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Inactive state-selective KRAS(G12C) inhibitors.sup.1-8 demonstrate a 30-40% response rate and result in approximately 6-month median progression-free survival in patients with lung cancer.sup.9. The genetic basis for resistance to these first-in-class mutant GTPase inhibitors remains under investigation. Here we evaluated matched pre-treatment and post-treatment specimens from 43 patients treated with the KRAS(G12C) inhibitor sotorasib. Multiple treatment-emergent alterations were observed across 27 patients, including alterations in KRAS, NRAS, BRAF, EGFR, FGFR2, MYC and other genes. In preclinical patient-derived xenograft and cell line models, resistance to KRAS(G12C) inhibition was associated with low allele frequency hotspot mutations in KRAS(G12V or G13D), NRAS(Q61K or G13R), MRAS(Q71R) and/or BRAF(G596R), mirroring observations in patients. Single-cell sequencing in an isogenic lineage identified secondary RAS and/or BRAF mutations in the same cells as KRAS(G12C), where they bypassed inhibition without affecting target inactivation. Genetic or pharmacological targeting of ERK signalling intermediates enhanced the antiproliferative effect of G12C inhibitor treatment in models with acquired RAS or BRAF mutations. Our study thus suggests a heterogenous pattern of resistance with multiple subclonal events emerging during G12C inhibitor treatment. A subset of patients in our cohort acquired oncogenic KRAS, NRAS or BRAF mutations, and resistance in this setting may be delayed by co-targeting of ERK signalling intermediates. These findings merit broader evaluation in prospective clinical trials. Multiple treatment-emergent alterations appear in patients with advanced-stage cancer who were treated with a KRAS inhibitor., Author(s): Yulei Zhao [sup.1] , Yonina R. Murciano-Goroff [sup.2] , Jenny Y. Xue [sup.1] [sup.3] , Agnes Ang [sup.4] , Jessica Lucas [sup.1] , Trang T. Mai [sup.1] , Arnaud [...]

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients--247 home-isolated and 65 hospitalized--comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination. Analysis of a prospectively enrolled cohort of patients with SARS-CoV-2 infections in Bergen, Norway, reveals a high proportion of patients who experienced long COVID symptoms at 6 months, despite being relatively young and having only mild to moderate acute COVID-19 symptoms., Author(s): Bjørn Blomberg [sup.1] [sup.2] [sup.3] , Kristin Greve-Isdahl Mohn [sup.3] [sup.4] , Karl Albert Brokstad [sup.5] [sup.6] , Fan Zhou [sup.4] , Dagrun Waag Linchausen [sup.7] , Bent-Are Hansen [...]

This study explores potential implications of Arctic oil and gas exploration for public finance, with the Norwegian Lofoten region as a valuation case. A model is calibrated to turn oil and gas resource estimates into projections for investment, production, and net cash flows, which are discounted to assess the direct impact for the government budget. With the Norwegian oil fund mechanism and fiscal policy rule, Lofoten oil and gas revenues could add fiscal capacity in the range of 0.1-2.4 per cent of the current government budget, implying a permanent increase in annual government spending (or tax relief) of 24-220 USD per capita. Corresponding implications for other resource-rich countries in the Arctic depend on their resource potential and the relative role of oil and gas in their economy. Keywords: Petroleum economics, Resource revenue management, Public finance, 1. INTRODUCTION The Arctic holds a substantial potential in terms of petroleum resources. According to the USGS (2008), more than 400 billion oe of oil and natural gas are yet [...]

Chimerical Can you say that again and really project? I yell. I'm trapped in a corner of the room. My students are weary, waiting to be dazzled. Tell us, what [...]

Biased perspectives of fisheries researchers may hinder scientific progress and effective management if limiting factors controlling productivity go unrecognized. We investigated whether river and lake researchers used different approaches when studying salmonid production and whether any differences were ecologically supported. We assessed 564 peer- reviewed papers published between 1966 and 2012 that studied salmonid production or surrogate variables (e.g., abundance, growth, biomass, population) and classified them into five major predictor variable categories: physical habitat, fertility (i.e., nutrients, bottom-up), biotic, temperature, and pollution. The review demonstrated that river researchers primarily analyzed physical habitat (65% of studies) and lake researchers primarily analyzed fertility (45%) and biotic (51%) variables. Nevertheless, understudied variables were often statistically significant predictors of production for lake and river systems and, combined with other evidence, suggests that unjustified a priori assumptions may dictate the choice of independent variables studied. Broader consideration of potential limiting factors on fish production, greater research effort on understudied genera, and increased publication in broadly scoped journals would likely promote integration between lentic and lotic perspectives and improve fisheries management. Les perspectives biaisees de chercheurs du domaine des peches pourraient faire entrave a des avancees scientifiques et a une gestion efficace, si cela devait se traduire par la non-reconnaissance de facteurs qui limitent la productivite. Nous avons verifie si les chercheurs travaillant en riviere, d'une part, et en lac, d'autre part, utilisent des approches differentes pour etudier la production de salmonides et si certaines differences sont appuyees par des considerations ecologiques. Nous avons examine 564 articles evalues par des pairs publies de 1966 a 2012 et portant sur la production de saumons ou des variables substitutives (p. ex. abondance, croissance, biomasse, population) et les avons classes selon cinq grandes categories de variables explicatives, soit celles reliees a l'habitat physique, a la fertilite (c.-a-d. nutriments, effet ascendant), au biote, a la temperature et a la pollution. Cet examen demontre que les chercheurs travaillant en riviere analysent principalement l'habitat physique (65% des etudes), alors que les chercheurs travaillant en lac analysent principalement des variables associees a la fertilite (45%) et au biote (51%). Cela etant, des variables sous-etudiees constituent souvent des variables explicatives statistiquement significatives de la production de systemes lacustres et fluviaux ce qui, combine a d'autres observations, semble indiquer que des hypotheses a priori non justifiees pourraient dicter le choix des variables independantes etudiees. Une plus grande prise en consideration de facteurs qui pourraient limiter la production de poissons, plus de recherche axee sur des genres sous-etudies et un nombre accru de publications dans des revues a grande portee favoriseraient probablement l'integration des perspectives lentique et lotique et amelioreraient la gestion des peches. [Traduit par la Redaction], Introduction One of the primary objectives in the study of freshwater ecosystems is to better understand controls on primary and secondary production, particularly the production of fish species of economic, [...]

In seasonally breeding birds annual changes occur in hormone production by the hypothalamic-pituitary-gonadal (HPG) axis as individuals transition between breeding and non-breeding condition. Typically, some external environmental cue induces the observed changes; changes in day length, corresponding to change of seasons, are a strong cue for HPG axis activity in many species. Some species use cues other than day length as their primary initiator of breeding, and a number of light-sensitive species incorporate other cues to initiate breeding. Northern Cardinals (Cardinalis cardinalis) exhibit individual variation in when breeding begins and circulating testosterone is present throughout the year. Chemical tests of HPG axis responsiveness indicate that many individuals have an activated HPG axis as early as December. Here we use GnRH injections to assess whether individuals with active HPG axes prior to the winter solstice and increasing day lengths, may be influenced to initiate breeding by low temperatures experienced at the time of GnRH challenge. We found that while a significant number of individuals had active HPG axes prior to the winter solstice, there was no effect of low temperatures. We suggest that broader environmental patterns and additional cues may be influential to breeding in cardinals as opposed to only immediate temperature changes. Received 9 July 2013. Accepted 24 December 2013. Key words: Cardinalis cardinalis, GnRH challenge, Northern Cardinals, seasonality, testosterone., In seasonally breeding species there are significant annual changes in behavior and physiology as individuals move between breeding and nonbreeding condition (Dawson and Sharp 2007). During these transitions recrudescence and [...]

De novo mutations in ADNP, which encodes activity-dependent neuroprotective protein (ADNP), have recently been found to underlie Helsmoortel-Van der Aa syndrome, a complex neurological developmental disorder that also affects several other organ functions.sup.1. ADNP is a putative transcription factor that is essential for embryonic development.sup.2. However, its precise roles in transcriptional regulation and development are not understood. Here we show that ADNP interacts with the chromatin remodeller CHD4 and the chromatin architectural protein HP1 to form a stable complex, which we refer to as ChAHP. Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. Genetic ablation of ChAHP components in mouse embryonic stem cells results in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. Molecularly, ChAHP-mediated repression is fundamentally different from canonical HP1-mediated silencing: HP1 proteins, in conjunction with histone H3 lysine 9 trimethylation (H3K9me3), are thought to assemble broad heterochromatin domains that are refractory to transcription. ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. Together, our results reveal that ADNP, via the recruitment of HP1 and CHD4, regulates the expression of genes that are crucial for maintaining distinct cellular states and assures accurate cell fate decisions upon external cues. Such a general role of ChAHP in governing cell fate plasticity may explain why ADNP mutations affect several organs and body functions and contribute to cancer progression.sup.1,3,4. Notably, we found that the integrity of the ChAHP complex is disrupted by nonsense mutations identified in patients with Helsmoortel-Van der Aa syndrome, and this could be rescued by aminoglycosides that suppress translation termination.sup.5. Therefore, patients might benefit from therapeutic agents that are being developed to promote ribosomal read-through of premature stop codons.sup.6,7.ADNP interacts with the chromatin remodeller CHD4 and the heterochromatin protein HP1 to form a complex termed ChAHP that represses gene expression independently of the histone H3K9me3 modification., Author(s): Veronika Ostapcuk [sup.1] [sup.2] , Fabio Mohn [sup.1] , Sarah H. Carl [sup.1] [sup.3] , Anja Basters [sup.1] , Daniel Hess [sup.1] , Vytautas Iesmantavicius [sup.1] , Lisa Lampersberger [...]

The stock of Atlantic cod (Gadus morhua) on the eastern Scotian Shelf (ESS) collapsed in the early 1990s and showed no sign of recovery during a 15-year fishing moratorium, but has recently increased in abundance. Both the prolonged lack of recovery and the recent improvement have been attributed to changes in the biomass of forage fishes through effects of predation and competition by these fishes on early life stages of cod. An examination of the relationships between forage fish biomass and the population dynamics of ESS cod provided no support for this hypothesis. Contrary to expectations under this hypothesis, cod recruitment rate was unrelated to forage fish biomass. The main factor delaying recovery was high natural mortality (M) of adult cod. The recent improvement in ESS cod is due to the strong 2004 year class and a decline in M. These factors cannot be attributed to an effect of forage fishes. Both the delay in recovery and recent improvement of the ESS cod stock appear to be due to factors other than interactions with forage fishes. Le stock de morue (Gadus morhua)de l'est de la plate-forme neo-ecossaise (ESS) s'est effondre au debut des annees 1990 et n'a montre aucun signe de retablissement durant les 15 annees d'un moratoire sur la peche. Son abondance connait toutefois, depuis peu, une augmentation. L'absence prolongee d'un retablissement et l'amelioration recente ont toutes deux ete attribuees a des changements dans la biomasse de poissons fourrage qui se refletent dans des effets de la predation et de la concurrence par ces poissons sur les premieres etapes du cycle de vie de la morue. Un examen des relations entre la biomasse de poissons fourrage et la dynamique des populations de morue de l'ESS n'a fourni aucun appui a cette hypothese. Contrairement a ce que cette derniere predit, le taux de recrutement de morues n'etait pas relie a la biomasse de poissons fourrage. Le principal facteur ayant retarde le retablissement est une mortalite naturelle (M) elevee des morues adultes. L'amelioration recente du stock de morue de l'ESS est le fait de la forte classe d'age de 2004 et d'une diminution de la M. Ces facteurs ne peuvent etre attribues a aucun effet des poissons fourrage. Tant le retablissement tardif que l'amelioration recente du stock de morue de l' ESS semblent etre attribuables a des facteurs autres que les interactions avec les poissons fourrage. [Traduit par la Redaction], Introduction Most stocks of Atlantic cod (Gadus morhua) in the Northwest Atlantic collapsed in the early 1990s, predominantly because of overfishing. Nearly 20 years later, most of these stocks have [...]

Despite the widespread use of nourishment in California, few studies estimate the welfare benefits of increased beach width. This paper relies on panel data funded by National Oceanic and Atmospheric Administration and other agencies. Beach choices of respondents were combined with beach attribute data to reveal how changes in width affect choice and the economic value of beach visits. We use a random-utility approach to show that the value of beach width varies for different types of beach uses: water contact, sand-, and pavement-based activities. We also find that the marginal value of beach width depends on initial beach width. (JEL Q50), I. INTRODUCTION Beaches are among the most popular outdoor destinations because they offer archetypal tranquility--the repeating white noise of breaking waves, sun-warmed sand and cool breezes, the gentle cry of [...]

The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s) RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p=0.003 and p =0.001) and pubertal (p =0.002 and p=0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p=0.01 and pubertal p=0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p=0.003 and pubertal p=0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p=0.0004, r =-0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy. Keywords Type 1 diabetes * AGE * esRAGE * sRAGE * Diabetic nephropathy, Introduction Diabetic nephropathy (DN) is the main cause of morbidity and mortality in patients with type 1 diabetes with middle-long duration of diabetes [1]. Although overt nephropathy is usually detected [...]

Using the variables self-efficacy, self-estimates, and self-competencies in a hierarchical multiple regression and confirmatory factor analysis, the present study provided strong support for 3 of 6 RIASEC (Realistic, Investigative, Artistic, Social, Enterprising, and Conventional) interest domains regarding Holland's (1997) assertion that it is unnecessary to administer a separate measure of self-efficacy when using the Self-Directed Search (SDS; Holland, Powell, & Fritzsche, 1994) to measure interests in career counseling. Implications for the interpretation of SDS scores in light of self-efficacy assessment are discussed., The assessment of interests in career counseling has important implications for career decision making, and three of the more familiar elements in these assessments are ability self-estimates in relation to [...]

Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears. Keywords Kidney disease * Renal function impairment. Obesity * Insulin resistance * Children * Adolescents * Nitric oxide * Oxidative stress, Introduction Concomitant with the global obesity epidemic, there are a number of reports of obesity-related glomerulopathy, a secondary form of focal and segmental glomerulosclerosis characterized by proteinuria and progressive renal [...]

Polymer fibers are used for a wide range of materials in contact with the human body. Since bacterial contamination may cause diseases, it is desirable to provide fibers with antimicrobial properties. This work investigates the ability of siIver-tricalcium phosphate nanoparticles (Ag/TCP) to build a reactive system when incorporated in polyamide fibers. In the presence of bacteria, the TCP carrier particles are biodegraded and trigger the release of silver. For this work, Ag/TCP nanoparticles (1.3 wt% silver) were produced by flame spray synthesis and subsequently processed with polyamide 6 to fibers (125-µm thick, containing 260 ppm silver) with the aid of extrusion and melt-spinning for subsequent antibacterial testing. The fibers were contaminated with the clinically relevant strains Escherichia coli or Streptococcus sanguinis, respectively. The reactive fibers demonstrated significantly reduced plate count within 24 h (the number of colony forming units was reduced by 99.999% with E. coli and 99.6% with S. sanguinis compared with pure PA6 reference fibers). These reactive properties of easily integrated antibacterial silver suggest an implementation of intelligent fibers to a wide range of applications. POLYM. ENG. SCI., 51:71-77, 2011. [C]2010 Society of Plastics Engineers, INTRODUCTION Synthetic fibers - industrial and commercial - are omnipresent. In 2002, the global production of manufactured fibers was 36 million metric tons: Fiberglass pads build modern cars, polyesters form [...]

Treatment of bone defects generally requires a fixation device. Biodegradable implants can often prevent second operations in contrast to metallic implants that are surgically removed after healing. In this study, we investigate the preparation of a bone fixation device with additional bioactivity by adding nanoparticulate amorphous tricalcium phosphate (ATCP) to improve bonding to bone. Medically approved poly(lactide-co-glycolide) (PLGA) and spherical (ATCP) nanopar-ticles were blended directly or through a two-step approach, where ATCP was first dispersed in PLGA by solvent casting, extruded and hot pressed producing blocks and bone screws. The latter route yielded good particle dispersion while blending alone led to inhomo-geneous mixtures. Samples were immersed in simulated body fluid and showed rapid formation of surface hydroxy apatite layers (examined by X-ray diffraction and scanning electron microscopy) already after 3 days, thus confirming very high bioactivity. Polymer degradation during processing and upon simulated implantation conditions was followed by gel permeation chromatography. The elevated temperature during extrusion was the strongest single factor contributing to PLGA degradation. Screws could be machined out of extruded cylinders and demonstrated the ability to process PLGA/ATCP 90/10 composites with regular workshop tools. These properties suggest the use of such composites as improved, bioactive, and degrad-able bone fixation systems particularly in oral and maxillofacial surgery. POLYM. ENG. SCI., 50:952-960, 2010. [C] 2009 Society of Plastics Engineers, INTRODUCTION Biomedical composites are used in temporal or permanent implant materials and they have gained significant clinical interest due to their ability to integrate into the body (l-3). The advantage [...]

Resolving individual atoms has always been the ultimate goal of surface microscopy. The scanning tunneling microscope images atomic-scale features on surfaces, but resolving single atoms within an adsorbed molecule remains a great challenge because the tunneling current is primarily sensitive to the local electron density of states dose to the Fermi level. We demonstrate imaging of molecules with unprecedented atomic resolution by probing the short-range chemical forces with use of noncontact atomic force microscopy. The key step is functionalizing the microscope's tip apex with suitable, atomically well-defined terminations, such as CO molecules. Our experimental findings are corroborated by ab initio density functional theory calculations. Comparison with theory shows that Pauli repulsion is the source of the atomic resolution, whereas van der Waals and electrostatic forces only add a diffuse attractive background.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.dsr.2009.03.009 Byline: Florian Peine (a), Robert Turnewitsch (b), Christian Mohn (c), Theresa Reichelt (d), Barbara Springer (a), Manfred Kaufmann (e) Keywords: Thorium-234/uranium-238 disequilibria; Sediment dynamics; Bottom boundary layer; Topography; Seamounts; Internal tides; Northeast Atlantic; Eastern Mediterranean Abstract: Key aspects of deep-ocean fluid dynamics such as basin-scale (residual) and tidal flow are believed to have changed over glacial/interglacial cycles, with potential relevance for climatic change. To constrain the mechanistic links, magnitudes and temporal succession of events analyses of sedimentary paleo-records are of great importance. Efforts have been underway for some time to reconstruct residual-flow patterns from sedimentary records. Attempts to reconstruct tidal flow characteristics from deep-sea sediment deposits, however, are at a very early stage and first require a better understanding of the reflection of modern tides in sediment dynamics. In this context internal (baroclinic) tides, which are formed by the surface (barotropic) tide interacting with seafloor obstacles, are believed to play a particularly important role. Here we compare two modern deep-sea environments with respect to the effect of tides on sediment dynamics. Both environments are influenced by kilometre-scale topographic features but with vastly different tidal forcing: (1) two sites in the Northeast Atlantic (NEA) being surrounded by, or located downstream of, fields of short seamounts (maximum barotropic tidal current velocities [approximately equal to]5cms.sup.-1); and (2) a site next to the Anaximenes seamount in the Eastern Mediterranean (EMed) (maximum barotropic tidal current velocities [approximately equal to]0.5cms.sup.-1). With respect to other key fluid-dynamical parameters both environments are very similar. Signals of sedimentary particle dynamics, as influenced by processes taking place in the bottom boundary layer, were traced by the vertical water-column distribution of radioactive disequilibria (daughter/parent activity ratios[not equal to]1) between the naturally occurring, short-lived (half-life: 24.1d) particulate-matter tracer.sup.234Th relative to its very long-lived and non-particle-reactive parent nuclide.sup.238U. Activity ratios of.sup.234Th/.sup.238U1). The results of this study, therefore, add to the evidence suggesting that tides in the deep sea of the open oceans are more important for sediment dynamics than previously thought. It is hypothesised that (a) tide/seamount interactions in the deep open ocean control the local distribution of erosivity proxies (e.g., distributions of sediment grain sizes, heavy minerals and particle-reactive radionuclides) in sedimentary deposits and (b) the aforementioned topographically controlled sedimentary imprints of (internal) tides are useful in the reconstruction of past changes of tidal forcing in the deep sea. Author Affiliation: (a) Department of Marine Biology, Biosciences, University of Rostock, Albert-Einstein-Str. 3, 18051 Rostock, Germany (b) The Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban PA37 1QA, UK (c) Department of Earth and Ocean Sciences, Martin Ryan Institute, National University of Ireland Galway, Ireland (d) Institute of Oceanography, University of Hamburg, Bundesstr. 53, 20146 Hamburg, Germany (e) Department of Biology & Centre of Macaronesian Studies, University of Madeira, Marine Biology Station of Funchal, Cais do Carvao 9000-107 Funchal, Madeira Island, Portugal Article History: Received 21 October 2008; Revised 6 March 2009; Accepted 23 March 2009

Charge states of atoms can be investigated with scanning tunneling microscopy, but this method requires a conducting substrate. We investigated the charge-switching of individual adsorbed gold and silver atoms (adatoms) on ultrathin NaCl films on Cu(111) using a qPlus tuning fork atomic force microscope (AFM) operated at 5 kelvin with oscillation amplitudes in the subangstrom regime. Charging of a gold atom by one electron charge increases the force on the AFM tip by a few piconewtons. Moreover, the local contact potential difference is shifted depending on the sign of the charge and allows the discrimination of positively charged, neutral, and negatively charged atoms. The combination of single-electron charge sensitivity and atomic lateral resolution should foster investigations of molecular electronics, photonics, catalysis, and solar photoconversion.

Byline: Paola. Di Filippo, Alessandra. Scaparrotta, Marianna. Petrosino, Marina. Attanasi, Sabrina. Di Pillo, Francesco. Chiarelli, Angelika. Mohn Chronic cough in childhood is associated with a high morbidity and decreased quality [...]

To achieve a regular quadratic particle arrangement, gas phase prepared FePt nanoparticles which were annealed in flight in order to obtain the highly anisotropic tetragonal [L1.sub.0] structure are deposited onto the regular 2-D bacterial surface-protein layer (S layer) of Bacillus sphaericus NCTC 9602 which exhibits a four-fold lattice symmetry with a lattice constant of 12.5 nm. The degree of regularity is studied by the statistical evaluation of the particles positions observed by transmission electron microscopy. Although the obtained regularity for the annealed hard magnetic particles is less than for previously studied disordered fcc FePt nanoparticles, a template-directed transfer of both lattice symmetry and periodicity from the 2-D protein crystal to the particle arrangement is observed. In addition, particle agglomeration which has been shown to have a strong effect on the arrangement's regularity, is clearly reduced for the annealed particles because of the mutual magnetic repulsion of adjacent particles. Index Terms--Arrays, biomembranes, FePt, nanoparticles, self organization.

High oil prices and gradual resource depletion have raised global concerns for security of energy supply. Successful exploration activity is a critical factor for future oil production. Based on standard neoclassical producer behavior and modern time series econometrics, this study reveals new insights into the process of oil and gas exploration. I find that reserve additions are enhanced by an increase in the oil price, due to responses both in effort and efficiency of exploration. Moreover, oil companies accept higher exploration risk in response to an oil price increase, implying lower success rates and higher expected discovery size., 1. INTRODUCTION With brisk economic growth and high oil prices, issues of energy supply have ascended on the geopolitical agenda. Global oil demand has been fuelled by strong growth, both [...]

A real-time simulation method is described that has incorporated a real miniaturized High Temperature Superconducting (HTS) power cables into the simulated 22.9 kV utility power network system by using Real Time Digital Simulator (RTDS). The miniaturized HTS power cables are manufactured and the transient phenomenon of HTS power cable system is analyzed in the simulated utility power network.

The 80-kb dit cluster of Burkhoideria xenovorans LB400 encodes the catabolism of abietane diterpenoids. This cluster includes ditQ and ditU, predicted to encode cytochromes P450 (P450s) belonging to the poorly characterized CYP226A subfamily. Using proteomics, we identified 16 dit-encoded proteins that were significantly more abundant in LB400 cells grown on dehydroabietic acid (DhA) or abietic acid (AbA) than in succinategrown cells. A key difference in the catabolism of DhA and AbA lies in the differential expression of the P450s; DitU was detected only in the AbA-grown cells, whereas DitQ was expressed both during growth on DhA and during growth on AbA. Analyses of insertion mutants showed that ditQ was required for growth on DhA, ditU was required for growth on AbA, and neither gene was required for growth on the central intermediate, 7-oxo-DhA. In cell suspension assays, patterns of substrate removal and metabolite accumulation confirmed the role of DitU in AbA transformation and the role of DitQ in DhA transformation. Spectral assays revealed that DitQ binds both DhA (dissociation constant, 0.98 [+ or -] 0.01 [micro]M) and palustric acid. Finally, DitQ transformed DhA to 7-hydroxy-DhA in vitro. These results demonstrate the distinct roles of the P450s DitQ and DitU in the transformation of DhA and AbA, respectively, to 7-oxo-DhA in a convergent degradation pathway.

Proteomics and targeted gene disruption were used to investigate the catabolism of benzene, styrene, biphenyl, and ethylbenzene in Rhodococcusjostii RHAI, a well-studied soil bacterium whose potent polychlorinated biphenyl (PCB)-transforming properties are partly due to the presence of the related Bph and Etb pathways. Of 151 identified proteins, 22 Bph/Etb proteins were among the most abundant in biphenyl-, ethylbenzene-, benzene-, and styrene-grown cells. Cells grown on biphenyl, ethylbenzene, or benzene contained both Bph and Etb enzymes and at least two sets of lower Bph pathway enzymes. By contrast, styrene-grown cells contained no Etb enzymes and only one set of lower Bph pathway enzymes. Gene disruption established that biphenyl dioxygenase (BPDO) was essential for growth of RHA1 on benzene or styrene but that ethylbenzene dioxygenase (EBDO) was not required for growth on any of the tested substrates. Moreover, whole-cell assays of the [DELTA]bphAa and etbAal::cmrA etbAa2::aphH mutants demonstrated that while both dioxygenases preferentially transformed biphenyl, only BPDO transformed styrene. Deletion of pcaL of the [beta]-ketoadipate pathway disrupted growth on benzene but not other substrates. Thus, styrene and benzene are degraded via meta-and ortho-cleavage, respectively. Finally, catalases were more abundant during growth on nonpolar aromatic compounds than on aromatic acids. This suggests that the relaxed specificities of BPDO and EBDO that enable RHA1 to grow on a range of compounds come at the cost of increased uncoupling during the latter's initial transformation. The stress response may augment RHA1's ability to degrade PCBs and other pollutants that induce similar uncoupling.

Abietane diterpenoids are defense compounds synthesized by trees that are abundant in natural environments and occur as significant pollutants from pulp and paper production. Burkholderia xenovorans LB400 has diverse catabolic capabilities and represents an important group of heterotrophic bacteria in soil environments. The genome sequence of LB400 revealed homologs of the dit genes of Pseudomonas abietaniphila BKME-9, which encode abietane diterpenoid degradation. LB400 grew on abietic acid (AbA), dehydroabietic acid (DhA), palustric acid (PaA), and 7-oxo-DhA. A Xeotron microarray set, with probes for 8450 of the estimated 9000 LB400 genes, was used to compare the transcriptomes of LB400 growing on DhA versus on succinate. On DhA, 97 genes were upregulated, 43 of which were within an 80-kb cluster located on the 1.47-Mbp megaplasmid of LB400. Upregulated genes in this cluster encode a permease, a ring-hydroxylating dioxygenase system (DitA), a ring-cleavage dioxygenase (DitC), a P450 monooxygenase (DitQ), and enzymes catalyzing beta-oxidation-type reactions. Disruption of the ditA1 gene, encoding the alpha-subunit of DitA, abolished growth on these abietanes. Analyses of the metabolism of abietanes by cell suspensions of wild-type LB400 and the ditA1 mutant indicate a convergent pathway, with 7-oxo-DhA as a common intermediate for ring hydroxylation by DitA. Also, 7-oxo-PaA was identified as a metabolite of both AbA and PaA. Sequence analysis indicates that genes encoding this pathway have been horizontally transferred among Betaproteobacteria and Gammaproteobacteria.

Phthalate isomers and their esters are important pollutants whose biodegradation is not well understood. Rhodococcus sp. strain RHA1 is notable for its ability to degrade a wide range of aromatic compounds. RHA1 was previously shown to degrade phthalate (PTH) and to have genes putatively encoding terephthalate (TPA) degradation. Transcriptomic analysis of 8,213 genes indicated that 150 were up-regulated during growth on PTH and that 521 were up-regulated during growth on TPA. Distinct ring cleavage dioxygenase systems were differentially expressed during growth on PTH and TPA. Genes encoding the protocatechuate (PCA) pathway were induced on both substrates, while genes encoding the catechol branch of the PCA pathway were additionally induced only on TPA. Accordingly, protocatechuate-3,4-dioxygenase activity was induced in cells grown on both substrates, while catechol-1,2-dioxygenase activity was induced only in cells grown on TPA. Knockout analysis indicated that pcaL, encoding 3-oxoadipate enol-lactone hydrolase and 4-carboxymuconolactone decarboxylase, was required for growth on both substrates but that pcaB, encoding [BETA]-carboxy-cis,cis-muconate lactonizing enzyme, was required for growth on PTH only. These results indicate that PTH is degraded solely via the PCA pathway, whereas TPA is degraded via a bifurcated pathway that additionally includes the catechol branch of the PCA pathway.

Rhodococcus sp. strain RHA1, a soil bacterium related to Mycobacterium tuberculosis, degrades an exceptionally broad range of organic compounds. Transcriptomic analysis of cholesterol-grown RHA1 revealed a catabolic pathway predicted to proceed via 4-androstene-3,17-dione and 3,4-dihydroxy-9,10-seconandrost-1,3,5(10)-triene9,17-dione (3,4-DHSA). Inactivation of each of the hsaC, supAB, and mce4 genes in RHA1 substantiated their roles in cholesterol catabolism. Moreover, the hsaC- mutant accumulated 3,4-DHSA, indicating that Hsa[C.sub.RHA1], formerly annotated as a biphenyl-degrading dioxygenase, catalyzes the oxygenolytic cleavage of steroid ring A. Bioinformatic analyses revealed that 51 rhodococcal genes specifically expressed during growth on cholesterol, including all predicted to specify the catabolism of rings A and B, are conserved within an 82-gene cluster in M. tuberculosis H37Rv and Mycobacterium bovis bacillus Calmette--Guerin. M. bovis bacillus Calmette--Guerin grew on cholesterol, and hsaC and kshA were up-regulated under these conditions. Heterologously produced Hsa[C.sub.H37Rv] and Hsa[D/.sub.H37Rv] transformed 3,4-DHSA and its ring-cleaved product, respectively, with apparent specificities [approximately or equal to] 40-fold higher than for the corresponding biphenyl metabolites. Overall, we annotated 28 RHA1 genes and proposed physiological roles for a similar number of mycobacterial genes. During survival of M. tuberculosis in the macrophage, these genes are specifically expressed, and many appear to be essential. We have delineated a complete suite of genes necessary for microbial steroid degradation, and pathogenic mycobacteria have been shown to catabolize cholesterol. The results suggest that cholesterol metabolism is central to M. tuberculosis's unusual ability to survive in macrophages and provide insights into potential targets for novel therapeutics. catabolic pathway | oxygenase | Rhodococcus | steroid degradation

Using an econometric model of stock market values of the oil and gas industry, the current trends of the industry are analyzed. The need for the industry to focus on production growth and acquisition of long-term reserves is discussed.

Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil actinomycete that catabolizes a wide range of compounds and represents a genus of considerable industrial interest. RHA1 has one of the largest bacterial genomes sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear chromosome and three linear plasmids. A targeted insertion methodology was developed to determine the telomeric sequences. RHA1's 9,145 predicted protein-encoding genes are exceptionally rich in oxygenases (203) and ligases (192). Many of the oxygenases occur in the numerous pathways predicted to degrade aromatic compounds (30) or steroids (4). RHA1 also contains 24 nonribosomal peptide synthase genes, six of which exceed 25 kbp, and seven polyketide synthase genes, providing evidence that rhodococci harbor an extensive secondary metabolism. Among sequenced genomes, RHA1 is most similar to those of nocardial and mycobacterial strains. The genome contains few recent gene duplications. Moreover, three different analyses indicate that RHA1 has acquired fewer genes by recent horizontal transfer than most bacteria characterized to date and far fewer than Burkholderia xenovorans LB400, whose genome size and catabolic versatility rival those of RHA1. RHA1 and LB400 thus appear to demonstrate that ecologically similar bacteria can evolve large genomes by different means. Overall, RHA1 appears to have evolved to simultaneously catabolize a diverse range of plant-derived compounds in an [O.sub.2]-rich environment. In addition to establishing RHA1 as an important model for studying actinomycete physiology, this study provides critical insights that facilitate the exploitation of these industrially important microorganisms. biodegradation | actinomycete | linear chromosome | aromatic pathways | oxygenase

The complete genome sequence of Rhodococcus sp. strain RHA1 is analyzed in the biphenyl pathway (BPH) and a microarray with probe for 8,313 genes is developed and employed. The analysis suggests that up to 22 enzymes, including 8 newly identified ones, may function in the BPH pathway of RHA1.