Showing papers by "Hokkaido University published in 2013"

Physical hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity

Abstract: Hydrogels attract great attention as biomaterials as a result of their soft and wet nature, similar to that of biological tissues. Recent inventions of several tough hydrogels show their potential as structural biomaterials, such as cartilage. Any given application, however, requires a combination of mechanical properties including stiffness, strength, toughness, damping, fatigue resistance and self-healing, along with biocompatibility. This combination is rarely realized. Here, we report that polyampholytes, polymers bearing randomly dispersed cationic and anionic repeat groups, form tough and viscoelastic hydrogels with multiple mechanical properties. The randomness makes ionic bonds of a wide distribution of strength. The strong bonds serve as permanent crosslinks, imparting elasticity, whereas the weak bonds reversibly break and re-form, dissipating energy. These physical hydrogels of supramolecular structure can be tuned to change multiple mechanical properties over wide ranges by using diverse ionic combinations. This polyampholyte approach is synthetically simple and dramatically increases the choice of tough hydrogels for applications.

Recruited brown adipose tissue as an antiobesity agent in humans

Abstract: Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related accumulation of body fat in humans. Thus, the recruitment of BAT may be effective for body fat reduction. In this study, we examined the effects of repeated stimulation by cold and capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction.

Eemian interglacial reconstructed from a Greenland folded ice core

Abstract: Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.

Theory of multiple proton–electron transfer reactions and its implications for electrocatalysis

Abstract: This perspective article outlines a simple but general theoretical analysis for multiple proton–electron transfer reactions, based on the microscopic theory of proton-coupled electron transfer reactions, recent developments in the thermodynamic theory of multi-step electron transfer reactions, and the experimental realization that many multiple proton-coupled electron transfer reactions feature decoupled proton–electron steps in their mechanism It is shown that decoupling of proton and electron transfer leads to a strong pH dependence of the overall catalytic reaction, implying an optimal pH for high catalytic turnover, and an associated optimal catalyst at the optimal pH When more than one catalytic intermediate is involved, scaling relationships between intermediates may dictate the optimal catalyst and limit the extent of reversibility that may be achievable for a multiple proton–electron transfer reaction The theory is discussed in relation to the experimental results for a number of redox reactions that are of importance for sustainable energy conversion, primarily focusing on their pH dependence

Reduced TiO2 nanotube arrays for photoelectrochemical water splitting

Abstract: We report a facile one-step chemical method to synthesize partially reduced TiO2 nanotube arrays (NTAs). The NaBH4 treatment introduces oxygen vacancies on the surface and interior of TiO2. Oxygen vacancy extends the photocatalytic activity of TiO2 NTAs from the UV to visible light region, and enhances the electrical conductivity as well as charge transportation. Surface oxygen vacancies serve as charge carrier traps as well as adsorption sites where the charge transfer to adsorbed species inhibits the surface charge recombination, whereas bulk oxygen vacancies tend to act as charge carrier traps where e–h recombination occurs. The optimally reduced TiO2 NTAs yield a photocurrent density of 0.73 mA cm−2 at 1.23 VRHE and a highest photoconversion efficiency of 1.31% at a rather low bias of 0.40 VRHE under a standard AM 1.5G solar illumination. Not only does the incident photon to current conversion efficiency (IPCE) spectrum increase in the UV region, but photoactivity in visible light also emerged. Surface oxygen vacancies, serving as electron donors, cause a noticeable negative flatband shift and increase the donor density of TiO2 NTAs 2-fold. Electron paramagnetic resonance (EPR) spectra confirm the presence of oxygen vacancies on the surface and interior of TiO2. Benefitting from the oxygen vacancy, a narrowed band gap of 2.46 eV and suitable localized states for hydrogen production are observed.

Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in Vivo

Abstract: This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunological responses in vivo and in vitro for the production of antibodies for West Nile virus (WNV). We prepared spherical (20 and 40 nm in diameter), rod (40 × 10 nm), and cubic (40 × 40 × 40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. We measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody production, we next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that...

Graphene Oxide Nanosheet with High Proton Conductivity

Abstract: We measured the proton conductivity of bulk graphite oxide (GO'), a graphene oxide/proton hybrid (GO-H), and a graphene oxide (GO) nanosheet for the first time. GO is a well-known electronic insulator, but for proton conduction we observed the reverse trend, as it exhibited superionic conductivity. The hydrophilic sites present in GO as -O-, -OH, and -COOH functional groups attract the protons, which propagate through hydrogen-bonding networks along the adsorbed water film. The proton conductivities of GO' and GO-H at 100% humidity were ∼10(-4) and ∼10(-5) S cm(-1), respectively, whereas that for GO was amazingly high, nearly 10(-2) S cm(-1). This finding indicates the possibility of GO-based perfect two-dimensional proton-conductive materials for applications in fuel cells, sensors, and so on.

IMILAST: A Community Effort to Intercompare Extratropical Cyclone Detection and Tracking Algorithms

Abstract: The variability of results from different automated methods of detection and tracking of extratropical cyclones is assessed in order to identify uncertainties related to the choice of method. Fifteen international teams applied their own algorithms to the same dataset—the period 1989–2009 of interim European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERAInterim) data. This experiment is part of the community project Intercomparison of Mid Latitude Storm Diagnostics (IMILAST; see www.proclim.ch/imilast/index.html). The spread of results for cyclone frequency, intensity, life cycle, and track location is presented to illustrate the impact of using different methods. Globally, methods agree well for geographical distribution in large oceanic regions, interannual variability of cyclone numbers, geographical patterns of strong trends, and distribution shape for many life cycle characteristics. In contrast, the largest disparities exist for the total numbers of cyclones, the detection of wea...

A regenerative approach to the treatment of multiple sclerosis

Abstract: Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission. To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

Abstract: OBJECTIVE: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. MATERIALS AND METHODS: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. RESULTS: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). CONCLUSIONS: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

Systematic exploration of the mechanism of chemical reactions: the global reaction route mapping (GRRM) strategy using the ADDF and AFIR methods

Abstract: Global reaction route mapping (GRRM), a fully-automated search for all important reaction pathways relevant to a given purpose, on the basis of quantum chemical calculations enables systematic elucidation of complex chemical reaction mechanisms However, GRRM had previously been limited to very simple systems This is mainly because such calculations are highly demanding even in small systems when a brute-force sampling is considered Hence, we have developed two independent but complementary methods: anharmonic downward distortion following (ADDF) and artificial force induced reaction (AFIR) methods ADDF can follow reaction pathways starting from local minima on the potential energy surface (PES) toward transition structures (TSs) and dissociation channels AFIR can find pathways starting from two or more reactants toward TSs for their associative reactions In other words, ADDF searches for A → X type isomerization and A → X + Y type dissociation pathways, whereas AFIR finds A + B → X (+ Y) type associative pathways Both follow special paths called the ADDF path and the AFIR path, and these tend to pass through near TSs of corresponding reaction pathways, giving approximate TSs Such approximate TSs can easily be re-optimized to corresponding true TSs by standard geometry optimizations On the basis of these two methods, we have proposed practical strategies of GRRM The GRRM strategies have been applied to a variety of chemical systems ranging from thermal- and photochemical-reactions in small systems to organometallic- and enzyme-catalysis, on the basis of quantum chemical calculations In this perspective, we present an overview of the GRRM strategies and some results of applications Their practical usage for systematic prediction is also discussed

Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier

Abstract: Ligand-mediated drug delivery systems have enormous potential for improving the efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising ligand molecules for targeting αvβ3/αvβ5 integrins, which are overexpressed in angiogenic sites and tumors, such as intractable human glioblastoma (U87MG). We here achieved highly efficient drug delivery to U87MG tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM) with cyclic Arg-Gly-Asp (cRGD) ligand molecules. Intravital confocal laser scanning microscopy revealed that the cRGD-linked polymeric micelles (cRGD/m) accumulated rapidly and had high permeability from vessels into the tumor parenchyma compared with the PM having nontargeted ligand, “cyclic-Arg-Ala-Asp” (cRAD). As both cRGD/m- and cRAD-linked polymeric micelles have similar characteristics, including their size, surface charge, and the amount of incorporated drugs, it is likely that the selective and accelerated accumulation of cRGD/m into tumors occurred via...

Stratospheric Temperature Changes: Observations and Model Simulations

Abstract: This paper reviews observations of stratospheric temperatures that have been made over a period of several decades. Those observed temperatures have been used to assess variations and trends in stratospheric temperatures. A wide range of observation datasets have been used, comprising measurements by radiosonde (1940s to the present), satellite (1979 - present), lidar (1979 - present) and rocketsonde (periods varying with location, but most terminating by about the mid-1990s). In addition, trends have also been assessed from meteorological analyses, based on radiosonde and/or satellite data, and products based on assimilating observations into a general circulation model. Radiosonde and satellite data indicate a cooling trend of the annual-mean lower stratosphere since about 1980. Over the period 1979-1994, the trend is 0.6K/decade. For the period prior to 1980, the radiosonde data exhibit a substantially weaker long-term cooling trend. In the northern hemisphere, the cooling trend is about 0.75K/decade in the lower stratosphere, with a reduction in the cooling in mid-stratosphere (near 35 km), and increased cooling in the upper stratosphere (approximately 2 K per decade at 50 km). Model simulations indicate that the depletion of lower stratospheric ozone is the dominant factor in the observed lower stratospheric cooling. In the middle and upper stratosphere both the well-mixed greenhouse gases (such as CO) and ozone changes contribute in an important manner to the cooling.

Characterization of H7N9 influenza A viruses isolated from humans

Abstract: Avian influenza A viruses rarely infect humans; however, when human infection and subsequent human-to-human transmission occurs, worldwide outbreaks (pandemics) can result. The recent sporadic infections of humans in China with a previously unrecognized avian influenza A virus of the H7N9 subtype (A(H7N9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission, and the lack of pre-existing immunity among humans to viruses of this subtype. Here we characterize two early human A(H7N9) isolates, A/Anhui/1/2013 (H7N9) and A/Shanghai/1/2013 (H7N9); hereafter referred to as Anhui/1 and Shanghai/1, respectively. In mice, Anhui/1 and Shanghai/1 were more pathogenic than a control avian H7N9 virus (A/duck/Gunma/466/2011 (H7N9); Dk/GM466) and a representative pandemic 2009 H1N1 virus (A/California/4/2009 (H1N1pdm09); CA04). Anhui/1, Shanghai/1 and Dk/GM466 replicated well in the nasal turbinates of ferrets. In nonhuman primates, Anhui/1 and Dk/GM466 replicated efficiently in the upper and lower respiratory tracts, whereas the replicative ability of conventional human influenza viruses is typically restricted to the upper respiratory tract of infected primates. By contrast, Anhui/1 did not replicate well in miniature pigs after intranasal inoculation. Critically, Anhui/1 transmitted through respiratory droplets in one of three pairs of ferrets. Glycan arrays showed that Anhui/1, Shanghai/1 and A/Hangzhou/1/2013 (H7N9) (a third human A(H7N9) virus tested in this assay) bind to human virus-type receptors, a property that may be critical for virus transmissibility in ferrets. Anhui/1 was found to be less sensitive in mice to neuraminidase inhibitors than a pandemic H1N1 2009 virus, although both viruses were equally susceptible to an experimental antiviral polymerase inhibitor. The robust replicative ability in mice, ferrets and nonhuman primates and the limited transmissibility in ferrets of Anhui/1 suggest that A(H7N9) viruses have pandemic potential.

The polyethyleneglycol dilemma: advantage and disadvantage of PEGylation of liposomes for systemic genes and nucleic acids delivery to tumors.

Abstract: Gene and nucleic acid therapy is expected to play a major role in the next generation of agents for cancer treatment. We have recently developed a multifunctional envelope-type nano device (MEND) for use as a novel nonviral gene delivery system. The modification of polyethyleneglycol (PEG), i.e., PEGylation, is a useful method for achieving a longer circulation time for the delivery of MEND to a tumor via the enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results in significant loss of activity of the delivery system. For successful nucleic acid delivery for cancer treatment, the crucial problem associated with the use of PEG, i.e., the "PEG dilemma" must be resolved. In this review, we describe the development and applications of MEND and discuss various strategies for overcoming the PEG dilemma based on the manipulation of both pharmacokinetics and intracellular trafficking of cellular uptake and endosomal release. To increase cellular uptake, target ligands including proteins, peptides, antibodies and aptamers that recognize molecules specifically expressed on tumors are first introduced. Second, cleavable PEG systems are described. The cleavage of PEG from carriers was achieved in response to the intracellular environment as well as the tumor microenvironment, which improvs cellular uptake and endosomal escape. Then, endosomal fusogenic peptides are discussed. Finally, pH-sensitive liposomes using pH-sensitive lipids are described.

Reversible redox reactions in an epitaxially stabilized SrCoO(x) oxygen sponge.

Abstract: Fast, reversible redox reactions in solids at low temperatures without thermomechanical degradation are a promising strategy for enhancing the overall performance and lifetime of many energy materials and devices. However, the robust nature of the cation's oxidation state and the high thermodynamic barrier have hindered the realization of fast catalysis and bulk diffusion at low temperatures. Here, we report a significant lowering of the redox temperature by epitaxial stabilization of strontium cobaltites (SrCoO(x)) grown directly as one of two distinct crystalline phases, either the perovskite SrCoO(3-δ) or the brownmillerite SrCoO(2.5). Importantly, these two phases can be reversibly switched at a remarkably reduced temperature (200-300 °C) in a considerably short time (< 1 min) without destroying the parent framework. The fast, low-temperature redox activity in SrCoO(3-δ) is attributed to a small Gibbs free-energy difference between two topotatic phases. Our findings thus provide useful information for developing highly sensitive electrochemical sensors and low-temperature cathode materials.

Direct imaging of a cold jovian exoplanet in orbit around the sun-like star gj 504

Abstract: Several exoplanets have recently been imaged at wide separations of >10?AU from their parent stars. These span a limited range of ages ( 0.5?mag), implying thick cloud covers. Furthermore, substantial model uncertainties exist at these young ages due to the unknown initial conditions at formation, which can lead to an order of magnitude of uncertainty in the modeled planet mass. Here, we report the direct-imaging discovery of a Jovian exoplanet around the Sun-like star GJ 504, detected as part of the SEEDS survey. The system is older than all other known directly imaged planets; as a result, its estimated mass remains in the planetary regime independent of uncertainties related to choices of initial conditions in the exoplanet modeling. Using the most common exoplanet cooling model, and given the system age of 160?Myr, GJ 504b has an estimated mass of 4 Jupiter masses, among the lowest of directly imaged planets. Its projected separation of 43.5?AU exceeds the typical outer boundary of ~30?AU predicted for the core accretion mechanism. GJ 504b is also significantly cooler (510 K) and has a bluer color (J ? H = ?0.23?mag) than previously imaged exoplanets, suggesting a largely cloud-free atmosphere accessible to spectroscopic characterization. Thus, it has the potential of providing novel insights into the origins of giant planets as well as their atmospheric properties.

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970–2010

Abstract: Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Capabilities and performance of Elmer/Ice, a new-generation ice sheet model

Abstract: The Fourth IPCC Assessment Report concluded that ice sheet flow models, in their current state, were unable to provide accurate forecast for the increase of polar ice sheet discharge and the associated contribution to sea level rise. Since then, the glaciological community has undertaken a huge effort to develop and improve a new generation of ice flow models, and as a result a significant number of new ice sheet models have emerged. Among them is the parallel finite-element model Elmer/Ice, based on the open-source multi-physics code Elmer. It was one of the first full-Stokes models used to make projections for the evolution of the whole Greenland ice sheet for the coming two centuries. Originally developed to solve local ice flow problems of high mechanical and physical complexity, Elmer/Ice has today reached the maturity to solve larger-scale problems, earning the status of an ice sheet model. Here, we summarise almost 10 yr of development performed by different groups. Elmer/Ice solves the full-Stokes equations, for isotropic but also anisotropic ice rheology, resolves the grounding line dynamics as a contact problem, and contains various basal friction laws. Derived fields, like the age of the ice, the strain rate or stress, can also be computed. Elmer/Ice includes two recently proposed inverse methods to infer badly known parameters. Elmer is a highly parallelised code thanks to recent developments and the implementation of a block preconditioned solver for the Stokes system. In this paper, all these components are presented in detail, as well as the numerical performance of the Stokes solver and developments planned for the future.

Neuroprotective function of DJ-1 in Parkinson's disease.

Abstract: Parkinson's disease (PD) is caused by dopaminergic neuronal death in the substantia nigra, resulting in a reduced level of dopamine in the striatum. Oxidative stress and mitochondrial dysfunction are thought to be major causes of neurodegeneration in PD. Although genetic and environmental factors are thought to affect the onset of PD, precise mechanisms at the molecular level have not been elucidated. The DJ-1 gene is a causative gene for familial PD (park7) and also an oncogene. DJ-1 has various functions, including transcriptional regulation, antioxidative stress reaction, and chaperone, protease, and mitochondrial regulation, and its activity is regulated by its oxidative status, especially that of cysteine 106 (C106) of DJ-1. Excess oxidation of DJ-1, which renders DJ-1 inactive, has been observed in patients with sporadic PD and Alzheimer's disease, suggesting that DJ-1 also participates in the onset and pathogenesis of sporadic PD as well as familial PD. DJ-1 is also a stress sensor and its expression is increased upon various stresses, including oxidative stress. In this review, we describe functions of DJ-1 against oxidative stress and possible roles of DJ-1 in the pathogenesis of PD.

Generalized ocean color inversion model for retrieving marine inherent optical properties

Abstract: Ocean color measured from satellites provides daily, global estimates of marine inherent optical properties (IOPs). Semi-analytical algorithms (SAAs) provide one mechanism for inverting the color of the water observed by the satellite into IOPs. While numerous SAAs exist, most are similarly constructed and few are appropriately parameterized for all water masses for all seasons. To initiate community-wide discussion of these limitations, NASA organized two workshops that deconstructed SAAs to identify similarities and uniqueness and to progress toward consensus on a unified SAA. This effort resulted in the development of the generalized IOP (GIOP) model software that allows for the construction of different SAAs at runtime by selection from an assortment of model parameterizations. As such, GIOP permits isolation and evaluation of specific modeling assumptions, construction of SAAs, development of regionally tuned SAAs, and execution of ensemble inversion modeling. Working groups associated with the workshops proposed a preliminary default configuration for GIOP (GIOP-DC), with alternative model parameterizations and features defined for subsequent evaluation. In this paper, we: (1) describe the theoretical basis of GIOP; (2) present GIOP-DC and verify its comparable performance to other popular SAAs using both in situ and synthetic data sets; and, (3) quantify the sensitivities of their output to their parameterization. We use the latter to develop a hierarchical sensitivity of SAAs to various model parameterizations, to identify components of SAAs that merit focus in future research, and to provide material for discussion on algorithm uncertainties and future emsemble applications.

Mechanical stimulation and solid seeding trigger single-crystal-to-single-crystal molecular domino transformations

Abstract: Numerous studies have focused on the mechanical control of solid structures and phase changes in molecular crystals. However, the molecular-level understanding of how macroscopic forces affect the molecules in a solid remains incomplete. Here we report that a small mechanical stimulus or solid seeding can trigger a single-crystal-to-single-crystal transformation from a kinetically isolated polymorph of phenyl(phenyl isocyanide)gold(I) exhibiting blue photoluminescence to a thermodynamically stable polymorph exhibiting yellow emission without the need for heating or solvent. The phase transformation initiates at the location of the mechanical stimulation or seed crystal, extends to adjacent crystals, and can be readily monitored visually by the accompanying photoluminescent colour change from blue to yellow. The transformation was characterized using single crystal X-ray analysis. Our results suggest that the transformation proceeds through self-replication, causing the complex to behave as 'molecular dominoes'.

Exosomes Derived from Epstein-Barr Virus-Infected Cells Are Internalized via Caveola-Dependent Endocytosis and Promote Phenotypic Modulation in Target Cells

Abstract: Epstein-Barr virus (EBV), a human gammaherpesvirus, establishes a lifelong latent infection in B lymphocytes and epithelial cells following primary infection. Several lines of evidence suggest that exosomes derived from EBV-infected cells are internalized and transfer viral factors, including EBV-encoded latent membrane protein and microRNAs, to the recipient cells. However, the detailed mechanism by which exosomes are internalized and their physiological impact on the recipient cells are still poorly understood. In this study, we visualized the internalization of fluorescently labeled exosomes derived from EBV-uninfected and EBV-infected B cells of type I and type III latency into EBV-negative epithelial cells. In this way, we demonstrated that exosomes derived from all three cell types were internalized into the target cells in a similar fashion. Internalization of exosomes was significantly suppressed by treatment with an inhibitor of dynamin and also by the knockdown of caveolin-1. Labeled exosomes were colocalized with caveolae and subsequently trafficked through endocytic pathways. Moreover, we observed that exosomes derived from type III latency cells upregulated proliferation and expression of intercellular adhesion molecule 1 (ICAM-1) in the recipient cells more significantly than did those derived from EBV-negative and type I latency cells. We also identified the EBV latent membrane protein 1 (LMP1) gene as responsible for induction of ICAM-1 expression. Taken together, our data indicate that exosomes released from EBV-infected B cells are internalized via caveola-dependent endocytosis, which, in turn, contributes to phenotypic changes in the recipient cells through transferring one or more viral factors.