Estimation of cosmological parameters using adaptive importance sampling

We present a Bayesian sampling algorithm called adaptive importance sampling or population Monte Carlo (PMC), whose computational workload is easily parallelizable and thus has the potential to considerably reduce the wall-clock time required for sampling, along with providing other benefits. To assess the performance of the approach for cosmological problems, we use simulated and actual data consisting of CMB anisotropies, supernovae of type Ia, and weak cosmological lensing, and provide a comparison of results to those obtained using state-of-the-art Markov chain Monte Carlo (MCMC). For both types of data sets, we find comparable parameter estimates for PMC and MCMC, with the advantage of a significantly lower wall-clock time for PMC. In the case of WMAP5 data, for example, the wall-clock time scale reduces from days for MCMC to hours using PMC on a cluster of processors. Other benefits of the PMC approach, along with potential difficulties in using the approach, are analyzed and discussed.

Profiling ellagic acid content: The importance of form and ascorbic acid levels

As the importance of plant-based antioxidants to human health becomes clearer there is a rapidly expanding search for rich sources of these compounds. Much attention is currently focussed on the antioxidant potential of ellagic acid (EA). Making assessment difficult is that EA occurs in different forms: free EA, EA glycosides and polymeric ellagitannins. The overall structure of these forms has a pronounced effect on their antioxidant efficiency and is responsible for widely differing reactivity, solubility and hence bioavailability properties. Often associated with EA is vitamin C which also contributes to the plant foods total antioxidant activity. Previous studies have suggested that ascorbic acid may have protective effects on the polyphenol content of plants. With a view to gaining evidence that the bioactive forms of vitamin C influence EA content, several fruits with a range of EA and vitamin C contents were examined. To facilitate a more detailed assessment of the selected fruits antioxidant potential the relative proportions of EA forms were also determined. In strawberries and boysenberries EA content was predominantly in the polymeric form (21% and 12% free EA plus EA glycoside vs total EA levels for strawberry and boysenberry respectively), while in Kakadu plum it was mainly in the free form (70% of total EA). An increasing percentage of dehydroascorbic acid (9 to 14% of total vitamin C) indicating enhanced transformation of ascorbic acid to its oxidative degradation product together with stable free EA levels (≈ 950 mg/100 g DW) over the 4 month frozen storage period for the Kakadu plum samples are consistent with a possible protective effect of EA by ascorbic acid.

Importance of non-conserved distal carboxyl terminal amino acids in two peptidases belonging to the M1 family: Thermoplasma acidophilum Tricorn interacting factor F2 and Escherichia coli Peptidase N

Enzymes belonging to the M1 family play important cellular roles and the key amino acids (aa) in the catalytic domain are conserved. However, C-terminal domain aa are highly variable and demonstrate distinct differences in organization. To address a functional role for the C-terminal domain, progressive deletions were generated in Tricorn interacting factor F2 from Thermoplasma acidophilum (F2) and Peptidase N from Escherichia coli (PepN). Catalytic activity was partially reduced in PepN lacking 4 C-terminal residues (PepNΔC4) whereas it was greatly reduced in F2 lacking 10 C-terminal residues (F2ΔC10) or PepN lacking eleven C-terminal residues (PepNΔC11). Notably, expression of PepNΔC4, but not PepNΔC11, in E. coliΔpepN increased its ability to resist nutritional and high temperature stress, demonstrating physiological significance. Purified C-terminal deleted proteins demonstrated greater sensitivity to trypsin and bound stronger to 8-amino 1-napthalene sulphonic acid (ANS), revealing greater numbers of surface exposed hydrophobic aa. Also, F2 or PepN containing large aa deletions in the C-termini, but not smaller deletions, were present in high amounts in the insoluble fraction of cell extracts probably due to reduced protein solubility. Modeling studies, using the crystal structure of E. coli PepN, demonstrated increase in hydrophobic surface area and change in accessibility of several aa from buried to exposed upon deletion of C-terminal aa. Together, these studies revealed that non-conserved distal C-terminal aa repress the surface exposure of apolar aa, enhance protein solubility, and catalytic activity in two soluble and distinct members of the M1 family.

Choosing physical science courses: The importance of cultural and social capital in the enrolment decisions of high achieving students

This paper reports and discusses findings from a recent study which explored the science enrolment decisions of high achieving, or ‘science proficient’ secondary level students in Australia (Lyons 2003). The research was prompted by the increasing reluctance of such students to enrol in postcompulsory science courses, particularly in physics and chemistry. The study investigated the influences on students’ deliberations about taking a range of science courses. However, this report confines itself to decisions about enrolling in the physical sciences. The paper summarises the students’ experiences and conceptions of school science, as well as the characteristics of their ‘family worlds’ found to be influential in their decisions1. The paper discusses the important roles of cultural and social capital in these decisions, and concludes that enrolment in physical science courses was associated with congruence between the students’ conceptions of school science, and characteristics of their family backgrounds.

The neuroscience of inspirational leadership: the importance of collective-oriented language and shared group membership

Effective leaders are believed to inspire followers by providing inclusive visions of the future that followers can identify with. In the present study, we examined the neural mechanisms underlying this process, testing key hypotheses derived from transformational and social identity approaches to leadership. While undergoing functional MRI, supporters from the two major Australian political parties (Liberal vs. Labor) were presented with inspirational collective-oriented and noninspirational personal-oriented statements made by in-group and out-group leaders. Imaging data revealed that inspirational (rather than noninspirational) statements from in-group leaders were associated with increased activation in the bilateral rostral inferior parietal lobule, pars opercularis, and posterior midcingulate cortex: brain areas that are typically implicated in controlling semantic information processing. In contrast, for out-group leaders, greater activation in these areas was associated with noninspirational statements. In addition, noninspirational statements by in-group (but not out-group) leaders resulted in increased activation in the medial prefrontal cortex, an area typically associated with reasoning about a person’s mental state. These results show that followers processed identical statements qualitatively differently as a function of leaders’ group membership, thus demonstrating that shared identity acts as an amplifier for inspirational leadership communication.

Bioavailability and toxicity of chemicals in inland waters : the importance of prevailing water chemistry and implications for risk assessment

Physicochemical characterization of freshwater samples from Finland, Sweden, the Netherlands, and Spain revealed that water hardness and pH decreased and the quantity and quality of humic substances changed considerably in this geographical series from south to north. Since the ambient water chemistry may affect the availability of chemicals, the total aqueous concentration of a chemical may be insufficient to predict the bioconcentration, subsequent biological response, and thus risk. In addition, organisms could be affected directly by water quality characteristics. In this context the main objective of this thesis was to investigate the bioavailability of selected ecotoxicologically relevant chemicals (cadmium, benzo(a)pyrene, and pyrene) in various European surface waters and to show the importance of certain water chemistry characteristics in interpreting the bioavailability and toxicity results. The bioavailability of cadmium to Daphnia magna was examined in very soft humic lake water. Humic substances as natural ligands decreased the free and bioavailable proportion of cadmium in soft lake water. As a consequence the uptake rate and the acute toxicity decreased compared with the humic-free reference. When the hardness of humic lake water was artificially elevated, the acute toxicity of cadmium decreased, although the proportion of free cadmium increased. The decreased bioavailability of cadmium in hard water was a result of effective competition for uptake by the hardness cations, especially calcium ions. The protective role of humic substances and water hardness against cadmium toxicity was also observed in Lumbriculus variegatus, although D. magna was more sensitive to cadmium. The bioavailability of two polycyclic aromatic hydrocarbons (PAHs), pyrene and benzo(a)pyrene, was studied in European surface waters of varying water chemistry. Humic substances acted as complexing ligands with both PAHs, but the bioavailability of the more lipophilic benzo(a)pyrene to D. magna was affected more by humic substances than that of pyrene. In addition, not only the quantity of humic substances, but also their quality affected the bioavailability of benzo(a)pyrene. Nevertheless, the humic substances played a protective role in the photo-enhanced toxicity of pyrene under UV-B radiation. Water hardness had no effect on pyrene toxicity. Results indicate that the typical physicochemical characteristics of boreal freshwaters should be considered carefully in local and regional risk assessment of chemicals concerning the Fennoscandian region.

Benthic-pelagic coupling in the northern Baltic Sea: importance of bioturbation and benthic predation

Benthic-pelagic coupling describes processes that operate across and between the seafloor and open-water ecosystems. In soft-sediment communities, bioturbation by sediment-dwelling and epibenthic organisms may strongly shape habitat characteristics and influence processes, e.g. biogeochemical cycling, which supplies bioavailable nutrients to pelagic primary producers. In addition, benthic fauna may mediate benthic-pelagic coupling by affecting the survival and hatching of zooplankton dormant eggs in the sediment. In the shallow waters and seasonally fluctuating environment of the Baltic Sea, emergence from the seafloor essentially contributes to the dynamics of zooplankton pelagic populations. In this thesis, I examine how benthic organisms with different functional traits affect the link between the benthic and pelagic systems in the northern Baltic Sea. By means of experimental laboratory studies, the effects of sediment-dwelling (Monoporeia affinis, Macoma balthica and Marenzelleria spp.) and nectobenthic (Mysis spp.) taxa on the survival and hatching of zooplankton benthic eggs and on benthic nutrient fluxes and sediment structure were investigated. In the predation studies, the nectobenthic mysids Mysis spp. preyed upon benthic eggs of the cladoceran Bosmina longispina maritima (syn. B. coregoni maritima), both in pelagic and benthic environments. Of the sediment-dwelling species, the amphipod M. affinis and the bivalve M. balthica reduced the number of cladoceran eggs in the sediment, whereas the polychaetes Marenzelleria spp. had no effects on cladoceran eggs. Both M. balthica and M. affinis also increased the mortality rates of benthic eggs of copepods and rotifers. It was estimated that zooplankton eggs provide an additional carbon source for food-limited benthic communities. The results indicate that predation pressure on zooplankton benthic eggs may be strong, but varies widely depending on the season and the functional characteristics of the macrofauna. Macoma balthica buried cladoceran eggs and a fluorescent tracer from the sediment surface to a depth of 3 4 cm, indicating efficient sediment mixing. In contrast, the other taxa had fewer effects on particle distributions. In addition to organic matter mineralization, particle mixing is crucial to the success of benthic recruitment of zooplankton, since only eggs close to the sediment surface may hatch. Macoma balthica and M. affinis altered the patterns of zooplankton emergence from the sediment. In general, the highest emergence rates were observed in the absence of macroscopic fauna, and M. balthica exerted a stronger suppressive effect than M. affinis. Moreover, copepods were less severely affected than cladocerans, while only one species (Temora longicornis) clearly benefited from the presence of the macrofauna. These differences probably result from species-specific differences in the resistance of eggs to disturbances. The results show that benthic fauna may considerably alter the patterns of zooplankton emergence from the seafloor, thereby shaping zooplankton pelagic populations. The semi-motile M. balthica and Marenzelleria spp. increased the fluxes of phosphate and ammonium from the sediment to the water, whereas the motile M. affinis and Mysis mixta had a contrasting effect. In the eutrophied Baltic Sea, efficient internal cycling of bioavailable nutrients forms a strong feedback inhibiting the recovery of the ecosystem. Based on the results, a change in species dominance from the two motile taxa, susceptible to oxygen deficiency, to the more tolerant semi-motile taxa provides additional feedback, strengthening internal nutrient cycling and accelerating eutrophication, with deteriorating near-bottom oxygen conditions and changes in the benthic communities. In shallow-water ecosystems, benthic nutrient regeneration plays a key role in determining the overall productivity of the ecosystem. In addition, the results of this study show that the communities in the benthos may essentially contribute to the structure of those in the plankton.

The importance of context in engaging students large first year management classes: A case study

Engaging large first year classes in tertiary education poses a number of significant challenges, most of which have been discussed by others. One area that has not received the kind of attention that it warrants is the context within which the engagement activities take place. This paper examines both the processes used to engage a large first year management class in a major city university and how the context of the classes shaped activities and student responses to these activities. It was recognised that students had certain types of learning styles, but given the total number of students (in excess of 1200) it was realised that is would be impossible to cater to all possibilities. A key outcome of the exercise was the importance of context in shaping student behaviours.

Importance of tyrosine residues of Bacillus stearothermophilus serine hydroxymethyltransferase in cofactor binding and l-allo-Thr cleavage

Serine hydroxymethyltransferase (SHMT) from Bacillus stearothermophilus (bsSHMT) is a pyridoxal 5'-phosphate-dependent enzyme that catalyses the conversion of l-serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. In addition, the enzyme catalyses the tetrahydrofolate-independent cleavage of 3-hydroxy amino acids and transamination. In this article, we have examined the mechanism of the tetrahydrofolate-independent cleavage of 3-hydroxy amino acids by SHMT. The three-dimensional structure and biochemical properties of Y51F and Y61A bsSHMTs and their complexes with substrates, especially l-allo-Thr, show that the cleavage of 3-hydroxy amino acids could proceed via Cα proton abstraction rather than hydroxyl proton removal. Both mutations result in a complete loss of tetrahydrofolate-dependent and tetrahydrofolate-independent activities. The mutation of Y51 to F strongly affects the binding of pyridoxal 5'-phosphate, possibly as a consequence of a change in the orientation of the phenyl ring in Y51F bsSHMT. The mutant enzyme could be completely reconstituted with pyridoxal 5'-phosphate. However, there was an alteration in the λmax value of the internal aldimine (396 nm), a decrease in the rate of reduction with NaCNBH3 and a loss of the intermediate in the interaction with methoxyamine (MA). The mutation of Y61 to A results in the loss of interaction with Cα and Cβ of the substrates. X-Ray structure and visible CD studies show that the mutant is capable of forming an external aldimine. However, the formation of the quinonoid intermediate is hindered. It is suggested that Y61 is involved in the abstraction of the Cα proton from 3-hydroxy amino acids. A new mechanism for the cleavage of 3-hydroxy amino acids via Cα proton abstraction by SHMT is proposed.

Importance of carbon dioxide physiological forcing to future climate change

An increase in atmospheric carbon dioxide (CO2) concentration influences climate both directly through its radiative effect (i.e., trapping longwave radiation) and indirectly through its physiological effect (i.e., reducing transpiration of land plants). Here we compare the climate response to radiative and physiological effects of increased CO2 using the National Center for Atmospheric Research (NCAR) coupled Community Land and Community Atmosphere Model. In response to a doubling of CO2, the radiative effect of CO2 causes mean surface air temperature over land to increase by 2.86 ± 0.02 K (± 1 standard error), whereas the physiological effects of CO2 on land plants alone causes air temperature over land to increase by 0.42 ± 0.02 K. Combined, these two effects cause a land surface warming of 3.33 ± 0.03 K. The radiative effect of doubling CO2 increases global runoff by 5.2 ± 0.6%, primarily by increasing precipitation over the continents. The physiological effect increases runoff by 8.4 ± 0.6%, primarily by diminishing evapotranspiration from the continents. Combined, these two effects cause a 14.9 ± 0.7% increase in runoff. Relative humidity remains roughly constant in response to CO2-radiative forcing, whereas relative humidity over land decreases in response to CO2-physiological forcing as a result of reduced plant transpiration. Our study points to an emerging consensus that the physiological effects of increasing atmospheric CO2 on land plants will increase global warming beyond that caused by the radiative effects of CO2.

Prognostic importance of the tumour microenvironment in follicular lymphoma patients treated with immunochemotherapy

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma. It is an indolent and clinically heterogeneous disease, which is generally considered incurable. Currently, immunochemotherapy has significantly improved the outcome of FL patients. This is based on the combination of rituximab, a monoclonal anti-CD20 antibody, with chemotherapy, and is used at present as a standard first-line therapy in FL. Thus far, however, patients have been selected for treatment based on clinical risk factors and indices that were developed before the rituximab era. Therefore, there is a growing need to understand the molecular mechanisms underlying the disease, which would not only provide information to predict survival in the rituximab era, but also enable the design of more targeted therapeutic strategies. In this study, our aim was to identify genes predicting the outcome in FL patients treated with immunochemotherapy. Thus, we performed a cDNA microarray with 24 FL patients. When gene expression differences from diagnostic tumour samples were related to the clinical outcome, we identified novel genes with a prognostic impact on survival. The expression of selected genes was further characterized with quantitative PCR and immunohistochemistry (IHC). Interestingly, the prognostic influence of these genes was often associated with their expression in non-malignant cells instead of tumour cells. Based on the observed gene expression patterns, we analyzed the abundance and prognostic value of non-malignant immune cells in 95-98 FL patients treated with immunochemotherapy. We observed that a high content of tumour-associated macrophages was a marker of a favourable prognosis. In contrast, the accumulation of mast cells correlated with a poor outcome and was further associated with tumour vascularity. Increased microvessel density also correlated with an inferior outcome. In addition, we used the same microarray data with a systems biology approach to identify signalling pathways or groups of genes capable of separating patients with favourable or adverse outcomes. Among the transcripts, there were many genes associated with signal transducers and activators of the transcription (STAT5a) pathway. When IHC was used as validation, STAT5a expression was mostly observed in T-cells and follicular dendritic cells, and expression was found to predict a favourable outcome. In cell cultures, rituximab was observed to induce the expression of STAT5a-associated interleukins in human lymphoma cell lines, which might provide a possible link for the cross-talk between rituximab-induced FL cells and their microenvironment. In conclusion, we have demonstrated that the microenvironment has a prognostic role in FL patients treated with immunochemotherapy. The results also address the importance of re-evaluating the prognostic markers in the rituximab era of lymphoma therapies.