bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondria and Huntington's Disease Pathogenesis
Authors: Browne Susan E.
Published: July 2010

A mechanistic link between cellular energetic defects and the pathogenesis of Huntington's disease (HD) has long been hypothesized based on the cardinal observations of progressive weight loss in patients and metabolic defects in brain and muscle. Identification of respiratory chain deficits in HD postmortem brain led to the use of mitochondrial complex II inhibitors to generate acute toxicity models that replicate aspects of HD striatal pathology in vivo. Subsequently, the generation of progressive genetic animal models has enabled characterization of numerous cellular and systematic changes over disease etiology, including mitochondrial modifications that impact cerebral metabolism, calcium handling, oxidative damage, and apoptotic cascades. This review focuses on how HD animal models have influenced our understanding of mechanisms underlying HD pathogenesis, concentrating on insight gained into the roles of mitochondria in disease etiology. One outstanding question concerns the hierarchy of mitochondrial alterations in the cascade of events following mutant huntingtin (mhtt)‐induced toxicity. One hypothesis is that a direct interaction of mhtt with mitochondria may trigger the neuronal damage and degeneration that occurs in HD. While there is evidence that mhtt associates with mitochondria, deleterious consequences of this interaction have not yet been established. Contrary evidence suggests that a primary nuclear action of mhtt may detrimentally influence mitochondrial function via effects on gene transcription. Irrespective of whether the principal toxic action of mhtt directly or secondarily impacts mitochondria, the repercussions of sufficient mitochondrial dysfunction are catastrophic to cells and may arguably underlie many of the other disruptions in cellular processes that evolve during HD pathogenesis.
Structural Diversity of Mitochondria
Authors: Mannella Carmen A.
Published: July 2010

Mitochondria display considerable structural diversity particularly in terms of the folding of the energy‐transducing inner membrane. The hypothesis is forwarded that the topology of the mitochondrial inner membrane is not random but rather is a regulated cell parameter. Its effects on internal diffusion of metabolites and soluble proteins can influence such mitochondrial processes as ATP production and protein release during apoptosis. Progress toward understanding the factors that control mitochondrial inner‐membrane curvature and dynamics (fusion and fission) is summarized, with a focus on remodeling events associated with apoptosis and oxidative stress.
Small Molecule Activation of Adaptive Gene Expression
Authors: Ratan Rajiv R. , Siddiq Ambreena , Aminova Leila , Langley Brett , McConoughey Stephen , Karpisheva Ksenia , Lee Hsin‐Hwa , Carmichael Thomas , Kornblum Harley , Coppola Giovanni , Geschwind Daniel H. , Hoke Ahmet , Smirnova Natalya , Rink Cameron , Roy Sashwati , Sen Chandan , Beattie Michael S. , Hart Ron P. , Grumet Martin , Sun Dongming , Freeman Robert S. , Semenza Gregg L. , Gazaryan Irina
Published: July 2010

A major challenge for neurological therapeutics is the development of small molecule drugs that can activate a panoply of downstream pathways without toxicity. Over the past decade our group has shown that a family of enzymes that regulate posttranscriptional and transcriptional adaptive responses to hypoxia are viable targets for neuronal protection and repair. The family is a group of iron, oxygen, and 2‐oxoglutarate‐dependent dioxygenases, known as the HIF prolyl 4‐hydroxylases (HIF PHDs). We have previously shown that pluripotent protection offered by iron chelators is mediated, in part, via the ability of these agents to inhibit the HIF PHDs. Our group and others have implicated the transcriptional activator HIF‐1 in some of the salutary effects of iron chelation‐induced PHD inhibition. While some iron chelators are currently employed in humans for conditions such as hemochromatosis, the diverse utilization of iron in physiological processes in the brain makes the development of HIF activators that do not bind iron a high priority. Here we report the development of a high throughput screen to develop novel HIF activators and/or PHD inhibitors for therapeutic use in the central nervous system (CNS). We show that tilorone, a low‐molecular weight, antiviral, immunomodulatory agent is the most effective activator of the HIF pathway in a neuronal line. We also show that tilorone enhances HIF protein levels and increases the expression of downstream target genes independent of iron chelation and HIF PHD inhibition in vitro. We further demonstrate that tilorone can activate an HIF‐regulated reporter gene in the CNS. These studies confirm that tilorone can penetrate the blood–brain barrier to activate HIF in the CNS. As expected from these findings, we show that tilorone provides effective prophylaxis against permanent ischemic stroke and traumatic spinal cord injury in male rodents. Altogether these findings identify tilorone as a novel and potent modulator of HIF‐mediated gene expression in neurons with neuroprotective properties.
Urocortin 2 Lowers Blood Pressure and Reduces Plasma Catecholamine Levels in Mice with Hyperadrenergic Activity
Authors: Gu Yusu , Zhang Kuixing , Biswas Nilima , Friese Ryan S. , Lin Dennis H. , Mahata Sushil K. , Hoshijima Masahiko , O'Connor Daniel T. , Peterson Kirk L. , Brar Bhawanjit K.
Published: July 2010

Exaggerated adrenergic activity is associated with human hypertension. The peptide urocortin 2 (Ucn 2) inhibits catecholamine synthesis and secretion from adrenal chromaffin cells in vitro and administration to mammals lowers blood pressure (BP). The chromogranin A-null mouse (Chga−/−) manifests systemic hypertension because of excessive catecholamine secretion from the adrenal and decreased catecholamine storage. In the present study, we investigated whether systemic administration of Ucn 2 could reduce BP and adrenal and plasma levels of catecholamines in vivo. Ucn 2 peptide was administered to freely moving, conscious Chga−/− and wild-type control mice. Telemetry and HPLC measured changes in BP and catecholamine levels, respectively. In both groups of mice, Ucn 2 dose-dependently decreased BP, and this effect was mediated by corticotropin factor-receptor type 2. However, in Chga−/− mice, the maximal percentage decrease of systolic BP from basal systolic BP was 37% compared with only a 23% reduction in wild-type mice (P = 0.04). In Chga−/− mice only, Ucn 2 decreased adrenal and plasma levels of catecholamines as well as adrenal levels of tyrosine hydroxylase protein and phosphorylation. In vitro mechanistic studies demonstrated that Ucn 2 reduces both catecholamine secretion and tyrosine hydroxylase promoter activity, suggesting that the exaggerated action of Ucn 2 to reduce BP in the Chga−/− mouse is mediated through inhibition of both catecholamine synthesis and secretion. The data suggest that Ucn 2 may be therapeutically useful in regulating the exaggerated sympathoadrenal function of hyperadrenergic hypertension.
Improved Survival in Patients with Stage II Adrenocortical Carcinoma Followed Up Prospectively by Specialized Centers
Authors: Fassnacht Martin , Johanssen Sarah , Fenske Wiebke , Weismann Dirk , Agha Ayman , Beuschlein Felix , Führer Dagmar , Jurowich Christian , Quinkler Marcus , Petersenn Stephan , Spahn Martin , Hahner Stefanie , Allolio Bruno ,   on behalf of the German ACC Registry Group, Führer-Sakel Dagmar
Published: July 2010

Context: Median survival in stage II adrenocortical carcinoma (ACC) differs widely in published series ranging between 23 and more than 60 months. We hypothesized that these results may have been affected by a referral bias because many patients may contact specialized centers only after recurrence.

Objective: The objective of the study was a comparison of outcome in patients with stage II ACC who were followed up prospectively early after surgery and were counseled by a specialized center (prospective group) with patients who registered with the German ACC registry later than 4 months after diagnosis (retrospective group).

Patients/Methods: The study was a cohort analysis in 149 adult patients with stage II ACC.

Results: Patients who were followed up prospectively (n = 30) had a lower recurrence rate and a superior 5-yr survival compared with the 119 patients in the retrospective group (30 vs. 74%, P < 0.01 and 96 vs. 55%, P < 0.05, respectively). In the retrospective group, 67% of the patients had registered only after disease recurrence. In the remaining patients, the recurrence rate was low (21%), and the 5-yr survival was greater than 95%. More patients in the prospective group received adjuvant mitotane (53 vs. 16%, P < 0.001), and adjuvant mitotane was associated with improved survival [hazard risk 0.35 (95% confidence interval 0.13–0.97); P = 0.04]. However, the survival advantage was maintained when only patients without mitotane therapy were analyzed.

Conclusions: Patients who are followed up prospectively after surgery for stage II ACC and receive early specialized care have a much better prognosis than previously reported due to a major referral bias in previous series and use of adjuvant mitotane. These findings will impact on the perception of prognosis in newly diagnosed stage II ACC.
Hfp inhibitsDrosophila myctranscription and cell growth in a TFIIH/Hay-dependent manner
Authors: Mitchell Naomi C. , Johanson Timothy M. , Cranna Nicola J. , Er Amanda Lee Jue , Richardson Helena E. , Hannan Ross D. , Quinn Leonie M.
Published: July 2010

An unresolved question regarding the RNA-recognition motif (RRM) protein Half pint (Hfp) has been whether its tumour suppressor behaviour occurs by a transcriptional mechanism or via effects on splicing. The data presented here demonstrate that Hfp achieves cell cycle inhibition via an essential role in the repression of Drosophila myc (dmyc) transcription. We demonstrate that regulation of dmyc requires interaction between the transcriptional repressor Hfp and the DNA helicase subunit of TFIIH, Haywire (Hay). In vivo studies show that Hfp binds to the dmyc promoter and that repression of dmyc transcription requires Hfp. In addition, loss of Hfp results in enhanced cell growth, which depends on the presence of dMyc. This is consistent with Hfp being essential for inhibition of dmyc transcription and cell growth. Further support for Hfp controlling dmyc transcriptionally comes from the demonstration that Hfp physically and genetically interacts with the XPB helicase component of the TFIIH transcription factor complex, Hay, which is required for normal levels of dmyc expression, cell growth and cell cycle progression. Together, these data demonstrate that Hfp is crucial for repression of dmyc, suggesting that a transcriptional, rather than splicing, mechanism underlies the regulation of dMyc and the tumour suppressor behaviour of Hfp.
The Effects of Investing Social Security Funds in the Stock Market When Fixed Costs Prevent Some Households from Holding Stocks
Authors: Abel Andrew B
Published: July 2010

With fixed costs of participating in the stock market, consumers with high income will participate in the stock market, but consumers with lower income will not participate. If a fully funded defined-contribution Social Security system tries to exploit the equity premium by selling a dollar of bonds per capita and buying a dollar of equity per capita, consumers who save but do not participate in the stock market will increase their consumption, thereby reducing saving and capital accumulation. Calibration of a general-equilibrium model indicates that this policy could reduce the aggregate capital stock substantially, by about 50 cents per capita. (JEL H55)
Gamma Discounting
Authors: Weitzman Martin L
Published: July 2010

By incorporating the probability distribution directly into the analysis, this paper proposes a new theoretical approach to resolving the perennial dilemma of being uncertain about what discount rate to use in cost-benefit analysis. A numerical example is constructed from the results of a survey based on the opinions of 2,160 economists. The main finding is that even if every individual believes in a constant discount rate, the wide spread of opinion on what it should be makes the effective social discount rate decline significantly over time. Implications and ramifications of this proposed “gamma-discounting” approach are discussed. (JEL H43)
The Personal Discount Rate: Evidence from Military Downsizing Programs
Authors: Warner John T , Pleeter Saul
Published: July 2010

The military drawdown program of the early 1990's provides an opportunity to obtain estimates of personal discount rates based on large numbers of people making real choices involving large sums. The program offered over 65,000 separatees the choice between an annuity and a lump-sum payment. Despite break-even discount rates exceeding 17 percent, most of the separatees selected the lump sum—saving taxpayers $1.7 billion in separation costs. Estimates of discount rates range from 0 to over 30 percent and vary with education, age, race, sex, number of dependents, ability test score, and the size of payment. (JEL D91)
Naive Diversification Strategies in Defined Contribution Saving Plans
Authors: Benartzi Shlomo , Thaler Richard H
Published: July 2010

There is a worldwide trend toward defined contribution saving plans and growing interest in privatized Social Security plans. In both environments, individuals are given some responsibility to make their own asset-allocation decisions, raising concerns about how well they do at this task. This paper investigates one aspect of the task, namely diversification. We show that some investors follow the “1/n strategy”: they divide their contributions evenly across the funds offered in the plan. Consistent with this naive notion of diversification, we find that the proportion invested in stocks depends strongly on the proportion of stock funds in the plan. (JEL G11, G23, H55)
Vertical Integration, Market Foreclosure, and Consumer Welfare in the Cable Television Industry
Authors: Chipty Tasneem
Published: July 2010

I examine the effects of vertical integration between programming and distribution in the cable television industry. I assess the effects of ownership structure on program offerings, prices, and subscriptions, and I compare consumer welfare across integrated and unintegrated markets. The results of this analysis suggest two general conclusions. First, integrated operators tend to exclude rival program services, suggesting that certain program services cannot gain access to the distribution networks of vertically integrated cable system operators. Second, vertical integration does not harm, and may actually benefit, consumers because of the associated efficiency gains. (JEL L10, L22, L40)
The Optimal Allocation of Prizes in Contests
Authors: Moldovanu Benny , Sela Aner
Published: July 2010

We study a contest with multiple, nonidentical prizes. Participants are privately informed about a parameter (ability) affecting their costs of effort. The contestant with the highest effort wins the first prize, the contestant with the second-highest effort wins the second prize, and so on until all the prizes are allocated. The contest's designer maximizes expected effort. When cost functions are linear or concave in effort, it is optimal to allocate the entire prize sum to a single “first” prize. When cost functions are convex, several positive prizes may be optimal. (JEL D44, J31, D72, D82)
Simulating Fundamental Tax Reform in the United States
Authors: Altig David , Auerbach Alan J , Kotlikoff Laurence J , Smetters Kent A , Walliser Jan
Published: July 2010

This paper uses a new, large-scale, dynamic life-cycle simulation model to compare the welfare and macroeconomic effects of transitions to five fundamental alternatives to the U.S. federal income tax, including a proportional consumption tax and a flat tax. The model incorporates intragenerational heterogeneity and a detailed specification of alternative tax systems. Simulation results project significant long-run increases in output for some reforms. For other reforms, namely those that seek to insulate the poor and initial older generations from adverse welfare changes, long-run output gains are modest. (JEL H20, C68)
Is a Uniform Social Policy Better? Fiscal Federalism and Factor Mobility
Authors: Perotti Roberto
Published: July 2010

This paper develops a two-country model to study two questions. How do the degrees of centralization of redistribution and of factor mobility affect the productive efficiency of the economies? What degrees of centralization of redistribution and of factor mobility are likely to be chosen by majority rule? The model shows that a system of centralized redistribution can lead to less efficient outcomes if labor or capital are not mobile; and an inefficient outcome, with incomplete or no factor mobility, receives a majority of votes in both countries, whenever the structure of labor markets is very different in the two countries. (JEL D72, E62, H50, H77)
Increasing Returns Versus National Product Differentiation as an Explanation for the Pattern of U.S.–Canada Trade
Authors: Head Keith , Ries John
Published: July 2010

We evaluate two alternative models of international trade in differentiated products. An increasing returns model where varieties are linked to firms predicts home market effects: increases in a country's share of demand cause disproportionate increases in its share of output. In contrast, a constant returns model with national product differentiation predicts a less than proportionate increase. We examine a panel of U.S. and Canadian manufacturing industries to test the models. Although we find support for either model, depending on whether we estimate based on within or between variation, the preponderance of the evidence supports national product differentiation. (JEL F12, F15)
Is Free Trade Good for the Environment?
Authors: Antweiler Werner , Copeland Brian R , Taylor M. Scott
Published: July 2010

This paper investigates how openness to international goods markets affects pollution concentrations. We develop a theoretical model to divide trade's impact on pollution into scale, technique, and composition effects and then examine this theory using data on sulfur dioxide concentrations. We find international trade creates relatively small changes in pollution concentrations when it alters the composition of national output. Estimates of the trade-induced technique and scale effects imply a net reduction in pollution from these sources. Combining our estimates of all three effects yields a somewhat surprising conclusion: freer trade appears to be good for the environment. (JEL F11, Q25)
A Theory of Political Transitions
Authors: Acemoglu Daron , Robinson James A
Published: July 2010

We develop a theory of political transitions inspired by the experiences of Western Europe and Latin America. Nondemocratic societies are controlled by a rich elite. The initially disenfranchised poor can contest power by threatening revolution, especially when the opportunity cost is low, for example, during recessions. The threat of revolution may force the elite to democratize. Democracy may not consolidate because it is redistributive, and so gives the elite an incentive to mount a coup. Highly unequal societies are less likely to consolidate democracy, and may end up oscillating between regimes and suffer substantial fiscal volatility. (JEL D72, D74, O15, P16)
Monetary Policy Rules Based on Real-Time Data
Authors: Orphanides Athanasios
Published: July 2010

This paper examines the magnitude of informational problems associated with the implementation and interpretation of simple monetary policy rules. Using Taylor's rule as an example, I demonstrate that real-time policy recommendations differ considerably from those obtained with ex post revised data. Further, estimated policy reaction functions based on ex post revised data provide misleading descriptions of historical policy and obscure the behavior suggested by information available to the Federal Reserve in real time. These results indicate that reliance on the information actually available to policy makers in real time is essential for the analysis of monetary policy rules. (JEL E52, E58)
The Information-Technology Revolution and the Stock Market: Evidence
Authors: Hobijn Bart , Jovanovic Boyan
Published: July 2010

Why did the stock market decline so much in the early 1970's and remain low until the early 1980's? We argue that it was because information technology arrived on the scene and the stock-market incumbents of the day were not ready to implement it. Instead, new firms would bring in the new technology after the mid-1980's. Investors foresaw this in the early 1970's and stock prices fell right away. In our model, new capital destroys old capital, but with a lag. The prospect of this causes the value of the old capital to fall right away. (JEL G12, O16, O33)
Does Money Illusion Matter?
Authors: Fehr Ernst , Tyran Jean-Robert
Published: July 2010

This paper shows that a small amount of individual-level money illusion may cause considerable aggregate nominal inertia after a negative nominal shock. In addition, our results indicate that negative and positive nominal shocks have asymmetric effects because of money illusion. While nominal inertia is quite substantial and long lasting after a negative shock, it is rather small after a positive shock. (JEL C92, E32, E52)
Learning from Experience and Learning from Others: An Exploration of Learning and Spillovers in Wartime Shipbuilding
Authors: Thornton Rebecca Achee , Thompson Peter
Published: July 2010

A new data set facilitates study of learning spillovers in World War II shipbuilding. Our results contain two principal but contrasting themes. First, learning spillovers were a significant source of productivity growth, and may have contributed more than conventional learning effects. Second, the size of the learning externalities across yards, as measured by Spence's θ, were small. These findings, which are not mutually inconsistent, suggest an optimistic view of learning spillovers: they are a significant source of productivity growth, but the market failures induced by learning externalities may be modest. (JEL D24, N72, O3)
The Colonial Origins of Comparative Development: An Empirical Investigation
Authors: Acemoglu Daron , Johnson Simon , Robinson James A
Published: July 2010

We exploit differences in European mortality rates to estimate the effect of institutions on economic performance. Europeans adopted very different colonization policies in different colonies, with different associated institutions. In places where Europeans faced high mortality rates, they could not settle and were more likely to set up extractive institutions. These institutions persisted to the present. Exploiting differences in European mortality rates as an instrument for current institutions, we estimate large effects of institutions on income per capita. Once the effect of institutions is controlled for, countries in Africa or those closer to the equator do not have lower incomes. (JEL O11, P16, P51)
Ten Little Treasures of Game Theory and Ten Intuitive Contradictions
Authors: Goeree Jacob K , Holt Charles A
Published: July 2010

This paper reports laboratory data for games that are played only once. These games span the standard categories: static and dynamic games with complete and incomplete information. For each game, the treasure is a treatment in which behavior conforms nicely to predictions of the Nash equilibrium or relevant refinement. In each case, however, a change in the payoff structure produces a large inconsistency between theoretical predictions and observed behavior. These contradictions are generally consistent with simple intuition based on the interaction of payoff asymmetries and noisy introspection about others' decisions. (JEL C72, C92)
Strategy and PowerPoint: An Inquiry into the Epistemic Culture and Machinery of Strategy Making
Authors: Kaplan Sarah
Published: July 2010

PowerPoint has come to dominate organizational life in general and strategy making in particular. The technology is lauded by its proponents as a powerful tool for communication and excoriated by its critics as dangerously simplifying. This study takes a deeper look into how PowerPoint is mobilized in strategy making through an ethnographic study inside one organization. It treats PowerPoint as a technology embedded in the discursive practices of strategic knowledge production and suggests that these practices make up the epistemic or knowledge culture of the organization. Conceptualizing culture as composed of practices foregrounds the “machineries” of knowing. Results from a genre analysis of PowerPoint use suggest that it should not be characterized simply as effective or ineffective, as current PowerPoint controversies do. Instead, I show how the affordances of PowerPoint enabled the difficult task of collaborating to negotiate meaning in an uncertain environment, creating spaces for discussion, making recombinations possible, allowing for adjustments as ideas evolved, and providing access to a wide range of actors. These affordances also facilitated cartographic efforts to draw boundaries around the scope of a strategy by certifying certain ideas and allowing document owners to include or exclude certain slides or participants. These discursive practices—collaboration and cartography—are part of the “epistemic machinery” of strategy culture. This analysis demonstrates that strategy making is not only about analysis of industry structure, competitive positioning, or resources, as assumed in content-based strategy research, but it is also about how the production and use of PowerPoint documents that shape these ideas.
What I Like About You: A Multilevel Study of Shareholder Discontent with Director Monitoring
Authors: Hillman Amy J. , Shropshire Christine , Certo S. Trevis , Dalton Dan R. , Dalton Catherine M.
Published: July 2010

Each year shareholders, via exercise of their proxy votes, have the opportunity to voice their support or displeasure with firms and director nominees. Examining over 2,000 Fortune 500 director nominees, we explore those indicators available to shareholders at the time of directors' (re)election to provide insight into shareholder discontent with director monitoring. By studying actual voting behaviors, we provide new perspective to understanding director elections as a governance process. Employing a multilevel approach, we find support for agency-theoretic relationships between several firm and director characteristics and shareholder opposition to directors seeking (re)election to the board. At the firm level, we find that CEO compensation level and board size are positively related to the withholding of shareholder votes in director elections, a behavior indicative of shareholder discontent. Complementing these findings, at the director level, we find that affiliated director status, tenure, and number of outside directorships are positively related, and director block ownership is negatively related to shareholder discontent with director monitoring.
More Than Adopters: Competing Influences in the Interlocking Directorate
Authors: Connelly Brian L. , Johnson Jonathan L. , Tihanyi Laszlo , Ellstrand Alan E.
Published: July 2010

This study explores the competing influences of different types of board interlocks on diffusion of a strategic initiative among a population of firms. We examine a broad social network of interlocking directors in U.S. firms over a period of 17 years and consider the likelihood that these firms will adopt a strategy of expansion into China. Results show that ties to adopters that unsuccessfully implement this strategy have a nearly equal and opposing effect on the likelihood of adoption as do ties to those that successfully implement the strategy. Ties to those that do not implement the strategy also have a suppressive effect on the likelihood of adoption. Furthermore, we examine a firm's position in the core-periphery structure of the interlocking directorate, finding that ties to adopters closer to the network core positively affect the likelihood of adoption. We discuss the implications of our study for social network analysis, governance, and internationalization research.
Spurious increase in serum chromogranin A: the role of heterophilic antibodies
Authors: Giovanella Luca , Ceriani Luca
Published: July 2010

Background:The aim of the study was to examine the prevalence of heterophilic antibody (HAb) interference on serum chromogranin A (CgA) measurements.

Methods:Serum CgA was measured in 672 serum samples before and following incubation in heterophilic antibody blocking tubes (HBTs). Results showing more than 3 and 5 SD percentage difference from the original result were considered to be affected by possible or definite HAb interference, respectively. All possible interferences were confirmed or excluded by non-linear or linear dilution tests.

Results:Following HBT treatment, CgA concentrations fell >3 SD percent compared with the original result in seven specimens, six of which also showed non-linear dilution (0.9%). A clinically relevant increase in serum CgA occurred in five patients (0.7%). No samples showed a significant increase of >3 SD percent following HBT treatment.

Conclusions:Interference from HAb occurred in up to 0.9% of sera tested for serum CgA. If an increased CgA result does not fit the clinical picture, pretreatment of serum in HBT tubes may prevent unwarranted investigations or therapies.

Clin Chem Lab Med 2010;48:1497–9.
Investigation on wax-impregnated wood. Part 2: Study of void spaces filled with air by He pycnometry, Hg intrusion porosimetry, and 3D X-ray imaging
Authors: Scholz Gunthard , Zauer Mario , Van den Bulcke Jan , Van Loo Denis , Pfriem Alexander , Van Acker Joris , Militz Holger
Published: July 2010

The quantification of wax and remaining voids filled with air in wax-treated wood has not been described in detail in the literature, although such products are commercially available. In this paper, Scots pine (Pinus sylvestris L.) and beech (Fagus sylvatica L.) samples were impregnated with a hot melting amide wax and characterized. The apparent densities were measured with helium pycnometry and mercury intrusion porosimetry. The pore size distribution was determined by means of mercury intrusion porosimetry and samples were visualized with 3D X-ray tomography. The remaining void spaces were calculated based on the data of all three methods. The apparent densities range from 1.18 to 1.19 g cm-3 for treated pine and from 1.21 to 1.23 g cm-3 for treated beech. As a result of the wax impregnation, the pore volume decreases from 65–68% to 12–13% for pine and from 53–58% to 7–9% for beech. The pore size distribution shifts to smaller pores. The amount of the micropores measured by mercury intrusion porosimetry is overestimated. On the one hand, blocked large pores are compressed by the movement of wax deposits under high pressure during the mercury intrusion porosimetry (“movement-effect”). On the other hand, large pores remain inaccessible or are only accessible via smaller openings (“bottle-neck-effect”). Non-invasive 3D X-ray imaging detects such macropores but the size of the detected pores is limited by the given resolution of the method. Therefore, mercury intrusion porosimetry and X-ray tomography are complementary techniques.
Analysis of water vapour sorption of oleo-thermal modified wood of Acacia mangium and Endospermum malaccense by a parallel exponential kinetics model and according to the Hailwood-Horrobin model
Authors: Jalaludin Zaihan , Hill Callum A.S. , Samsi Hashim W. , Husain Hamdan , Xie Yanjun
Published: July 2010

Two Malaysian hardwoods, acacia (Acacia mangium Wild.) and sesendok (Endospermum malaccense Bent. ex Müll. Arg.) that had been previously subjected to oleo-thermal modification, were studied to determine their dynamic sorption kinetic behaviour. All specimens were thermally modified in palm oil at 180°C, 200°C, and 220°C and 3 h treatment time. Data were analysed using the parallel exponential kinetics (PEK) model, and excellent fits to the experimental data were obtained. The relation between the monolayer water and polylayer water was also examined by the Hailwood-Horrobin (H-H) model at a range of relative humidity (RH) values. The PEK model divides the sorption kinetics curve into a fast and slow sorption processes. Characteristic times of the two processes at various RH showed sorption hysteresis with all of the specimens only in the slow process. However, with mass change data, sorption hysteresis occurred with both the slow and fast processes. By comparing H-H and PEK models, it was found that the fast and slow sorption process of untreated and treated E.
malaccense could possibly be linked, respectively, to monolayer and polylayer formation from 5 to 40% RH. No such correlation was found for A. mangium, however.
Spray Drift Reduction Evaluations of Spray Nozzles Using a Standardized Testing Protocol
Authors: Hoffmann W. Clint , Fritz Bradley K. , Thornburg Jonathan W. , Bagley W. E. , Birchfield Norman B. , Ellenberger Jay
Published: July 2010

The development and testing of drift reduction technologies (DRTs) have come to the forefront of application research in the past few years in the United States. DRTs can be spray nozzles, sprayer modifications, spray delivery assistance, spray property modifiers (adjuvants), and/or landscape modifications. A protocol for testing DRTs in high speed wind tunnels has been previously reported and was expanded to test spray nozzles. This manuscript reports on the initial implementation of the DRT program for conducting DRT evaluations of three spray nozzles under high speed conditions (i.e.,45–65 m/s (100–140 mph)), which are relevant to the aerial application of crop production and protection materials. The spray nozzles were evaluated in the USDA-Agriculture Research Service High Speed Wind Tunnel facility. The droplet size of each of the nozzles with different airspeeds, spray pressures, and orientation was measured with a Sympatec Helos laser diffraction instrument. The droplet size spectra for each test were input in a spray dispersion model (AGDISP), which calculates the downwind drift expected from a typical aerial application scenario. As compared to the reference nozzle, the three spray nozzles reduced spray drift by 70–84 % as compared to the reference nozzle. The nozzles generated spray droplets with volume median diameters 60–80 μm larger than the reference nozzle. One of the aerial application industry’s best management practices (BMPs) is to not spray directly on the downwind edge of a field. The spray swath near this edge is moved upwind (i.e., offset) by 1/2 to 1 swath width. When this BMP was combined with the drift reductions from the spray nozzles, the amount of drift reduction was slightly increased; however, application efficiencies increased to 93–96 %. These results demonstrate the possibility of combining multiple drift reduction techniques and technologies to greatly reduce spray drift.
Intrinsic Connectivity Networks, Alpha Oscillations, and Tonic Alertness: A Simultaneous Electroencephalography/Functional Magnetic Resonance Imaging Study
Authors: Sadaghiani Sepideh , Scheeringa René , Lehongre Katia , Morillon Benjamin , Giraud Anne-Lise , Kleinschmidt Andreas
Published: July 2010

Trial-by-trial variability in perceptual performance on identical stimuli has been related to spontaneous fluctuations in ongoing activity of intrinsic functional connectivity networks (ICNs). In a paradigm requiring sustained vigilance for instance, we previously observed that higher prestimulus activity in a cingulo-insular-thalamic network facilitated subsequent perception. Here, we test our proposed interpretation that this network underpins maintenance of tonic alertness. We used simultaneous acquisition of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) in the absence of any paradigm to test an ensuing hypothesis, namely that spontaneous fluctuations in this ICN′s activity (as measured by fMRI) should show a positive correlation with the electrical signatures of tonic alertness (as recorded by concurrent EEG). We found in human subjects (19 male, 7 female) that activity in a network comprising dorsal anterior cingulate cortex, anterior insula, anterior prefrontal cortex and thalamus is positively correlated with global field power (GFP) of upper alpha band (10–12 Hz) oscillations, the most consistent electrical index of tonic alertness. Conversely, and in line with earlier findings, alpha band power was negatively correlated with activity in another ICN, the so-called dorsal attention network which is most prominently involved in selective spatial attention. We propose that the cingulo-insular-thalamic network serves maintaining tonic alertness through generalized expression of cortical alpha oscillations. Attention is mediated by activity in other systems, e.g., the dorsal attention network for space, selectively disrupts alertness-related suppression and hence manifests as local attenuation of alpha activity.
Rapid Activation of Dormant Presynaptic Terminals by Phorbol Esters
Authors: Chang Chun Yun , Jiang Xiaoping , Moulder Krista L. , Mennerick Steven
Published: July 2010

Presynaptic stimulation stochastically recruits transmission according to the release probability (Pr) of synapses. The majority of central synapses have relatively lowPr, which includes synapses that are completely quiescent presynaptically. The presence of presynaptically dormant versus active terminals presumably increases synaptic malleability when conditions demand synaptic strengthening or weakening, perhaps by triggering second messenger signals. However, whether modulator-mediated potentiation involves recruitment of transmission from dormant terminals remains unclear. Here, by combining electrophysiological and fluorescence imaging approaches, we uncovered rapid presynaptic awakening by select synaptic modulators. A phorbol ester phorbol 12,13-dibutyrate (PDBu) (a diacylglycerol analog), but not forskolin (an adenylyl cyclase activator) or elevated extracellular calcium, recruited neurotransmission from presynaptically dormant synapses. This effect was not dependent on protein kinase C activation. After PDBu-induced awakening, these previously dormant terminals had a synapticPrspectrum similar to basally active synapses naive to PDBu treatment. Dormant terminals did not seem to have properties of nascent or immature synapses, judged by NR2B NMDAR (NMDA receptor) receptor subunit contribution after PDBu-stimulated awakening. Strikingly, synapses rendered inactive by prolonged depolarization, unlike basally dormant synapses, were not awakened by PDBu. These results suggest that the initial release competence of synapses can dictate the acute response to second messenger modulation, and the results suggest multiple pathways to presynaptic dormancy and awakening.
Chronic Systemic Infection Exacerbates Ischemic Brain Damage via a CCL5 (Regulated on Activation, Normal T-Cell Expressed and Secreted)-Mediated Proinflammatory Response in Mice
Authors: Dénes Ádám , Humphreys Neil , Lane Thomas E. , Grencis Richard , Rothwell Nancy
Published: July 2010

Infection and systemic inflammation are risk factors for cerebrovascular diseases and poststroke infections impair outcome in stroke patients, although the mechanisms of their contribution are mostly unknown. No preclinical studies have identified how chronic infection affects ischemic brain damage and which key inflammatory mediators are involved. We used a well established model of gut infection (Trichuris muris) to study how chronic infection contributes to brain injury. We show that, in mice, infection that leads to a chronic Th1-polarized immune response dramatically (60%) exacerbates brain damage caused by experimental stroke. Chronic Th1-type infection resulted in systemic upregulation of proinflammatory mediators and profoundly altered stroke-induced early (40 min to 4 h) and late (48 h) inflammation in the brain and peripheral tissues. Using the same infection, we show that a Th1-, but not Th2-polarized response augments brain injury by increasing the Th1 chemokine CCL5 [regulated on activation, normal T-cell expressed and secreted (RANTES)] systemically. This infection-associated response paralleled altered regulatory T-cell response, accelerated platelet aggregation in brain capillaries, and increased microvascular injury and matrix metalloproteinase activation after stroke. Antibody neutralization of RANTES reversed the effect of chronic infection on brain damage, microvascular MMP-9 activation, and cellular inflammatory response. Our results suggest that chronic infection exacerbates ischemic brain damage via a RANTES-mediated systemic inflammatory response, which leads to delayed resolution of inflammation and augmented microvascular injury in the brain.
Disruption of Peripheral Circadian Timekeeping in a Mouse Model of Huntington's Disease and Its Restoration by Temporally Scheduled Feeding
Authors: Maywood Elizabeth S. , Fraenkel Eloise , McAllister Catherine J. , Wood Nigel , Reddy Akhilesh B. , Hastings Michael H. , Morton A. Jennifer
Published: July 2010

Behavioral circadian rhythms disintegrate progressively in the R6/2 mouse model of Huntington's disease (HD), recapitulating the sleep–wake disturbance seen in HD patients. Here we show that disturbances in circadian pacemaking are not restricted to the brain, but also encompass peripheral metabolic pathways in R6/2 mice. Notably, circadian rhythms of clock-driven genes that are key metabolic outputs in the liver are abolishedin vivo. This deficiency is accompanied by arrhythmic expression of the clock genesCry1andDbp, and a phase-advancedPer2cycle. Compromised circadian metabolic cycles are not, however, a consequence of deficient pacemaking intrinsic to the liver, because when culturedin vitro, R6/2 liver slices exhibit self-sustained circadian bioluminescence rhythms. We therefore propose that compromised metabolic cycles arise from an internal desynchronization secondary to altered feeding patterns and impaired circadian signaling from the central pacemaker of the suprachiasmatic nucleus (SCN). Importantly, the SCN-independent food-entrainable oscillator remains intact in R6/2 mice and, when invoked, can restore daily behavioral cycles and reverse some of the metabolic abnormalities seen in the liver. Disturbances of metabolism have long been thought to be an important feature of HD. Uncoupling liver metabolism from circadian drives will reduce metabolic efficiency and cause imbalances in metabolites known to be deleterious to brain function. Thus, even subtle imbalances in liver function may exacerbate symptoms of HD, where neurological function is already compromised.
Amyloid β Precursor Protein Regulates Male Sexual Behavior
Authors: Park Jin Ho , Bonthius Paul J. , Tsai Houng-Wei , Bekiranov Stefan , Rissman Emilie F.
Published: July 2010

Sexual behavior is variable between individuals, ranging from celibacy to sexual addictions. Within normal populations of individual men, ranging from young to middle aged, testosterone levels do not correlate with libido. To study the genetic mechanisms that contribute to individual differences in male sexual behavior, we used hybrid B6D2F1 male mice, which are a cross between two common inbred strains (C57BL/6J and DBA/2J). Unlike most laboratory rodent species in which male sexual behavior is highly dependent upon gonadal steroids, sexual behavior in a large proportion of these hybrid male mice after castration is independent of gonadal steroid hormones and their receptors; thus, we have the ability to discover novel genes involved in this behavior. Gene expression arrays, validation of gene candidates, and transgenic mice that overexpress one of the genes of interest were used to reveal genes involved in maintenance of male sexual behavior. Several genes related to neuroprotection and neurodegeneration were differentially expressed in the hypothalamus of males that continued to mate after castration. Male mice overexpressing the human form of one of these candidate genes, amyloid β precursor protein (APP), displayed enhanced sexual behavior before castration and maintained sexual activity for a longer duration after castration compared with controls. Our results reveal a novel and unexpected relationship between APP and male sexual behavior. We speculate that declining APP during normal aging in males may contribute to the loss of sexual function.
Long-Lasting Adaptations of the NR2B-Containing NMDA Receptors in the Dorsomedial Striatum Play a Crucial Role in Alcohol Consumption and Relapse
Authors: Wang Jun , Lanfranco Maria Fe , Gibb Stuart L. , Yowell Quinn V. , Carnicella Sebastien , Ron Dorit
Published: July 2010

A growing number of studies suggest that the development of compulsive drug seeking and taking depends on dorsostriatal mechanisms. We previously observed thatex vivoacute exposure of the dorsal striatum to, and withdrawal from, alcohol induces long-term facilitation (LTF) of the activity of NR2B-containing NMDA receptors (NR2B-NMDARs) in a mechanism that requires the Src family protein tyrosine kinase (PTK), Fyn (Wang et al., 2007). In the present study, we first compared alcohol's actions in rat dorsomedial (DMS) and the dorsolateral (DLS) subregions of the striatum, which differ in their anatomical connectivity and function. We found that alcohol-mediated induction of LTF of NR2B-NMDAR activity is centered in the DMS. Next, we tested whetherin vivoexposure of rats to alcohol leads to long-term adaptations of the NMDAR system in the DMS. We observed that repeated daily administration of alcohol results in a long-lasting increase in the activity of the NR2B-NMDARs in the DMS. The same procedure leads to a prolonged activation of Fyn, increased NR2B phosphorylation, and membrane localization of the subunit. Importantly, similar electrophysiological and biochemical modifications were observed in the DMS of rats that consumed large quantities of alcohol. Finally, we show that inhibition of NR2B-NMDARs or Src family PTKs in the DMS, but not in the DLS, significantly decreases operant self-administration of alcohol and reduces alcohol-priming-induced reinstatement of alcohol seeking. Our results suggest that the upregulation of NR2B-NMDAR activity within the DMS by alcohol contributes to the maladaptive synaptic changes that lead to excessive alcohol intake and relapse.
Symmetry Breakdown in the ON and OFF Pathways of the Retina at Night: Functional Implications
Authors: Pandarinath Chethan , Victor Jonathan D. , Nirenberg Sheila
Published: July 2010

Several recent studies have shown that the ON and OFF channels of the visual system are not simple mirror images of each other, that their response characteristics are asymmetric (Chichilnisky and Kalmar, 2002; Sagdullaev and McCall, 2005). How the asymmetries bear on visual processing is not well understood. Here, we show that ON and OFF ganglion cells show a strong asymmetry in their temporal adaptation to photopic (day) and scotopic (night) conditions and that the asymmetry confers a functional advantage. Under photopic conditions, the ON and OFF ganglion cells show similar temporal characteristics. Under scotopic conditions, the two cell classes diverge—ON cells shift their tuning to low temporal frequencies, whereas OFF cells continue to respond to high. This difference in processing corresponds to an asymmetry in the natural world, one produced by the Poisson nature of photon capture and persists over a broad range of light levels. This work characterizes a previously unknown divergence in the ON and OFF pathways and its utility to visual processing. Furthermore, the results have implications for downstream circuitry and thus offer new constraints for models of downstream processing, since ganglion cells serve as building blocks for circuits in higher brain areas. For example, if simple cells in visual cortex rely on complementary interactions between the two pathways, such as push–pull interactions (Alonso et al., 2001; Hirsch, 2003), their receptive fields may be radically different under scotopic conditions, when the ON and OFF pathways are out of sync.