Challenges in Data Intensive Analysis at Scientific Experimental User Facilities

Today's scientific challenges such as routes to a sustainable energy future, materials by design or biological and chemical environmental remediation methods, are complex problems that require the integration of a wide range of complementary expertise to be addressed successfully. Experimental and computational science research methods can hereby offer fundamental insights for their solution. Experimental facilities in particular can contribute through a large variety of investigative methods, which can span length scales from millions of kilometers (radar) to the sub-nucleus (LHC). These methods are used to probe structure, properties, and function of objects from single elements to whole communities. Hereby direct imaging techniques are a powerful means to develop an atomistic understanding of scientific issues. For example, the identification ofmechanisms associated with chemical, material, and biological transformations requires the direct observation of the reactions to build up an understanding of the atom-by-atom structural and chemical changes. Computational science can aid the planning of such experiments, correlate results, explain or predict the phenomena as they would be observed and thus aid their interpretation. Furthermore computational science can be essential for the investigation of phenomena that are difficult to observe due to their scale, reaction time or extreme conditions. Combining experimental and computational techniques provides scientists with the ability to research structures and processes at various levels of theory, e.g. providing molecular 'movies' of complex reactions that show bond breaking and reforming in natural time scales, along with the intermediate states to understand the mechanisms that govern the chemical transformations. This chapter will discuss the critical data intensive analysis challenges faced by the experimental science community at large scale and laboratory based facilities. The chapter will highlight current solutions and lay out perspectives for the future, such as methods to achieve real time analysis capabilities and the challenges and opportunities of data integration across experimental scales, levels of theory, and varying techniques

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change

Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes

We studied personality, subjective well-being, and hair cortisol level, in common marmosets Callithrix jacchus, a small, cooperatively breeding New World monkey, by examining their associations with one another and genotypes. Subjects were 68 males and 9 females that lived in the RIKEN Center for Life Science Technologies. Personality and subjective well-being were assessed by keeper ratings on two questionnaires, hair samples were obtained to assay cortisol level and buccal swabs were used to assess AVPR1a, OPRM1 and DAT genotypes. Three personality domains—Dominance, Sociability, and Neuroticism—were identified. Consistent with findings in other species, Sociability and Neuroticism were related to higher and lower subjective well-being, respectively. Sociability was also associated with higher hair cortisol levels. The personality domains and hair cortisol levels were heritable and associated with genotypes: the short form of AVPR1a was associated with lower Neuroticism and the AA genotype of the A111T SNP of OPRM1 was related to lower Dominance, lower Neuroticism, and higher hair cortisol level. Some genetic associations were not in directions that one would expect given findings in other species. These findings provide insights into the proximate and ultimate bases of personality in common marmosets, other primates and humans

A Comparison of Levels of Select Minerals in Scalp Hair Samples with Estimated Dietary Intakes of These Minerals in Women of Reproductive Age

The objective of this study was to evaluate daily intake of minerals and concentrations of minerals in hair in women of reproductive age. The study included 77 menstruating women, aged 35.9 ± 9.7 years. Subjects were divided into three groups according to age. All women were healthy. Hair samples were taken from several points of the occipital scalp. The content of minerals in hair samples was determined by flame atomic absorption spectrometry. Dietary intake of the analysed minerals was assayed on the basis of dietary intake interviews from three preceding days and evaluated using the dietetic computer programme. It was shown that calcium and iron daily intake by the women was below the recommended value. Only few women had low concentrations (below reference values) of magnesium, copper and zinc in hair. Statistically significant differences were shown between age groups. Generally, the concentrations of minerals in hair in the younger (19–30 years) and the older women (41–50 years) were higher than in hair of middle-aged women (31–40 years). The content of calcium, magnesium, iron and zinc in daily diets of women correlated inversely with copper level in their hair. Food products with good bioavailability of iron and calcium should be recommended for women of childbearing age in all age groups

Falls in young, middle-aged and older community dwelling adults: perceived cause, environmental factors and injury

BACKGROUND: Falls in older people have been characterized extensively in the literature, however little has been reported regarding falls in middle-aged and younger adults. The objective of this paper is to describe the perceived cause, environmental influences and resultant injuries of falls in 1497 young (20–45 years), middle-aged (46–65 years) and older (> 65 years) men and women from the Baltimore Longitudinal Study on Aging. METHODS: A descriptive study where participants completed a fall history questionnaire describing the circumstances surrounding falls in the previous two years. RESULTS: The reporting of falls increased with age from 18% in young, to 21% in middle-aged and 35% in older adults, with higher rates in women than men. Ambulation was cited as the cause of the fall most frequently in all gender and age groups. Our population reported a higher percentage of injuries (70.5%) than previous studies. The young group reported injuries most frequently to wrist/hand, knees and ankles; the middle-aged to their knees and the older group to their head and knees. Women reported a higher percentage of injuries in all age groups. CONCLUSION: This is the first study to compare falls in young, middle and older aged men and women. Significant differences were found between the three age groups with respect to number of falls, activities engaged in prior to falling, perceived causes of the fall and where they fell

Working people with type 1 diabetes in the Finnish population

Peer reviewe

Cystic Echinococcosis in Spain: Current Situation and Relevance for Other Endemic Areas in Europe

Cystic echinococcosis (CE) remains an important health problem in many regions of the world, both where no control measures have been implemented, and where control programs have been incompletely successful with ensuing re-emergence of the disease. In Spain, official data on CE show an increase in the proportion of intermediate hosts with CE during the last few years, and autochthonous pediatric patients have been reported, a sign of active local transmission of disease. A similar picture emerges from data reported to the European Food Safety Authority by other European countries. Nevertheless, several crucial aspects related to CE that would help better understand and control the disease have not been tackled appropriately, in particular the emergence of infection in specific geographical areas. In this respect, while some data are missing, other data are conflicting because they come from different databases. We review the current situation of CE in Spain compared with areas in which similar problems in the CE field exist, and offer recommendations on how to overcome those limitations. Specifically, we believe that the introduction of national registries for CE with online data entry, following the example set by the European Registry for Alveolar Echinococcosis, would help streamline data collection on CE by eliminating the need for evaluating and integrating data from multiple regions, by avoiding duplication of data from patients who access several different health facilities over time, and by providing much needed clinical and epidemiological data that are currently accessible only to clinicians

Cognition and resective surgery for diffuse infiltrative glioma: an overview

Compared to classical oncological outcome measures such as time to progression and survival, the importance of cognitive functioning in patients with diffuse infiltrative brain tumors has only recently been recognized. Apart from the relatively low incidence and the invariably fatal outcome of gliomas, the general assumption that cognitive assessment is time-consuming and burdensome contributes to this notion. Our understanding of the effects of brain surgery on cognition, for instance, is largely based on studies in surgical patients with refractory epilepsy, with only a limited number of studies in surgical patients with gliomas. The impact of other factors affecting cognition in glioma patients such as direct tumor effects, radiotherapy and chemotherapy, and medical treatment, including anti-epileptic drugs and steroids, have been studied more extensively. The purpose of this paper is to provide an overview of cognition in patients with diffuse infiltrative gliomas and the impact of resective surgery as well as other tumor and treatment-related factors

Distinguishing the Impacts of Inadequate Prey and Vessel Traffic on an Endangered Killer Whale (Orcinus orca) Population

Managing endangered species often involves evaluating the relative impacts of multiple anthropogenic and ecological pressures. This challenge is particularly formidable for cetaceans, which spend the majority of their time underwater. Noninvasive physiological approaches can be especially informative in this regard. We used a combination of fecal thyroid (T3) and glucocorticoid (GC) hormone measures to assess two threats influencing the endangered southern resident killer whales (SRKW; Orcinus orca) that frequent the inland waters of British Columbia, Canada and Washington, U.S.A. Glucocorticoids increase in response to nutritional and psychological stress, whereas thyroid hormone declines in response to nutritional stress but is unaffected by psychological stress. The inadequate prey hypothesis argues that the killer whales have become prey limited due to reductions of their dominant prey, Chinook salmon (Oncorhynchus tshawytscha). The vessel impact hypothesis argues that high numbers of vessels in close proximity to the whales cause disturbance via psychological stress and/or impaired foraging ability. The GC and T3 measures supported the inadequate prey hypothesis. In particular, GC concentrations were negatively correlated with short-term changes in prey availability. Whereas, T3 concentrations varied by date and year in a manner that corresponded with more long-term prey availability. Physiological correlations with prey overshadowed any impacts of vessels since GCs were lowest during the peak in vessel abundance, which also coincided with the peak in salmon availability. Our results suggest that identification and recovery of strategic salmon populations in the SRKW diet are important to effectively promote SRKW recovery