Changes in American and British Stature Since the Mid-Eighteenth Century: A Prelimanary Report on the Usefulness of Data on Height...

This paper is a progress report on the usefulness of data on physical height for the analysis of long-ten changes in the level of nutrition and health on economic, social, and demographic behavior. It is based on a set of samples covering the U.S. and several other nations over the years from 1750 to the present. The preliminary results indicate that native-born. American Revolution, but there were long periods of declining nutrition and height during the 19th century. Similar cycling has been established for England. A variety of factors, including crop mix, urbanization, occupation, intensity of labor, and immigration affected the level of height and nutrition, although the relative importance of these factors has changed over time. There is evidence that nutrition affected labor productivity. In one of the samples individuals who were one standard deviation above the mean height (holding weight per inch of height constant) were about 8% more productive than individuals one standard deviation below the mean height. Another finding is that death did not choose people at random. Analysis of data for Trinidad indicates that the annual death rate for the shortest quintile of males was more than twice as great as for the tallest quintile of males.

Thermal Structures Technology Development for Reusable Launch Vehicle Cryogenic Propellant Tanks

Analytical and experimental studies conducted at the NASA, Langley Research Center (LaRC) for investigating integrated cryogenic propellant tank systems for a reusable launch vehicle (RLV) are described. The cryogenic tanks are investigated as an integrated tank system. An integrated tank system includes the tank wall, cryogenic insulation, thermal protection system (TPS) attachment sub-structure, and TPS. Analysis codes are used to size the thicknesses of cryogenic insulation and TPS insulation for thermal loads, and to predict tank buckling strengths at various ring frame spacings. The unique test facilities developed for the testing of cryogenic tank components are described. Testing at cryogenic and high-temperatures verifies the integrity of materials, design concepts, manufacturing processes, and thermal/structural analyses. Test specimens ranging from the element level to the subcomponent level are subjected to projected vehicle operational mechanical loads and temperatures. The analytical and experimental studies described in this paper provide a portion of the basic information required for the development of light-weight reusable cryogenic propellant tanks

Information theory explanation of the fluctuation theorem, maximum entropy production and self-organized criticality in non-equilibrium stationary states

Jaynes' information theory formalism of statistical mechanics is applied to the stationary states of open, non-equilibrium systems. The key result is the construction of the probability distribution for the underlying microscopic phase space trajectories. Three consequences of this result are then derived : the fluctuation theorem, the principle of maximum entropy production, and the emergence of self-organized criticality for flux-driven systems in the slowly-driven limit. The accumulating empirical evidence for these results lends support to Jaynes' formalism as a common predictive framework for equilibrium and non-equilibrium statistical mechanics.Comment: 21 pages, 0 figures, minor modifications, version to appear in J. Phys. A. (2003

Temporal Stream Logic: Synthesis beyond the Bools

Reactive systems that operate in environments with complex data, such as mobile apps or embedded controllers with many sensors, are difficult to synthesize. Synthesis tools usually fail for such systems because the state space resulting from the discretization of the data is too large. We introduce TSL, a new temporal logic that separates control and data. We provide a CEGAR-based synthesis approach for the construction of implementations that are guaranteed to satisfy a TSL specification for all possible instantiations of the data processing functions. TSL provides an attractive trade-off for synthesis. On the one hand, synthesis from TSL, unlike synthesis from standard temporal logics, is undecidable in general. On the other hand, however, synthesis from TSL is scalable, because it is independent of the complexity of the handled data. Among other benchmarks, we have successfully synthesized a music player Android app and a controller for an autonomous vehicle in the Open Race Car Simulator (TORCS.

The use of hot and cold high pressure homogenization to enhance the loading capacity and encapsulation efficiency of nanostructured lipid carriers for the hydrophilic antiretroviral drug, didanosine for potential administration to paediatric patients

A major obstacle to the application of nanostructured lipid carriers (NLCs) as carriers for hydrophilic drugs is the limited loading capacity (LC) and encapsulation efficiency (EE) of NLCs for these molecules. The purpose of this research was to design and implement a strategy to enhance the LC and EE of NLCs for the hydrophilic drug, didanosine (DDI). DDI was dispersed in Transcutol® HP and the particle size of DDI in the liquid lipid was reduced gradually using hot high pressure homogenization (HPH). The product obtained thereafter was added to Precirol® ATO 5 and the hot mixture was immediately dried using liquid nitrogen. The dried materials were then ground and passed through a 200 μm sieve and the solid lipid particles were dispersed in a surfactant solution and subsequently used to manufacture DDI-loaded NLCs using cold HPH. The LC and EE of NLCs for DDI manufactured using the new strategy were 3.39 ± 0.63% and 51.58 ± 1.31%, respectively, compared to 0.079 ± 0.001% and 32.45 ± 0.08%, respectively, obtained when DDI-loaded NLCs were produced using conventional hot HPH. The enhanced LC and EE for DDI make NLCs a potential technology for the oral administration of DDI to paediatric patients

Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly

<p>Abstract</p> <p>Background</p> <p>Histone deacetylase (HDAC) inhibitors are currently undergoing clinical evaluation as anti-cancer agents. Dietary constituents share certain properties of HDAC inhibitor drugs, including the ability to induce global histone acetylation, turn-on epigenetically-silenced genes, and trigger cell cycle arrest, apoptosis, or differentiation in cancer cells. One such example is sulforaphane (SFN), an isothiocyanate derived from the glucosinolate precursor glucoraphanin, which is abundant in broccoli. Here, we examined the time-course and reversibility of SFN-induced HDAC changes in human colon cancer cells.</p> <p>Results</p> <p>Cells underwent progressive G₂/M arrest over the period 6-72 h after SFN treatment, during which time HDAC activity increased in the vehicle-treated controls but not in SFN-treated cells. There was a time-dependent loss of class I and selected class II HDAC proteins, with HDAC3 depletion detected ahead of other HDACs. Mechanism studies revealed no apparent effect of calpain, proteasome, protease or caspase inhibitors, but HDAC3 was rescued by cycloheximide or actinomycin D treatment. Among the protein partners implicated in the HDAC3 turnover mechanism, silencing mediator for retinoid and thyroid hormone receptors (SMRT) was phosphorylated in the nucleus within 6 h of SFN treatment, as was HDAC3 itself. Co-immunoprecipitation assays revealed SFN-induced dissociation of HDAC3/SMRT complexes coinciding with increased binding of HDAC3 to 14-3-3 and peptidyl-prolyl cis/trans isomerase 1 (Pin1). Pin1 knockdown blocked the SFN-induced loss of HDAC3. Finally, SFN treatment for 6 or 24 h followed by SFN removal from the culture media led to complete recovery of HDAC activity and HDAC protein expression, during which time cells were released from G₂/M arrest.</p> <p>Conclusion</p> <p>The current investigation supports a model in which protein kinase CK2 phosphorylates SMRT and HDAC3 in the nucleus, resulting in dissociation of the corepressor complex and enhanced binding of HDAC3 to 14-3-3 or Pin1. In the cytoplasm, release of HDAC3 from 14-3-3 followed by nuclear import is postulated to compete with a Pin1 pathway that directs HDAC3 for degradation. The latter pathway predominates in colon cancer cells exposed continuously to SFN, whereas the former pathway is likely to be favored when SFN has been removed within 24 h, allowing recovery from cell cycle arrest.</p

A general framework for understanding the response of the water cycle to global warming over land and ocean

Climate models project increases in globally averaged atmospheric specific humidity that are close to the Clausius–Clapeyron (CC) value of around 7% K−1 whilst projections for mean annual global precipitation (P) and evaporation (E) are somewhat muted at around 2% K−1. Such global projections are useful summaries but do not provide guidance at local (grid box) scales where impacts occur. To bridge that gap in spatial scale, previous research has shown that the "wet get wetter and dry get drier" relation, Δ(P − E) &propto; P − E, follows CC scaling when the projected changes are averaged over latitudinal zones. Much of the research on projected climate impacts has been based on an implicit assumption that this CC relation also holds at local (grid box) scales but this has not previously been examined. In this paper we find that the simple latitudinal average CC scaling relation does not hold at local (grid box) scales over either ocean or land. This means that in terms of P − E, the climate models do not project that the "wet get wetter and dry get drier" at the local scales that are relevant for agricultural, ecological and hydrologic impacts. In an attempt to develop a simple framework for local-scale analysis we found that the climate model output shows a remarkably close relation to the long-standing Budyko framework of catchment hydrology. We subsequently use the Budyko curve and find that the local-scale changes in P − E projected by climate models are dominated by changes in P while the changes in net irradiance at the surface due to greenhouse forcing are small and only play a minor role in changing the mean annual P − E in the climate model projections. To further understand the apparently small changes in net irradiance we also examine projections of key surface energy balance terms. In terms of global averages, we find that the climate model projections are dominated by changes in only three terms of the surface energy balance: (1) an increase in the incoming long-wave irradiance, and the respective responses (2) in outgoing long-wave irradiance and (3) in the evaporative flux, with the latter change being much smaller than the former two terms and mostly restricted to the oceans. The small fraction of the realised surface forcing that is partitioned into E explains why the hydrologic sensitivity (2% K−1) is so much smaller than CC scaling (7% K−1). Much public and scientific perception about changes in the water cycle has been based on the notion that temperature enhances E. That notion is partly true but has proved an unfortunate starting point because it has led to misleading conclusions about the impacts of climate change on the water cycle. A better general understanding of the potential impacts of climate change on water availability that are projected by climate models will surely be gained by starting with the notion that the greater the enhancement of E, the less the surface temperature increase (and vice versa). That latter notion is based on the conservation of energy and is an underlying basis of climate model projections

Evaluation of the in vitro differential protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (NLCs) for potential targeting to the brain

The preferential in vitro adsorption of apolipoprotein E (Apo E) onto the surface of colloidal drug carriers may be used as a strategy to evaluate the in vivo potential for such systems to transport drugs to the brain. The aim of this research was to investigate the in vitro protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (DDI-NLCs), using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), in order to establish the potential for NLCs to deliver DDI to the brain. NLC formulations were manufactured using high-pressure homogenization using a lipid matrix consisting of a mixture of Precirol® ATO 5 and Transcutol® HP. The 2-D PAGE analysis revealed that NLCs in formulations stabilized using Solutol® HS 15 alone or with a ternary surfactant system consisting of Solutol® HS 15, Tween® 80, and Lutrol® F68, preferentially adsorbed proteins, such as Apo E. Particles stabilized with Tween® 80 and Lutrol® F68 did not adsorb Apo E in these studies, which could be related to the relatively large particle size and hence small surface area observed for these NLCs. These findings have revealed that DDI-loaded NLCs may have the potential to deliver DDI to the brain in vivo and, in addition, to Tween® 80, which has already been shown to have the ability to facilitate the targeting of colloidal drug delivery systems to the brain. Solutol® HS 15–stabilized nanoparticles may also achieve a similar purpose