bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a More Systematic Approach to Secure Systems Design and Analysis
Authors: Miller Simon , Appleby Susan , Garibaldi Jonathan M. , Aickelin Uwe
Published: April 2013

The task of designing secure software systems is fraught with uncertainty, as data on uncommon attacks is limited, costs are difficult to estimate, and technology and tools are continually changing. Consequently, experts may interpret the security risks posed to a system in different ways, leading to variation in assessment. This paper presents research into measuring the variability in decision making between security professionals, with the ultimate goal of improving the quality of security advice given to software system designers. A set of thirty nine cyber-security experts took part in an exercise in which they independently assessed a realistic system scenario. This study quantifies agreement in the opinions of experts, examines methods of aggregating opinions, and produces an assessment of attacks from ratings of their components. The authors show that when aggregated, a coherent consensus view of security emerges which can be used to inform decisions made during systems design.
Searching for Alternatives
Authors: Drake John R. , Byrd Terry Anthony
Published: April 2013

In the decision-making process, vast quantities of information is often parsed into a manageable set of top choices in order to meaningful select the best option. But what individual traits and dispositions impact this process? In this exploratory research effort, the authors address three such dispositions and their impact on selecting alternatives for a decision. Conducting two surveys for two different contexts, they find that motivational dispositions do have some impact on product searches, but may have minimal impact on information searches. The authors conclude that context has a major impact on the decision-making process and that technology/disposition fit may be a useful concept to guide the design of search technologies.
Multiple Dimensions of Multitasking Phenomenon
Authors: Lin Lin
Published: April 2013

Multitasking is defined as conducting two or more tasks simultaneously or switching quickly between two or more tasks. While multitasking is not a new concept, it has caught more attention in recent years. Whether one sees it as an illusion, a fad, a new phenomenon, or an evolving human capacity, it is important to establish a baseline of what activities are involved in multitasking for scholarly inquiries and discoveries. This paper examines the multitasking phenomenon through personal stories of 43 undergraduate students (age 21-29) and 30 children (age 6-11). The stories revealed a wide range of perceptions and experiences of multitasking, from walking while breathing, to doing homework while watching TV and surfing online, to texting while driving, and to performing complex professional skills. This vast range of experiences may have contributed to the varied views and debates on human beings’ capabilities of multitasking to date. The purpose of this paper, therefore, is to bring to light the multiple dimensions of multitasking as it relates to attention, ability, expertise, technology, and environment. This endeavor serves as a foundation for further studies on human’s capacity for multitasking.
Exploring the Effects of Display Characteristics on Presence and Emotional Responses of Game Players
Authors: Lin Tao , Wu Zhiming , Tang Ningjiu , Wu Shaomei
Published: April 2013

Large displays are becoming ubiquitous and one important property of large displays is that they afford larger visual angles and physically larger screen sizes. However, there has been little investigation of the effects of large displays on users; furthermore, few studies have employed physiological measures, nor isolated the effects on presence and emotional responses of large visual angle and physically large screen size. This study, then, examines specifically the effects of these two properties of large displays on presence and emotional responses, using physiological as well as subjective methods. The results indicate that the larger visual angle offered by a large display can increase the sense of presence, engagement, and emotional responses when players are playing games. More interestingly, the physically larger sizes offered by a large display seem to also be able to affect these player experiences, even at identical visual angles with small displays.
Identification of Key Issues in Adopting a Web 2.0 E-Portfolio Strategy
Authors: McKenna Gary F. , Stansfield Mark H.
Published: April 2013

The purpose of the paper is to identify key issues relating to best practice and sustainability in Web 2.0 as an e-Learning strategy for supporting e-portfolios in Higher Education. A practical guidelines framework was developed for best practices, which can be justified by the lack of available frameworks in the e-Learning literature. A literature search was undertaken covering publications dated from 2000 to 2009 to ascertain the level of progress made on tackling issues on implementing Web 2.0 as an e-Learning campus wide educational strategy. The findings show that the recent adoption of e-Learning and Web 2.0 initiatives has been marred by lack of research into the issues associated with long term strategy, implementation, best practice frameworks and solutions. The paper fulfils an identified information need and offers practical help to institutions implementing an e-portfolio Web 2.0 initiative.
A Phosphatidylinositol Species Acutely Generated by Activated Macrophages Regulates Innate Immune Responses
Authors: Gil-de-Gómez Luis , Astudillo Alma M. , Meana Clara , Rubio Julio M. , Guijas Carlos , Balboa María A. , Balsinde Jesús
Published: April 2013

Activation of macrophages with stimuli of the innate immune response results in the intense remodeling of arachidonate-containing phospholipids, leading to the mobilization of large quantities of this fatty acid for conversion into biologically active eicosanoids. As a consequence of this process, the arachidonate levels in membrane phospholipids markedly decrease. We have applied mass spectrometry–based lipid profiling to study the levels of arachidonate-containing phospholipids under inflammatory activation of macrophages. We identify an unusual inositol phospholipid molecule, PI(20:4/20:4), the levels of which do not decrease but actually increase by 300% after activation of the macrophages. PI(20:4/20:4) is formed and degraded rapidly, suggesting a role for this molecule in regulating cell signaling events. Using a metabolipidomic approach consisting in exposing the cells to deuterium-labeled arachidonate at the time they are exposed to stimuli, we show that PI(20:4/20:4) biosynthesis occurs via the sequential incorporation of arachidonate, first into the sn-2 position of a preformed phosphatidylinositol (PI) molecule, followed by the rapid introduction of a second arachidonate moiety into the sn-1 position. Generation requires the participation of cytosolic phospholipase A2α and CoA-dependent acyltransferases. PI(20:4/20:4) formation is also detected in vivo in murine peritonitis exudates. Elevating the intracellular concentration of PI(20:4/20:4) by introducing the lipid into the cells results in enhancement of the microbicidal capacity of macrophages, as measured by reactive oxygen metabolite production and lysozyme release. These findings suggest that PI(20:4/20:4) is a novel bioactive inositol phospholipid molecule that regulates innate immune responses in macrophages.
Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis
Authors: Jones Clinton
Published: April 2013

α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts.
Effectiveness of Rapid Transport of Victims and Community Health Education on Snake Bite Fatalities in Rural Nepal
Authors: Sharma Sanjib K. , Bovier Patrick , Jha Nilambar , Alirol Emilie , Loutan Louis , Chappuis François
Published: April 2013

Snake bite is a major public problem in the rural tropics. In southern Nepal, most deaths caused by neurotoxic envenomation occur in the village or during transport to health centers. The effectiveness of victims' transport by motorcycle volunteers to a specialized treatment center, combined with community health education, was assessed in a non-randomized, single-arm, before-after study conducted in four villages (population = 62,127). The case-fatality rate of snake bite decreased from 10.5% in the pre-intervention period to 0.5% during the intervention (relative risk reduction = 0.949, 95% confidence interval = 0.695–0.999). The snake bite incidence decreased from 502 bites/100,000 population to 315 bites/100,000 population in the four villages (relative risk reduction = 0.373, 95% confidence interval = 0.245–0.48), but it remained constant in other villages. Simple educational messages and promotion of immediate and rapid transport of victims to a treatment center decreased the mortality rate and incidence of snake bite in southeastern Nepal. The impact of similar interventions should be assessed elsewhere.
Influence of Oxidizing Ion Concentration on the Corrosion Resistance of Type 304L Stainless Steel in Nitric Acid Medium
Authors: Priya R. , Ningshen S. , Mudali U. Kamachi
Published: April 2013

The influence of the oxidizing ions Fe3+ and Cr6+ with two different concentrations on the corrosion resistance of Type 304L (UNS S30403) stainless steel in 3 M and 6 M nitric acid (HNO3) medium has been determined. The corrosion resistance and passive film behavior of Type 304L stainless steel in the presence of oxidizing ions were evaluated using electrochemical potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and x-ray photoelectron spectroscopy (XPS) techniques. The corrosion resistance was observed to decrease with an increase in acid concentration and oxidizing ions. The concentrations of oxidizing ions were found to have a profound effect on the corrosion potential and passive current density when compared to that in nitric acid without oxidizing ions. XPS results revealed a significant reduction of chromium(III) oxide (Cr2O3) on the passive film as the concentration of oxidizing ions in nitric acid increases. An oxide layer thickness of ~13 nm enriched with iron oxide could be estimated for the passivated sample in the nitric acid medium with higher oxidizing ion concentration compared to 1 nm thick oxide film in nitric acid without oxidizing ions. Both XPS and EIS analyses confirmed the detrimental effect of oxidizing species on the passive film leading to increased corrosion with an increase in nitric acid and oxidizing ion concentration. The corrosion results could be correlated with microstructural observations.
Inverse estimation of source parameters of oceanic radioactivity dispersion models associated with the Fukushima accident
Authors: Miyazawa Y. , Masumoto Y. , Varlamov S. M. , Miyama T. , Takigawa M. , Honda M. , Saino T.
Published: April 2013

Abstract. With combined use of the ocean–atmosphere simulation models and field observation data, we evaluate the parameters associated with the total caesium-137 amounts of the direct release into the ocean and atmospheric deposition over the western North Pacific caused by the accident of Fukushima Daiichi nuclear power plant (FNPP) that occurred in March 2011. The Green's function approach is adopted for the estimation of two parameters determining the total emission amounts for the period from 12 March to 6 May 2011. It is confirmed that the validity of the estimation depends on the simulation skill near FNPP. The total amount of the direct release is estimated as 5.5–5.9 × 1015 Bq, while that of the atmospheric deposition is estimated as 5.5–9.7 × 1015 Bq, which indicates broader range of the estimate than that of the direct release owing to uncertainty of the dispersion widely spread over the western North Pacific.
Climate and vegetation changes during the Lateglacial and early–middle Holocene at Lake Ledro (southern Alps, Italy)
Authors: Joannin S. , Vannière B. , Galop D. , Peyron O. , Haas J. N. , Gilli A. , Chapron E. , Wirth S. B. , Anselmetti F. , Desmet M. , Magny M.
Published: April 2013

Abstract. Adding to the on-going debate regarding vegetation recolonisation (more particularly the timing) in Europe and climate change since the Lateglacial, this study investigates a long sediment core (LL081) from Lake Ledro (652 m a.s.l., southern Alps, Italy). Environmental changes were reconstructed using multiproxy analysis (pollen-based vegetation and climate reconstruction, lake levels, magnetic susceptibility and X-ray fluorescence (XRF) measurements) recorded climate and land-use changes during the Lateglacial and early–middle Holocene. The well-dated and high-resolution pollen record of Lake Ledro is compared with vegetation records from the southern and northern Alps to trace the history of tree species distribution. An altitude-dependent progressive time delay of the first continuous occurrence of Abies (fir) and of the Larix (larch) development has been observed since the Lateglacial in the southern Alps. This pattern suggests that the mid-altitude Lake Ledro area was not a refuge and that trees originated from lowlands or hilly areas (e.g. Euganean Hills) in northern Italy. Preboreal oscillations (ca. 11 000 cal BP), Boreal oscillations (ca. 10 200, 9300 cal BP) and the 8.2 kyr cold event suggest a centennial-scale climate forcing in the studied area. Picea (spruce) expansion occurred preferentially around 10 200 and 8200 cal BP in the south-eastern Alps, and therefore reflects the long-lasting cumulative effects of successive boreal and the 8.2 kyr cold event. The extension of Abies is contemporaneous with the 8.2 kyr event, but its development in the southern Alps benefits from the wettest interval 8200–7300 cal BP evidenced in high lake levels, flood activity and pollen-based climate reconstructions. Since ca. 7500 cal BP, a weak signal of pollen-based anthropogenic activities suggest weak human impact. The period between ca. 5700 and ca. 4100 cal BP is considered as a transition period to colder and wetter conditions (particularly during summers) that favoured a dense beech (Fagus) forest development which in return caused a distinctive yew (Taxus) decline. We conclude that climate was the dominant factor controlling vegetation changes and erosion processes during the early and middle Holocene (up to ca. 4100 cal BP).
Dynamical and biogeochemical control on the decadal variability of ocean carbon fluxes
Authors: Séférian R. , Bopp L. , Swingedouw D. , Servonnat J.
Published: April 2013

Abstract. Several recent observation-based studies suggest that ocean anthropogenic carbon uptake has slowed down due to the impact of anthropogenic forced climate change. However, it remains unclear whether detected changes over the recent time period can be attributed to anthropogenic climate change or rather to natural climate variability (internal plus naturally forced variability) alone. One large uncertainty arises from the lack of knowledge on ocean carbon flux natural variability at the decadal time scales. To gain more insights into decadal time scales, we have examined the internal variability of ocean carbon fluxes in a 1000 yr long preindustrial simulation performed with the Earth System Model IPSL-CM5A-LR. Our analysis shows that ocean carbon fluxes exhibit low-frequency oscillations that emerge from their year-to-year variability in the North Atlantic, the North Pacific, and the Southern Ocean. In our model, a 20 yr mode of variability in the North Atlantic air-sea carbon flux is driven by sea surface temperature variability and accounts for ~40% of the interannual regional variance. The North Pacific and the Southern Ocean carbon fluxes are also characterised by decadal to multi-decadal modes of variability (10 to 50 yr) that account for 20–40% of the interannual regional variance. These modes are driven by the vertical supply of dissolved inorganic carbon through the variability of Ekman-induced upwelling and deep-mixing events. Differences in drivers of regional modes of variability stem from the coupling between ocean dynamics variability and the ocean carbon distribution, which is set by large-scale secular ocean circulation.
The potential of an observational data set for calibration of a computationally expensive computer model
Authors: McNeall D. J. , Challenor P. G. , Gattiker J. R. , Stone E. J.
Published: April 2013

Abstract. We measure the potential of an observational data set to constrain a set of inputs to a complex and computationally expensive computer model. We use each member in turn of an ensemble of output from a computationally expensive model, corresponding to some observable part of a modelled system, as a proxy for an observational data set. We argue that our ability to constrain uncertain parameter inputs to a model using its own output as data, provides a maximum bound for our ability to constrain the model inputs using observations of the real system. The ensemble provides a set of known parameter input and model output pairs, which we use to build a computationally efficient statistical proxy for the full computer model, termed an emulator. We use the emulator to find and rule out ''implausible" values for the inputs of held-out ensemble members, given the computer model output. As we know the true values of the inputs for the ensemble, we can compare our constraint of the model inputs with the true value of the input for any ensemble member. Measures of the quality of constraint have the potential to inform strategy for data collection campaigns, before any real-world data is collected, as well as acting as an effective sensitivity analysis. We use an ensemble of the ice sheet model Glimmer to demonstrate our measures of quality of constraint. The ensemble has 250 model runs with 5 uncertain input parameters, and an output variable representing the pattern of the thickness of ice over Greenland. We have an observation of historical ice sheet thickness that directly matches the output variable, and offers an opportunity to constrain the model. We show that different ways of summarising our output variable (ice volume, ice surface area and maximum ice thickness) offer different potential constraints on individual input parameters. We show that combining the observational data gives increased power to constrain the model. We investigate the impact of uncertainty in observations or in model biases on our measures, showing that even a modest uncertainty can seriously degrade the potential of the observational data to constrain the model.
Socio-hydrology: conceptualising human-flood interactions
Authors: Di Baldassarre G. , Viglione A. , Carr G. , Kuil L. , Salinas J. L. , Blöschl G.
Published: April 2013

Abstract. Over history, humankind has tended to settle near streams because of the role of rivers as transportation corridors and the fertility of riparian areas. However, human settlements in floodplains have been threatened by the risk of flooding. Possible responses have been to resettle away and/or modify the river system by building flood control structures. This has led to a complex web of interactions and feedback mechanisms between hydrological and social processes in settled floodplains. This paper is an attempt to conceptualise these interplays for hypothetical human-flood systems. We develop a simple, dynamic model to represent the interactions and feedback loops between hydrological and social processes. The model is then used to explore the dynamics of the human-flood system and the effect of changing individual characteristics, including external forcing such as technological development. The results show that the conceptual model is able to reproduce reciprocal effects between floods and people as well as the emergence of typical patterns. For instance, when levees are built or raised to protect floodplain areas, their presence not only reduces the frequency of flooding, but also exacerbates high water levels. Then, because of this exacerbation, higher flood protection levels are required by the society. As a result, more and more flooding events are avoided, but rare and catastrophic events take place.
Arctic Ocean sea ice snow depth evaluation and bias sensitivity in CCSM
Authors: Blazey B. A. , Holland M. M. , Hunke E. C.
Published: April 2013

Abstract. Sea ice cover in the Arctic Ocean is a continued focus of attention. This study assesses the capability of hindcast simulations of the Community Climate System Model (CCSM) to reproduce observed snow depths and densities overlying the Arctic Ocean sea ice. The model is evaluated using measurements provided by historic Russian polar drift stations. Following the identification of seasonal biases produced in the simulations, the thermodynamic transfer through the snow – ice column is perturbed to determine model sensitivity to these biases. This study concludes that perturbations on the order of the observed biases result in modification of the annual mean conductive flux of 0.5 W m−2 relative to an unmodified simulation. The results suggest that the ice has a complex response to snow characteristics, with ice of different thicknesses producing distinct reactions. Consequently, we suggest that the inclusion of additional snow evolution processes such as blowing snow, densification, and seasonal changes in snow conductivity in sea ice models would increase the fidelity of the model with respect to the physical system. Moreover, our results suggest that simulated high latitude precipitation biases have important effects on the simulated ice conditions, resulting in impacts on the Arctic climate in general in large-scale climate.
Rescribir el horror. Historia y poética de la memoria en la obra de Roberto Bolaño
Authors: Solà Garcia Alba
Published: April 2013

Con los horrores del siglo XX, el mal ha caído en un vacío ontológico que lo hace ininteligible: la desemantización de su lenguaje y la atrofia de sus fórmulas niegan la posibilidad de erigir un discurso válido, sea éste en el plano moral, político o filosófico. La literatura, sin embargo, se aventura a resignificar el espacio del mal a partir de su reelaboración en la dimensión simbólica de la ficción. Roberto Bolaño reconstruye el discurso histórico chileno en Estrella distante y Nocturno de Chile, denunciando el fenómeno del mal y su reiterada aparición en la Historia y resignificando su lenguaje a partir de una poética del ocultamiento y la sugerencia que permite visibilizar el horror y sus espacios, convirtiendo sus ficciones en documentos testimoniales que reelaboran la memoria histórica latinoamericana y reivindican sus episodios olvidados.
As recomendações da Wonca para a Saúde das Populações Rurais
Authors: Targa Leonardo Vieira , Ando Nilson Massakazu , Silva André Luiz da , Silveira Rodrigo Pinheiro , Porto Magda Moura de Almeida , Amaral Filho Ricardo César Garcia , Lima Mônica Correia , Savassi Leonardo Cançado Monteiro , Silva Dijon Hosana Souza , Horta Thereza Cristina Gomes
Published: April 2013

A Associação Mundial de Médicos de Família, através do seu grupo de trabalho de saúde rural, vem desenvolvendo ações, participando de projetos e realizando recomendações relacionados a diversos temas ligados à saúde rural. O Grupo de Trabalho em Medicina Rural da Sociedade Brasileira de Medicina de Família e Comunidade traduz para a língua portuguesa, neste número, os principais documentos que devem servir como referência para a construção de políticas e práticas nesta área. Abaixo um breve resumo dos artigos que se encontram neste volume.
Política de formação para a prática rural
Authors: WONCA Working Party on Rural Practice
Published: April 2013

A escassez mundial de médicos de família rurais contribui diretamente para as dificuldades com prestação de cuidados médicos adequados em áreas rurais e remotas, tanto em países desenvolvidos, quanto nos menos desenvolvidos. A Wonca acredita que há uma necessidade urgente de implementar estratégias para melhorar os serviços de saúde rural em todo o mundo. Isso vai exigir um número suficiente de médicos de família rurais qualificados para fornecer os serviços necessários. Para atingir este objetivo, a Wonca recomenda:1. Aumentar o número de estudantes de medicina recrutados de áreas rurais.2. Exposição substancial da prática rural no currículo médico de graduação.3. Programas de treinamento vocacional em medicina rural específicos, flexíveis, integrados e coordenados.4. Educação continuada específica adaptada e programas de desenvolvimento profissional que satisfaçam as necessidades identificadas dos médicos de família rurais.5. Posições acadêmicas apropriadas, desenvolvimento profissional e apoio financeiro para médicos-professores rurais para incentivar a pesquisa e educação rural.6. Escolas médicas devem assumir a responsabilidade de formar médicos devidamente qualificados para atender às necessidades da sua região geográfica geral, incluindo áreas carentes, e desempenhar um papel fundamental no fornecimento de apoio regional para os profissionais de saúde e cuidados de saúde terciários acessíveis.7. Desenvolvimento das necessidades rurais adequadas de base e recursos culturalmente sensíveis para cuidados de saúde rural com o envolvimento da comunidade local, com a cooperação regional e apoio do governo.8. Melhoria das condições profissionais e pessoais/familiares na prática rural para promover a retenção de médicos rurais.9. Desenvolvimento e implementação de estratégias nacionais de saúde rural, com apoio do governo central.
Homeowners' decision‐making in a premise plumbing failure–prone area
Authors: Lee Juneseok , Kleczyk Ewa , Bosch Darrell J. , Dietrich Andrea M. , Lohani Vinod K. , Loganathan G.V.
Published: April 2013

Two formal preference‐elicitation methodologies—conjoint analysis and the analytical hierarchical process—were applied to examine the actions taken by homeowners living in a premise plumbing failure‐prone area and the decision‐making they used to minimize their risk resulting from corrosion, cost, and other issues related to home plumbing. Most households preferred simply to stay with their current plumbing materials rather than install an upgrade to reduce the risk of corrosion or purchase insurance against corrosion damage. Health, taste, and odor were dominant considerations for consumers. It was interesting that some survey respondents answered one way when stating preferences but behaved differently when making real‐life choices. This information will be helpful for policy experts and utility companies seeking new ways to deal with premise plumbing issues.
Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice
Authors: Shimomura Kazuhiro , Kumar Vivek , Koike Nobuya , Kim Tae-Kyung , Chong Jason , Buhr Ethan D , Whiteley Andrew R , Low Sharon S , Omura Chiaki , Fenner Deborah , Owens Joseph R , Richards Marc , Yoo Seung-Hee , Hong Hee-Kyung , Vitaterna Martha H , Bass Joseph , Pletcher Mathew T , Wiltshire Tim , Hogenesch John , Lowrey Phillip L , Takahashi Joseph S
Published: April 2013

Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the ClockΔ19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the ClockΔ19 mutation to a ∼900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals.
SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion
Authors: Chen Xiao-Wei , Wang He , Bajaj Kanika , Zhang Pengcheng , Meng Zhuo-Xian , Ma Danjun , Bai Yongsheng , Liu Hui-Hui , Adams Elizabeth , Baines Andrea , Yu Genggeng , Sartor Maureen A , Zhang Bin , Yi Zhengping , Lin Jiandie , Young Stephen G , Schekman Randy , Ginsburg David
Published: April 2013

The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes.
Designer antiandrogens join the race against drug resistance
Authors: Josan Jatinder S , Katzenellenbogen John A
Published: April 2013

By using in silico models of the complexes formed by analogues of a cancer drug and its receptor, it may be possible to strategically redesign existing drugs and win the race against mutations that lead to drug resistance in prostate cancer.
Multifunctional Graphene–PEDOT Microelectrodes for On‐Chip Manipulation of Human Mesenchymal Stem Cells
Authors: Hsiao Yu‐Sheng , Kuo Chiung‐Wen , Chen Peilin
Published: April 2013

All‐solution‐processed multifunctional organic bioelectronics composed of reduced graphene oxide (rGO) and dexamethasone 21‐phosphate disodium salt (DEX)‐loaded poly(3,4‐ethylenedioxythiophene) (PEDOT) microelectrode arrays on indium tin oxide glass are reported. They can be used to manipulate the differentiation of human mesenchymal stem cells (hMSCs). In the devices, the rGO material functions as an adhesive coating to promote the adhesion and alignment of hMSC cells and to accelerate their osteogenic differentiation. The poly(L‐lysine‐graft‐ethylene glycol) (PLL‐g‐PEG)‐coated PEDOT electrodes serve as electroactive drug‐releasing electrodes. In addition, the corresponding three‐zone parallel devices operate as efficient drug‐releasing components through spatial‐temporal control of the release of the drug DEX from the PEDOT matrix. Such devices can be used for long‐term cell culturing and controlled differentiation of hMSCs through electrical stimulation.
Leaf‐like Graphene Oxide with a Carbon Nanotube Midrib and Its Application in Energy Storage Devices
Authors: Guo Ziyang , Wang Jie , Wang Fei , Zhou DanDan , Xia Yongyao , Wang Yonggang
Published: April 2013

Graphene oxide (GO) has recently attracted a great deal of attention because of its heterogeneous chemical and electronic structures and its consequent exhibition of a wide range of potential applications, such as plastic electronics, optical materials, solar cells, and biosensors. However, its insulating nature also limits its application in some electronic and energy storage devices. In order to further widen the applications of GO, it is necessary to keep its inherent characteristics while improving its conductivity. Here, a novel leaf‐like GO with a carbon nanotube (CNT) midrib is developed using vapor growth carbon fiber (VGCF) through the conventional Hummers method. The CNT midrib provides a natural electron diffusion path for the leaf‐like GO, and therefore, this leaf‐like GO with a CNT midrib displays excellent performance when applied in energy storage devices, including Li‐O2 batteries, Li‐ion batteries, and supercapacitors.
Ex Vivo Human Trabecular Bone Model for Biocompatibility Evaluation of Calcium Phosphate Composites Modified with Spray Dried Biodegradable Microspheres
Authors: Schnieders Julia , Gbureck Uwe , Germershaus Oliver , Kratz Marita , Jones David B. , Kissel Thomas
Published: April 2013

Our aim was to study the suitability of the ex‐vivo human trabecular bone bioreactor ZetOS to test the biocompatibility of calcium phosphate bone cement composites modified with spray dried, drug loaded microspheres. We hypothesized, that this bone bioreactor could be a promising alternative to in vivo assessment of biocompatibility in living human bone over a defined time period. Composites consisting of tetracycline loaded poly(lactic‐co‐glycolic acid) microspheres and calcium phosphate bone cement, were inserted into in vitro cultured human femora head trabecular bone and incubated over 30 days at 37°C in the incubation system. Different biocompatibility parameters, such as lactate dehydrogenase activity, alkaline phosphatase release and the expression of relevant cytokines, IL‐1β, IL‐6, and TNF‐α, were measured in the incubation medium. No significant differences in alkaline phosphatase, osteocalcin, and lactate dehydrogenase activity were measured compared to control samples. Tetracycline was released from the microspheres, delivered and incorporated into newly formed bone. In this study we demonstrated that ex vivo biocompatibility testing using human trabecular bone in a bioreactor is a potential alternative to animal experiments since bone metabolism is still maintained in a physiological environment ex vivo.
Double Gold‐Catalysed Annulation of Indoles by Enynones
Authors: Heffernan Stephen J. , Tellam James P. , Queru Marine E. , Silvanus Andrew C. , Benito David , Mahon Mary F. , Hennessy Alan J. , Andrews Benjamin I. , Carbery David R.
Published: April 2013

The gold‐catalysed double functionalisation of indoles is presented. Enynones are used to annulate indoles via a double sodium tetrachloroaurate‐catalysed process involving a mixture of CH activation and alkyne activation modes of promotion. Good yields for the formation of medicinally relevant [6,5,7]‐tricyclic indoles are realised.
Synthesis of novel photoresponsive molecularly imprinted polymer microspheres with special binding properties
Authors: Li Xiao‐Jing , Zhong Shi‐An , Li Cui‐E
Published: April 2013

An azobenzene‐containing molecularly imprinting polymer microsphere with photoresponsive binding properties toward 2,4‐dichlorophenoxyacetic acid (2,4‐D) was successful prepared via silica surface polymerization. The number‐average diameters of silica and imprinting polymer microsphere are 0.5 and 0.7 μm, respectively. The static adsorption, binding and selectivity experiments were performed to investigate the adsorption properties and recognition characteristics of the polymers for 2,4‐D. The equilibrium adsorptive experiments indicated that 2,4‐D‐SMIP(surface molecularly imprinted polymers) has significantly higher adsorption capacity for 2,4‐D than its nonimprinted polymers (SNIP).The binding constant Kd and apparent maximum number Qmax of the imprinted polymer were determined by Scatchard analysis as 0.054 mmol L−1 and 0.167 mmol g−1, respectively. The result of photoregulated release and uptake of 2,4‐D experiment demonstrated that azo‐containing SMIP can make use of light and change it into mechanical properties to release and take up the template molecules. It means that the SMIP can be controlled by light. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 869‐876, 2013
Effect of the host polymer on the nanomechanical and morphological properties of templated polymer films
Authors: Antwi‐Boampong Sadik , Liu Yuan , Richter Asta , BelBruno Joseph J.
Published: April 2013

Atomic force microscopy and nanoindentation have been applied to the study of thin molecularly templated polymer films. The template was chosen to be the readily hydrogen‐bonded cotinine molecule and three different polymer hosts, Elvamide® nylon, Nylon‐6, and poly(4‐vinylphenol) were compared. The host polymer was shown to affect the nature of the template‐host interaction resulting in varying surface morphologies and differences in the nanohardness. These observations were shown to reflect differences in the underlying interaction chemistry, specifically, whether or not the polymer may be imprinted in the film production process. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 877‐883, 2013
A simple model to explain evolutionary trends of eukaryotic gene architecture and expression
Authors: Catania Francesco , Lynch Michael
Published: April 2013

Enormous phylogenetic variation exists in the number and sizes of introns in protein‐coding genes. Although some consideration has been given to the underlying role of the population‐genetic environment in defining such patterns, the influence of the intracellular environment remains virtually unexplored. Drawing from observations on interactions between co‐transcriptional processes involved in splicing and mRNA 3′‐end formation, a mechanistic model is proposed for splice‐site recognition that challenges the commonly accepted intron‐ and exon‐definition models. Under the suggested model, splicing factors that outcompete 3′‐end processing factors for access to intronic binding sites concurrently favor the recruitment of 3′‐end processing factors at the pre‐mRNA tail. This hypothesis sheds new light on observations such as the intron‐mediated enhancement of gene expression and the negative correlation between intron length and levels of gene expression.
Folding of RNA tertiary structure: Linkages between backbone phosphates, ions, and water
Authors: Draper David E.
Published: April 2013

The functional forms of many RNAs have compact architectures. The placement of phosphates within such structures must be influenced not only by the strong electrostatic repulsion between phosphates, but also by networks of interactions between phosphates, water, and mobile ions. This review first explores what has been learned of the basic thermodynamic constraints on these arrangements from studies of hydration and ions in simple DNA molecules, and then gives an overview of what is known about ion and water interactions with RNA structures. A brief survey of RNA crystal structures identifies several interesting architectures in which closely spaced phosphates share hydration shells or phosphates are buried in environments that provide intramolecular hydrogen bonds or site‐bound cations. Formation of these structures must require strong coupling between the uptake of ions and release of water. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1105–1113, 2013.
Three Carbons for Complexity! Recent Developments of Palladium‐Catalyzed Reactions of Allenes
Authors: Lechel Tilman , Pfrengle Fabian , Reissig Hans‐Ulrich , Zimmer Reinhold
Published: April 2013

The three carbon atoms of allene moieties allow unique transformations and rapid generation of complexity. Not surprisingly, allenes became extremely versatile building blocks in organic synthesis. Transition‐metal‐catalyzed reactions of these cumulene π‐systems have been particularly successful, and many applications in the synthesis of complex products have been reported. This review summarizes the palladium‐catalyzed transformation of allenes published during the last decade. Many of the examples presented are impressive multicomponent processes or cascade reactions involving two or more steps leading to molecular complexity in simple one‐pot operations. Consequently, several reactions have been developed with the goal of delivering new synthetic routes to natural products.
Formation of Trinuclear Rhodium‐Hydride Complexes [{Rh(PP*)H}3‐ (μ2‐H)3(μ3‐H)][anion]2—During Asymmetric Hydrogenation?
Authors: Kohrt C. , Baumann W. , Spannenberg A. , Drexler H.‐J. , Gridnev I. D. , Heller D.
Published: April 2013

Recently described and fully characterized trinuclear rhodium‐hydride complexes [{Rh(PP*)H}3(μ2‐H)3(μ3‐H)][anion]2 have been investigated with respect to their formation and role under the conditions of asymmetric hydrogenation. Catalyst–substrate complexes with mac (methyl (Z)‐ N‐acetylaminocinnamate) ([Rh(tBu‐BisP*)(mac)]BF4, [Rh(Tangphos)(mac)]BF4, [Rh(Me‐BPE)(mac)]BF4, [Rh(DCPE)(mac)]BF4, [Rh(DCPB)(mac)]BF4), as well as rhodium‐hydride species, both mono‐([Rh(Tangphos)‐ H2(MeOH)2]BF4, [Rh(Me‐BPE)H2(MeOH)2]BF4), and dinuclear ([{Rh(DCPE)H}2(μ2‐H)3]BF4, [{Rh(DCPB)H}2(μ2‐H)3]BF4), are described. A plausible reaction sequence for the formation of the trinuclear rhodium‐hydride complexes is discussed. Evidence is provided that the presence of multinuclear rhodium‐hydride complexes should be taken into account when discussing the mechanism of rhodium‐promoted asymmetric hydrogenation.
Screening the Thermodynamics of Trimethylaluminum‐Hydrolysis Products and Their Co‐Catalytic Performance in Olefin‐Polymerization Catalysis
Authors: Linnolahti Mikko , Laine Anniina , Pakkanen Tapani A.
Published: April 2013

Herein, we introduce an approach for the computational screening of stoichiometric reactions between trimethylaluminum (TMA) and water. The thermodynamic products of these reactions are methylaluminoxanes (MAOs) with different compositions, which have the general formula (AlOMe)n(AlMe3)m, in which n describes the degree of oligomerization and m is the number of associated TMA molecules. These reaction products were thoroughly explored up to n=4, thus demonstrating the thermodynamically preferable association of up to four AlMe3 molecules, that is, TMA molecules in their monomeric form. The relative Lewis acidities of the Al sites in these MAOs were systematically explored and we found that the associated TMA molecules were a key ingredient for co‐catalytic activity in olefin‐polymerization catalysis. This conclusion was supported by computational studies on catalyst activation, which revealed an exergonic insertion of ethene into the metallocene/MAO complex.
Carbon Dots Prepared by Hydrothermal Treatment of Dopamine as an Effective Fluorescent Sensing Platform for the Label‐Free Detection of Iron(III) Ions and Dopamine
Authors: Qu Konggang , Wang Jiasi , Ren Jinsong , Qu Xiaogang
Published: April 2013

A facile, economic and green one‐step hydrothermal synthesis route using dopamine as source towards photoluminescent carbon nanoparticles (CNPs) is proposed. The as‐prepared CNPs have an average size about 3.8 nm. The emission spectra of the CNPs are broad, ranging from approximately 380 (purple) to approximately 525 nm (green), depending on the excitation wavelengths. Due to the favorable optical properties, the CNPs can readily enter into A549 cells and has been used for multicolor biolabeling and bioimaging. Most importantly, the as‐prepared CNPs contain distinctive catechol groups on their surfaces. Due to the special response of catechol groups to Fe3+ ions, we further demonstrate that such wholly new CNPs can serve as a very effective fluorescent sensing platform for label‐free sensitive and selective detection of Fe3+ ions and dopamine with a detection limit as low as 0.32 μM and 68 nM, respectively. The new “mix‐and‐detect” strategy is simple, green, and exhibits high sensitivity and selectivity. The present method was also applied to the determination of Fe3+ ions in real water samples and dopamine in human urine and serum samples successfully.
Crystal Structures and Phase‐Transition Dynamics of Cobaltocenium Salts with Bis(perfluoroalkylsulfonyl)amide Anions: Remarkable Odd–Even Effect of the Fluorocarbon Chains in the Anion
Authors: Mochida Tomoyuki , Funasako Yusuke , Inagaki Takashi , Li Meng‐Jiao , Asahara Kotaro , Kuwahara Daisuke
Published: April 2013

Crystal structures and thermal properties of cobaltocenium salts with bis(perfluoroalkylsulfonyl)amide (CnF2n+1SO2)2N anions [n=0 (1), 1 (1 a), 2 (1 b), 3 (1 c), and 4 (1 d)] and the 1,1,2,2,3,3‐hexafluoropropane‐1,3‐disulfonylamide anion (2) were investigated. In these solids, the cations are surrounded by four anions around their C5 axis, and stacking of these local structures forms two kinds of assembled structures. In the salts with even n (1, 1 b, and 1 d), the cation and anion are arranged alternately to form mixed‐stack columns in the crystal. In contrast, in the salts with odd n (1 a and 1 c), the cations and anions independently form segregated‐stack columns. An odd–even effect was also observed in the sum of the phase‐change entropies from crystal to melt. All of the salts exhibited phase transitions in the solid state. The phase transitions to the lowest‐temperature phase in 1, 1 a, and 2 are accompanied by order–disorder of the anions and symmetry lowering of the space group, which results in the formation of an ion pair. Solid‐state 13C NMR measurements on 1 a and 1 b revealed enhanced molecular motions of the cation in the higher‐temperature phases.
Indirect Transformation of Coordination‐Polymer Particles into Magnetic Carbon‐Coated Mn3O4 (Mn3O4@C) Nanowires for Supercapacitor Electrodes with Good Cycling Performance
Authors: Wang Kuaibing , Ma Xiaoyan , Zhang Zhiyang , Zheng Mingbo , Geng Zhirong , Wang Zhilin
Published: April 2013

Carbon‐coated Mn3O4 nanowires (Mn3O4@C NWs) have been synthesized by the reduction of well‐shaped carbon‐coated bixbyite networks and characterized by TEM, X‐ray diffraction, X‐ray photoelectron spectroscopy, and electrochemical experiments. To assess the properties of 1D carbon‐coated nanowires for their use in supercapacitors, cyclic voltammetry and galvanostatic charging–discharging measurements were performed. Mn3O4@C NWs could be charged and discharged faster and had higher capacitance than bare Mn3O4 nanostructures and other commercial materials. The capacitance of the Mn3O4@C NWs was 92 % retained after 3000 cycles at a charging rate of 5 A g−1. This improvement can be attributed to the carbon shells, which promote fast Faradaic charging and discharging of the interior Mn3O4 core and also act as barriers to protect the inner core. These Mn3O4@C NWs could be a promising candidate material for high‐capacity, low‐cost, and environmentally friendly electrodes for supercapacitors. In addition, the magnetic properties of the as‐synthesized samples are also reported to investigate the influence of the carbon coating.