The individual and combined effects of creatine monohydrate and lithium chloride supplementation on brain creatine uptake in male and female rats.

During ischemia and traumatic brain injuries (TBIs), phosphocreatine (PCr) acts as a temporal energy buffer preventing rapid decreases in intracellular ATP concentrations. Though, the brain has limited stored creatine and it therefore relies heavily on exogenous substrates. Moreover, creatine monohydrate (CrM) supplementation can significantly increase brain total creatine concentration (TCr). Creatine’s ability to enter the brain is dependent on creatine transporters, and limited evidence suggests lithium (Li), through GSK3 inhibition, upregulates this transport. Therefore, the purpose of this research was to investigate the individual and combined influences of in vivo creatine monohydrate and lithium chloride on creatine concentrations in the rat brain. 64 Sprague-Dawley rats (32 males, 32 females), given ad libitum access to a pelleted 14% certified protein rodent maintenance diet, were randomized into four experimental groups: control (CON), creatine (Cr), lithium (Li), and creatine-lithium (Cr-Li). CrM at 5g/L (0.412g/kg/day) and lithium chloride (LiCl) at 0.2g/L (0.018g/kg/day) were supplemented in the reverse osmosis drinking water. Brain [TCr] was greater with LiCl (p=0.0002), irrespective of CrM, and greater with CrM (p<0.0001), irrespective of LiCl. For slc6a8 mRNA expression, there was a trend for increased expression with LiCl (p=0.12). The female Li group also had a trend greater (p=0.06) than the Cr group. Relative daily CrM consumption was higher without LiCl (p<0.0001) and higher in females (p=0.0001). Relative daily LiCl consumption was higher among females than males (p<0.0001). LiCl inhibited GSK3 activity through an increase in pGSK3a, pGSK3b, ratio of pGSK3a:GSK3a, and ratio of pGSK3b:GSK3b and there was a trend for reduced total GSK3 activity (p=0.11) with LiCl. In conclusion, this study demonstrated that CrM and LiCl supplementation alone and in combination similarly increased brain TCr, with no synergistic or additive effects when combined

Patterns of recruitment and injury in a heterogeneous airway network model

In respiratory distress, lung airways become flooded with liquid and may collapse due to surface-tension forces acting on air-liquid interfaces, inhibiting gas exchange. This pa- per proposes a mathematical multiscale model for the mechanical ventilation of a network of occluded airways, where air is forced into the network at a fixed tidal volume, allowing investigation of optimal recruitment strategies. The temporal response is derived from mechanistic models of individual airway reopening, incorporating feedback on the airway pressure due to recruitment. The model accounts for stochastic variability in airway di- ameter and stiffness across and between generations. For weak heterogeneity, the network is completely ventilated via one or more avalanches of recruitment (with airways recruited in quick succession), each characterised by a transient decrease in the airway pressure; avalanches become more erratic for airways that are initially more flooded. However, the time taken for complete ventilation of the network increases significantly as the network becomes more heterogeneous, leading to increased stresses on airway walls. The model predicts that the most peripheral airways are most at risk of ventilation-induced damage. A positive-end-expiratory pressure (PEEP) reduces the total recruitment time but at the cost of larger stresses exerted on airway walls

Executive pay and performance: did bankers’ bonuses cause the crisis?

This paper examines the pay-performance relationship between executive cash compensation (including bonuses) and company performance for a sample of large UK companies, focusing particularly on the financial services industry, since incentive misalignment has been blamed as one of the factors causing the global financial crisis of 2007–2008. Although we find that pay in the financial services sector is high, the cash-plus-bonus pay-performance sensitivity of financial firms is not significantly higher than in other sectors. Consequently, we conclude that it unlikely that incentive structures could be held responsible for inducing bank executives to focus on short-term results

Design-by-analogy: experimental evaluation of a functional analogy search methodology for concept generation improvement

Design-by-analogy is a growing field of study and practice, due to its power to augment and extend traditional concept generation methods by expanding the set of generated ideas using similarity relationships from solutions to analogous problems. This paper presents the results of experimentally testing a new method for extracting functional analogies from general data sources, such as patent databases, to assist designers in systematically seeking and identifying analogies. In summary, the approach produces significantly improved results on the novelty of solutions generated and no significant change in the total quantity of solutions generated. Computationally, this design-by-analogy facilitation methodology uses a novel functional vector space representation to quantify the functional similarity between represented design problems and, in this case, patent descriptions of products. The mapping of the patents into the functional analogous words enables the generation of functionally relevant novel ideas that can be customized in various ways. Overall, this approach provides functionally relevant novel sources of design-by-analogy inspiration to designers and design teams.SUTD-MIT International Design Centre (IDC)National Science Foundation (U.S.) (Grant Numbers CMMI-0855326, CMMI-0855510, and CMMI-08552930

Function Based Design-by-Analogy: A Functional Vector Approach to Analogical Search

Design-by-analogy is a powerful approach to augment traditional concept generation methods by expanding the set of generated ideas using similarity relationships from solutions to analogous problems. While the concept of design-by-analogy has been known for some time, few actual methods and tools exist to assist designers in systematically seeking and identifying analogies from general data sources, databases, or repositories, such as patent databases. A new method for extracting functional analogies from data sources has been developed to provide this capability, here based on a functional basis rather than form or conflict descriptions. Building on past research, we utilize a functional vector space model (VSM) to quantify analogous similarity of an idea's functionality. We quantitatively evaluate the functional similarity between represented design problems and, in this case, patent descriptions of products. We also develop document parsing algorithms to reduce text descriptions of the data sources down to the key functions, for use in the functional similarity analysis and functional vector space modeling. To do this, we apply Zipf's law on word count order reduction to reduce the words within the documents down to the applicable functionally critical terms, thus providing a mapping process for function based search. The reduction of a document into functional analogous words enables the matching to novel ideas that are functionally similar, which can be customized various ways. This approach thereby provides relevant sources of design-by-analogy inspiration. As a verification of the approach, two original design problem case studies illustrate the distance range of analogical solutions that can be extracted. This range extends from very near-field, literal solutions to far-field cross-domain analogies.National Science Foundation (U.S.) (Grant CMMI-0855326)National Science Foundation (U.S.) (Grant CMMI-0855510)National Science Foundation (U.S.) (Grant CMMI-0855293)SUTD-MIT International Design Centre (IDC

Facilitating Design-by-Analogy: Development of a Complete Functional Vocabulary and Functional Vector Approach to Analogical Search

Design-by-analogy is an effective approach to innovative concept generation, but can be elusive at times due to the fact that few methods and tools exist to assist designers in systematically seeking and identifying analogies from general data sources, databases, or repositories, such as patent databases. A new method for extracting analogies from data sources has been developed to provide this capability. Building on past research, we utilize a functional vector space model to quantify analogous similarity between a design problem and the data source of potential analogies. We quantitatively evaluate the functional similarity between represented design problems and, in this case, patent descriptions of products. We develop a complete functional vocabulary to map the patent database to applicable functionally critical terms, using document parsing algorithms to reduce text descriptions of the data sources down to the key functions, and applying Zipf’s law on word count order reduction to reduce the words within the documents. The reduction of a document (in this case a patent) into functional analogous words enables the matching to novel ideas that are functionally similar, which can be customized in various ways. This approach thereby provides relevant sources of design-by-analogy inspiration. Although our implementation of the technique focuses on functional descriptions of patents and the mapping of these functions to those of the design problem, resulting in a set of analogies, we believe that this technique is applicable to other analogy data sources as well. As a verification of the approach, an original design problem for an automated window washer illustrates the distance range of analogical solutions that can be extracted, extending from very near-field, literal solutions to far-field cross-domain analogies. Finally, a comparison with a current patent search tool is performed to draw a contrast to the status quo and evaluate the effectiveness of this work.National Science Foundation (U.S.) (grant number CMMI-0855510)National Science Foundation (U.S.) (grant number CMMI-0855326)National Science Foundation (U.S.) (grant number CMMI-0855293)SUTD-MIT International Design Centre (IDC

Novel ultrastructures of Treponema primitia and their implications for motility

Members of the bacterial phylum Spirochaetes are generally helical cells propelled by periplasmic flagella. The spirochete Treponema primitia is interesting because of its mutualistic role in the termite gut, where it is believed to cooperate with protozoa that break down cellulose and produce H2 as a by-product. Here we report the ultrastructure of T. primitia as obtained by electron cryotomography of intact, frozen-hydrated cells. Several previously unrecognized external structures were revealed, including bowl-like objects decorating the outer membrane, arcades of hook-shaped proteins winding along the exterior and tufts of fibrils extending from the cell tips. Inside the periplasm, cone-like structures were found at each pole. Instead of the single peptidoglycan layer typical of other Gram-negative bacteria, two distinct periplasmic layers were observed. These layers formed a central open space that contained two flagella situated adjacent to each other. In some areas, the inner membrane formed flattened invaginations that protruded into the cytoplasm. High-speed light microscopic images of swimming T. primitia cells showed that cell bodies remained rigid and moved in a helical rather than planar motion. Together, these findings support the 'rolling cylinder' model for T. primitia motility that posits rotation of the protoplasmic cylinder within the outer sheath

Fermi surface evolution through a heavy fermion superconductor-to-antiferromagnet transition: de Haas-van Alphen effect in Cd-substituted CeCoIn5_5

We report the results of de-Haas-van-Alphen (dHvA) measurements in Cd doped CeCoIn$_5$ and LaCoIn$_5$. Cd doping is known to induce an antiferromagnetic order in the heavy fermion superconductor CeCoIn$_5$, whose effect can be reversed with applied pressure. We find a slight but systematic change of the dHvA frequencies with Cd doping in both compounds, reflecting the chemical potential shift due to the addition of holes. The frequencies and effective masses are close to those found in the nominally pure compounds with similar changes apparent in the Ce and La compounds with Cd substitution. We observe no abrupt changes to the Fermi surface in the high field paramagnetic state for $x \sim x_c$ corresponding to the onset of antiferromagnetic ordering at H=0 in CeCo(In$_{1-x}$Cd$_x$)$_5$. Our results rule out $f-$electron localization as the mechanism for the tuning of the ground state in CeCoIn$_5$ with Cd doping