Fluctuating selection and global change: a synthesis and review on disentangling the roles of climate amplitude, predictability and novelty.

A formidable challenge for global change biologists is to predict how natural populations will respond to the emergence of conditions not observed at present, termed novel climates. Popular approaches to predict population vulnerability are based on the expected degree of novelty relative to the amplitude of historical climate fluctuations experienced by a population. Here, we argue that predictions focused on amplitude may be inaccurate because they ignore the predictability of environmental fluctuations in driving patterns of evolution and responses to climate change. To address this disconnect, we review major findings of evolutionary theory demonstrating the conditions under which phenotypic plasticity is likely to evolve in natural populations, and how plasticity decreases population vulnerability to novel environments. We outline key criteria that experimental studies should aim for to effectively test theoretical predictions, while controlling for the degree of climate novelty. We show that such targeted tests of evolutionary theory are rare, with marine systems being overall underrepresented in this venture despite exhibiting unique opportunities to test theory. We conclude that with more robust experimental designs that manipulate both the amplitude and predictability of fluctuations, while controlling for the degree of novelty, we may better predict population vulnerability to climate change.

NWChem: Past, present, and future.

Specialized computational chemistry packages have permanently reshaped the landscape of chemical and materials science by providing tools to support and guide experimental efforts and for the prediction of atomistic and electronic properties. In this regard, electronic structure packages have played a special role by using first-principle-driven methodologies to model complex chemical and materials processes. Over the past few decades, the rapid development of computing technologies and the tremendous increase in computational power have offered a unique chance to study complex transformations using sophisticated and predictive many-body techniques that describe correlated behavior of electrons in molecular and condensed phase systems at different levels of theory. In enabling these simulations, novel parallel algorithms have been able to take advantage of computational resources to address the polynomial scaling of electronic structure methods. In this paper, we briefly review the NWChem computational chemistry suite, including its history, design principles, parallel tools, current capabilities, outreach, and outlook.

Improving organic tandem solar cells based on water-processed nanoparticles by quantitative 3D nanoimaging.

Organic solar cells have great potential for upscaling due to roll-to-roll processing and a low energy payback time, making them an attractive sustainable energy source for the future. Active layers coated with water-dispersible Landfester particles enable greater control of the layer formation and easier access to the printing industry, which has reduced the use of organic solvents since the 1980s. Through ptychographic X-ray computed tomography (PXCT), we image quantitatively a roll-to-roll coated photovoltaic tandem stack consisting of one bulk heterojunction active layer and one Landfester particle active layer. We extract the layered morphology with structural and density information including the porosity present in the various layers and the silver electrode with high resolution in 3D. The Landfester particle layer is found to have an undesired morphology with negatively correlated top- and bottom interfaces, wide thickness distribution and only partial surface coverage causing electric short circuits through the layer. By top coating a polymer material onto the Landfester nanoparticles we eliminate the structural defects of the layer such as porosity and roughness, and achieve the increased performance larger than 1 V expected for a tandem cell. This study highlights that quantitative imaging of weakly scattering stacked layers of organic materials has become feasible by PXCT, and that this information cannot be obtained by other methods. In the present study, this technique specifically reveals the need to improve the coatability and layer formation of Landfester nanoparticles, thus allowing improved solar cells to be produced.

Specific interactions between Smad proteins and AP-1 components determine TGFß-induced breast cancer cell invasion.

Deregulation of the transforming growth factor ß (TGFß) signal transduction cascade is functionally linked to cancer. In early phases, TGFß acts as a tumor suppressor by inhibiting tumor cell proliferation, whereas in late phases, it can act as a tumor promoter by stimulating tumor cell invasion and metastasis. Smad transcriptional effectors mediate TGFß responses, but relatively little is known about the Smad-containing complexes that are important for epithelial-mesenchymal transition and invasion. In this study, we have tested the hypothesis that specific members of the AP-1 transcription factor family determine TGFß signaling specificity in breast cancer cell invasion. Using a 3D model of collagen-embedded spheroids of MCF10A-MII premalignant human breast cancer cells, we identified the AP-1 transcription factor components c-Jun, JunB, c-Fos and Fra1 as essential factors for TGFß-induced invasion and found that various mesenchymal and invasion-associated TGFß-induced genes are co-regulated by these proteins. In situ proximity ligation assays showed that TGFß signaling not only induces complexes between Smad3 and Smad4 in the nucleus but also complexes between Smad2/3 and Fra1, whereas complexes between Smad3, c-Jun and JunB could already be detected before TGFß stimulation. Finally, chromatin immunoprecipitations showed that c-Jun, JunB and Fra1, but not c-Fos, are required for TGFß-induced binding of Smad2/3 to the mmp-10 and pai-1 promoters. Together these results suggest that in particular formation of Smad2/3-Fra1 complexes may reflect activation of the Smad/AP-1-dependent TGFß-induced invasion program.

Fast and direct measurements of the electrical properties of graphene using micro four-point probes.

We present measurements of the electronic properties of graphene using a repositionable micro four-point probe system, which we show here to have unique advantages over measurements made on lithographically defined devices; namely speed, simplicity and lack of a need to pattern graphene. Measurements are performed in ambient, vacuum and controlled environmental conditions using an environmental scanning electron microscope (SEM). The results are comparable to previous results for microcleaved graphene on silicon dioxide (SiO(2)). We observe a pronounced hysteresis of the charge neutrality point, dependent on the sweep rate of the gate voltage; and environmental measurements provide insight into the sensor application prospects of graphene. The method offers a fast, local and non-destructive technique for electronic measurements on graphene, which can be positioned freely on a graphene flake.

High cortisol awakening response is associated with an impairment of the effect of bright light therapy.

OBJECTIVE: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non-seasonal major depression. METHOD: Patients were treated with sertraline in combination with bright or dim light therapy for a 5-week period. Saliva cortisol levels were measured in 63 patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time-points: awakening and 20 and 60 min after awakening. RESULTS: Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas patients with a high CAR had no effect of bright light therapy compared with dim light therapy. CONCLUSION: High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from that of antidepressants.

Structure, optical properties and defects in nitride (III-V) nanoscale cage clusters.

Density Functional Theory calculations are reported on cage structured BN, AlN, GaN and InN sub- and low nanosize stoichiometric clusters, including two octahedral families of T(d) and T(h) symmetry. The structures and energetics are determined, and we observe that BN clusters in particular show high stability with respect to the bulk phase. The cluster formation energy is demonstrated to include a constant term that we attribute to the curvature energy and the formation of six tetragonal defects. The (BN)(60) onion double-bubble structure was found to be particularly unstable. In contrast, similar or greater stability was found for double and single shell cages for the other nitrides. The optical absorption spectra have been first characterised by the one-electron Kohn-Sham orbital energies for all compounds, after which we concentrated on BN where we employed a recently developed Time Dependent Density Functional Theory approach. The one-electron band gaps do not show a strong and consistent size dependency, in disagreement with the predictions of quantum confinement theory. The density of excited bound states and absorption spectrum have been calculated for four smallest BN clusters within the first ionisation potential cut-off energy. The relative stability of different BN clusters has been further explored by studying principal point defects and their complexes including topological B-N bond rotational defects, vacancies, antisites and interstititials. The latter have the lowest energy of formation.

Application of adjoint Monte Carlo to accelerate simulations of mono-directional beams in treatment planning for boron neutron capture therapy.

This paper deals with the application of the adjoint transport theory in order to optimize Monte Carlo based radiotherapy treatment planning. The technique is applied to Boron Neutron Capture Therapy where most often mixed beams of neutrons and gammas are involved. In normal forward Monte Carlo simulations the particles start at a source and lose energy as they travel towards the region of interest, i.e., the designated point of detection. Conversely, with adjoint Monte Carlo simulations, the so-called adjoint particles start at the region of interest and gain energy as they travel towards the source where they are detected. In this respect, the particles travel backwards and the real source and real detector become the adjoint detector and adjoint source, respectively. At the adjoint detector, an adjoint function is obtained with which numerically the same result, e.g., dose or flux in the tumor, can be derived as with forward Monte Carlo. In many cases, the adjoint method is more efficient and by that is much quicker when, for example, the response in the tumor or organ at risk for many locations and orientations of the treatment beam around the patient is required. However, a problem occurs when the treatment beam is mono-directional as the probability of detecting adjoint Monte Carlo particles traversing the beam exit (detector plane in adjoint mode) in the negative direction of the incident beam is zero. This problem is addressed here and solved first with the use of next event estimators and second with the application of a Legendre expansion technique of the angular adjoint function. In the first approach, adjoint particles are tracked deterministically through a tube to a (adjoint) point detector far away from the geometric model. The adjoint particles will traverse the disk shaped entrance of this tube (the beam exit in the actual geometry) perpendicularly. This method is slow whenever many events are involved that are not contributing to the point detector, e.g., neutrons in a scattering medium. In the second approach, adjoint particles that traverse an adjoint shaped detector plane are used to estimate the Legendre coefficients for expansion of the angular adjoint function. This provides an estimate of the adjoint function for the direction normal to the detector plane. In a realistic head model, as described in this paper, which is surrounded by 1020 mono-directional neutron/gamma beams and from which the best ones are to be selected, the example calculates the neutron and gamma fluxes in ten tumors and ten organs at risk. For small diameter beams (5 cm), and with comparable relative errors, forward Monte Carlo is seen to be 1.5 times faster than the adjoint Monte Carlo techniques. For larger diameter neutron beams (10 and 15 cm), the Legendre technique is found to be 6 and 20 times faster, respectively. In the case of gammas alone, for the 10 and 15 cm diam beams, both adjoint Monte Carlo Legendre and point detector techniques are respectively 2 and 3 times faster than forward Monte Carlo.

Design of a rotating facility for extracorporal treatment of an explanted liver with disseminated metastases by boron neutron capture therapy with an epithermal neutron beam.

In 2001, at the TRIGA reactor of the University of Pavia (Italy), a patient suffering from diffuse liver metastases from an adenocarcinoma of the sigmoid was successfully treated by boron neutron capture therapy (BNCT). The procedure involved boron infusion prior to hepatectomy, irradiation of the explanted liver at the thermal column of the reactor, and subsequent reimplantation. A complete response was observed. This encouraging outcome stimulated the Essen/Petten BNCT group to investigate whether such an extracorporal irradiation could be performed at the BNCT irradiation facility at the HFR Petten (The Netherlands), which has very different irradiation characteristics than the Pavia facility. A computational study has been carried out. A rotating PMMA container with a liver, surrounded by PMMA and graphite, is simulated using the Monte Carlo code MCNP. Due to the rotation and neutron moderation of the PMMA container, the initial epithermal neutron beam provides a nearly homogeneous thermal neutron field in the liver. The main conditions for treatment as reported from the Pavia experiment, i.e. a thermal neutron fluence of 4 x 10(12) +/- 20% cm(-2), can be closely met at the HFR in an acceptable time, which, depending on the defined conditions, is between 140 and 180 min.

Starting SCF calculations by superposition of atomic densities.

We describe the procedure to start an SCF calculation of the general type from a sum of atomic electron densities, as implemented in GAMESS-UK. Although the procedure is well known for closed-shell calculations and was already suggested when the Direct SCF procedure was proposed, the general procedure is less obvious. For instance, there is no need to converge the corresponding closed-shell Hartree-Fock calculation when dealing with an open-shell species. We describe the various choices and illustrate them with test calculations, showing that the procedure is easier, and on average better, than starting from a converged minimal basis calculation and much better than using a bare nucleus Hamiltonian.

Probing spacetime foam with extragalactic sources.

Because of quantum fluctuations, spacetime is probably "foamy" on very small scales. We propose to detect this texture of spacetime foam by looking for halo structures in the images of distant quasars. We find that the Very Large Telescope interferometer will be on the verge of being able to probe the fabric of spacetime when it reaches its design performance. Our method also allows us to use spacetime foam physics and physics of computation to infer the existence of dark energy or matter, independent of the evidence from recent cosmological observations.

Gelina neutron target optimisation.

A study is being performed on the properties of the Geel Electron Linear Accelerator (GELINA), a powerful white neutron source, designed for the high-energy resolution time-of-flight measurements. The main aim of this study is to reduce the time spread of neutrons of the given energy without compromising the neutron yield. Both time spread and neutron intensity influence the experimental accuracy of high-resolution neutron cross section measurements, which are particularly important in the resonance region. The quantities of interest have been simulated with coupled electron-photon-neutron steady state and transient MCNP4C3 calculations. Following benchmarking of the code to the properties of the existing target, neutron yield, energy spectra, resolution functions, and neutron and heat spatial distributions have been determined for various alternative geometries and materials. At a fixed accelerator power, actinides deliver the highest neutron yield and a small target provides the best time resolution. The resulting high-power density requires a joint optimisation of the thermal hydraulics and neutronics properties.

Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales.

OBJECTIVE: To investigate the use of bright light therapy as an adjunct treatment to sertraline in non-seasonal major depression. METHOD: In a randomised double-blind trial, 102 patients were treated for 5 weeks with either white bright light (10 000 lux, 1 h daily) or red dim light (50 lux, 30 min daily). All patients were treated with sertraline in a fixed dose of 50 mg daily. The clinician-rated depression scales used were the Hamilton Depression Rating Scale (HAM-D17), Hamilton six-item subscale (HAM-D6), Melancholia Scale (MES) and the seven 'atypical' items from the SIGH-SAD. RESULTS: One-hundred and two patients were included in the study. Analyses showed that the reduction in depression scores in the bright light group was statistically significantly larger than in the dim light group on all scales. The scale most sensitive at endpoint was the HAM-D(6), which includes the core symptoms of depression. CONCLUSION: The study results support the use of bright light as an adjunct treatment to antidepressants in non-seasonal depression.

Adjunctive bright light in non-seasonal major depression: results from patient-reported symptom and well-being scales.

OBJECTIVE: In this study, we tested the efficacy of bright light therapy as an adjunct to antidepressant treatment (sertraline) in patients with non-seasonal major depression. METHOD: In a randomized double-blind controlled trial, 102 patients were treated for 5 weeks with either white bright light (10.000 lx, 1 h/day) or red dim light (50 lx, 30 min/day). All patients received sertraline in a dosage of 50 mg daily. The self-assessment scales used were the Major Depression Inventory (MDI), the Psychological General Well-Being Scale (PGWB) and the Symptom Check List (SCL-90R). RESULTS: On all three questionnaires the score differences between baseline and endpoint were greatest in the bright light group. On the SCL-90R, the difference reached statistical significance. Results and effect sizes are compared with results from Danish national population studies applying PGWB and SCL-90R. CONCLUSION: The results advocate the use of bright light as an adjunct treatment of non-seasonal depression.

A parameter study to determine the optimal source neutron energy in boron neutron capture therapy of brain tumours.

The values of the parameters used in boron neutron capture therapy (BNCT) to calculate a given dose to human tissue vary with patients due to different physical, biological and/or medical circumstances. Parameters include the tissue dimensions, the 10B concentration and the relative biological effectiveness (RBE) factors for the different dose components associated with BNCT. Because there is still no worldwide agreement on RBE values, more often than not, average values for these parameters are used. It turns out that the RBE-problem can be circumvented by taking into account all imaginable parameter values. Approaching this quest from another angle: the outcome will also provide the parameters (and values) which influence the optimal source neutron energy. For brain tumours it turns out that the 10B concentration, the RBE factors for 10B as well as fast neutrons, together with the dose limit set for healthy tissue, affect the optimal BNCT source neutron energy. By using source neutrons of a few keV together with neutrons of a few eV, it ensures that, under all imaginable circumstances, a maximum of alpha (and lithium) particles can be delivered in the tumour.

Synthesis, structure, and magnetic properties of the fullerene-based ferromagnets Eu3C70 and Eu9C70.

Intercalation of C(70) with europium affords two kinds of magnetic compounds, a canted antiferromagnet Eu(x)C(70) (x approximately 3) and a ferromagnet Eu(x)C(70) (x approximately 9) with transition temperatures (T(C)) of 5 and 38 K, respectively. The Curie constants in the paramagnetic phase and the saturation moment in the ferromagnetic phase are both understood by the full moment of Eu(2+) for both systems. The structure of Eu(3)(-)(delta)C(70) (delta approximately 0.27) is pseudo-monoclinic, derived by a simple deformation of the parent face-centered cubic (fcc) structure. Eu(9)(-)(delta)C(70) (delta approximately 0.2) forms an fcc structure, in which cuboctahedral clustering of Eu(2+) ions is observed in the enhanced size octahedral holes. The observed T(C) of the Eu(9)(-)(delta)C(70) ferromagnet is comparable to or larger than those of simple binary Eu-based ferromagnets, such as Eu chalcogenides or carbides, despite the low atomic ratio of Eu in the chemical formulas. This can be understood by the short Eu(2+)-Eu(2+) distances and high coordination numbers permitted by the multiple occupation by Eu(2+) ions of the expanded octahedral interstitial sites in higher fullerene-based solids.

Platelet serotonin transporter in stroke patients.

OBJECTIVES: Post-stroke depression can be treated with serotonin transport inhibitors suggesting a role for the serotonin system in these patients. The number of platelet serotonin transporters in stroke patients and in control subjects have been measured in this study. MATERIAL AND METHODS: Newly admitted stroke patients who did develop or who did not develop a post-stroke depression, non-acute patients who previously had had a stroke and control subjects were compared. The number of platelet serotonin transporters was analysed by ligand binding methodology. RESULTS: The number of platelet serotonin transporters was low shortly after a stroke compared with normal subjects; no difference was found between the stroke patients who developed a post-stroke depression and those who did not. CONCLUSION: A low number of platelet serotonin transporters may be a non-specific state marker for a condition as acute stroke.