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In megabar shock waves, materials compress and undergo a phase transition to a dense charged-particle system that is dominated by strong correlations and quantum effects. This complex state, known as warm dense matter, exists in planetary interiors and many laboratory experiments (for example, during high-power laser interactions with solids or the compression phase of inertial confinement fusion implosions). Here, we apply record peak brightness X-rays at the Linac Coherent Light Source to resolve ionic interactions at atomic (ångström) scale lengths and to determine their physical properties. Our in situ measurements characterize the compressed lattice and resolve the transition to warm dense matter, demonstrating that short-range repulsion between ions must be accounted for to obtain accurate structure factor and equation of state data. In addition, the unique properties of the X-ray laser provide plasmon spectra that yield the temperature and density with unprecedented precision at micrometre-scale resolution in dynamic compression experiments. [ABSTRACT FROM AUTHOR]

Overweight and obesity during pregnancy is associated with risk of a range of adverse health outcomes. While intervention studies aim to promote behavioral change, little is known about the underlying psychological mechanisms facilitating and hindering change. The aim of this study was to evaluate overweight and obese women’s perceptions of making behavior change during pregnancy. We explored beliefs through self-administrated questionnaires (n = 464) and semi-structured face-to-face interviews (n = 26). Questions were designed according to the Health Belief Model. A triangulation protocol was followed to combine quantitative and qualitative data. A total of 269 women (58 %) indicated that high gestational weight gain is a concern, with 348 (75 %) indicating excessive weight gain is associated with complications during pregnancy or child birth. Women were aware of maternal complications associated with high gestational weight gain, but had more limited awareness of neonatal complications. While most women indicated in questionnaires that healthy eating and physical activity were associated with improved health during pregnancy, they were unable to identify specific benefits at interview. Barriers to making healthy behavior changes were highly individualized, the main barrier being lack of time. While the majority (91 %) of women indicated that they would make behavior changes if the change made them feel better, only half felt confident in their ability to do so. Interventions for overweight and obese pregnant women should incorporate education about neonatal health consequences and benefits of healthy behavior change in addition to incorporating strategies to enhance self-efficacy. [ABSTRACT FROM AUTHOR]

Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta cells, which might in turn contribute to the age-related decline in insulin secretory capacity. We quantified mtDNA copy number in isolated human islet preparations from 15 pancreas donors aged between 17 and 75 years. Islets ( n = 20) were individually hand-picked and pooled from each donor isolate for the quantification of mtDNA copy number and deleted mtDNA (%), which were determined using real-time PCR methods. There was a significant negative correlation between mtDNA copy number and islet donor age ( r = –0.53, p = 0.044). mtDNA copy number was significantly decreased in islet preparations from donors aged ≥50 years ( n = 8) compared with those aged <50 years ( n = 7) (median [interquartile range]: 418 [236–503] vs 596 [554–729] mtDNA copy number/diploid genome; p = 0.032). None of the islet preparations harboured high levels of deleted mtDNA affecting the major arc. Given the correlation between mtDNA content and respiratory chain activity, the age-related decrease in mtDNA copy number that we observed in human pancreatic islet preparations may contribute to the age-dependent decline in pancreatic beta cell insulin secretory capacity. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the association between depression, anxiety and general stress symptoms with hospital readmissions after coronary artery bypass graft surgery. Two hundred and twenty six coronary artery bypass graft patients completed baseline self-report measures of depression, anxiety and stress and 222 patients completed these measures after surgery on the hospital ward. The hospital readmission outcomes at six months were analyzed using multivariable proportional hazard models. When analyzed as continuous variables in multivariable analyses, preoperative anxiety and postoperative depression predicted readmissions independent of medical covariates. In multivariable analyses with dichotomized anxiety, depression and stress, more than two-fold increase in readmission risk was attributable to preoperative anxiety and postoperative depression, independent of covariates. These results lend further support to previous research that has shown the symptoms of depression and anxiety are associated with morbidity following coronary artery bypass graft surgery. The findings highlight the need to develop suitable interventions for anxiety and depression among coronary artery bypass graft surgery patients. [ABSTRACT FROM AUTHOR]

The aims of this study were (1) to determine the prevalence and rate of progression in diabetes secondary to mitochondrial DNA (mtDNA) mutations; and (2) to determine whether percentage heteroplasmy predicts clinical outcome in patients carrying the m.3243A>G mutation. We prospectively assessed 242 patients attending a specialist neuromuscular clinic using a validated mitochondrial disease rating scale. Retrospective clinical data on these patients from up to 25 years of follow-up were also included. Percentage heteroplasmy in blood, urine and muscle was determined for the m.3243A>G group and correlated against clinical features. Patients carrying the m.3243A>G mutation formed the largest group of patients with diabetes (31/81 patients). The highest prevalence of diabetes was in the m.12258C>A group (2/2 patients), the lowest in the multiple mtDNA deletions group (3/43 patients). The earliest age of onset was in the m.3243A>G group (37.9 years) with the highest age of presentation in the multiple deletion group (56.3 years). Of patients presenting with m.3243A>G, 12.9% required insulin; an additional 32.3% progressed to insulin requirement over a mean of 4.2 years after presentation. Percentage heteroplasmy in blood, urine or muscle did not predict progression of diabetes or risk of developing complications. Early age of presentation with diabetes did predict poor clinical outcome. Although patients carrying the m.3243A>G mutation account for the majority of cases of diabetes secondary to mtDNA mutations, several other genotypes are also associated with the development of diabetes, some with high penetrance. All show a gradual progression to insulin requirement. Percentage heteroplasmy is a poor predictor of severity of diabetes in the m.3243A>G group. [ABSTRACT FROM AUTHOR]

Aims: To assess the visual function of patients with chronic progressive external ophthalmoplegia (CPEO) using the Visual Function Index (VF-14). To identify discriminatory questions that reflect visual disability in mitochondrial ocular myopathies. To investigate the relationship between visual impairment and the ocular parameters routinely measured in clinical practice.Methods: We studied 40 CPEO patients. Each patient underwent ophthalmological assessment, including best-corrected visual acuity, ptosis measures, and fundus examination for pigmentary retinopathy, and orthoptic assessment including cover test in the primary position, assessment of diplopia, and measurement of uniocular fields of fixation using the Goldmann perimeter. Patients were interviewed by telephone by an independent observer and their visual function was assessed using the VF-14.Results: A total of 38 patients (95%) were visually impaired. The mean VF-14 was 72 (95% CI 66-79). Patients reported having the most difficulty with reading small print and driving at night. No significant correlation was found between the VF-14 and ocular motility parameters, ptosis, or pigmentary retinopathy.Conclusions: CPEO is associated with significant visual impairment. Measures of visual disability should be included in studies of natural history and treatment of mitochondrial ocular myopathies. [ABSTRACT FROM AUTHOR]

CONCLUSION:Almost all patients had an exo-deviation. Diplopia was more common than expected. The majority of patients had symmetry of EOM limitation.Eye (2005) 19, 258-263. doi:10.1038/sj.eye.6701488 Published online 23 July 2004 [ABSTRACT FROM AUTHOR]

Human mitochondria contain their own genome, mtDNA. This small molecule encodes 24 RNA species and 13 polypeptides, which are essential components of the mitochondrial respiratory chain. The mitochondrial genome is present in hundreds or thousands of copies in each cell and is believed to turnover throughout the life of the cell. Defects of the mitochondrial genome (mtDNA) cause a variety of multisystemic disorders routinely affecting the muscle and nervous system. There is currently no effective treatment for patients with defects of the mitochondrial genome. In many patients, defective cells harbour two sub-populations of mtDNA (a situation termed heteroplasmy), one being normal, the other containing the pathogenic mutation. The mutated copy is often recessive, with biochemical and clinical defects only becoming apparent when the levels of mutated mtDNA outweigh the normal copies. It has therefore been postulated that by selectively preventing replication of the mutated mtDNA, the normal copy will propagate, restoring biochemical function. The search has therefore been on during recent years to identify an antigenomic molecule that will fulfil this criterion. Following evidence that peptide nucleic acids could selectively inhibit replication of templates carrying a known pathogenic mtDNA mutation in vitro, we report on the progress of this approach and the various modifications that are now being used to improve the efficacy of PNA-based antigenomic inhibition. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis. To examine whether there is a high content of mutated mitochondrial DNA in individual pancreatic beta cells from a patient with the A3243G mitochondrial DNA mutation. Methods. Tissues were available from a patient with diabetes and the A3243G mutation including pancreatic tissue. We quantified the amount of mutated mitochondrial DNA in tissue homogenates and single pancreatic beta cells using hot last cycle PCR. Results. The percentage ratio of mutated to wild-type mtDNA was high in tissues such as muscle and brain (>60%), but surprisingly low in both pancreatic islets and in individual beta cells from these islets. The islets were smaller in the patient than in control subjects in keeping with a decreased beta-cell mass. Conclusions/interpretation. These observations suggest that either the beta cells show increased sensitivity to the effects mtDNA mutations on respiratory chain function, and/or cells with a high mutant load are preferentially removed leading to a progressive decrease in the islet beta-cell mass. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effect of propofol on the change in airway pressure produced by diaphragmatic contraction. Design and Setting: Prospective, controlled study in patients anaesthetised with propofol in a university hospital. Patients and Methods: We stimulated the phrenic nerves before and immediately after induction of anaesthesia in 11 subjects, using a pair of 43-mm mean diameter double magnetic coils and measured the change in airway pressure at the mouth (TwPmo) produced by the resulting diaphragmatic contraction. Supramaximality of stimulation was confirmed with electromyogram and pressure measurements. We recorded the change in Resting End Expiratory Position (REEP) using a spirometer. We applied an approximate correction for the effect of lung volume on the amplitude of twitch pressure produced by diaphragmatic contraction. Intervention: Following the initial stimulations, the patients were anaesthetised with a propofol infusion. Once stable, repeat measurements were made. Measurements and Results: Following induction, REEP fell by mean 0.3 l standard deviation (SD) 0.2 l. TwPmo fell by mean 14.2% SD 14.0% ( P = 0.01), mean 22.3% SD 11.7% corrected ( P < 0.001). Twitch transdiaphragmatic pressure fell by 18.1% and 20.0% (25.8% and 27.7% corrected) in two further subjects studied with oesophageal and gastric balloon catheters. Conclusion: Propofol does reduce the effectiveness with which diaphragmatic contraction produces changes of pressure in the airway. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) is the only autonomously replicating source of DNA outside the nucleus. The mitochondrial genome encodes thirteen essential polypeptides of the mitochondrial respiratory chain. Defects of the mitochondrial genome can cause severe neurological and multi-systemic disorders. In many patients there is a mixture of mutated and wild-type mtDNA in the same cell (a situation termed heteroplasmy). In these patients the ratio of mutated to wild-type mtDNA is crucial and a biochemical defect only occurs with relatively high levels of mutated mtDNA within an individual cell. This threshold also seems to be critical in the development of mtDNA disease. Since the genetic defect causes a dysfunction in the terminal stage of oxidative metabolism, there is little potential for pharmacological intervention. Molecular techniques must be developed to reverse the ratio of mutated and wild-type mtDNA. In this paper we summarise our approach using both antigenomic peptide nucleic acids and cell necrosis. [ABSTRACT FROM AUTHOR]

Peptide nucleic acids (PNAs) are synthetic polynucleobase molecules, which bind to DNA and RNA with high affinity and specificity. Although PNAs have enormous potential as anti-sense agents, the success of PNA-mediated gene therapy will require efficient cellular uptake and sub-cellular trafficking. At present these mechanisms are poorly understood. To address this, we have studied the uptake of biotinylated PNAs into cultured cell lines using fluorescence confocal microscopy. In human myoblasts, initial punctate staining was followed by the release of PNAs into the cytosol and subsequent localisation and concentration in the nucleus. To determine whether PNAs could also be used as therapeutic agents for mtDNA disease, we attempted to localise PNAs to the mitochondrial matrix. When attached to the presequence peptide of the nuclear-encoded human cytochrome c oxidase (COX) subunit VIII, the biotinylated PNA was successfully imported into isolated organelles in vitro. Furthermore, delivery of the biotinylated peptide-PNA to mitochondria in intact cells was confirmed by confocal microscopy. These studies demonstrate that biotinylated PNAs can be directed across cell membranes and to a specific sub-cellular compartment within human cells – highlighting the importance of these novel molecules for human gene therapy. [ABSTRACT FROM AUTHOR]

The segregation of a heteroplasmic silent polymorphism in the mitochondrial ND6 gene has been followed in a human maternal lineage comprising eight individuals and spanning three generations. Heteroplasmy persisted in all eight maternally related family members. More importantly, the frequencies of the two alleles showed relatively little variation among individuals or between generations. In contrast to the findings in other mammalian lineages, the present results indicate relatively slow mitochondrial gene segregation. A narrow bottleneck in the number of mitochondrial DNA (mtDNA) molecules, which occurs at some stage of oogenesis, has been advanced to explain rapid mammalian mitochondrial gene segregation. It is suggested here that the segregation of mitochondrial genes may be more complex than initially envisaged, and that models need to be developed that account for both rapid and slow segregation. One possibility, which reconciles both physical and genetic studies of mammalian mtDNA, is that the unit of mitochondrial segregation is the organelle itself, each containing multiple mtDNA molecules. [ABSTRACT FROM AUTHOR]

We report on the selective-area metalorganic chemical vapor deposition of GaN stripes in the size range of 50 to 125 urn and the characterization of the morphology, topography, and optical properties of these stripes. GaN films (∼1–3 μm) grown on (0001) sapphire are used as the substrates. Excellent surface morphology is achieved under optimized growth conditions which include a higher V/III ratio than broad area growth. It is found that, under certain growth conditions, (0001) terraces of ~5 µm in width develop at the edges of all stripes, independent of stripe size and orientation. The selectively grown GaN yields stronger band-edge emission than the “substrate” GaN which indicates an improvement in optical quality. However, the donor-acceptor pair recombination (or conduction band to acceptor transition) and yellow emission are also enhanced in certain areas of the stripes. The spatial correlation of these emission bands is established by cathodoluminescence wavelength imaging, and the origin of these emissions is speculated. [ABSTRACT FROM AUTHOR]

The effect of rapid thermal annealing (RTA) on important detector characteristics such as dark current, absolute response, noise, and detectivity is investigated for quantum-well infrared photodetectors (QWIP) operating in the 8–12 µm wavelength regime. A comprehensive set of experiments is conducted on QWIPs fabricated from both as-grown and annealed multiple-quantum-well structures. RTA is done at an anneal temperature of 850°C for 30 s using an SiO2 encapsulant. In general, a decrease in performance is observed for RTA QWIPs when compared to the as-grown detectors. The peak absolute response of the annealed QWIPs is lower by almost a factor of four, which results in a factor of four decrease in quantum efficiency. In addition, a degraded noise performance results in a detectivity which is five times lower than that of QWIPs using asgrown structures. Theoretical calculations of the absorption coefficient spectrum are in excellent agreement with the experimental data. [ABSTRACT FROM AUTHOR]

High quality GaN films have been grown on sapphire substrates (C face and A face) by atmospheric pressure metalorganic chemical vapor deposition (MOCVD) using a new buffer layer. With our reactor configuration and growth parameters, a GaN film grown on a single GaN buffer layer appears opaque with high density of hexagonal pits. Using a single A1N buffer layer results in extremely nonuniform morphology with mirror-like areas near the edge of the substrates and opaque areas in the center. The double buffer layer we report here, with GaN as the first layer and A1N as the second, each with an optimized thickness, leads to mirror-like films across the entire substrate. Scanning electron microscopy, photoluminescence, x-ray diffraction, and van der Pauw geometry Hall measurement data are presented to establish the quality of our films. The mechanism for this new buffer layer is also discussed. [ABSTRACT FROM AUTHOR]

Hexokinase II (HKII) plays a central role in the intracellular metabolism of glucose in skeletal muscle, catalysing the phosphorylation of glucose to glucose 6-phosphate. It is therefore considered to be a potentially important candidate gene in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to screen the HKII gene for mutations in NIDDM subjects from insulin-resistant families. Insulin sensitivity was assessed in unaffected first degree relatives from families with two or more living NIDDM subjects, and 15 families were identified as being insulin resistant. In 15 NIDDM subjects (one from each family) and 4 normoglycaemic control subjects, all 18 exons of the HKII gene were amplified by the polymerase chain reaction, and the products screened for mutations using a combination of single-stranded conformational polymorphism analysis and direct sequencing. Six sequence variations were detected in the NIDDM subjects; four silent polymorphisms [GAT vs GAC at codon 251 in exon 7, AAT vs AAC at codon 692 in exon 15, CCG vs CCC at codon 736 in exon 15, and CTG vs CTA at codon 766 in exon 16]; a single base change [T→C], 22 base pairs distal to the exon-intron junction of exon 17 in the 5′-splice donor; and a single amino acid substitution [Gln→His] in exon 4, which was identified in 6 of the 15 NIDDM subjects. The frequency of the mutated codon 142 allele however, was comparable between NIDDM subjects with familial NIDDM ( n=56) and normoglycaemic control subjects ( n=48) (18.8% and 14.6% for NIDDM subjects and control subjects respectively; χ=0.6, p>0.25). In addition, measures of insulin sensitivity were comparable in normal glucose tolerant subjects with ( n=20) and without ( n=40) the codon 142 polymorphism. In conclusion: (1) mutations in the coding regions of the HKII gene are unlikely to be major determinants in the development of insulin resistance and familial NIDDM; although (2) the influence of the codon 142 mutation in combination with other abnormalities of the insulin-signalling pathway on insulin action remain to be addressed. [ABSTRACT FROM AUTHOR]

Glassy metals exhibit short range order which is almost as well developed as, but is topologically distinct from, that in crystalline metals. Their 'defectiveness' is due only to the absence of long range spatial correlations of the local configurations. The mechanical and magnetic behavior of glassy metals will be interpreted in terms of current structural models, in conjunction with hypotheses concerning dilatational and flow disordering and softening. [ABSTRACT FROM AUTHOR]

Dissolution of lamellar precipitates by cell boundary migration in a Pb-5.5 at. pct Sn alloy has been studied in the temperature range between 44° and 83°C by optical microscopy. Morphological observation shows that it is a cellular mode of transformation. The cell boundary, acting as a short circuit path of diffusion, recedes, thereby dissolving the precipitates. The orientation of the transformed matrix is found to follow the same relationship as that in cellular precipitation. Measurements of the rate of dissolution are in agreement with a kinetic analysis that assumes a boundary diffusion limited process. A critical temperature, defined as the temperature at which the receding boundary ceased moving, was found to exist slightly below the solvus temperature of the alloy. By balancing driving forces at both sides of the cell boundary at the critical temperature, we evaluated the upper limit of the interlamellar surface tension of Pb−Sn alloy as 232 erg per sq cm. This value is six to ten times smaller and is believed to be more realistic than those values calculated from the precipitation kinetics. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding the importance of intermediate expansions in type II diabetes.

Presents the correction of an error made in the article on peptide nucleid acid delivery to human mitochondria for gene therapy.