Optically induced metastability in Cu(In,Ga)Se2.

Cu(In,Ga)Se2 (CIGS) is presently the most efficient thin-film photovoltaic technology with efficiencies exceeding 22%. An important factor impacting the efficiency is metastability, where material changes occur over timescales of up to weeks during light exposure. A previously proposed (V Se -V Cu ) divacancy model presents a widely accepted explanation. We present experimental evidence for the optically induced metastability transition and expand the divacancy model with first-principles calculations. Using photoluminescence excitation spectroscopy, we identify a sub-bandgap optical transition that severely deteriorates the carrier lifetime. This is in accordance with the expanded divacancy model, which predicts that states below the conduction band are responsible for the metastability change. We determine the density-capture cross-section product of the induced lifetime-limiting states and evaluate their impact on device performance. The experimental and theoretical findings presented can allow assessment of metastability characteristics of leading thin-film photovoltaic technologies.

Competing ultrafast energy relaxation pathways in photoexcited graphene.

For most optoelectronic applications of graphene, a thorough understanding of the processes that govern energy relaxation of photoexcited carriers is essential. The ultrafast energy relaxation in graphene occurs through two competing pathways: carrier-carrier scattering, creating an elevated carrier temperature, and optical phonon emission. At present, it is not clear what determines the dominating relaxation pathway. Here we reach a unifying picture of the ultrafast energy relaxation by investigating the terahertz photoconductivity, while varying the Fermi energy, photon energy and fluence over a wide range. We find that sufficiently low fluence (≲4 µJ/cm(2)) in conjunction with sufficiently high Fermi energy (≳0.1 eV) gives rise to energy relaxation that is dominated by carrier-carrier scattering, which leads to efficient carrier heating. Upon increasing the fluence or decreasing the Fermi energy, the carrier heating efficiency decreases, presumably due to energy relaxation that becomes increasingly dominated by phonon emission. Carrier heating through carrier-carrier scattering accounts for the negative photoconductivity for doped graphene observed at terahertz frequencies. We present a simple model that reproduces the data for a wide range of Fermi levels and excitation energies and allows us to qualitatively assess how the branching ratio between the two distinct relaxation pathways depends on excitation fluence and Fermi energy.

MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer.

BACKGROUND: Methylenetetrahydrofolate reductase is a pivotal enzyme in folate metabolism and 5-fluorouracil (5-FU) cytotoxicity. Two common single-nucleotide polymorphisms (SNPs), MTHFR 677C>T (rs1801133) and 1298A>C (rs1801131), reduce enzyme activity. Initially, these SNPs were claimed to predict clinical efficacy, but further studies have yielded contradictory results. We tested whether these two polymorphisms are determinants of clinical outcome in a large patient group with a long follow-up time. PATIENTS AND METHODS: We included 331 patients who had been treated with adjuvant 5-FU/leucovorin chemotherapy after intended curative resection between 1997 and 2003. Clinical data, including relapse rates, overall survival, and tumor stage, were collected. DNA was extracted from formalin-fixed tumor tissue and analyzed for the MTHFR 677C>T and 1298A>C SNPs with real-time PCR. RESULTS: The MTHFR 677C>T and 1298A>C polymorphisms were not associated with survival or relapse-free survival (P > 0.2). The 677 CC genotype was associated to toxicity (odds ratio = 1.83, P = 0.01). CONCLUSIONS: The MTHFR 677C>T and 1298A>C polymorphisms probably do not predict efficacy of adjuvant 5-FU treatment in colorectal cancer after complete resection; however, the 677C>T polymorphism may be associated with lower toxicity in 5-FU treatment. Implementation of SNP analysis for these polymorphisms for individualized treatment is premature.

Fatal ulcerative colitis in a western lowland gorilla (Gorilla gorilla gorilla).

A captive western lowland gorilla (Gorilla gorilla gorilla) presented with watery diarrhoea that progressed to become profuse and haemorrhagic. Faecal analyses revealed Balantidium (B.) coli trophozoites and salmonella-like bacteria. Despite treatment the gorilla died on the 5th day after onset of symptoms. Post-mortem examination revealed a severe erosive-ulcerative superficial and deep colitis. Histological examination of post-mortem samples of the colon showed plentiful B. coli invading into the mucosa and submucosa, whilst PCR screening of bacterial DNA could not confirm any bacteria species which could be connected to the clinical picture. As B. coli is usually a non-pathogenic gut commensal, and as this animal previously showed evidence of non-symptomatic infection of B. coli, it is possible that the switch in pathogenicity was triggered by an acute bacterial infection. Despite successful treatment of the bacterial infection the secondary deep invasion of B. coli was not reversed, possibly because of the failure of the treatment regimen, and led to the death of the gorilla.

The prevalence of chronic critical lower limb ischaemia in a population of 20,000 subjects 40-69 years of age.

OBJECTIVE: To study the prevalence and possible risk factors for chronic critical lower limb ischaemia (CLI) in an unselected population of 20,291 Norwegian men and women 40-69 years of age. METHODS: Between 1995 and 1997, all residents 20 years or older in Nord-Trøndelag County, Norway, were invited to participate in a population study (the HUNT 2 Study). Among the 71.2% who attended, 20,291 participants 40-69 years of age responded to questions specifically aimed at identifying CLI. Chronic critical ischaemia was suspected if participants indicated: (1) ulcers on toes, foot or ankle that had failed to heal and/or; (2) persistent pain in the forefoot while in the supine position, but with relief of this pain when standing up. Using logistic regression analyses, we estimated the association between the prevalence of CLI and smoking, diabetes mellitus, previous cardiovascular events, blood lipids and glucose levels, and body mass index (BMI). RESULTS: The age-adjusted prevalence of CLI was 0.26% among men and 0.24% among women, and there was no gender difference in any age group (age-adjusted OR = 0.91, 95% CI = 0.52-1.58). The presence of increased age, diabetes mellitus, angina pectoris, high triglyceride levels, and high BMI were all independently associated with higher prevalence of CLI. CONCLUSION: The prevalence of CLI was 0.24%, similar for both genders, and increased with age. Risk factors usually seen in atherosclerotic patients were associated with suspected CLI.

Serum lipids and anthropometric factors related to the prevalence of intermittent claudication.

PURPOSE: To study serum lipids, body mass index (BMI), and body shape in relation to intermittent claudication (IC) in 19,748 men and women 40-69 years of age. METHOD: All residents (1995-1997) in Nord-Trøndelag County, Norway, were invited to attend the cross sectional study and received a Norwegian translation of the WHO/Rose questionnaire on intermittent claudication and the Edinburgh claudication questionnaire. Blood lipids and anthropometric data were measured at a consecutive examination. Odds ratios (OR) were estimated for associations with IC by multiple regression analysis. RESULTS: The ratio of total cholesterol to HDL cholesterol (TC/HDL cholesterol) (P trend(men)=.023; P trend(women)<.001) and triglycerides (P trend(men)=.029; P trend(women)=.002) were positively associated with the prevalence of IC. HDL cholesterol was negatively (P trend(men)=.131; P trend(women)<.001) associated, whereas BMI (P trend(women)=.032), waist circumference (P trend(women)=.021), and hip circumference (P trend(women)=.020) were positively associated with IC in women, but not in men. Adjustment for smoking, diabetes, and systolic or diastolic blood pressure did not change the results. CONCLUSION: TC/HDL cholesterol and triglycerides were positively, and HDL cholesterol negatively associated with IC in both genders. In women, but not in men, BMI, waist and hip circumference were positively associated with IC.

Effect of intravenous N-acetylcysteine infusion on haemostatic parameters in healthy subjects.

BACKGROUND AND AIMS: N-acetylcysteine is used to treat paracetamol overdose but depresses the activity of plasma coagulation factors II, VII, and X, which are often used to assess liver injury. The aim of this study was to investigate the effect of N-acetylcysteine on haemostasis in normal volunteers. METHODS: Haemostatic parameters in 10 healthy subjects were analysed before and following intravenous infusion of therapeutic doses of N-acetylcysteine, as well as in vitro. RESULTS: N-acetylcysteine induced significant decreases in plasma levels of vitamin K dependent haemostatic proteins in vivo, being maximal at one hour following the start of infusion, with maximal decreases from 1.00 to 0.73 (0.67-0.79) (mean (95% confidence interval)), 0.66 (0.58-0.73), 0.81 (0.73-0.90), 0.64 (0.57-0.70), 0.74 (0.65-0.82), and 0.61 (0.54-0.67) for factor II, VII, IX, and X activities, protein C activity, and free protein S reactivity, respectively. These data suggest that N-acetylcysteine induces protein modifications affecting activity. Five subjects developed an adverse reaction to infusion of N-acetylcysteine and these were associated with a rapid increase in levels of factor VIII and its carrier protein von Willebrand factor (vWf) from 1.0 to 1.85 (1.08-2.62) and 1.77 (0.83-2.71), respectively, which suggests that the allergic reaction induced release of vWf from endothelial cells. N-acetylcysteine did not affect factor VIII or vWf in subjects without adverse reactions, and nor did it affect factor V or antithrombin in any of the subjects. CONCLUSION: Therapeutic doses of N-acetylcysteine cause abnormal haemostatic activity, and this should be taken into account when using haemostatic function tests as an indicator of hepatic injury.

Emotional reactivity in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study examined Barkley's (1997b) theory regarding the emotional regulation of children with Attention-Deficit/Hyperactivity Disorder (ADHD). METHOD: Mothers of children with and without ADHD between the ages of 6 and 15 were asked to rate their child's emotional response on each of three measures. RESULTS: Children with ADHD were rated as significantly more emotionally reactive to both immediate and future events than were children without ADHD. Differences at both the immediate and future time periods were stronger in response to negative as opposed to positive emotional events. In response to the consequences of their behavior, however, children with ADHD were rated as less emotionally reactive than children without ADHD. DISCUSSION: Conclusions are made in reference to Barkley's theory and implications are explored.

The prevalence of intermittent claudication. Sex-related differences have been eliminated.

OBJECTIVES: to investigate the prevalence of intermittent claudication (IC) in an unselected population of nearly 20000 individuals between 40 and 69 years of age. DESIGN: epidemiologic investigation of residents in Nord-Trøndelag County, Norway. MATERIAL AND METHODS: between 1995 and 1997, all residents 20 years of age or older in Nord-Trøndelag County, Norway, were invited to attend the HUNT Study. A total of 19748 participants between 40 and 69 years of age responded to questions related to the symptoms of intermittent claudication. We estimated the prevalence of IC based on these questions. RESULTS: the age-adjusted prevalence of intermittent claudication in the total population was 1.1% for men and 1.2% for women. We found an increase in the prevalence of IC by age, however, no sex differences were observed. CONCLUSION: the prevalence of intermittent claudication increased gradually by age. However, in contrast to previous reports, there was no difference by sex.

The prevalence of asymptomatic arterial obstruction in the lower extremities among men and women 60 to 69 years of age.

AIM: To estimate the prevalence of asymptomatic arterial obstruction in the lower extremities in men and women 60 to 69 years of age. METHODS: A sample of 333 participants between 60 to 69 years of age attended a physical examination as part of a population based health study in Nord-Trøndelag County, Norway (the HUNT Study). The total prevalence of arterial obstruction was defined as the proportion of subjects with ankle brachial pressure index lower than 0.9 (ABPI<0.9). Further, the proportion of participants with arterial obstruction who also reported symptoms of intermittent claudication was defined as having symptomatic arterial obstruction. Finally, the prevalence of asymptomatic arterial obstruction was calculated as the difference between the total prevalence of arterial obstruction and the prevalence of symptomatic arterial obstruction. RESULTS: The total prevalence of arterial obstruction as defined by ABPI<0.9 was 7.8%. The prevalence was slightly higher among men (9.2%) than among women (6.9%), but the difference was not statistically significant (p-value=0.5). The prevalence of asymptomatic arterial obstruction was 6.3%, indicating that asymptomatic disease was approximately 4 times as frequent as symptomatic arterial obstruction (1.5%). The prevalence of asymptomatic arterial obstruction was nearly identical for men (6.2%) and women (6.4%). CONCLUSION: The total prevalence of arterial obstruction as defined by an ABPI<0.9 was 7.8% in this age group, and the prevalence of asymptomatic disease was 6.3%. Thus, only 1 in 5 persons who had objectively measured arterial obstruction indicated symptoms of intermittent claudication.

Hydrophobic domains of human tropoelastin interact in a context-dependent manner.

Tropoelastin is the soluble precursor of elastin, the major component of the extracellular elastic fiber. Tropoelastin undergoes self-association via an inverse temperature transition termed coacervation, which is a crucial step in elastogenesis. Coacervation of tropoelastin takes place through multiple intermolecular interactions of its hydrophobic domains. Previous work has implicated those hydrophobic domains located near the center of the polypeptide as playing a dominant role in coacervation. Short constructs of domains 18, 20, 24, and a mutated form of domain 26 were largely disordered at 20 degrees C but displayed increased order on heating that was consistent with the formation of beta-structures. However, their conformational transitions were not sensitive to physiological temperature in contrast to the observed behavior of the native domain 26. A polypeptide consisting of domains 17-27 of tropoelastin coacervated at temperatures above 60 degrees C, whereas individually expressed hydrophobic regions were not capable of coacervation. We conclude that coacervation depends on the hydrophobicity of the molecule and, by inference, the number of hydrophobic domains. Tropoelastin mutants were constructed to contain a Pro --> Ala mutation in domain 26, separate deletions of domains 18 and 26, and a displacement of domain 26. These constructs displayed unequal capacities for coacervation, even when they contained the same number of hydrophobic regions and comparable levels of secondary structure. Thus, the capability for coacervation is determined by contributions from individual hydrophobic domains for which function should be considered in the context of their positions in the intact tropoelastin molecule.

Protein interaction studies of MAGP-1 with tropoelastin and fibrillin-1.

Elastic fibers consist primarily of an amorphous elastin core associated with microfibrils, 10-12 nm in diameter, containing fibrillins and microfibril-associated glycoproteins (MAGPs). To investigate the interaction of MAGP-1 with tropoelastin and fibrillin-1, we expressed human MAGP-1 as a T7-tag fusion protein in Escherichia coli. Refolding of the purified protein produced a soluble form of MAGP-1 that displayed saturable binding to tropoelastin. Fragments of tropoelastin corresponding to the N-terminal, C-terminal, and central regions of the molecule were used to characterize the MAGP-1 binding site. Cleavage of tropoelastin with kallikrein, which cleaves after Arg(515) in the central region of the molecule, disrupted the interaction, suggesting that the separated N- and C-terminal fragments were insufficient to determine MAGP-1 binding to intact tropoelastin. In addition, no evidence of an interaction was observed between MAGP-1 and a tropoelastin construct consisting of domains 17-27 that brackets the kallikrein cleavage site, suggesting a complex mechanism of interaction between the two molecules. Binding of MAGP-1 was also tested with overlapping recombinant fibrillin-1 fragments. MAGP-1 bound to a region at the N terminus of fibrillin-1 in a calcium-dependent manner. In summary, these results suggest a model for the interaction of elastin with the microfibrillar scaffold.

Liver gene regulation in rats following both 70 or 90% hepatectomy and endotoxin treatment.

BACKGROUND: The metabolic state effect of liver failure on liver gene regulation was evaluated in a rat model. METHODS: Following 70 or 90% hepatectomy and lipopolysaccharide or vehicle treatment at intervals up to 24 h, the liver remnants were analyzed for mRNA levels for acute-phase, liver-specific and growth-related proteins. RESULTS: After 70% hepatectomy mRNA for alpha 1-acid glycoprotein, alpha 2-macroglobulin, thiostatin and fibrinogen, haptoglobin increased three- to sevenfold (P < 0.05), and mRNA for cyclin D and histone 3 increased seven- and 15-fold (P < 0.05), respectively. After lipopolysaccharide injection and 70% hepatectomy were done, mRNA for acute-phase proteins raised significantly (P < 0.05), more to five to 20-fold, while mRNA for growth-related proteins raised significantly (P < 0.05) less to three- to fourfold. After 90% hepatectomy, acute-phase protein mRNA increased five- to ninefold (P < 0.05) more than after 70% hepatectomy, while mRNA for histone 3 and cyclin D did not increase within 24 h, which indicates a delayed growth after 90% hepatectomy. In 90% of hepatectomized rats treated with lipopolysaccharide, acute-phase protein mRNA raised three- to sixfold (P < 0.05) less than after vehicle treatment. CONCLUSION: In endotoxemia from liver failure, the synthesis of acute-phase proteins is upregulated by gene regulation at the expense of that for regeneration, which may be an appropriate response for immediate survival. In severe liver failure, endotoxin may interfere with the appropriate gene regulation.

[Therapeutic monitoring by blood concentrations with the focus on cyclosporin A]. / Terapistyring efter blodkoncentrationer med fokus på ciclosporin A.

Cyclosporin A therapeutic drug monitoring with through concentrations results in a high frequency of toxicity or therapeutic failure. There is no simple relation between the through and the mean concentration, and thus the therapeutic effect. Estimation of the AUC on sparse sampling or population pharmacokinetic analysis and the Bayesian fit of the parameters are discussed.

Domain 26 of tropoelastin plays a dominant role in association by coacervation.

The temperature-dependent association of tropoelastin molecules through coacervation is an essential step in their assembly leading to elastogenesis. The relative contributions of C-terminal hydrophobic domains in coacervation were assessed. Truncated tropoelastins were constructed with N termini positioned variably downstream of domain 25. The purified proteins were assessed for their ability to coacervate. Disruption to domain 26 had a substantial effect and abolished coacervation. Circular dichroism spectroscopy of an isolated peptide comprising domain 26 showed that it undergoes a structural transition to a state of increased order with increasing temperature. Protease mapping demonstrated that domain 26 is flanked by surface sites and is likely to be in an exposed position on the surface of the tropoelastin molecule. These results suggest that the hydrophobic domain 26 is positioned to play a dominant role in the intermolecular interactions that occur during coacervation.

Antioxidants, DNA damage and gene expression.

Reactive oxygen species (ROS) are generated from incomplete reduction in the respiratory chain. On one hand they pose a serious threat of deleterious effects on important macromolecules, among which DNA is considered most important since it carries the genetic information and changes will be carried on to future generations, or will fundamentally change the behaviour of the cells. On the other hand, it is becoming evident that there are important changes in the cells in response to redox changes. This review summarises the genes, the intracellular signalling elements and molecules that presently are known to be regulated by oxidative stress. It is now clear that both oxidants and antioxidants can regulate a multitude of different cellular functions, signal transduction pathways and gene expression. However, the quantitative importance is unknown and as of yet there are no examples of regulation exclusively by oxidative stress. Also the response to oxidative stress is variable, can be up-regulation as well as down-regulation, and different responses to dose or magnitude of the oxidative stress can be demonstrated. The effect from supplementation with an antioxidant is difficult to predict, and ultimately must be assessed in clinical trials.

Comparison of the cleaning efficacy of passive sonic activation and passive ultrasonic activation after hand instrumentation in molar root canals.

The purpose of this study was to compare the cleaning efficacy of passive ultrasonic activation with that of passive sonic activation after hand instrumentation. Sixty curved molar canals were hand-instrumented to size 35 and divided into three groups. Group 1 received no further treatment. Group 2 received 3 min of passive sonic activation. Group 3 received 3 min of passive ultrasonic activation. The roots were split and photomicrographs (x20) were made of the apical 6 mm of canal. A transparent grid was placed over projected images, and the total number of squares covering the apical 6 mm of canal space and the number of squares containing debris were counted. A debris score was calculated for each specimen by dividing the number of squares with debris by the total number of squares. The mean debris scores were 31.6% for hand instrumentation only, 15.1% for the sonic group, and 16.7% for the ultrasonic group. The debris scores for the sonic and ultrasonic activation groups were significantly lower than that for the hand instrumentation only group (p < 0.01); however, there was no significant difference between the sonic and ultrasonic activation groups. Passive sonics after hand instrumentation produces a cleaner canal than hand instrumentation alone and is comparable with that of passive ultrasonics.

Effects of growth hormone on steroid-induced increase in ability of urea synthesis and urea enzyme mRNA levels.

Growth hormone (GH) reduces the catabolic side effects of steroid treatment due to its effects on tissue protein synthesis/degradation. Little attention is focused on hepatic amino acid degradation and urea synthesis. Five groups of rats were given 1) placebo, 2) prednisolone, 3) placebo, pair fed to the steroid group, 4) GH, and 5) prednisolone and GH. After 7 days, the in vivo capacity of urea N synthesis (CUNS) was determined by saturating alanine infusion, in parallel with measurements of liver mRNA levels of urea cycle enzymes, N contents of organs, N balance, and hormones. Prednisolone increased CUNS (micromol . min-1 . 100 g-1, mean +/- SE) from 9.1 +/- 1.0 (pair-fed controls) to 13.2 +/- 0.8 (P < 0.05), decreased basal blood alpha-amino N concentration from 4.2 +/- 0.5 to 3.1 +/- 0.3 mmol/l (P < 0.05), increased mRNA levels of the rate- and flux-limiting urea cycle enzymes by 20 and 65%, respectively (P < 0. 05), and decreased muscle N contents and N balance. In contrast, GH decreased CUNS from 6.1 +/- 0.9 (free-fed controls) to 4.2 +/- 0.5 (P < 0.05), decreased basal blood alpha-amino N concentration from 3. 8 +/- 0.3 to 3.2 +/- 0.2, decreased mRNA levels of the rate- and flux-limiting urea cycle enzymes to 60 and 40%, respectively (P < 0. 05), and increased organ N contents and N balance. Coadministration of GH abolished all steroid effects. We found that prednisolone increases the ability of amino N conversion into urea N and urea cycle gene expression. GH had the opposite effects and counteracted the N-wasting side effects of prednisolone.