Realization of a single Josephson junction for Bose-Einstein condensates

We report on the realization of a double-well potential for Rubidium-87 Bose-Einstein condensates. The experimental setup allows the investigation of two different dynamical phenomena known for this system - Josephson oscillations and self-trapping. We give a detailed discussion of the experimental setup and the methods used for calibrating the relevant parameters. We compare our experimental findings with the predictions of an extended two-mode model and find quantitative agreement

Volatility forecasting in the Chinese commodity futures market with intraday data

Given the unique institutional regulations in the Chinese commodity futures market as well as the characteristics of the data it generates, we utilize contracts with three months to delivery, the most liquid contract series, to systematically explore volatility forecasting for aluminum, copper, fuel oil, and sugar at the daily and three intraday sampling frequencies. We adopt popular volatility models in the literature and assess the forecasts obtained via these models against alternative proxies for the true volatility. Our results suggest that the long memory property is an essential feature in the commodity futures volatility dynamics and that the ARFIMA model consistently produces the best forecasts or forecasts not inferior to the best in statistical terms

Large differences in regional precipitation change between a first and second 2 K of global warming

For adaptation and mitigation planning, stakeholders need reliable information about regional precipitation changes under different emissions scenarios and for different time periods. A significant amount of current planning effort assumes that each K of global warming produces roughly the same regional climate change. Here using 25 climate models, we compare precipitation responses with three 2 K intervals of global ensemble mean warming: a fast and a slower route to a first 2 K above pre-industrial levels, and the end-of-century difference between high-emission and mitigation scenarios. We show that, although the two routes to a first 2 K give very similar precipitation changes, a second 2 K produces quite a different response. In particular, the balance of physical mechanisms responsible for climate model uncertainty is different for a first and a second 2 K of warming. The results are consistent with a significant influence from nonlinear physical mechanisms, but aerosol and land-use effects may be important regionally

A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

A large ozone-circulation feedback and its implications for global warming assessments.

State-of-the-art climate models now include more climate processes which are simulated at higher spatial resolution than ever1. Nevertheless, some processes, such as atmospheric chemical feedbacks, are still computationally expensive and are often ignored in climate simulations1,2. Here we present evidence that how stratospheric ozone is represented in climate models can have a first order impact on estimates of effective climate sensitivity. Using a comprehensive atmosphere-ocean chemistry-climate model, we find an increase in global mean surface warming of around 1°C (~20%) after 75 years when ozone is prescribed at pre-industrial levels compared with when it is allowed to evolve self-consistently in response to an abrupt 4×CO2 forcing. The difference is primarily attributed to changes in longwave radiative feedbacks associated with circulation-driven decreases in tropical lower stratospheric ozone and related stratospheric water vapour and cirrus cloud changes. This has important implications for global model intercomparison studies1,2 in which participating models often use simplified treatments of atmospheric composition changes that are neither consistent with the specified greenhouse gas forcing scenario nor with the associated atmospheric circulation feedbacks3-5.We thank the European Research Council for funding through the ACCI project, project number 267760. The model development was part of the QESM-ESM project supported by the UK Natural Environment Research Council (NERC) under contract numbers RH/H10/19 and R8/H12/124. We acknowledge use of the MONSooN system, a collaborative facility supplied under the Joint Weather and Climate Research Programme, which is a strategic partnership between the UK Met Office and NERC. A.C.M. acknowledges support from an AXA Postdoctoral Research Fellowship.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/nclimate/journal/v5/n1/full/nclimate2451.html

Removal of Heterologous Sequences from Plasmodium falciparum Mutants Using FLPe-Recombinase

Genetically-modified mutants are now indispensable Plasmodium gene-function reagents, which are also being pursued as genetically attenuated parasite vaccines. Currently, the generation of transgenic malaria-parasites requires the use of drug-resistance markers. Here we present the development of an FRT/FLP-recombinase system that enables the generation of transgenic parasites free of resistance genes. We demonstrate in the human malaria parasite, P. falciparum, the complete and efficient removal of the introduced resistance gene. We targeted two neighbouring genes, p52 and p36, using a construct that has a selectable marker cassette flanked by FRT-sequences. This permitted the subsequent removal of the selectable marker cassette by transient transfection of a plasmid that expressed a 37°C thermostable and enhanced FLP-recombinase. This method of removing heterologous DNA sequences from the genome opens up new possibilities in Plasmodium research to sequentially target multiple genes and for using genetically-modified parasites as live, attenuated malaria vaccines

The Phylogeny of the Four Pan-American MtDNA Haplogroups: Implications for Evolutionary and Disease Studies

Only a limited number of complete mitochondrial genome sequences belonging to Native American haplogroups were available until recently, which left America as the continent with the least amount of information about sequence variation of entire mitochondrial DNAs. In this study, a comprehensive overview of all available complete mitochondrial DNA (mtDNA) genomes of the four pan-American haplogroups A2, B2, C1, and D1 is provided by revising the information scattered throughout GenBank and the literature, and adding 14 novel mtDNA sequences. The phylogenies of haplogroups A2, B2, C1, and D1 reveal a large number of sub-haplogroups but suggest that the ancestral Beringian population(s) contributed only six (successful) founder haplotypes to these haplogroups. The derived clades are overall starlike with coalescence times ranging from 18,000 to 21,000 years (with one exception) using the conventional calibration. The average of about 19,000 years somewhat contrasts with the corresponding lower age of about 13,500 years that was recently proposed by employing a different calibration and estimation approach. Our estimate indicates a human entry and spread of the pan-American haplogroups into the Americas right after the peak of the Last Glacial Maximum and comfortably agrees with the undisputed ages of the earliest Paleoindians in South America. In addition, the phylogenetic approach also indicates that the pathogenic status proposed for various mtDNA mutations, which actually define branches of Native American haplogroups, was based on insufficient grounds

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function <it>in vivo</it>. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c.</p> <p>Methods</p> <p>In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth.</p> <p>Results</p> <p>These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival.</p> <p>Conclusions</p> <p>We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number can identify genes that are likely important for chemotherapy response. Our findings suggest a new approach to identify candidate genes that are critical for anti-tumor therapy.</p