HYDRA: Distributed Multi-Objective Optimization for Designers

Architectural design problems can be quite involved, as there is a plethora of – usually conflicting – criteria that one has to address in order to find an optimal, performative solution. Multi-Objective Optimization (MOO) techniques can thus prove very useful, as they provide solution spaces which can traverse the different trade-offs of convoluted design options. Nevertheless, they are not widely used as (a) they are computationally expensive and (b) the resulting solution space can be proven difficult to visualize and navigate, particularly when dealing with higher dimensional spaces. This paper will present a system, which merges bespoke multi-objective optimization with a parametric CAD system, enhanced by supercomputing, into a single, coherent workflow, in order to address the above issues. The system architecture ensures optimal use of existing compute resources and enables massive performance speed-up, allowing for fast review and delivery cycles. The application aims to provide architects, designers and engineers with a better understanding of the design space, aiding the decision-making process by procuring tangible data from different objectives and finally providing fit (and sometimes unforeseen) solutions to a design problem. This is primarily achieved by a graphical interface of easy to navigate solution spaces of design options, derived from their respective Pareto fronts, in the form of a web-based interactive dashboard. Since understanding high-dimensionality data is a difficult task, multivariate analysis techniques were implemented to post-process the data before displaying it to end users. Visual Data Mining (VDM) and Machine Learning (ML) techniques were incorporated to facilitate knowledge discovery and exploration of large sets of design options at an early design stage. The system is demonstrated and assessed on an applied design case study of a master-planning project, where the benefits of the process are more evident, especially due to its complexity and size

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Role of TNFα in pulmonary pathophysiology

Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily. In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases. Of the various pulmonary diseases, TNFα is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFα in the cytotoxicity. Thus, pharmacological agents that can either suppress the production of TNFα or block its biological actions may have potential therapeutic value against a wide variety of diseases. Despite some immunological side effects, anti-TNFα therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death

Brain Potentials Highlight Stronger Implicit Food Memory for Taste than Health and Context Associations

Increasingly consumption of healthy foods is advised to improve population health. Reasons people give for choosing one food over another suggest that non-sensory features like health aspects are appreciated as of lower importance than taste. However, many food choices are made in the absence of the actual perception of a food's sensory properties, and therefore highly rely on previous experiences of similar consumptions stored in memory. In this study we assessed the differential strength of food associations implicitly stored in memory, using an associative priming paradigm. Participants (N = 30) were exposed to a forced-choice picture-categorization task, in which the food or non-food target images were primed with either non-sensory or sensory related words. We observed a smaller N400 amplitude at the parietal electrodes when categorizing food as compared to non-food images. While this effect was enhanced by the presentation of a food-related word prime during food trials, the primes had no effect in the non-food trials. More specifically, we found that sensory associations are stronger implicitly represented in memory as compared to non-sensory associations. Thus, this study highlights the neuronal mechanisms underlying previous observations that sensory associations are important features of food memory, and therefore a primary motive in food choice.</p

A General Enhancement of Autonomic and Cortisol Responses During Social Evaluative Threat.

OBJECTIVE: The idea that distinct psychosocial factors may underlie specific patterns of neuroendocrine stress responses has been a topic of recurrent debate. We examined a recent contribution to this debate, the Social Self Preservation Theory, which predicts that stressors involving social evaluative threat (SET) characteristically activate the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Sixty-one healthy university students (31 females) performed a challenging speech task in one of three conditions that aimed to impose increasing levels of SET: performing the task alone (no social evaluation), with 1 evaluating observer, or with 4 evaluating observers. Indices of sympathetic (pre-ejection period) and parasympathetic (heart rate variability) cardiac drive were obtained by impedance- and electrocardiography. Salivary cortisol was used to index HPA activity. Questionnaires assessed affective responses. RESULTS: Affective responses (shame/embarrassment, anxiety, negative affect, and self-esteem), cortisol, heart rate, sympathetic, and parasympathetic activation all differentiated evaluative from non-evaluative task conditions (p<.001). The largest effect-sizes were observed for cardiac autonomic responses. Physiological reactivity increased in parallel with increasing audience size (p<.001). A rise in cortisol was predicted by sympathetic activation during the task (p<.001), but not by affective responses. CONCLUSION: It would appear that SET determines the magnitude, rather than the pattern, of physiological activation. This potential to broadly perturb multiple physiological systems may help explain why social stress has been associated with a range of health outcomes. We propose a threshold-activation model as a physiological explanation for why engaging stressors, such as those involving social evaluation or uncontrollability, may appear to selectively induce cortisol release

Optimizing Exogenous Surfactant as a Pulmonary Delivery Vehicle for Chicken Cathelicidin-2

The rising incidence of antibiotic-resistant lung infections has instigated a much-needed search for new therapeutic strategies. One proposed strategy is the use of exogenous surfactants to deliver antimicrobial peptides (AMPs), like CATH-2, to infected regions of the lung. CATH-2 can kill bacteria through a diverse range of antibacterial pathways and exogenous surfactant can improve pulmonary drug distribution. Unfortunately, mixing AMPs with commercially available exogenous surfactants has been shown to negatively impact their antimicrobial function. It was hypothesized that the phosphatidylglycerol component of surfactant was inhibiting AMP function and that an exogenous surfactant, with a reduced phosphatidylglycerol composition would increase peptide mediated killing at a distal site. To better understand how surfactant lipids interacted with CATH-2 and affected its function, isothermal titration calorimetry and solid-state nuclear magnetic resonance spectroscopy as well as bacterial killing curves against Pseudomonas aeruginosa were utilized. Additionally, the wet bridge transfer system was used to evaluate surfactant spreading and peptide transport. Phosphatidylglycerol was the only surfactant lipid to significantly inhibit CATH-2 function, showing a stronger electrostatic interaction with the peptide than other lipids. Although diluting the phosphatidylglycerol content in an existing surfactant, through the addition of other lipids, significantly improved peptide function and distal killing, it also reduced surfactant spreading. A synthetic phosphatidylglycerol-free surfactant however, was shown to further improve CATH-2 delivery and function at a remote site. Based on these in vitro experiments synthetic phosphatidylglycerol-free surfactants seem optimal for delivering AMPs to the lung

Catalytic asymmetric carbon–carbon bond formation via allylic alkylations with organolithium compounds

Carbon–carbon bond formation is the basis for the biogenesis of nature’s essential molecules. Consequently, it lies at the heart of the chemical sciences. Chiral catalysts have been developed for asymmetric C–C bond formation to yield single enantiomers from several organometallic reagents. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general catalytic methodology for enantioselective C–C formation has proven elusive, until now. Here, we report a copper-based chiral catalytic system that allows carbon–carbon bond formation via allylic alkylation with alkyllithium reagents, with extremely high enantioselectivities and able to tolerate several functional groups. We have found that both the solvent used and the structure of the active chiral catalyst are the most critical factors in achieving successful asymmetric catalysis with alkyllithium reagents. The active form of the chiral catalyst has been identified through spectroscopic studies as a diphosphine copper monoalkyl species.

A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers

10.1007/s00280-007-0598-1Cancer Chemotherapy and Pharmacology622243-251CCPH