bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Power Prospects in the USA: The Continuing Problem of the Waste Issue
Authors: Bezdek Roger H.
Published: April 2009

This paper addresses two questions concerning the economics and prospects for nuclear power in the USA: 1) What is the long term economic future of nuclear energy? 2) Is the inability to solve the nuclear waste issue a factor that will limit new nuclear plant development? With respect to the first question, we find that the long term economic future of nuclear energy is uncertain, at best. Despite recent interest in a “nuclear renaissance,” objective, rigorous studies have concluded that, at present, new nuclear power plants are not economically competitive with coal or natural gas for electricity generation and will not be for the foreseeable future. With respect to the second question, we find that the inability to solve the nuclear waste issue will likely limit new nuclear plant development. Nuclear waste disposal poses a serous, seemingly intractable problem for the future of nuclear power, and the waste issue could be a show stopper for new nuclear plants. Thus, while some new nuclear power plants will likely be built in the U.S. over the next two decades, a major “nuclear renaissance” is unlikely.
Potential Impacts of Integrated Oil and Gas Plant on Ambient Air Quality
Authors: Sonibare Jacob Ademola , Ede Precious Nwobidi
Published: April 2009

The ISCST-3 model has been used to study the ground level concentrations of carbon monoxide (CO), oxides of nitrogen (NOX), particulate matter less than 10.0 microns in diameter (PM10) and sulphur dioxide (SO2). The purpose was to predict air quality effects from an integrated oil and gas project (IOGP) proposed for the Niger Delta, Nigeria. The emissions of 12 elevated point sources for criteria air pollutants were considered with eight different scenarios. Both natural gas-fired and diesel (AGO) fired equipment were considered for the identified emission sources. Five years of hourly meteorological observations were used in the prediction of the ground level concentration of the pollutants.

The model outputs show a general maximum ground level concentration between 0.5 – 3.5 km, with easterly and north-easterly receptors having the greatest concentration. The pollutants emitted in the greatest concentration in their order of magnitude were CO, NOx and PM10. Maximum ground level concentration for 1, 8 and 24 – hr periods for CO were below regulatory standards (less than 10 %) for scenarios 1 – 4 when the fuel is natural gas. The 8 – hr ground level concentrations were about 1.3 folds of the World Bank Standard in scenarios 5 – 8 when the fuel sources are switched to AGO. However in these scenarios, the Nigerian environment and petroleum ministries' emission limits were not breached for all the averaging periods. Modelled NOX concentrations were significant in all the scenarios except 3 and 4. Though NOX concentrations were within the standards for all the averaging periods in scenarios 1 – 4, except the 1 – hr limit that was breached in scenarios 1 and 2, these concentrations were about 1.1 – 2.8 folds in all the averaging periods of all the standards in scenarios 5 – 8. The predicted PM10 and SO2 concentrations are all below the guideline limits. If the use of AGO is completely avoided in the entire life of the proposed IOGP, the air quality of its immediate vicinity can be protected. Furthermore, the declaration of a radius 1.75 km natural forest buffer around the plant and continuous monitoring of ground level concentrations of CO, NOX, PM10, and SO2 may further assist in guaranteeing the safety of people in terms of air quality. The study shows the need for policy formulation that will integrate comprehensive cumulative impacts assessment of air quality in the environmental laws regulating the gas development projects in Nigeria.
Public Engagement with Community-Based Energy Service Provision: An Exploratory Case Study
Authors: Devine-Wright Patrick , Devine-Wright Hannah
Published: April 2009

While the adoption of an energy services approach is regarded as an important aspect of a low carbon economy, potentially involving greater consumer participation in delivering energy services, relatively few energy service providers (e.g. Energy Service Companies: ESCOs) exist in the UK, and little research has been conducted upon the kinds of beliefs associated with such organisations by members of the public, including ESCO customers. This research begins to address this research gap by means of a case study of a refurbished, mixed-use development in Linthwaite, Yorkshire: Titanic Mill. The project is notable for claims of carbon neutrality and lower fuel bills, the installation of low carbon technologies and intention to create a resident-owned ESCO (Mill Energy Services). Case study methods included content analysis of materials promulgated by the developers and a group discussion with residents. These suggest that Titanic Mill is characterised by passive rather than active roles for residents in delivering energy services, at both individual and collective levels. Some residents already express disappointment with actual bills, despite developers' claims. It is concluded that co-provision is unlikely to be achieved unless all actors (developers, energy consultants and residents) recast how energy services are conceived and communicated, both visually and verbally. Residents' enthusiasm for rethinking demand feedback, as well as some individuals' willingness to participate in the ESCO, suggest a platform upon which a transformation towards collective co-provision of energy services could occur, in the uncertain and dynamic contexts of a gradually emerging sense of community, and fluctuating energy markets.
Irreproducible Results in Thompson Et Al., “Abrupt Tropical Climate Change: Past and Present” (PNAS 2006)
Authors: McCulloch J. Huston
Published: April 2009

In a prestigious and influential article in the Proceedings of the National Academy of Sciences ( PNAS), Thompson et al. [1] put forward a Tropical Composite Z-score series ( TCZ), purportedly computed from ice core d18O ratios, as evidence of tropical warming over the past 2000 years. This note demonstrates that it bears no replicable linear relationship to the seven series on which they claim it is based, as archived by the authors themselves on the PNAS website. Although TCZ does equal the average of the two Himalayan and Andean component series ( HCZ and ACZ) to within rounding error, HCZ cannot be constructed linearly from the four Himalayan isotope ratio series with an error less than 100 times the expected rounding error, and ACZ cannot be constructed from the three Andean isotope ratio series with an error less than 30 times the expected rounding error.

The authors should provide PNAS with corrected and internally consistent data sets and figures for these series.
Is Climate Change the “Defining Challenge of Our Age”?
Authors: Goklany Indur M.
Published: April 2009

Climate change, some claim, is this century's most important environmental challenge. Mortality estimates for the year 2000 from the World Health Organization (WHO) indicate, however, that a dozen other risk factors contribute more to global mortality and global burden of disease. Moreover, the state-of-the-art British-sponsored fast track assessments (FTAs) of the global impacts of climate change show that through 2085–2100, climate change would contribute less to human health and environmental threats than other risk factors. Climate change is, therefore, unlikely to be the 21stcentury's most important environmental problem. Combining the FTA results with WHO's mortality estimates indicates that halting climate change would reduce cumulative mortality from hunger, malaria, and coastal flooding, by 4–10 percent in 2085 while the Kyoto Protocol would lower it by 0.4–1 percent. FTA results also show that reducing climate change will increase populations-at-risk from water stress and, possibly, threats to biodiversity. But adaptive measures focused specifically on reducing vulnerability to climate sensitive threats would reduce cumulative mortality by 50–75 percent at a fraction of the Kyoto Protocol's cost without adding to risks from water stress or to biodiversity. Such “focused adaptation” would, moreover, reduce major hurdles to the developing world's sustainable economic development, lack of which is the major reason for its vulnerability to climate change (and any other form of adversity). Thus, focused adaptation can combat climate change and advance global well-being, particularly of the world's most vulnerable populations, more effectively than aggressive GHG reductions. Alternatively, these benefits and more — reductions in poverty, and infant and maternal mortality by 50–75%; increased access to safe water and sanitation; and universal literacy — can be obtained by broadly advancing sustainable economic development through policies, institutions and measures (such as those that would meet the UN Millennium Development Goals) at a cost approximating that of the Kyoto Protocol. However, in order to deal with climate change beyond the 2085–2100 timeframe, the paper also recommends expanding research and development of mitigation options, reducing barriers to implementing such options, and active science and monitoring programs to provide early warning of any “dangerous” climate change impacts.
Solar Radiation as Large-Scale Resource for Energy-Short World
Authors: Liu Quanhua , Yu Gengfa , Liu Jue J.
Published: April 2009

Many but not all energy and environmental issues are believed to be consequences of the huge consumption of carbon-based fuels by humanity. This study found that the thermal energy released in 2006 by the complete combustion may be up to 4.84 × 1020 joules. This thermal energy contributes about 14% of the total thermal energy forcing in the atmosphere and ocean. Not only greenhouse gases but also the thermal energy released by fossil fuel burning needs to be considered in climate change studies. Solar energy is a promising clean energy source for solving the issues in energy shortage. We have studied solar energy resources at the Earth's surface and propose eight areas for potential solar power plants. The proposed sites are located in deserts in Southwest Asia, China, Australia, Southern South America, United States and Mexico. We calculate that 10% (assuming a conversion efficiency of 10%) of the solar energy resource over the eight sites is 18 times larger than current global energy consumption. If we could construct a solar energy network as an international cooperative project or store daily solar energy for use at night time, these eight sites could supply 24-hour electric power every day for the whole world. A more realistic approach to generate electricity at night and during cloudy days would be to store solar heat energy for use on demand.
Can Screening Measurements of Building Insulation Be Made Easier and More Convenient?
Authors: Dodd George , Schmid Gian , Li Ming
Published: April 2009

Noise complaints in New Zealand suggest that multi-family domestic buildings are not providing for the sound insulation needs associated with modern ways of living. We argue that verification measurements should be more widely encouraged. The research described is aimed at developing screening techniques which are convenient and easy to carry out. The approach is to reduce measurement effort by minimising the amount and weight of equipment needed. It is demonstrated that airborne measurements are possible without using a loudspeaker source – for example using a tapping machine on a “radiation” box. Also it is shown that impact insulation can, in principle, be predicted from airborne insulation measurements alone i.e. without the use of a tapping machine. This requires a library of ‘corrections' factors. Values for some typical floor constructions and coverings are presented. Finally we demonstrate that a lightweight, single hammer, tapping machine can satisfactorily measure standardised impact sound pressure levels.
Impact Sound Transmission through Floor/Ceiling Systems
Authors: Scelo Thomas
Published: April 2009

The mechanisms responsible for the transmission of sound in building elements such as floor/ceiling systems are complex and not yet fully understood. In an attempt to understand some of these phenomena, an analytical model was developed for finite and non-periodical floor/ceiling systems to predict their low frequency response to impact excitations. The finite dimensions of the structure are taken into consideration by adopting a modal approach whereby the displacements and pressure fields are expanded into infinite series of admissible functions. The solution relies neither on the periodicity of the stiffened ceiling panels or suspension system nor on the infinite extend of the floor. The paper presents briefly the modelling approach leading to the prediction of the quadratic vibration velocity of the ceiling panel. Finally, comparisons are made between measurements and prediction.
Meta-Material Sound Insulation
Authors: Wester Eric C. , Brémaud Xavier , Smith Bryan
Published: April 2009

This paper describes a novel class of meta-materials that exhibit significantly greater transmission loss than conventional sound insulation systems of similar size and weight over selected frequency bands. This is achieved by the action of small resonator elements distributed throughout the wall at spacings much smaller than the wavelength of structural vibrations in the base wall material. The research reported here is at an early stage. Experiments are described which demonstrate enhanced transmission loss in small proof-of-concept samples and a simple theoretical model is presented.
The fraction of RNA that folds into the correct branched secondary structure determines hepatitis delta virus type 3 RNA editing levels
Authors: Linnstaedt Sarah D. , Kasprzak Wojciech K. , Shapiro Bruce A. , Casey John L.
Published: April 2009

RNA editing by the host RNA adenosine deaminase ADAR1 at the amber/W site of hepatitis delta virus RNA plays a central role in the viral replication cycle by affecting the balance between viral RNA synthesis and packaging. Previously, we found that HDV genotype III (HDV-3) RNA can form two secondary structures following transcription: an unbranched rod structure, which is characteristic of HDV, and a metastable branched structure that serves as the substrate for editing. The unstable nature of the branched editing substrate structure raised the possibility that structural dynamics of the RNA following transcription could determine the rate at which editing occurs. Here, editing and its control are examined in two HDV-3 isolates, from Peru and Ecuador. Analysis of editing in vitro by ADAR1 indicated that the branched structure formed by RNA derived from the Peruvian isolate is edited more efficiently than that from the Ecuadorian isolate. In contrast, in the context of replication, Peruvian RNA is edited less efficiently than RNA containing Ecuadorian sequences. Computational analyses of RNA folding using the massively parallel genetic algorithm (MPGAfold) indicated that the Peruvian RNA is less likely to form the branched structure required for editing than the Ecuadorian isolate. This difference was confirmed by in vitro transcription of these RNAs. Overall, our data indicate that HDV-3 controls RNA editing levels via (1) the fraction of the RNA that folds, during transcription, into the metastable branched structure required for editing and (2) the efficiency with which ADAR1 edits this branched substrate RNA.
SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and telomerase RNPs
Authors: Grozdanov Petar N. , Roy Sujayita , Kittur Nupur , Meier U. Thomas
Published: April 2009

Assembly of H/ACA RNPs in yeast is aided by at least two accessory factors, Naf1p and Shq1p. Although the function of Naf1p and its human ortholog NAF1 has been delineated in detail, that of Shq1p and its putative human ortholog SHQ1 remains obscure. We demonstrate that SHQ1 indeed functions in the biogenesis of human H/ACA RNPs and we dissect its mechanism of action. Like NAF1, SHQ1 binds the major H/ACA core protein and pseudouridine synthase NAP57 (aka dyskerin) but precedes the assembly role of NAF1 at nascent H/ACA RNAs because the interaction of SHQ1 with NAP57 in vivo and in vitro precludes that of NAF1 and of the other H/ACA core proteins that are present at the sites of H/ACA RNA transcription. The N-terminal heat shock protein 20-like CS domain of SHQ1 is dispensable for NAP57 binding. Consistent with its role as an assembly factor, SHQ1 localizes to the nucleoplasm and is excluded from nucleoli and Cajal bodies, the sites of mature H/ACA RNPs. In an in vitro assembly system of functional H/ACA RNPs that is dependent on NAF1, excess recombinant SHQ1 interferes with assembly. Importantly, knockdown of cellular SHQ1 prevents accumulation of a newly synthesized H/ACA reporter RNA and generally reduces the levels of endogenous H/ACA RNAs including telomerase RNA. In summary, the sequential action of SHQ1 and NAF1 is required for functional assembly of H/ACA RNPs in vivo and in vitro. This step-wise process could serve as an efficient means of quality control during H/ACA RNP assembly.
Post-transcriptional control of DGCR8 expression by the Microprocessor
Authors: Triboulet Robinson , Chang Hao-Ming , LaPierre Robert J. , Gregory Richard I.
Published: April 2009

The Microprocessor, comprising the RNase III Drosha and the double-stranded RNA binding protein DGCR8, is essential for microRNA (miRNA) biogenesis. In the miRNA processing pathway certain hairpin structures within primary miRNA (pri-miRNA) transcripts are specifically cleaved by the Microprocessor to release ∼60–70-nucleotide precursor miRNA (pre-miRNA) intermediates. Although both Drosha and DGCR8 are required for Microprocessor activity, the mechanisms regulating the expression of these proteins are unknown. Here we report that the Microprocessor negatively regulates DGCR8 expression. Using in vitro reconstitution and in vivo studies, we demonstrate that a hairpin, localized in the 5′ untranslated region (5′UTR) of DGCR8 mRNA, is cleaved by the Microprocessor. Accordingly, knockdown of Drosha leads to an increase in DGCR8 mRNA and protein levels in cells. Furthermore, we found that the DGCR8 5′UTR confers Microprocessor-dependent repression of a luciferase reporter gene in vivo. Our results uncover a novel feedback loop that regulates DGCR8 levels.
A C-terminal silencing domain in GW182 is essential for miRNA function
Authors: Eulalio Ana , Helms Sigrun , Fritzsch Christoph , Fauser Maria , Izaurralde Elisa
Published: April 2009

Proteins of the GW182 family are essential for miRNA-mediated gene silencing in animal cells; they interact with Argonaute proteins (AGOs) and are required for both the translational repression and mRNA degradation mediated by miRNAs. To gain insight into the role of the GW182–AGO1 interaction in silencing, we generated protein mutants that do not interact and tested them in complementation assays. We show that silencing of miRNA targets requires the N-terminal domain of GW182, which interacts with AGO1 through multiple glycine–tryptophan (GW)-repeats. Indeed, a GW182 mutant that does not interact with AGO1 cannot rescue silencing in cells depleted of endogenous GW182. Conversely, silencing is impaired by mutations in AGO1 that strongly reduce the interaction with GW182 but not with miRNAs. We further show that a GW182 mutant that does not localize to P-bodies but interacts with AGO1 rescues silencing in GW182-depleted cells, even though in these cells, AGO1 also fails to localize to P-bodies. Finally, we show that in addition to the N-terminal AGO1-binding domain, the middle and C-terminal regions of GW182 (referred to as the bipartite silencing domain) are essential for silencing. Together our results indicate that miRNA silencing in animal cells is mediated by AGO1 in complex with GW182, and that P-body localization is not required for silencing.
Structure–activity relationships in Kluyveromyces lactis γ-toxin, a eukaryal tRNA anticodon nuclease
Authors: Keppetipola Niroshika , Jain Ruchi , Meineke Birthe , Diver Melinda , Shuman Stewart
Published: April 2009

tRNA anticodon damage inflicted by secreted ribotoxins such as Kluyveromyces lactis γ-toxin and bacterial colicins underlies a rudimentary innate immune system that distinguishes self from nonself species. The intracellular expression of γ-toxin (a 232-amino acid polypeptide) arrests the growth of Saccharomyces cerevisiae by incising a single RNA phosphodiester 3′ of the modified wobble base of tRNAGlu. Fungal γ-toxin bears no primary structure similarity to any known nuclease and has no plausible homologs in the protein database. To gain insight to γ-toxin's mechanism, we tested the effects of alanine mutations at 62 basic, acidic, and polar amino acids on ribotoxin activity in vivo. We thereby identified 22 essential residues, including 10 lysines, seven arginines, three glutamates, one cysteine, and one histidine (His209, the only histidine present in γ-toxin). Structure–activity relations were gleaned from the effects of 44 conservative substitutions. Recombinant tag-free γ-toxin, a monomeric protein, incised an oligonucleotide corresponding to the anticodon stem–loop of tRNAGlu at a single phosphodiester 3′ of the wobble uridine. The anticodon nuclease was metal independent. RNA cleavage was abolished by ribose 2′-H and 2′-F modifications of the wobble uridine. Mutating His209 to alanine, glutamine, or asparagine abolished nuclease activity. We propose that γ-toxin catalyzes an RNase A-like transesterification reaction that relies on His209 and a second nonhistidine side chain as general acid–base catalysts.
Momentum and Mean Reversion in Strategic Asset Allocation
Authors: Koijen Ralph S. J. , Rodríguez Juan Carlos , Sbuelz Alessandro
Published: April 2009

We study a dynamic asset allocation problem in which stock returns exhibit short-run momentum and long-run mean reversion. We develop a tractable continuous-time model that captures these two predictability features and derive the optimal investment strategy in closed form. The model predicts negative hedging demands for medium-term investors, and an allocation to stocks that is nonmonotonic in the investor's horizon. Momentum substantially increases the economic value of hedging time variation in investment opportunities. These utility gains are preserved when we impose realistic borrowing and short-sales constraints and allow the investor to trade on a monthly frequency.
The Name-Your-Own-Price Channel in the Travel Industry: An Analytical Exploration
Authors: Wang Tuo , Gal-Or Esther , Chatterjee Rabikar
Published: April 2009

Name-your-own-price (NYOP) retailers, such as Priceline, offer an alternative distribution channel for service providers in the travel industry such as airlines, hotels, and car rental companies. Our research employs an analytical model to identify and understand key trade-offs driving the decision by a service provider to employ an NYOP channel, assuming that such a channel is available. This decision requires the existence of forces that counteract the adverse consequences of cannibalization of sales through traditional posted-price channels. Our analysis provides some insight into these forces. Contracting with the NYOP retailer facilitates market segmentation and price discrimination, and allows for disposal of excess capacity after meeting business travel demand. However, the cost of this flexibility is that the service provider can no longer credibly precommit to maintaining high prices when there is unsold capacity. Also, when contracting with an independent retailer, the service provider is unable to extract the entire revenue generated from NYOP consumers. A key insight from our model is that the rationale for contracting with an NYOP retailer is driven by the uncertainty in business travel demand, not the expectation of excess capacity. Indeed, all else equal, the larger the capacity, the less likely it is that contracting with an NYOP retailer is the right decision on the part of the service provider.
Long-Term Efficacy and Safety of TDM-Assisted Combination of Voriconazole plus Efavirenz in an AIDS Patient with Cryptococcosis and Liver Cirrhosis
Authors: Carbonara Sergio , Regazzi Mario , Ciracì Emanuela , Villani Paola , Stano Francesca , Cusato Maria , Heichen Manuela , Monno Laura
Published: April 2009

Objective

To report the efficacy, tolerability, and pharmacokinetic effects of combined voriconazole and efavirenz treatment administered at therapeutic drug monitoring (TDM)–based adjusted doses to a patient with AIDS, cryptococcosis, and mild liver cirrhosis.

Case Summary

A 40-year-old man with AIDS (hemophiliac, antiretroviral-naïve, plasma HIV-RNA = 290,000 copies/mL, CD4+ lymphocytes = 0), hepatitis C virus–related liver cirrhosis (Child-Pugh class A), and cryptococcal meningitis was failing standard antifungal therapies. He received an antifungal–antiretroviral combination treatment based on the association of voriconazole plus efavirenz. Doses of both drugs were serially adjusted based on their plasma concentrations, which were evaluated at steady-state of each dose combination at least once (week 3.1 or later) as full concentration–time profile (samples collected at 0, 1, 2, 3, 4, 6, 8, 12 h postdose). Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dose adjustment (voriconazole 200 mg twice daily plus efavirenz 300 mg once daily, both administered orally). The patient showed prompt and stable suppression of cryptococcosis and plasma viremia of HIV at long-term follow-up (66 wk), with no significant adverse events.

Discussion

Standard therapies for cryptococcosis in patients with AIDS are often not effective. Voriconazole, despite its promising anticryptococcal efficacy, is currently not approved for cryptococcosis therapy in the US and Europe, nor is it recommended for combination with efavirenz due to the significant pharmacokinetic interactions between the 2 compounds. Thus far, published studies regarding the effects of voriconazole in human cryptococcosis are scarce and none has described the clinical and pharmacokinetic outcomes of a voriconazole/efavirenz combination in patients with AIDS, either with or without liver cirrhosis.

Conlusions

The combination of voriconazole and efavirenz at TDM-assisted doses may represent a valuable therapeutic option in AIDS patients with cryptococcosis and mild liver cirrhosis.
Safety and Effectiveness of Varenicline in a Veteran Population with a High Prevalence of Mental Illness
Authors: Purvis Tara L , Mambourg Scott E , Balvanz Tracie M , Magallon Heather E , Pham Richard H
Published: April 2009

Background

Varenicline is a selective nicotinic receptor partial agonist used to aid in the process of smoking cessation. Research on varenicline's approval for marketing demonstrated that after 12 weeks of treatment, at least 44% of patients successfully quit smoking and, on average, 13% of individuals discontinued therapy due to an adverse drug event (ADE). Growing postmarketing data linked varenicline to an increase in neuropsychiatric symptoms.

Objective

To evaluate the safety profile, specifically psychiatric symptoms, and effectiveness of varenicline in a veteran population and to determine whether there is an association among specific baseline demographics and success rate.

Methods

The study was a retrospective review of a prospective performance measure involving veterans initiated on varenicline. Patients were contacted via telephone throughout treatment and at week 12 for effectiveness follow-up. Smoking history was obtained and medication counseling was provided. The primary endpoint was tobacco cessation between weeks 9 and 12 of therapy. Varenicline's safety profile and discontinuation rates due to ADEs were also analyzed.

Results

Of the 50 patients included in the study, 30% (n = 15) successfully quit smoking and 70% (n = 35) failed therapy (lack of effectiveness, n = 22; intolerability, n = 13). Prevalence of underlying mental illness in the success group (4/15; 27%) versus failure group (20/35; 57%) was statistically significant (p< 0.001). All patients who discontinued therapy due to an increase in mood and behavioral changes (n = 4) had an underlying psychiatric illness. The study results demonstrate a lower success rate and a higher incidence of discontinuation due to an ADE in our veteran population compared with premarketing data. An inverse association was shown between psychiatric disorders and success.

Conclusions

Cautious treatment initiation and close monitoring of veterans initiated on varenicline are warranted. Furthermore, the results from this study demonstrate the need for prospective effectiveness trials to determine the clinical significance of the results.
Structure-activity relationships of antitubercular scalaranes: Heteronemin revisited
Authors: Jaisamut Sunan , Thengyai Suriyan , Yuenyongsawad Supreeya , Karalai Chatchanok , Plubrukarn Anuchit , Suwanborirux Khanit
Published: April 2009

A series of heteronemin-related antitubercular scalaranes, both from natural products and from chemical derivatization, were subjected to structure-activity investigations. Based on the activity profile, three main regions; i.e., the substituted groups hovering over C-19/C-18 and furan moiety, the functionalities in the vicinity of C-16 and the right-hand side of ring D, and the substituted groups on C-12, were speculated as the areas influencing the antitubercular activity of the scalaranes. The results suggested the promising possibility for the further investigation towards the modes of actions and/or target sites of the compounds.
Prospective and Retrospective Memory Complaints in Mild Cognitive Impairment and Mild Alzheimer's Disease
Authors: Eschen Anne , Martin Mike , Gasser Ursula Schreiter , Kliegel Matthias
Published: April 2009

Current management attempts for Alzheimer's disease (AD) focus on the identification of individuals in the preclinical stage. This has led to the development of the diagnostic concept of Mild Cognitive Impairment (MCI), which applies to individuals with declining cognitive abilities but largely preserved everyday functioning. Previous findings indicate that prospective memory deficits are a sensitive marker of preclinical AD and that awareness of prospective memory failures is particularly high, based on its dependence on executive functions. Thus, the goal of this study was to evaluate the usefulness of subjective prospective versus retrospective memory complaints for an initial screening for MCI and their respective associations with executive functions. 71 healthy older adults, 27 MCI patients, and 9 patients with mild AD completed the Prospective and Retrospective Memory Questionnaire (PRMQ) and three executive functions tests. The healthy and the MCI group could not be distinguished by their level of subjective prospective or retrospective memory complaints, but the mild AD patients differed from the other groups by complaining more about retrospective than prospective memory failures. For the healthy older adults, the prospective memory complaints were correlated to an inhibition test, whereas they did not correlate with any of the executive function tests in the MCI patients. In contrast, in both groups the retrospective memory complaints were related to a task switching test. The findings are discussed with respect to differences between the three groups in cognitive abilities, attention to failures of, use of mnemonic aids for, and everyday demands of prospective and retrospective memory.
Design of a Portable Seating Accessory for Airport Maintenance Workers
Authors: Martínez Mercedes , Jasso José Luis , Cruz Víctor Manuel , Iturbide Fernando , Pérez Dora Miriam , Estrada Jacqueline
Published: April 2009

Maintenance of airport runway and taxiway lighting and visual aid systems requires workers to sit or squat on the ground for long periods, sometimes as much as five hours a day, causing pain in their waists and calves. This article describes a device we developed for Mexico's Airports and Auxiliary Services to reduce discomfort for maintenance workers.
A Novel Function for p53: Regulation of Growth Cone Motility through Interaction with Rho Kinase
Authors: Qin Qingyu , Baudry Michel , Liao Guanghong , Noniyev Albert , Galeano James , Bi Xiaoning
Published: April 2009

The transcription factor p53 suppresses tumorgenesis by regulating cell proliferation and migration. We investigated whether p53 could also control cell motility in postmitotic neurons. p53 isoforms recognized by phospho-p53-specific (at Ser-15) or “mutant” conformation-specific antibodies were highly and specifically expressed in axons and axonal growth cones in primary hippocampal neurons. Inhibition of p53 function by inhibitors, small interfering RNAs, or by dominant-negative forms, induced axonal growth cone collapse, whereas p53 overexpression led to larger growth cones. Furthermore, deletion of the p53 nuclear export signal blocked its axonal distribution and induced growth cone collapse. p53 inhibition-induced axonal growth cone collapse was significantly reduced by the Rho kinase (ROCK) inhibitor, Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide]. Our results reveal a new function for p53 as a critical regulator of axonal growth cone behavior by suppressing ROCK activity.
Learning Signals from the Superior Colliculus for Adaptation of Saccadic Eye Movements in the Monkey
Authors: Kaku Yuki , Yoshida Kaoru , Iwamoto Yoshiki
Published: April 2009

Vital to motor learning is information about movement error. Using this information, the brain creates neural learning signals that instruct a plasticity mechanism to produce appropriate behavioral learning. Little is known, however, about brain structures that generate learning signals for voluntary movements. Here we show that signals from the superior colliculus (SC) can drive learning in saccadic eye movements in the monkey. Electrical stimulation of the SC deeper layers, subthreshold for evoking saccades, was applied immediately (∼60 ms) after the end of horizontal saccades in one or both directions. The target disappeared during saccades and remained invisible for 1 s to eliminate effects of postsaccadic visual information. Repetitive pairing of saccades with SC stimulation produced a marked, two-dimensional shift in movement endpoint relative to the target location. The elicited endpoint shift took a gradual, approximately exponential course over several hundred saccades as in visually induced saccade adaptation. The shift in movement endpoint remained nearly unchanged after stimulation was discontinued, indicating involvement of neuronal plasticity. When both rightward and leftward saccades were paired with stimulation, their endpoints shifted in similar directions. The endpoint shift was directed contralaterally to the stimulated SC. The direction and size of the endpoint shift depended on the stimulation site in the SC. We propose that the SC, a brainstem structure long known to be crucial for saccade execution, is involved in motor learning and sends signals that dictate the direction of adaptive shift in saccade endpoint.
Cross-Seeding Fibrillation of Q/N-Rich Proteins Offers New Pathomechanism of Polyglutamine Diseases
Authors: Furukawa Yoshiaki , Kaneko Kumi , Matsumoto Gen , Kurosawa Masaru , Nukina Nobuyuki
Published: April 2009

A pathological hallmark of the Huntington's disease (HD) is intracellular inclusions containing a huntingtin (Htt) protein with an elongated polyglutamine tract. Aggregation of mutant Htt causes abnormal protein–protein interactions, and the functional dysregulation of aggregate-interacting proteins (AIPs) has been proposed as a pathomechanism of HD. Despite this, a molecular mechanism remains unknown how Htt aggregates sequester AIPs. We note an RNA-binding protein, TIA-1, as a model of AIPs containing a Q/N-rich sequence and suggest thatin vitroandin vivoHtt fibrillar aggregates function as a structural template for inducing insoluble fibrillation of TIA-1. It is also plausible that such a cross-seeding activity of Htt aggregates represses the physiological function of TIA-1. We thus propose that Htt aggregates act as an intracellular hub for the cross-seeded fibrillation of Q/N-rich AIPs and that a cross-seeding reaction is a molecular origin to cause diverse pathologies in a polyglutamine disease.
Cerebellar Neurons Possess a Vesicular Compartment Structurally and Functionally Similar to Glut4-Storage Vesicles from Peripheral Insulin-Sensitive Tissues
Authors: Bakirtzi Kyriaki , Belfort Gabriel , Lopez-Coviella Ignacio , Kuruppu Darshini , Cao Lei , Abel E. Dale , Brownell Anna-Liisa , Kandror Konstantin V.
Published: April 2009

The insulin-sensitive isoform of the glucose transporting protein, Glut4, is expressed in fat as well as in skeletal and cardiac muscle and is responsible for the effect of insulin on blood glucose clearance. Recent studies have revealed that Glut4 is also expressed in the brain, although the intracellular compartmentalization and regulation of Glut4 in neurons remains unknown. Using sucrose gradient centrifugation, immunoadsorption and immunofluorescence staining, we have shown that Glut4 in the cerebellum is localized in intracellular vesicles that have the sedimentation coefficient, the buoyant density, and the protein composition similar to the insulin-responsive Glut4-storage vesicles from fat and skeletal muscle cells. In cultured cerebellar neurons, insulin stimulates glucose uptake and causes translocation of Glut4 to the cell surface. Using18FDG (18fluoro-2-deoxyglucose) positron emission tomography, we found that physical exercise acutely increases glucose uptake in the cerebellumin vivo. Prolonged physical exercise increases expression of the Glut4 protein in the cerebellum. Our results suggest that neurons have a novel type of translocation-competent vesicular compartment which is regulated by insulin and physical exercise similar to Glut4-storage vesicles in peripheral insulin target tissues.
Two Mechanisms for Task Switching in the Prefrontal Cortex
Authors: Hyafil Alexandre , Summerfield Christopher , Koechlin Etienne
Published: April 2009

Measuring the cognitive and neural sequelae of switching between tasks permits a window into the flexible functioning of the executive control system. Prolonged reaction times (RTs) after task switches are accompanied by increases in brain activity in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC), but the contribution made by these regions to task level control remains controversial. Here, subjects performed a hybrid spatial Stroop/task-switching paradigm, requiring them to respond with a joystick movement to congruent or incongruent spatial/verbal cues. Relative to the previous trial, the active task either switched or remained the same. Calculating switch costs as a function of current and previous trial congruency, we observed both a general RT increase on every switch trial, and additional slowing and impairment to performance when the switch occurred on the second of two successive incongruent trials (iItrials). Imaging data revealed corresponding neural concomitants of these two switch costs: the ACC was activated by task switches regardless of trial type (including congruent trials in which task-relevant and task-irrelevant information did not clash), whereas the caudal dlPFC exhibited a switch cost that was unique toiItrials. We argue that the ACC configures the priorities associated with a new task, whereas the dlPFC tackles interference from recently active, rivalrous task sets. These data contribute to a literature arguing that human cognitive flexibility benefits from the setting of new priorities for future action as well as the overcoming of interference from previously active task sets.
Identification of Candidate Genes and Gene Networks Specifically Associated with Analgesic Tolerance to Morphine
Authors: Tapocik Jenica D. , Letwin Noah , Mayo Cheryl L. , Frank Bryan , Luu Troung , Achinike Ovokeraye , House Carrie , Williams Russell , Elmer Greg I. , Lee Norman H.
Published: April 2009

Chronic morphine administration may alter the expression of hundreds to thousands of genes. However, only a subset of these genes is likely involved in analgesic tolerance. In this report, we used a behavior genetics strategy to identify candidate genes specifically linked to the development of morphine tolerance. Two inbred genotypes [C57BL/6J (B6), DBA2/J (D2)] and two reciprocal congenic genotypes (B6D2, D2B6) with the proximal region of chromosome 10 (Chr10) introgressed into opposing backgrounds served as the behavior genetic filter. Tolerance after therapeutically relevant doses of morphine developed most rapidly in the B6 followed by the B6D2 genotype and did not develop in the D2 mice and only slightly in the D2B6 animals indicating a strong influence of the proximal region of Chr10 in the development of tolerance. Gene expression profiling and pattern matching identified 64, 53, 86, and 123 predisposition genes and 81, 96, 106, and 82 tolerance genes in the periaqueductal gray (PAG), prefrontal cortex, temporal lobe, and ventral striatum, respectively. A potential gene network was identified in the PAG in which 19 of the 34 genes were strongly associated with tolerance. Eleven of the network genes were found to reside in quantitative trait loci previously associated with morphine-related behaviors, whereas seven were predictive of tolerance (morphine-naive condition). Overall, the genes modified by chronic morphine administration show a strong presence in canonical pathways representative of neuroadaptation. A potentially significant role for the micro-RNA and epigenetic mechanisms in response to chronic administration of pharmacologically relevant doses of morphine was highlighted by candidate genes Dicer and H19.
Role of Protein Kinase C in the Induction and Maintenance of Serotonin-Dependent Enhancement of the Glutamate Response in Isolated Siphon Motor Neurons ofAplysia californica
Authors: Villareal Greg , Li Quan , Cai Diancai , Fink Ann E. , Lim Travis , Bougie Joanna K. , Sossin Wayne S. , Glanzman David L.
Published: April 2009

Serotonin (5-HT) mediates learning-related facilitation of sensorimotor synapses inAplysia californica. Under some circumstances 5-HT-dependent facilitation requires the activity of protein kinase C (PKC). One critical site of PKC's contribution to 5-HT-dependent synaptic facilitation is the presynaptic sensory neuron. Here, we provide evidence that postsynaptic PKC also contributes to synaptic facilitation. We investigated the contribution of PKC to enhancement of the glutamate-evoked potential (Glu-EP) in isolated siphon motor neurons in cell culture. A 10 min application of either 5-HT or phorbol ester, which activates PKC, produced persistent (> 50 min) enhancement of the Glu-EP. Chelerythrine and bisindolylmaleimide-1 (Bis), two inhibitors of PKC, both blocked the induction of 5-HT-dependent enhancement. An inhibitor of calpain, a calcium-dependent protease, also blocked 5-HT's effect. Interestingly, whereas chelerythrine blocked maintenance of the enhancement, Bis did not. Because Bis has greater selectivity for conventional and novel isoforms of PKC than for atypical isoforms, this result implicates an atypical isoform in the maintenance of 5-HT's effect. Although induction of enhancement of the Glu-EP requires protein synthesis (Villareal et al., 2007), we found that maintenance of the enhancement does not. Maintenance of 5-HT-dependent enhancement appears to be mediated by a PKM-type fragment generated by calpain-dependent proteolysis of atypical PKC. Together, our results suggest that 5-HT treatment triggers two phases of PKC activity within the motor neuron, an early phase that may involve conventional, novel or atypical isoforms of PKC, and a later phase that selectively involves an atypical isoform.
The Hippocampus Codes the Uncertainty of Cue–Outcome Associations: An Intracranial Electrophysiological Study in Humans
Authors: Vanni-Mercier Giovanna , Mauguière François , Isnard Jean , Dreher Jean-Claude
Published: April 2009

Learning to predict upcoming outcomes based on environmental cues is essential for adaptative behavior. In monkeys, midbrain dopaminergic neurons code two statistical properties of reward: a prediction error at the outcome and uncertainty during the delay period between cues and outcomes. Although the hippocampus is sensitive to reward processing, and hippocampal–midbrain functional interactions are well documented, it is unknown whether it also codes the statistical properties of reward information. To address this question, we recorded local field potentials from intracranial electrodes in human hippocampus while subjects learned to associate cues of slot machines with various monetary reward probabilities (P). We found that the amplitudes of negative event-related potentials covaried with uncertainty at the outcome, being maximal forP= 0.5 and minimal forP= 0 andP= 1, regardless of winning or not. These results show that the hippocampus computes an uncertainty signal that may constitute a fundamental mechanism underlying the role of this brain region in a number of functions, including attention-based learning, associative learning, probabilistic classification, and binding of stimulus elements.
Staircase Currents in Motoneurons: Insight into the Spatial Arrangement of Calcium Channels in the Dendritic Tree
Authors: Carlin Kevin P. , Bui Tuan V. , Dai Yue , Brownstone Robert M.
Published: April 2009

In spinal motoneurons, activation of dendritically located depolarizing conductances can lead to amplification of synaptic inputs and the production of plateau potentials. Immunohistochemical and computational studies have implicated dendritic CaV1.3 channels in this amplification and suggest that CaV1.3 channels in spinal motoneurons may be organized in clusters in the dendritic tree. Our goal was to provide physiological evidence for the presence of multiple discrete clusters of voltage-gated calcium channels in spinal motoneurons and to explore the spatial arrangement of these clusters in the dendritic tree. We recorded voltage-gated calcium currents from spinal motoneurons in slices of mature mouse spinal cords. We demonstrate that single somatic voltage-clamp steps can elicit multiple inward currents with varying delays to onset, resulting in a current with a “staircase”-like appearance. Recordings from cultured dorsal root ganglion cells at different stages of neurite development provide evidence that these currents arise from the unclamped portions of the dendritic tree. Finally, both voltage- and current-clamp data were used to constrain computer models of a motoneuron. The resultant simulations impose two conditions on the spatial distribution of CaVchannels in motoneuron dendrites: one of asymmetry relative to the soma and another of spatial separation between clusters of CaVchannels. We propose that this compartmentalization would provide motoneurons with the ability to process multiple sources of input in parallel and integrate this processed information to produce appropriate trains of action potentials for the intended motor behavior.