial vibrational states, the theory reproduces the overall shape of the spectrum with only a small overestimation of slow protons. The agreement between theory and experiment can be made perfect by using a non-Frank-Condon initial distribution characteristic for H-2(+) (D-2(+)) targets produced by strong-field ionization of H-2 (D-2). For comparison, we also present results obtained by two different tunneling models for this process.

Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration

PURPOSE. Diabetic patients who also have retinitis pigmentosa (RP) appear to have fewer and less severe retinal microvascular lesions. Diabetic retinopathy may be linked to increased inner retinal hypoxia, with the possibility that this is exacerbated by oxygen usage during the dark-adaptation response. Therefore, patients with RP with depleted rod photoreceptors may encounter proportionately less retinal hypoxia, and, when diabetes is also present, there may be fewer retinopathic lesions. This hypothesis was tested in rhodopsin knockout mice (Rho(-/-)) as an RP model in which the diabetic milieu is superimposed. The study was designed to investigate whether degeneration of the outer retina has any impact on hypoxia, to examine diabetes-related retinal gene expression responses, and to assess lesions of diabetic retinopathy.

Murine model of autosomal dominant retinitis pigmentosa generated by targeted deletion at codon 307 of the rds-peripherin gene

We introduced a targeted single base deletion at codon 307 of the rds-peripherin gene in mice, similar mutations being known to cause autosomal dominant retinitis pigmentosa (RP) in man. Histopathological and electroretinographic analysis indicate that the retinopathy in mice homozygous for the codon 307 mutation appears more rapid than that in the naturally occurring null mutant, the rds(-/-) mouse, suggesting that the rds-307 mutation displays a dominant negative phenotype in combination with that due to haplosufficiency. RP is the most prevalent cause of registered visual handicap in those of working age in developed countries, the 50 or so mutations so far identified within the RDS-peripherin gene accounting for up to 10% of dominant cases of the disease. Given the sequence homologies that exist between the murine rds-peripherin and the human RDS-peripherin gene, this disease model, the first to be generated for peripherin-based RP using gene targeting techniques, should in principle be of value in the work-up in mice of therapeutics capable of targeting transcripts derived from the human gene.

Creating advantage in peripheral regions: The role of publicly funded R&D centres

Regional investment in R&D, technological development and innovation is perceived as being strongly associated with productivity, growth and sustained international competitiveness. One policy instrument by which policy makers have attempted to create regional advantage has been the establishment of publicly funded research centres (PRCs). In this paper we develop a logic model for this type of regional intervention and examine the outputs and longer-term outcomes from a group of (18) publicly funded R&D centres. Our results suggest some positive regional impacts but also identify significant differences in terms of innovation, additionality and sustainability between university-based and company-based PRCs. University-based PRCs have higher levels of short-term additionality, demonstrate higher levels of organisational innovation but prove less sustainable. Company-based PRCs demonstrate more partial additionality in the short-term but ultimately prove more sustainable.

Myocardial infarction in the C57BL/6J mouse - A quantifiable and highly reproducible experimental model

Introduction: The laboratory mouse is a powerful tool in cardiovascular research. In this report, we describe a method for a reproducible mouse myocardial infarction model that would allow subsequent comparative and quantitative studies on molecular and pathophysiological variables. Methods: (A) The distribution of the major coronary arteries including the septal artery in the left ventricle of the C57BL/6J mice (n=20) was mapped by perfusion of latex dye or fluorescent beads through the aorta. (B) The territory of myocardial infarction after the ligation of the most proximal aspect of the left anterior descending (LAD) coronary artery was quantified. (C) The consistency in the histological changes parallel to the infarction at different time points was analyzed. Results: (A) The coronary artery tree of the mouse is different from human and, particularly, in regard to the blood supply of the septum. (B) Contrary to previous belief, the septal coronary artery in the mouse is variable in origin. (C) A constant ligation of the LAD immediately below the left auricular level ensures a statistically significant reproducible infarct size. (D) The ischemic changes can be monitored at a histological level in a way similar to what is described in the human. Conclusion: We illustrate a method for maximal reproducibility of experimental acute myocardial infarction in the mouse model, due to a consistent loss of perfusion in the lower half of the left ventricle. This will allow the study of molecular and physiological variables in a controlled and quantifiable experimental model environment. (C) 2004 Elsevier Inc. All rights reserved.

Sub-Wavelength Profile 2-D Leaky-Wave Antennas With Two Periodic Layers

A fast and accurate analysis and synthesis technique for high-gain sub-wavelength 2-D Fabry-Perot leaky-wave antennas (LWA) consisting of two periodic metallodielectric arrays over a ground plane is presented. Full-wave method of moments (MoM) together with reciprocity is employed for the estimation of the near fields upon plane wave illumination and the extraction of the radiation patterns of the LWA. This yields a fast and rigorous tool for the characterisation of this type of antennas. A thorough convergence study for different antenna designs is presented and the operation principles of these antennas as well as the radiation characteristics are discussed. Moreover, design guidelines to tailor the antenna profile, the dimensions of the arrays as well as the antenna directivity and bandwidth are provided. A study on the radiation efficiency for antennas with different profiles is also presented and the trade off between directivity and radiation bandwidth is discussed. Numerical examples are given throughout to demonstrate the technique. A finite size antenna model is simulated using commercial software (CST Microstripes 2009) which validates the technique.

Regulation of cyclin D<sub>1 by the BRCA1-BARD1 complex

Background BRCA1 and cyclin D<sub>1 are both essential for normal breast development and mutation or aberration of their expression is associated with breast cancer [1,2]. Cyclin D<sub>1 is best known as a G₁ cyclin where it regulates the G₁ to S phase transition by acting as a rate-limiting subunit of CDK4/6 kinase activity. More recently, however, Stacey has demonstrated that cyclin D<sub>1 levels in G₂/M determine whether a cell continues to proliferate or exits the cell cycle [3]. The majority of BRCA1 in the cell is bound to BARD1 through their N-terminal RING domains. Heterodimerization is essential for the stability and correct localization of the complex and confers ubiquitin ligase activity to BRCA1. The importance of the ligase activity of BRCA1 to breast cancer development is inferred from the fact that N-terminal diseaseassociated mutations are proposed to reduce ligase activity [4]. Methods Protein–protein interactions were demonstrated using yeast-two-hybrid and coimmunoprecipitation. Protein levels were altered through overexpression, siRNA and antisense technology. The effect of proteasome inhibitors and cycloheximide treatment was also examined. Results We initially identified cyclin D<sub>1 as a binding partner of BARD1 in a yeast-two-hybrid screen and defined the minimal binding region as the N-terminus of BARD1. This interaction was confirmed in vivo by coimmunoprecipitation. The N-terminus of BARD1 also binds BRCA1 and imparts ubiquitin ligase activity to the complex. Covalent modification of proteins with ubiquitin is a common regulatory mechanism in eukaryotic cells. Traditionally polyubiquitin chains linked through lysine 48 target proteins for degradation by the 26 S proteasome. We have demonstrated that cyclin D<sub>1 protein levels are inversely related to BRCA1 and BARD1 levels in several model systems. Furthermore, regulation of cyclin D1 levels occurs through a post-transcriptional mechanism and requires the ligase activity of BRCA1. Interestingly, this phenomenon is cell-cycle regulated, occurring in G₂/M. Conclusion We propose that cyclin D<sub>1 is a potential substrate for BRCA1 ubiquitination and that this targets cyclin D<sub>1 for proteasomal-mediated degradation. Future work will focus on ascertaining the functional consequence of cyclin D<sub>1 regulation by the BRCA1–BARD1 complex; in particular, the impact of BRCA1, mediated through regulation of cyclin D<sub>1, on the proliferation versus differentiation decision.

Role of endoreduplication and apomeiosis during parthenogenetic reproduction in the model brown alga Ectocarpus

The filamentous brown alga Ectocarpus has a complex life cycle, involving alternation between independent and morphologically distinct sporophyte and gametophyte generations. In addition to this basic haploid–diploid life cycle, gametes can germinate parthenogenetically to produce parthenosporophytes. This article addresses the question of how parthenosporophytes, which are derived from a haploid progenitor cell, are able to produce meiospores in unilocular sporangia, a process that normally involves a reductive meiotic division.
We used flow cytometry, multiphoton imaging, culture studies and a bioinformatics survey of the recently sequenced Ectocarpus genome to describe its life cycle under laboratory conditions and the nuclear DNA changes which accompany key developmental transitions.
Endoreduplication occurs during the first cell cycle in about one-third of parthenosporophytes. The production of meiospores by these diploid parthenosporophytes involves a meiotic division similar to that observed in zygote-derived sporophytes. By contrast, meiospore production in parthenosporophytes that fail to endoreduplicate occurs via a nonreductive apomeiotic event.
Our results highlight Ectocarpus’s reproductive and developmental plasticity and are consistent with previous work showing that its life cycle transitions are controlled by genetic mechanisms and are independent of ploidy.

Cell cycles and endocycles in the model brown seaweed, Ectocarpus siliculosus

The recent announcement of the first genome sequence of a brown macroalga, the filamentous Ectocarpus, has been accompanied by a number of companion papers in New Phytologist. In a paper which contributes to this special issue, we classified the core cell cycle components of Ectocarpus, comparing them to the previously studied cell cycle components of diatoms. We then carried out fluorescence microscopy experiments to show that the Ectocarpus cell cycle could be deregulated during early development to give endopolyploid adults. We discuss here how our findings complement recent studies on endopolyploidy in plant and algal systems.