Differential expression of components of the cardiomyocyte adrenomedullin/intermedin receptor system following blood pressure reduction in nitric oxide-deficient hypertension.

Adrenomedullin (AM) and intermedin (IMD; adrenomedulln-2) are vasodilator peptides related to calcitonin gene-related peptide (CGRP). The actions of these peptides are mediated by the calcitonin receptor-like receptor (CLR) in association with one of three receptor activity-modifying proteins. CGRP is selective for CLR/receptor activity modifying protein (RAMP)1, AM for CLR/RAMP2 and -3, and IMD acts at both CGRP and AM receptors. In a model of pressure overload induced by inhibition of nitric-oxide synthase, up-regulation of AM was observed previously in cardiomyocytes demonstrating a hypertrophic phenotype. The current objective was to examine the effects of blood pressure reduction on cardiomyocyte expression of AM and IMD and their receptor components. Nomega-nitro-L-arginine methyl ester (L-NAME) (35 mg/kg/day) was administered to rats for 8 weeks, with or without concurrent administration of hydralazine (50 mg/kg/day) and hydrochlorothiazide (7.5 mg/kg/day). In left ventricular cardiomyocytes from L-NAME-treated rats, increases (-fold) in mRNA expression were 1.6 (preproAM), 8.4 (preproIMD), 3.4 (CLR), 4.1 (RAMP1), 2.8 (RAMP2), and 4.4 (RAMP3). Hydralazine/hydrochlorothiazide normalized systolic blood pressure (BP) and abolished mRNA up-regulation of hypertrophic markers sk-alpha-actin and BNP and of preproAM, CLR, RAMP2, and RAMP3 but did not normalize cardiomyocyte width nor preproIMD or RAMP1 mRNA expression. The robust increase in IMD expression indicates an important role for this peptide in the cardiac pathology of this model but, unlike AM, IMD is not associated with pressure overload upon the myocardium. The concordance of IMD and RAMP1 up-regulation indicates a CGRP-type receptor action; considering also a lack of response to BP reduction, IMD may, like CGRP, have an anti-ischemic function.

An investigation into the subambient behavior of aqueous mannitol solutions using differential scanning calorimetry, cold stage microscopy, and X-ray diffractometry

The subambient behavior of aqueous mannitol solutions is of considerable relevance to the preparation of freeze dried formulations. In this investigation the properties of 3% w/v mannitol solutions were investigated using differential scanning calorimetry (DSC), cold stage microscopy (CSM), and X-ray diffraction (XRD) to identify the thermal transitions and structural transformations undergone by this system. It was found that on cooling from ambient the system formed ice at circa -20°C while a further exotherm was seen at approximately -30°C. Upon reheating an endotherm was seen at circa -30°C followed immediately by an exotherm at circa -25°C. Temperature cycling indicated that the thermal transitions observed upon reheating were not reversible. Modulated temperature DSC (MTDSC) indicated that the transitions observed upon reheating corresponded to a glass transition immediately followed by recrystallization, XRD data showed that recrystallization was into the ß form. Annealing at -35°C for 40 min prior to cooling and reheating resulted in a maximum enthalpy being observed for the reheating exotherm. It is concluded that on cooling 3% w/v aqueous mannitol solutions an amorphous phase is formed that subsequently recrystallises into the ß form. The study has also shown that DSC, CSM, and XRD are useful complementary techniques for the study of frozen systems

Differential lifetime success and performance of native and non-native Atlantic salmon examined under communal natural conditions.

The lifetime success and performance characteristics of communally reared offspring of wild native Burrishoole (native), ranched native (ranched) and non-native (non-native) Atlantic salmon Salmo salar from the adjacent Owenmore River were compared. Non-native year parr showed a substantial downstream migration, which was not shown by native and ranched parr. This appears to have been an active migration rather than competitive displacement and may reflect an adaptation to environmental or physiographic conditions within the Owenmore River catchment where the main nursery habitat is downstream of the spawning area. There were no differences between native and ranched in smolt output or adult return. Both of these measures, however, were significantly lower for the non-native group. A greater proportion of the non-native Atlantic salmon was taken in the coastal drift nets compared to the return to the Burrishoole system, probably as a result of the greater size of the non-native fish. The overall lifetime success of the non-native group, from fertilized egg to returning adult, was some 35% of native and ranched. The ranched group showed a significantly greater male parr maturity, a greater proportion of 1+ year smolts, and differences in sex ratio and timing of freshwater entry of returning adults compared to native, which may have fitness implications under specific conditions.

Ion-Atom/Argon - Calculation of ionization cross sections by fast ion impact for neutral target atoms ranging from hydrogen to argon

A FORTRAN 90 program is presented which calculates the total cross sections, and the electron energy spectra of the singly and doubly differential cross sections for the single target ionization of neutral atoms ranging from hydrogen up to and including argon. The code is applicable for the case of both high and low Z projectile impact in fast ion-atom collisions. The theoretical models provided for the program user are based on two quantum mechanical approximations which have proved to be very successful in the study of ionization in ion-atom collisions. These are the continuum-distorted-wave (CDW) and continuum-distorted-wave eikonal-initial-state (CDW-EIS) approximations. The codes presented here extend previously published. codes for single ionization of. target hydrogen [Crothers and McCartney, Comput. Phys. Commun. 72 (1992) 288], target helium [Nesbitt, O'Rourke and Crothers, Comput. Phys. Commun. 114 (1998) 385] and target atoms ranging from lithium to neon [O'Rourke, McSherry and Crothers, Comput. Phys. Commun. 131 (2000) 129]. Cross sections for all of these target atoms may be obtained as limiting cases from the present code. Title of program: ARGON Catalogue identifier: ADSE Program summary URL: http://cpc.cs.qub.ac.uk/cpc/summaries/ADSE Program obtainable from: CPC Program Library Queen's University of Belfast, N. Ireland Licensing provisions: none Computer for which the program is designed and others on which it is operable: Computers: Four by 200 MHz Pro Pentium Linux server, DEC Alpha 21164; Four by 400 MHz Pentium 2 Xeon 450 Linux server, IBM SP2 and SUN Enterprise 3500 Installations: Queen's University, Belfast Operating systems under which the program has been tested: Red-hat Linux 5.2, Digital UNIX Version 4.0d, AIX, Solaris SunOS 5.7 Compilers: PGI workstations, DEC CAMPUS Programming language used: FORTRAN 90 with MPI directives No. of bits in a word: 64, except on Linux servers 32 Number of processors used: any number Has the code been vectorized or parallelized? Parallelized using MPI No. of bytes in distributed program, including test data, etc.: 32 189 Distribution format: tar gzip file Keywords: Single ionization, cross sections, continuum-distorted-wave model, continuum- distorted-wave eikonal-initial-state model, target atoms, wave treatment Nature of physical problem: The code calculates total, and differential cross sections for the single ionization of target atoms ranging from hydrogen up to and including argon by both light and heavy ion impact. Method of solution: ARGON allows the user to calculate the cross sections using either the CDW or CDW-EIS [J. Phys. B 16 (1983) 3229] models within the wave treatment. Restrictions on the complexity of the program: Both the CDW and CDW-EIS models are two-state perturbative approximations. Typical running time: Times vary according to input data and number of processors. For one processor the test input data for double differential cross sections (40 points) took less than one second, whereas the test input for total cross sections (20 points) took 32 minutes. Unusual features of the program: none (C) 2003 Elsevier B.V All rights reserved.

Thiazolidinediones: effects on insulin resistance and the cardiovascular system.

Abstract
Thiazolidinediones (TZDs) have been used for the treatment of hyperglycaemia in type 2 diabetes for the past 10 years. They may delay the development of type 2 diabetes in individuals at high risk of developing the condition, and have been shown to have potentially beneficial effects on cardiovascular risk factors. TZDs act as agonists of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) primarily in adipose tissue. PPAR-gamma receptor activation by TZDs improves insulin sensitivity by promoting fatty acid uptake into adipose tissue, increasing production of adiponectin and reducing levels of inflammatory mediators such as tumour necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor-1(PAI-1) and interleukin-6 (IL-6). Clinically, TZDs have been shown to reduce measures of atherosclerosis such as carotid intima-media thickness (CIMT). However, in spite of beneficial effects on markers of cardiovascular risk, TZDs have not been definitively shown to reduce cardiovascular events in patients, and the safety of rosiglitazone in this respect has recently been called into question. Dual PPAR-alpha/gamma agonists may offer superior treatment of insulin resistance and cardioprotection, but their safety has not yet been assured

Modelling the mechanical response of the Reed-mouthpiece-lip system of a clarinet. Part I. A one-dimensional distributed model

The motion of a clarinet reed that is clamped to a mouthpiece and supported by a lip is simulated in the time-domain using finite difference methods. The reed is modelled as a bar with non-uniform cross section, and is described using a one-dimensional, fourth-order partial differential equation. The interactions with the mouthpiece Jay and the player's lip are taken into account by incorporating conditional contact forces in the bar equation. The model is completed by clamped-free boundary conditions for the reed. An implicit finite difference method is used for discretising the system, and values for the physical parameters are chosen both from laboratory measurements and by accurate tuning of the numerical simulations. The accuracy of the numerical system is assessed through analysis of frequency warping effects and of resonance estimation. Finally, the mechanical properties of the system are studied by analysing its response to external driving forces. In particular, the effects of reed curling are investigated.

Differential Hox Expression in Murine Embryonic Stem Cell Models of Normal and Malignant Hematopoiesis.

The Hox family are master transcriptional regulators of developmental processes, including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4), and Meis1, along with several individual Hox proteins, are implicated in stem cell expansion during embryonic development, with gene dosage playing a significant role in the overall function of the integrated Hox network. To investigate the role of this network in normal and aberrant, early hematopoiesis, we employed an in vitro embryonic stem cell differentiation system, which recapitulates mouse developmental hematopoiesis. Expression profiles of Hox, Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic differentiation process and compared with the effects of expressing the leukemic oncogene Tel/PDGFRß. During normal differentiation the Hoxa cluster, Pbx1 and Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39) and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa cluster genes (a9, a10, a11, and a13) maintained or increased expression at the hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7 and a9, were differentially expressed after short-term oncogenic (Tel/PDGFRß) induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1, and Pbx have previously been implicated in regulating target genes involved in hematopoietic stem cell (HSC) expansion and leukemic progression. These results provide direct evidence that transcriptional flux through the Hox network occurs at very early stages during hematopoietic differentiation and validates embryonic stem cell models for gaining insights into the genetic regulation of normal and malignant hematopoiesis.

Evaluation of Random Delay Insertion against DPA on FPGAs

Side-channel attacks (SCA) threaten electronic cryptographic devices and can be carried out by monitoring the physical characteristics of security circuits. Differential Power Analysis (DPA) is one the most widely studied side-channel attacks. Numerous countermeasure techniques, such as Random Delay Insertion (RDI), have been proposed to reduce the risk of DPA attacks against cryptographic devices. The RDI technique was first proposed for microprocessors but it was shown to be unsuccessful when implemented on smartcards as it was vulnerable to a variant of the DPA attack known as the Sliding-Window DPA attack.Previous research by the authors investigated the use of the RDI countermeasure for Field Programmable Gate Array (FPGA) based cryptographic devices. A split-RDI technique wasproposed to improve the security of the RDI countermeasure. A set of critical parameters wasalso proposed that could be utilized in the design stage to optimize a security algorithm designwith RDI in terms of area, speed and power. The authors also showed that RDI is an efficientcountermeasure technique on FPGA in comparison to other countermeasures.In this article, a new RDI logic design is proposed that can be used to cost-efficiently implementRDI on FPGA devices. Sliding-Window DPA and realignment attacks, which were shown to beeffective against RDI implemented on smartcard devices, are performed on the improved RDIFPGA implementation. We demonstrate that these attacks are unsuccessful and we also proposea realignment technique that can be used to demonstrate the weakness of RDI implementations.