Showing papers by "University of Bergen published in 2012"

The accessible chromatin landscape of the human genome

Abstract: DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect ∼580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation. An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. This paper describes the first extensive map of human DNaseI hypersensitive sites — markers of regulatory DNA — in 125 diverse cell and tissue types. Integration of this information with other data sets generated by ENCODE (Encyclopedia of DNA Elements) identified new relationships between chromatin accessibility, transcription, DNA methylation and regulatory-factor occupancy patterns. Evolutionary-conservation analysis revealed signatures of recent functional constraint within DNaseI hypersensitive sites.

AD Model Builder: using automatic differentiation for statistical inference of highly parameterized complex nonlinear models

Abstract: Many criteria for statistical parameter estimation, such as maximum likelihood, are formulated as a nonlinear optimization problem. Automatic Differentiation Model Builder (ADMB) is a programming framework based on automatic differentiation, aimed at highly nonlinear models with a large number of parameters. The benefits of using AD are computational efficiency and high numerical accuracy, both crucial in many practical problems. We describe the basic components and the underlying philosophy of ADMB, with an emphasis on functionality found in no other statistical software. One example of such a feature is the generic implementation of Laplace approximation of high-dimensional integrals for use in latent variable models. We also review the literature in which ADMB has been used, and discuss future development of ADMB as an open source project. Overall, the main advantages of ADMB are flexibility, speed, precision, stability and built-in methods to quantify uncertainty.

Systematic text condensation: a strategy for qualitative analysis

Abstract: Aims: To present background, principles, and procedures for a strategy for qualitative analysis called systematic text condensation and discuss this approach compared with related strategies. Metho...

Changes in climate extremes and their impacts on the natural physical environment.

Abstract: This chapter addresses changes in weather and climate events relevant to extreme impacts and disasters. An extreme (weather or climate) event is generally defined as the occurrence of a value of a weather or climate variable above (or below) a threshold value near the upper (or lower) ends (‘tails’) of the range of observed values of the variable. Some climate extremes (e.g., droughts, floods) may be the result of an accumulation of weather or climate events that are, individually, not extreme themselves (though their accumulation is extreme). As well, weather or climate events, even if not extreme in a statistical sense, can still lead to extreme conditions or impacts, either by crossing a critical threshold in a social, ecological, or physical system, or by occurring simultaneously with other events. A weather system such as a tropical cyclone can have an extreme impact, depending on where and when it approaches landfall, even if the specific cyclone is not extreme relative to other tropical cyclones. Conversely, not all extremes necessarily lead to serious impacts. [3.1] Many weather and climate extremes are the result of natural climate variability (including phenomena such as El Nino), and natural decadal or multi-decadal variations in the climate provide the backdrop for anthropogenic climate changes. Even if there were no anthropogenic changes in climate, a wide variety of natural weather and climate extremes would still occur. [3.1] A changing climate leads to changes in the frequency, intensity, spatial extent, duration, and timing of weather and climate extremes, and can result in unprecedented extremes. Changes in extremes can also be directly related to changes in mean climate, because mean future conditions in some variables are projected to lie within the tails of present-day conditions. Nevertheless, changes in extremes of a climate or weather variable are not always related in a simple way to changes in the mean of the same variable, and in some cases can be of opposite sign to a change in the mean of the variable. Changes in phenomena such as the El Nino-Southern Oscillation or monsoons could affect the frequency and intensity of extremes in several regions simultaneously.

Hydroxyethyl Starch 130/0.42 versus Ringer's Acetate in Severe Sepsis

Abstract: A B S T R AC T Background Hydroxyethyl starch (HES) is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. Methods In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer’s acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modi fied intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer’s acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P = 0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer’s acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P = 0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P = 0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer’s acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.)

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

Abstract: CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination CD47 is therefore a validated target for cancer therapies

Development of a Facebook Addiction Scale.

Abstract: The Bergen Facebook Addiction Scale (BFAS), initially a pool of 18 items, three reflecting each of the six core elements of addiction (salience, mood modification, tolerance, withdrawal, conflict, and relapse), was constructed and administered to 423 students together with several other standardized self-report scales (Addictive Tendencies Scale, Online Sociability Scale, Facebook Attitude Scale, NEO-FFI, BIS/BAS scales, and Sleep questions). That item within each of the six addiction elements with the highest corrected item-total correlation was retained in the final scale. The factor structure of the scale was good (RMSEA = .046, CFI = .99) and coefficient alpha was .83. The 3-week test-retest reliability coefficient was .82. The scores converged with scores for other scales of Facebook activity. Also, they were positively related to Neuroticism and Extraversion, and negatively related to Conscientiousness. High scores on the new scale were associated with delayed bedtimes and rising times.

The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0

Abstract: The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arc ...

One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial.

Abstract: Context Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo. Objective To investigate the role of imatinib administration duration as adjuvant treatment of patients who have a high estimated risk for GIST recurrence after surgery. Design, Setting, and Patients Patients with KIT-positive GIST removed at surgery were entered between February 2004 and September 2008 to this randomized, open-label phase 3 study conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of GIST recurrence was estimated using the modified National Institutes of Health Consensus Criteria. Intervention Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery. Main Outcome Measures The primary end point was RFS; the secondary end points included overall survival and treatment safety. Results Two hundred patients were allocated to each group. The median follow-up time after randomization was 54 months in December 2010. Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to-treat population at a central pathology review. KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%) available for testing. Patients assigned for 36 months of imatinib had longer RFS compared with those assigned for 12 months (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P Conclusion Compared with 12 months of adjuvant imatinib, 36 months of imatinib improved RFS and overall survival of GIST patients with a high risk of GIST recurrence. Trial Registration clinicaltrials.gov Identifier: NCT00116935

Menarche, menopause, and breast cancer risk: Individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies

Abstract: BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.METHODS:Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.FINDINGS:Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).INTERPRETATION:The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.

Aliskiren, ALTITUDE, and the implications for ATMOSPHERE

Abstract: Blockade of the renin–angiotensin system (RAS) is a core therapeutic strategy in systolic heart failure.1 The value of angiotensin-converting enzyme (ACE) inhibitors was proven in two pivotal trials conducted >20 years ago. More recently, angiotensin receptor blockers (ARBs) have also been shown to be beneficial in systolic heart failure both as an alternative to and when added to an ACE inhibitor. Separately, mineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity when added to an ACE inhibitor or ARB (MRAs are not considered further here). The latest approach to RAS blockade to be tested in clinical practice is renin inhibition. Currently the efficacy and safety of the renin inhibitor aliskiren is being tested in two clinical trials in heart failure, the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failure (ATMOSPHERE) and the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT), described previously in this journal.2,3 However, on 20 December 2011, treatment in another study, the Aliskiren Trial In Type 2 Diabetes Using Cardio-Renal Disease Endpoints (ALTITUDE), was stopped on the recommendation of its Data Monitoring Committee (DMC).2,3 ALTITUDE was comparing placebo or aliskiren 300 mg once daily, added to background ACE inhibitor or ARB therapy in patients with diabetes and either (i) increased urinary albumin excretion or (ii) both a reduced estimated glomerular filtration rate (eGFR 30–60 mL/min/1.73 m2) and established cardiovascular disease. The primary outcome in ALTITUDE is a composite of cardiovascular death, resuscitated sudden death, non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalization for heart failure, end-stage renal disease, renal death, or doubling of baseline serum creatinine concentration, sustained for at least a month. As a result of the DMC recommendation, ALTITUDE is currently being closed out in an orderly fashion. The basis of the DMC recommendation was futility (i.e. no prospect of demonstrating the treatment benefit anticipated in the protocol) as well as safety concerns. These concerns included renal dysfunction, hyperkalaemia, and hypotension (which are unsurprising) as well as an excess of strokes. In the publically released information, the number of patients experiencing a non-fatal stroke in the placebo group was 85 (2.0%) and 112 (2.6%) in the aliskiren group (nominal, unadjusted, P-value 0.04).6 Although this unexpected finding has provoked concern and discussion, the reported numbers do not represent the final number of events in ALTITUDE (at the time of the DMC's recommendation it was estimated that approximately a third of events remained to be collected and adjudicated). Consequently, while the apparent imbalance in strokes may persist or increase, it may also attenuate. Furthermore, given all prior data relating use of antihypertensive therapy to a reduced incidence of stroke in patients with diabetes, it is also possible that the imbalance in strokes represents a chance finding.7–9 In response to these findings it has been recommended that dual aliskiren and ACE inhibitor/ARB therapy not be used in patients with both hypertension (the current indication for aliskiren) and diabetes or moderate to severe renal dysfunction (eGFR <60 mL/min/1.73 m2).10 This recommendation has led to questions about the use of dual aliskiren therapy in patients with diabetes in the ongoing ATMOSPHERE trial (and, to a lesser extent, also the ASTRONAUT trial which has almost finished recruitment and will complete follow-up this year). In ATMOSPHERE, patients with systolic heart failure and an elevated B-type natriuretic peptide (BNP) or N-terminal pro BNP ( NT-proBNP) concentration are randomized in equal proportions to receive either enalapril 10 mg twice daily, aliskiren 300 mg once daily, or the combination of both drugs.3 ATMOSPHERE is an event-driven trial with a primary composite outcome of cardiovascular death or heart failure hospitalization. We believe that the preliminary results of ALTITUDE should not lead to any alteration in the conduct of ATMOSPHERE. The reasons for taking this view are discussed in detail below.

Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype.

Abstract: Background: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552). Methods and Findings: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-a levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 nonsmoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p,0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p,0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice. Conclusions: Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.

Crafting a job on a daily basis: Contextual correlates and the link to work engagement

Abstract: Summary This study focused on daily job crafting and explored its contextual determinants and one motivational outcome (ie, work engagement) Job crafting was conceptualized as “seeking resources, ”“ seeking challenges,” and “reducing demands” Participants were 95 employees from several organizations who completed a 5-day diary survey As hypothesized, we found a 3-factor structure for the job crafting instrument, both at the general and day levels We hypothesized and found that the combination of high day-level work pressure and high day-level autonomy (active jobs) was associated with higher day-level seeking resources and lower day-level reducing demands Furthermore, we found that day-level seeking challenges (but not resources) was positively associated with day-level work engagement, whereas day-level reducing demands was negatively associated with day-level work engagement Findings suggest that job crafting is a daily employee behavior with implications for management practice and future research Copyright © 2012 John Wiley & Sons, Ltd

450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy

Abstract: Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear. Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy. Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K). Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke. Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.

Evidence for an excess of B̄→D( *)τ -ν ̄τ decays

Abstract: Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.

Outcomes of exposure to workplace bullying: A meta-analytic review

Abstract: This paper reports results from two meta-analyses of the potential individual-level outcomes of exposure to workplace bullying. After introducing a theoretical framework for the possible relationships between bullying and outcomes, Study 1 summarizes 137 cross-sectional effect sizes from 66 independent samples (N=77,721). The findings show that exposure to bullying is associated with both job-related and health- and well-being-related outcomes, such as mental and physical health problems, symptoms of post-traumatic stress, burnout, increased intentions to leave, and reduced job satisfaction and organizational commitment. Non-significant or weak associations were established for absenteeism, performance, self-perceptions, and sleep. Study 2 examines longitudinal relationships between bullying and mental health and absenteeism, respectively. Based on prospective associations from 13 samples (N=62,916), workplace bullying influenced mental health problems over time, while baseline mental health prob...

Identification of common variants associated with human hippocampal and intracranial volumes

Abstract: Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

Abstract: The interstitium describes the fluid, proteins, solutes, and the extracellular matrix (ECM) that comprise the cellular microenvironment in tissues. Its alterations are fundamental to changes in cell function in inflammation, pathogenesis, and cancer. Interstitial fluid (IF) is created by transcapillary filtration and cleared by lymphatic vessels. Herein we discuss the biophysical, biomechanical, and functional implications of IF in normal and pathological tissue states from both fluid balance and cell function perspectives. We also discuss analysis methods to access IF, which enables quantification of the cellular microenvironment; such methods have demonstrated, for example, that there can be dramatic gradients from tissue to plasma during inflammation and that tumor IF is hypoxic and acidic compared with subcutaneous IF and plasma. Accumulated recent data show that IF and its convection through the interstitium and delivery to the lymph nodes have many and diverse biological effects, including in ECM reorganization, cell migration, and capillary morphogenesis as well as in immunity and peripheral tolerance. This review integrates the biophysical, biomechanical, and biological aspects of interstitial and lymph fluid and its transport in tissue physiology, pathophysiology, and immune regulation.

The SuperMAG data processing technique

Abstract: [1] In this paper I outline the data processing technique which is used in the SuperMAG initiative. SuperMAG is a worldwide collaboration of organizations and national agencies that currently operate more than 300 ground based magnetometers. SuperMAG provides easy access to validated ground magnetic field perturbations in the same coordinate system, identical time resolution and with a common baseline removal approach. The purpose of SuperMAG is to provide scientists, teachers, students and the general public easy access to measurements of the magnetic field at the surface of the Earth. Easy access to data, plots and derived products maximizes the utilization of this unique data set. It is outlined how SuperMAG processes the observations obtained by the individual data provider. Data are rotated into a local magnetic coordinate system by determining a time dependent declination angle. This angle displays a slow gradual change and a yearly periodic variation attributed to changes in the Earth main field and season temperature variations. The baseline is determined from the data itself in a three step process: (1) a daily baseline, (2) a yearly trend, and (3) a residual offset. This technique does not require so-called quiet days and thus it avoids all the well-known problems associated with their identification. The residual offset for the N- and Z-components shows a distinct latitudinal dependence while the E-component is independent of the latitude. This result is interpreted as being due to a weak ring current (likely asymmetric) which is present even during official quiet days. For the purpose of M-I research using 1-min data I find no difference between observatories and variometers. I finally argue that there is no correct baseline determination technique since we do not have a set of ground-truth observations required to make an objective evaluation. Instead, the user must keep in mind the assumptions on which the baseline was determined and draw conclusions accordingly.

Electron performance measurements with the ATLAS detector using the 2010 LHC proton-proton collision data

Abstract: Detailed measurements of the electron performance of the ATLAS detector at the LHC are reported, using decays of the Z, W and J/psi particles. Data collected in 2010 at root s = 7 TeV are used, corresponding to an integrated luminosity of almost 40 pb(-1). The inter-alignment of the inner detector and the electromagnetic calorimeter, the determination of the electron energy scale and resolution, and the performance in terms of response uniformity and linearity are discussed. The electron identification, reconstruction and trigger efficiencies, as well as the charge misidentification probability, are also presented.

Metazoan promoters: emerging characteristics and insights into transcriptional regulation

Abstract: Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters and their features, helping researchers who are investigating functional categories of promoters and their modes of regulation. Additional features of promoters that are being characterized include types of histone modifications, nucleosome positioning, RNA polymerase pausing and novel small RNAs. In this Review, we discuss recent findings relating to metazoan promoters and how these findings are leading to a revised picture of what a gene promoter is and how it works.

Studying political microblogging: Twitter users in the 2010 Swedish election campaign:

Abstract: Among the many so-called microblogging services that allow their users to describe their current status in short posts, Twitter is probably among the most popular and well known. Since its launch i ...

The NAD metabolome — a key determinant of cancer cell biology

Abstract: NAD is a vital molecule in all organisms. It is a key component of both energy and signal transduction--processes that undergo crucial changes in cancer cells. NAD(+)-dependent signalling pathways are many and varied, and they regulate fundamental events such as transcription, DNA repair, cell cycle progression, apoptosis and metabolism. Many of these processes have been linked to cancer development. Given that NAD(+)-dependent signalling reactions involve the degradation of the molecule, permanent nucleotide resynthesis through different biosynthetic pathways is crucial for incessant cancer cell proliferation. This necessity supports the targeting of NAD metabolism as a new therapeutic concept for cancer treatment.

Reconsidering the Consequences of Selective Fisheries

Abstract: Concern about the impact of fishing on ecosystems and fisheries production is increasing ( 1 , 2 ). Strategies to reduce these impacts while addressing the growing need for food security ( 3 ) include increasing selectivity ( 1 , 2 ): capturing species, sexes, and sizes in proportions that differ from their occurrence in the ecosystem. Increasing evidence suggests that more selective fishing neither maximizes production nor minimizes impacts ( 4 – 7 ). Balanced harvesting would more effectively mitigate adverse ecological effects of fishing while supporting sustainable fisheries. This strategy, which challenges present management paradigms, distributes a moderate mortality from fishing across the widest possible range of species, stocks, and sizes in an ecosystem, in proportion to their natural productivity ( 8 ), so that the relative size and species composition is maintained.

Measurement of the azimuthal anisotropy for charged particle production in √ sNN = 2.76 TeV lead-lead collisions with the ATLAS detector

Abstract: Differential measurements of charged particle azimuthal anisotropy are presented for lead-lead collisions at root sNN = 2.76 TeV with the ATLAS detector at the LHC, based on an integrated luminosity of approximately 8 mu b(-1). This anisotropy is characterized via a Fourier expansion of the distribution of charged particles in azimuthal angle relative to the reaction plane, with the coefficients v(n) denoting the magnitude of the anisotropy. Significant v(2)-v(6) values are obtained as a function of transverse momentum (0.5 = 3 are found to vary weakly with both eta and centrality, and their p(T) dependencies are found to follow an approximate scaling relation, v(n)(1/n)(p(T)) proportional to v(2)(1/2)(p(T)), except in the top 5% most central collisions. A Fourier analysis of the charged particle pair distribution in relative azimuthal angle (Delta phi = phi(a)-phi(b)) is performed to extract the coefficients v(n,n) = . For pairs of charged particles with a large pseudorapidity gap (|Delta eta = eta(a) - eta(b)| > 2) and one particle with p(T) < 3 GeV, the v(2,2)-v(6,6) values are found to factorize as v(n,n)(p(T)(a), p(T)(b)) approximate to v(n) (p(T)(a))v(n)(p(T)(b)) in central and midcentral events. Such factorization suggests that these values of v(2,2)-v(6,6) are primarily attributable to the response of the created matter to the fluctuations in the geometry of the initial state. A detailed study shows that the v(1,1)(p(T)(a), p(T)(b)) data are consistent with the combined contributions from a rapidity-even v(1) and global momentum conservation. A two-component fit is used to extract the v(1) contribution. The extracted v(1) isobserved to cross zero at pT approximate to 1.0 GeV, reaches a maximum at 4-5 GeV with a value comparable to that for v(3), and decreases at higher p(T).

Open-source MATLAB implementation of consistent discretisations on complex grids

Abstract: Accurate geological modelling of features such as faults, fractures or erosion requires grids that are flexible with respect to geometry. Such grids generally contain polyhedral cells and complex grid-cell connectivities. The grid representation for polyhedral grids in turn affects the efficient implementation of numerical methods for subsurface flow simulations. It is well known that conventional two-point flux-approximation methods are only consistent for K-orthogonal grids and will, therefore, not converge in the general case. In recent years, there has been significant research into consistent and convergent methods, including mixed, multipoint and mimetic discretisation methods. Likewise, the so-called multiscale methods based upon hierarchically coarsened grids have received a lot of attention. The paper does not propose novel mathematical methods but instead presents an open-source Matlab® toolkit that can be used as an efficient test platform for (new) discretisation and solution methods in reservoir simulation. The aim of the toolkit is to support reproducible research and simplify the development, verification and validation and testing and comparison of new discretisation and solution methods on general unstructured grids, including in particular corner point and 2.5D PEBI grids. The toolkit consists of a set of data structures and routines for creating, manipulating and visualising petrophysical data, fluid models and (unstructured) grids, including support for industry standard input formats, as well as routines for computing single and multiphase (incompressible) flow. We review key features of the toolkit and discuss a generic mimetic formulation that includes many known discretisation methods, including both the standard two-point method as well as consistent and convergent multipoint and mimetic methods. Apart from the core routines and data structures, the toolkit contains add-on modules that implement more advanced solvers and functionality. Herein, we show examples of multiscale methods and adjoint methods for use in optimisation of rates and placement of wells.