bluuebunny/crossref_metadata_2025 huggingface dataset:
An Investigation of Numerical Grid Effects in Parameter Estimation
Authors: Zyvoloski George A. , Vesselinov Velimir V.
Published: May 2006

Modern ground water characterization and remediation projects routinely require calibration and inverse analysis of large three‐dimensional numerical models of complex hydrogeological systems. Hydrogeologic complexity can be prompted by various aquifer characteristics including complicated spatial hydrostratigraphy and aquifer recharge from infiltration through an unsaturated zone. To keep the numerical models computationally efficient, compromises are frequently made in the model development, particularly, about resolution of the computational grid and numerical representation of the governing flow equation. The compromise is required so that the model can be used in calibration, parameter estimation, performance assessment, and analysis of sensitivity and uncertainty in model predictions. However, grid properties and resolution as well as applied computational schemes can have large effects on forward‐model predictions and on inverse parameter estimates. We investigate these effects for a series of one‐ and two‐dimensional synthetic cases representing saturated and variably saturated flow problems. We show that “conformable” grids, despite neglecting terms in the numerical formulation, can lead to accurate solutions of problems with complex hydrostratigraphy. Our analysis also demonstrates that, despite slower computer run times and higher memory requirements for a given problem size, the control volume finite‐element method showed an advantage over finite‐difference techniques in accuracy of parameter estimation for a given grid resolution for most of the test problems.
Presidential Power and Congressional Acquiescence in the “War” on Terrorism: A New Constitutional Equilibrium?
Authors: Owens John E.
Published: May 2006

U.S. presidents have expanded executive power in times of war and emergency, sometimes aggressively so. This article builds on Burnham’s application of punctuated equilibria theory to suggest that the combination of President George W. Bush’s presidentialist doctrine, the external shock of the 9/11 atrocities and the president’s “war” on terror has consolidated a new, constitutional equilibrium between the president and the Congress. While some members of Congress contest the new order, the Congress collectively has acquiesced in its own marginalization. The article surveys a wide range of executive power assertions and legislative retreats AND argues that power assertions and consolidations generally draw on historical precedent and operate nonincrementally within a punctuated pattern.
The War on Terror and Contemporary U.S.‐European Relations
Authors: McCormick James M.
Published: May 2006

This article examines the evolution of the Bush Administration’s foreign policy approach and assesses how that evolution has affected European‐American relations in the recent past and how it may affect ties in the future. The twin concepts of a conceptual gap and an action gap between America and Europe over U.S. foreign policy are utilized as organizing themes. The former refers to the gap between Europe and America over the assumptions that govern U.S. foreign policy behavior; the latter refers to the gap in the policy behavior of these parties. The so‐called “war on terror” serves as the principal reference point in discussing these gaps. The article’s conclusion is ultimately an optimistic one. A conceptual gap in foreign policy will likely remain between Western Europe (and much of the European Union) and America, but the action gap between the two sides has already narrowed and will likely continue to do so.
Working with Allies: The United States, the United Kingdom, and the War on Terror
Authors: Dumbrell John
Published: May 2006

This article considers the special case of the United States’ relationship with Great Britain—America’s closest ally—in the context of the post‐9/11 debate over unilateralism and multilateralism. It explains the development of unilateral preferences in the post‐Cold War order and, latterly, in the foreign policies of the George W. Bush Administration. The Bush Administration’s outlook is seen as much more complex than many commentators assume, notwithstanding its acceptance of the logic of unilateralism and “coalitions of the willing” in pursuing the “War on Terror.” The putative “specialness” of the U.S.–U.K. relationship is examined through a skeptical eye, from both the U.S. and British perspectives. Its contemporary manifestation is placed to a considerable degree by the personal leadership style and convictions of Prime Minister Tony Blair of Britain. In the final part of the article, the U.S.–U.K. alliance is assessed in light of the broader debate about America’s need for allies in the new international order and its capacity to “work with allies” effectively.
Compromising Justice: Why the Bush Administration and the NGOs Are Both Wrong about the ICC
Authors: Rodman Kenneth A.
Published: May 2006

The critics of the ICC in the Bush administration and its supporters within the human rights community have one thing in common: they assume that the ICC can evolve into a powerful institution independent of states, either to constrain American power or to act on a duty to prosecute to end impunity for perpetrators. Both overestimate the ability of the court to pursue a legalism divorced from power realities. The former attribute to the court powers it is unlikely to exercise, particularly if the United States remains outside the treaty. This is due, in part, to the safeguards within the Rome Statute, but more importantly, to the court's dependence on sovereign cooperation, which will lead it to place a high premium on cultivating the good will of the most powerful states. The latter overestimate the degree to which courts by themselves can deter atrocities. The ICC's effectiveness in any particular case will therefore be dependent on the political consensus of those actors capable of wielding power in that area. They also underestimate the need to compromise justice – at least, prosecutorial justice – in cases in which bargaining and compromise are the central means of facilitating transitions from armed conflict or dictatorship, and in cases in which the strength of the perpetrators and the limits of one's power would make legal proceedings either futile or counterproductive to other interests and values. Hence, decisions to prosecute must first be subjected to a test of political prudence, and then take place according to due process and the rule of law.
Accountability and Global Governance: The Case of Iraq
Authors: Gordon Joy
Published: May 2006

This article explores issues concerning accountability and global governance by looking at three cases involving Iraq: the economic sanctions imposed by the Security Council; the operation of the Oil for Food Program; and the US-led occupation authority and its management of Iraqi funds. In all three cases the problems that emerge are rooted only in part in criminal acts or failures to meet legal responsibilities. The failures of accountability that took place in these cases included also abuses of power and forms of corruption that had been legitimated within legal institutional structures. An examination of these cases helps to illustrate what accountability can demand, as well as the kinds of diverse institutional arrangements that can undermine it. In the Oil for Food Program, there was corruption despite elaborate structures of oversight. In the case of the US-led occupation authority's management of Iraqi funds, the corruption was tied to systematic procedures that eliminated structures of oversight. I argue that the abuses that occurred in these cases were not due to a lack of understanding about what might bring greater integrity to the processes involved. Rather, they illustrate how well the structures of accountability and integrity were already understood, as evidenced in the systematic efforts to evade and compromise those structures.
The Ethics of Lustration
Authors: Meierhenrich Jens
Published: May 2006

One of the most important challenges for the occupation of Iraq has been making decisions about the status of people who were either responsible for or who passively benefited from the regime's past injustices. But how should such people—in this case, members of the Baath Party—be dealt with? And how have they been dealt with under the U.S. occupation? Although lustration is just one of many institutions ofjus post bellum, it is arguably one of the most important. The pursuit of administrative justice affects the reconstitution of the public sphere—literally and figuratively—in more fundamental ways than most other institutions of transitional justice. Yet our understanding of the ethics of occupation in the twenty-first century continues to be incomplete, and ethical principles are needed for guiding and clarifying how occupations may justly be carried out and for establishing a legitimate role for international morals in the conduct of peace. This article develops three such principles for guiding the practice of lustration, and argues that they have been widely flouted during the occupation of Iraq. This is problematic from the perspective ofjus post bellum, for to paraphrase Michael Walzer's argument inJust and Unjust Wars, the restraint ofpeaceis the beginning of peace.
Intensification of a Reaction by the Addition of a Minor Amount of Solvent: Diels-Alder Reaction of 2H-Pyran-2-ones with Alkynes
Authors: Kranjc Krištof , Kočevar Marijan
Published: May 2006

Diels-Alder transformation of substituted 3-benzoylamino-2H-pyran-2-ones 1 with a variety of alkynes 2 under microwave (MW) irradiation in a closed system can be intensified in a novel way by addition of a minor amount of butan-1-ol. When the reagents are not volatile under the used conditions, the reactions do not seem to be influenced by the addition of butan-1-ol, as demonstrated by the cycloaddition of a fused 2H-pyran-2-one 5 with N-ethylmaleimide (6) giving adduct 7.
Quantum-Chemical Investigations of 5-Bromo-2'-Deoxyuridine Derivatives with Antiviral Activity
Authors: Velkov Zhivko A. , Velkov Yasen Zh. , Tadjer Alia V. , Stankova Ivanka G.
Published: May 2006

The article describes the results of semiempirical quantum-chemical calculations for a series of 3',5'-esters of 5-bromo-2'-deoxyuridine with amino acids or peptides. These compounds were synthesized and tested for antiviral activity as potential prodrugs of the parent 5-bromonucleoside. It was not clear why only some of the compounds were active. On the basis of structure investigation and the calculated molecular descriptors, it was found that the determining factor for obtaining appropriate prodrugs of 5-bromo-2'-deoxyuridine is the lipophilicity of the esters.
Understanding the role parents play in tennis success: a national survey of junior tennis coaches
Authors: Gould D , Lauer L , Rolo C , Jannes C , Pennisi N
Published: May 2006

Objectives:To assess coaches’ perceptions about the role of parents and their positive and negative behaviours in junior tennis.

Methods:A national survey of 132 United States junior tennis coaches was completed. The extent and seriousness/impact of parent-child interaction problems and positive behaviours were rated.

Results:Parents were perceived as very important for junior tennis success. Most parents (59%) that these coaches had worked with were seen as having a positive influence on their player’s development. However, the respondents also felt that 36% of parents negatively influenced their child’s development. Positive parental behaviours included providing logistical, financial, and social-emotional support, as well as tennis opportunities and unconditional love. Negative parent behaviours included overemphasising winning, holding unrealistic expectations, and criticising their child.

Conclusions:Findings are discussed relative to current sport parenting and athletic talent development research and theorising. The need to educate parents is emphasised.
Differential Gene Expression in Hemodialysis Patients with "Cold" Zheng
Authors: Chen Chia-Sheng , Lin Li-Wei , Hsieh Chia-Chang , Chen Guang-Wei , Peng Wen-Huang , Hsieh Ming-Tsuen
Published: May 2006

The aim of the present study was to search for the differential gene expression and measure the serum level of a number of biochemical parameters in the cold Zheng (CZ) and non-cold Zheng (NCZ) in patients receiving hemodialysis. Hemodialysis (HD) patients were randomly selected from the CZ and NCZ groups. The between-group differences in gene expression were assessed using complementary DNA (cDNA) microarray. Differential gene expression was further validated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Our results demonstrated that the up-regulation of the inflammation-associated genes, ALOX5AP, S100A8 and S100A12, down-regulation of the genes related to immunity (DEFA4), metabolism (GNG11, PYGB, PRKAR2B), and growth/proliferation (HSF2, DDR2, TK1) were found in the CZ group. Furthermore, the CZ HD patients had significantly lower serum albumin levels compared with their NCZ counterparts (3.31 ± 0.08 g/dL versus 4.18 ± 0.12 g/dL ). It appears reasonable to conclude that up-regulated inflammatory-gene expression (ALOX5AP, S100A8 and S100A12) may play an important role in CZ HD patients.
Clinical and Molecular Evaluation of Warming and Tonic Herb Treatment for Sibling Patients of a Typical Kidney-yang Deficiency Family
Authors: Pan Ling , Wang Miqu , Wang J. G. , Wu Bin , Hui Kam M.
Published: May 2006

It is essential to explore the molecular therapeutic effect of warm and tonic herb treatment for individuals with typical kidney-yang deficiency. In this report, we have identified members of a family with a history of suffering from cold and kidney-yang deficiency syndromes. First, we have employed the accumulated scores of the 40-items clinical scoring indicators for kidney-yang deficiency and cold syndromes to clinically assess the presence or absence of the deficiency for 15 family members. We then proceeded to compare the gene expression profiles of RNA isolated from blood samples, prior to and post-herbal treatment, of a sibling (brother and younger sister) that are suffering from the deficiency using cDNA microarrays with 18816 genes. Following treatments with the warming and tonic herb, the accumulated clinical scores obtained from the 40-items clinical scoring indicators were compared to those obtained pre-treatment. It was observed that the accumulated clinical scores were reduced by 1/3 for the brother and 2/3 for his younger sister following the treatments. Furthermore, we have demonstrated that the level of gene expression for a total of 33 genes at pre-treatment was modulated after treatments with the warming and tonic herb and correlated well with the clinical improvements of their syndromes. These results suggest that the combination of gene profiling and the accumulated clinical scores obtained from the 40-items clinical scoring indicators may provide an accurate clinical assessment and a way to monitor the therapeutic efficacy of the warming and tonic herb treatment.
Changes of Metallothionein 1 and 3 mRNA Levels with Age in Brain of Senescence-Accelerated Mice and The Effects of Acupuncture
Authors: Wen Tingyi , Fan Xiaonong , Li Mingchun , Han Jingxian , Shi Xuemin , Xing Laijun
Published: May 2006

The effects of aging and acupuncture on brain MT1 and MT3 mRNA levels in senescence-accelerated mice (SAMP10) and accelerated senescence resistant mice (SAMR1) were analyzed by Northern blot analysis. Both MT1 and MT3 mRNA levels in SAMR1 were increased significantly from birth to month 4 and decreased gradually thereafter. In SAMP10, the MT3 mRNA level followed the same pattern as in SAMR1 before month 4, then decreased from month 4 to 6, but was over-expressed and exceeded the previous level at month 8. The MT1 mRNA expression in SAMP10 showed a zigzag pattern. Of two groups of SAMP10 mice treated with acupuncture, the Xingnao group (PC6 and Du26 as acupoints) and the Zibuganshen group (BL18 and BL23 as acupoints), both showed a higher MT1 mRNA level and a lower MT3 mRNA level than the age-matched control group. Meanwhile, in both of the acupuncture groups, the ratios of MT3 to MT1 were down-regulated to the normal range. Overall, these results suggested that over-expression of MT3 mRNA and the increase in MT3 to MT1 ratios in SAMP10 were correlated with aging, and could be an important physiological and pathological event in the aging process. Acupuncture altered the expression levels of MT1 and MT3 mRNA and differences between the effects of the two stimulated acupoints were seen. Therefore, maintenance of the balance between MTs mRNA expression and correct MTs concentrations is crucial for brain-endocrine-immune response and normal aging. Acupuncture could improve zinc ion bioavailability, by maintaining the balance between MT1 and MT3 mRNA expression levels and might explain one of the mechanisms by which acupuncture treatments defer aging and treat some age-related neurodegenerative diseases.
Pharmacological Effects of Ba-Wei-Xi-Lei Powder on Ulcerative Colitis in Rats with Enema Application
Authors: Liu Duan-Yong , Zhao Hai-Mei , Zhao Ning , Xin Zeng-Ping , Lu Ai-Ping
Published: May 2006

Ba-Wei-Xi-Lei powder is a classical herbal mixture, and is widely used for the treatment of oral ulcer and ulcerative colitis. This study aimed to explore the effect of Ba-Wei-Xi-Lei powder with enema application on ulcerative colitis in rats. Ulcerative colitis was induced by immunization with rabbit's colonic mucosal protein emulsified with Completely Freund's Adjuvant. The mucosal inflammatory reaction and ulcer have been observed in the model rats. Characteristic changes of ulceractive colitis include that CD4 lymphocyte increased in peripheral blood while CD8 lymphocyte decreased; CD8 lymphocyte and TNF-α expression area increased in colonic mucosa, while CD4 lymphocyte decreased. Ba-Wei-Xi-Lei powder and sulfasalazine with enema application could alleviate the pathological changes in the model rats. The results suggest that the pharmacological effects of Ba-Wei-Xi-Lei powder on ulcerative colitis in rats are similar to the effect of sulfasalazine.
Hepatoprotective Effect ofPhyllanthusin Taiwan on Acute Liver Damage Induced by Carbon Tetrachloride
Authors: Lee Chao-Ying , Peng Wen-Huang , Cheng Hao-Yuan , Chen Fei-Na , Lai Ming-Tsung , Chiu Tai-Hui
Published: May 2006

The effect of oral administration of Phyllanthus methanolic extracts (PME) (i.e. P. acidus, P. emblica, P. myrtifolius, P. multiflorus, P. amarus, P. debilis, P. embergeri, P. hookeri, P. tenellus, P. urinaria L.s. nudicarpus, P. urinaria L.s. urinaria) or gallic acid (GA) on the progression of acute liver damage induced by CCl4in rats was examined by morphological and biochemical methods. P. acidus, P. urinaria L.s. urinaria, GA at a dose of 0.5 g/kg, and P. emblica, P. urinaria L.s. nudicarpus at a dose of 1.0 g/kg attenuated CCl4-induced increase in serum glutamate-oxalate-transaminase (GOT). P. acidus, P. urinaria L.s. nudicarpus, P. urinaria L.s. urinaria, GA at a dose of 0.5 g/kg, and P. emblica, P. amarus, P. hookeri, P. tenellus at a dose of 1.0 g/kg attenuated CCl4-induced increase in serum glutamate-pyruvate-transaminase (GPT). Concurrently, P. acidus, P. multiflorus, P. embergeri, P. hookeri, P. tenellus and P. urinaria L.s. urinaria elevated the activity of liver reduced glutathione peroxidase (GSH-Px). Since the protective effects of P. acidus, P. emblica, P. myrtifolius, P. embergeri, P. urinaria L.s. nudicarpus, P. urinaria L.s. urinaria and GA correlate with a reduction in liver infiltration and focal necrosis observed using histological methods, these data demonstrate that P. acidus and P. urinaria L.s. urinaria are hepatoprotective and antioxidant agents.
An Extract of Morinda citrifolia Interferes with the Serum-Induced Formation of Filamentous Structures in Candida albicans and Inhibits Germination of Aspergillus nidulans
Authors: Banerjee Saswati , Johnson Andrew D. , Csiszar Katalin , Wansley Daniel L. , McGeady Paul
Published: May 2006

An aqueous extract of Morinda citrifolia was shown to interfere with the serum-induced morphological conversion of Candida albicans from a cellular yeast to a filamentous form in vitro. The conversion of C. albicans from a cellular yeast to a filamentous form in vivo is associated with pathogenicity. No significant effect on growth in serum-free media was seen at the concentrations used to interfere with the morphological change. The same extract also inhibited the germination of Apergillus nidulans spores. These results demonstrate that M. citrifolia contains a water-soluble component or components that interfere with the morphological conversion of C. albicans and the germination of A. nidulans and may have potential therapeutic value with regard to candidiasis and aspergillosis.
Antimicrobial Activities of Cinnamon Oil and Cinnamaldehyde from the Chinese Medicinal HerbCinnamomum cassiaBlume
Authors: Ooi Linda S. M. , Li Yaolan , Kam Sheung-Lau , Wang Hua , Wong Elaine Y. L. , Ooi Vincent E. C.
Published: May 2006

Both Cinnamomum verum J.S. Presl. and Cinnamomum cassia Blume are collectively called Cortex Cinnamonmi for their medicinal cinnamon bark. Cinnamomum verum is more popular elsewhere in the world, whereas C. cassia is a well known traditional Chinese medicine. An analysis of hydro-distilled Chinese cinnamon oil and pure cinnamaldehyde by gas chromatography/mass spectrometry revealed that cinnamaldehyde is the major component comprising 85% in the essential oil and the purity of cinnamaldehyde in use is high (> 98%). Both oil and pure cinnamaldehyde of C. cassia were equally effective in inhibiting the growth of various isolates of bacteria including Gram-positive (1 isolate, Staphylococcus aureus), and Gram-negative (7 isolates, E. coli, Enterobacter aerogenes, Proteus vulgaris, Pseudomonas aeruginosa, Vibrio cholerae, Vibrio parahaemolyticus and Samonella typhymurium), and fungi including yeasts (four species of Candida, C. albicans, C. tropicalis, C. glabrata, and C. krusei), filamentous molds (4 isolates, three Aspergillus spp. and one Fusarium sp.) and dermatophytes (three isolates, Microsporum gypseum, Trichophyton rubrum and T. mentagraphytes). Their minimum inhibition concentrations (MIC) as determined by agar dilution method varied only slightly. The MICs of both oil and cinnamaldehyde for bacteria ranged from 75 μg/ml to 600 μg/ml, for yeasts from 100 μg/ml to 450 μg/ml, for filamentous fungi from 75 μg/ml to 150 μg/ml, and for dermatophytes from 18.8 μg/ml to 37.5 μg/ml. The antimicrobial effectiveness of C. cassia oil and its major constituent is comparable and almost equivalent, which suggests that the broad-spectrum antibiotic activities of C. cassia oil are due to cinnamaldehyde. The relationship between structure and function of the main components of cinnamon oil is also discussed.
GENERAL RESISTIVITY IN NORMAL METALLIC STATES
Authors: KOO JE HUAN , GILL DOH-HYUN , CHO GUANGSUP
Published: May 2006

We investigate the resistivity in high transition temperature superconductors. It was shown that phonon-enhanced spin fluctuations drive this superconductivity once more, as was suggested by us [Phys. Rev. B61, 4289]. The resistivity in the presence of phonon-enhanced spin-flippings, different from pure Kondo ones, was calculated. We compared the resistivity from pure Kondo spins and that from phonon-enhanced spins, which are in good fit with the experimental data of Y-Ba-Cu-O . Using a basic method, different from conventional ones, we also calculated resistivities in other non-superconducting materials.
Z-SCAN DETERMINATION OF THE THIRD-ORDER OPTICAL NONLINEARITY OF ORGANIC DYE NILE BLUE CHLORIDE
Authors: ALI QUSAY MOHAMMED , PALANISAMY P. K.
Published: May 2006

The single beam Z-scan technique was used to determine the nonlinear optical properties of the organic dye Nile Blue chloride in the solvent ethanol. The experiments were performed with a He-Ne laser with a wavelength of 632.8 nm. The negative nonlinear refractive index and two-photon absorption coefficient were observed in this dye. The intensity-dependent nonlinear refractive index was investigated. The result shows that the dye exhibits a great nonlinear response with the real and imaginary parts of the third-order nonlinear optical susceptibility χ(3) being -4.12×10-5 esu and 1.35×10-6 esu, respectively. These results show that the Nile Blue chloride dye has potential applications in nonlinear optics.
SCALING CHEN'S ATTRACTOR
Authors: LI CHANGPIN , DENG WEIHUA
Published: May 2006

In this paper, Chen's attractor is scaled via the one-way coupling approach and the adaptive control approach. The proposed method is theoretically analyzed and numerically studied. And the numerical simulations are in line with the theoretical analysis.
ADVANCED MODELLING OF EPITAXIAL ORDERING OF ORGANIC LAYERS ON CRYSTALLINE SURFACES
Authors: MANNSFELD STEFAN C. B. , FRITZ TORSTEN
Published: May 2006

A fine balance between weak molecule-molecule interactions and usually only weakly laterally varying molecule-substrate interactions governs the physical structure of organic-inorganic and organic-organic heteroepitaxial thin films. Therefore, it is important to investigate the energetics of realistically large overlayer domains. So far, Potential calculations for large domains of organic overlayers on crystalline substrates were computationally demanding due to the vast number of atoms to be considered. Here, we present a technique which for the first time enables the calculation of both the molecule-substrate interaction potential and the molecule-molecule interaction potential for large molecular domains (up to several thousands of rather large molecules) by utilizing potential energy grid files. This technique does not only allow the investigation of the substrate influence but also full Monte-Carlo based structural optimizations, if applied to 2D crystalline overlayers. Furthermore, it provides an estimate for the energetic gain combined with the differently aligned overlayer domains. In several examples we will discuss the usefulness of this method. As a general result, we will provide evidence that energetically favorable lattice structures in OMBE systems are not restricted to commensurate unit cells or coincident super cells.
NUMERICAL SOLUTIONS FOR THE CHERIDITO-SONER-TOUZI SUPER-REPLICATION MODEL UNDER GAMMA CONSTRAINTS
Authors: TOURIN AGNÈS
Published: May 2006

We solve, by using a monotone and stable approximation, the fully nonlinear degenerate parabolic equation derived by Cheridito, Soner and Touzi [8] from the stochastic control problem of super-replicating a contingent claim under gamma constraints. We present some numerical results.
SECURITY MARKETS WITH PRICE LIMITS: A BAYESIAN APPROACH
Authors: HAREL ARIE , HARPAZ GIORA
Published: May 2006

Several financial markets impose daily price limits on individual securities. Once a price limit is triggered, investors observe either the limit floor or ceiling, but cannot know with certainty what the true equilibrium price would have been in the absence of such limits. The price limits in most exchanges are typically based on a percentage change from the previous day's closing price, and can be expressed as return limits. We develop a Bayesian forecasting model in the presence of return limits, assuming that security returns are governed by identically and independently shifted-exponential random variables with an unknown parameter. The unique features of our Bayesian model are the derivations of the posterior and predictive densities. Several numerical predictions are generated and depicted graphically. Our main theoretical result with policy implications is that when return-limit regulations are tightened, the price-discovery process is impeded and investor's welfare is reduced.
INFORMATION, MODEL PERFORMANCE, PRICING AND TRADING MEASURES IN INCOMPLETE MARKETS
Authors: HUANG JINGGANG , SANDOW SVEN , FRIEDMAN CRAIG
Published: May 2006

In the incomplete market setting, we define a generalized Kullback-Leibler relative entropy in terms of an investor's expected utility. We motivate, from an economic point of view, this quantity — the relative U-entropy. Relative U-entropy measures the discrepancy from a set of pricing measures to a single probability measure. We show that the relative U-entropy shares a number of important properties with the usual Kullback-Leibler relative entropy, and establish the link between this quantity and the pricing measure corresponding to the least favorable market completion. We also describe an economic performance measure for probabilistic models that may be used by an investor in an incomplete market setting. We then introduce a statistical learning paradigm suitable for investors who learn models and base investment decisions, in an incomplete market, on these models.
TESTING FOR RANDOM WALK AND STRUCTURAL BREAKS IN HEDGE FUNDS RETURNS
Authors: CERRATO MARIO , IANNELLI ANDREA
Published: May 2006

We investigate the presence of managerial skills in different categories of hedge funds. Our approach is more flexible that others [7, 10] since it does not make any a priori assumptions regarding the distribution of returns. We find that the Global Macro and Market Neutral funds do not follow a pure random walk. In fact, for both these models the drift parameter is statistically significant. This result rejects our initial hypothesis that hedge funds (expected-excess) returns are on average zero. Indeed, the positive intercept can be interpreted as evidence of managerial skill. We conclude that investors seeking to invest in hedge funds should consider Market Neutral funds and Global Macro funds as possible investments.
ON FINITE DIMENSIONAL REALIZATIONS FOR THE TERM STRUCTURE OF FUTURES PRICES
Authors: BJÖRK TOMAS , BLIX MAGNUS , LANDÉN CAMILLA
Published: May 2006

We consider HJM type models for the term structure of futures prices, where the volatility is allowed to be an arbitrary smooth functional of the present futures price curve. Using a Lie algebraic approach we investigate when the infinite dimensional futures price process can be realized by a finite dimensional Markovian state space model, and we give general necessary and sufficient conditions, in terms of the volatility structure, for the existence of a finite dimensional realization. We study a number of concrete applications including a recently developed model for gas futures. In particular we provide necessary and sufficient conditions for when the induced spot price is a Markov process. In particular we can prove that the only HJM type futures price models with spot price dependent volatility structures which generically possess a spot price realization are the affine ones. These models are thus the only generic spot price models from a futures price term structure point of view.
Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob/ob) mice
Authors: Iizuka Katsumi , Miller Bonnie , Uyeda Kosaku
Published: May 2006

The transcription factor carbohydrate response element-binding protein (ChREBP) mediates insulin-independent, glucose-stimulated gene expression of multiple liver enzymes responsible for converting excess carbohydrate to fatty acids for long-term storage. To investigate ChREBP's role in the development of obesity and obesity-associated metabolic dysregulation, ChREBP-deficient mice were intercrossed with ob/ob mice. As a result of deficient leptin expression, ob/ob mice overeat, become obese and resistant to insulin, and display marked elevations in hepatic lipogenesis, gluconeogenesis, and plasma glucose and triglycerides. mRNA expression of all hepatic lipogenic enzymes was significantly lower in ob/ob-ChREBP−/− than in ob/ob mice, resulting in decreased hepatic fatty acid synthesis and normalization of plasma free fatty acid and triglyceride levels. Overall weight gain in addition to adiposity was reduced in the doubly deficient mice. The former was largely attributable to decreased food intake and may result from decreased hypothalamic expression of the appetite-stimulating neuropeptide agouti-related protein. mRNA expression and activity of gluconeogenic enzymes also was lower in the doubly deficient mice, contributing to significantly lower blood glucose levels. The results of this study suggest that inactivation of ChREBP expression not only reduces fat synthesis and obesity in ob/ob mice but also results in improved glucose tolerance and appetite control.
Relationship between insulin sensitivity and in vivo mitochondrial function in skeletal muscle
Authors: Sirikul Bovorn , Gower Barbara A. , Hunter Gary R. , Larson-Meyer Dawnine E. , Newcomer Bradley R.
Published: May 2006

Recent data have shown that individuals with low insulin sensitivity (SI) also have reduced whole body maximal oxygen uptake. The objectives of this study were to determine 1) whether muscle mitochondrial function was independently related to SI after being adjusted for known determinants of SI and 2) whether lower SI among African-American (AA) vs. Caucasian-American (CA) women was due to lower muscle mitochondrial function among AA women. Subjects were 37 CA and 22 AA premenopausal women (age: 33.6 ± 6.3 yr). Mitochondrial function [time constant of ADP (ADPtc)] was assessed during a 90-s unilateral isometric contraction using 31P magnetic resonance spectroscopy, SI with an intravenous glucose tolerance test, body composition by dual-energy X-ray absorptiometry, and visceral adipose tissue (VAT) with computed tomography. ANOVA was used to compare AA and CA groups, and multiple linear regression modeling was used to identify independent predictors of SI. Between-race comparisons indicated that muscle oxidative capacity was lower among AAs vs. CAs (ADPtc: 25.6 ± 9.8 vs. 21.4 ± 9.9 s). Multiple linear regression models for the dependent variable SI contained 1) VAT and race and 2) VAT, race, and ADPtc. Significant independent effects for all predictor variables were observed in both the first ( r2 = 0.345) and second ( r2 = 0.410) models. The partial correlation for race was lower in the second model (−0.404 vs. −0.300), suggesting that muscle mitochondrial function contributed to the racial difference in SI. Lower muscle mitochondrial function among AAs may in part explain lower SI among them.
Fine mapping of Dyscalc1, the major genetic determinant of dystrophic cardiac calcification in mice
Authors: Korff Susanne , Schoensiegel Frank , Riechert Nora , Weichenhan Dieter , Katus Hugo A. , Ivandic Boris T.
Published: May 2006

Calcification of severely dystrophic muscle is occasionally observed in targeted mouse models of muscular dystrophy and cardiomyopathy. Intracellular calcium deposition occurs in necrotic myocytes in the absence of plasma calcium and phosphate imbalances. In the heart, this recessive trait is referred to as dystrophic cardiac calcinosis (DCC). We identified previously Dyscalc1, a major genetic determinant of DCC, in a 15.2-Mbp region on proximal chromosome 7. We report now further steps toward the identification of the Dyscalc1 gene by reverse genetics. Transferring the Dyscalc1 locus from susceptible mouse strain C3H/He onto a resistant C57BL/6 strain background, we generated congenic inbred strains B6.C3-( D7Mit56-D7Mit230) and B6.C3-( D7Nds5-D7Mit230). Three days after myocardial freeze-thaw injury, both strains exhibited calcification of necrotic lesions, confirming the pathogenetic relevance of Dyscalc1. Analysis of two (129S1 × C57BL/6) × 129S1 backcrosses allowed mapping of Dyscalc1 more precisely to a region spanning 0.76 Mbp between genes Fgf21 (39.70 Mbp) and Myod1 (40.46 Mbp). This interval contains 31 known and putative genes in three large, ancestral haplotypes shared by susceptible strains C3H/He, 129S1, and DBA/2. Thus we were able to exclude previously proposed candidate genes Bax and Hrc. Instead, a potential candidate may be the gene encoding the ATP-binding cassette C6. Mutations in the orthologous human ABCC6 gene cause pseudoxanthoma elasticum, or Gronblad-Strandberg syndrome, an elastic tissue disorder with cardiovascular calcifications.
Cd14,Gbp1, andPla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses
Authors: de Buhr Maike F. , Mähler Michael , Geffers Robert , Hansen Wiebke , Westendorf Astrid M. , Lauber Jörg , Buer Jan , Schlegelberger Brigitte , Hedrich Hans J. , Bleich Andre
Published: May 2006

Induction of inflammatory bowel (IBD)-like disease in mice by a targeted mutation in the Il10 gene ( Il10−/−) is inbred strain dependent. C3H/HeJBir (C3) mice are colitis susceptible, whereas C57BL/6J (B6) mice are resistant. Genetic dissection of this susceptibility revealed 10 colitogenic quantitative trait loci (QTL). The aim of this study was to identify valuable candidate genes by a combination of QTL mapping and microarray analyses. Sixteen genes were differentially expressed between B6- and C3- Il10−/−mice and were located within the QTL intervals. Three major candidate genes ( Cd14, Gbp1, Pla2g2a) showed prominent expression differences between B6- and C3- Il10−/−as well as between B6 and C3 wild-type mice, which was confirmed by semiquantitative or real-time RT-PCR. Because strain differences are known for Gbp1 and Pla2g2a, further analyses focused on Cd14. Western blot analysis revealed strain differences also on the protein level. Cd14 expression in animals with defective and intact Toll-like receptor (TLR)4 signaling (C3, C3H/HeN, B6, B6- Tlr4tm1Aki) make the TLR4 defect of C3 mice unlikely to be the reason for higher Cd14 expression. Less Cd14 expression in germ-free mice indicates a contribution of the microflora on Cd14 expression. Stimulation of naive peritoneal macrophages with bacterial antigens showed lower CD14 surface expression in B6 than in C3 mice. In conclusion, the large number of candidate genes was reduced to three major candidates that play an important role in inflammatory processes and immune response. Strain differences for them are already known or are shown in this study.
Heparin-induced thrombocytopenia (HIT)
Authors: Gallus Alex , Magnani Harry
Published: May 2006

Clinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed. Treatment in 1,291 episodes was for current HIT. Thromboembolism due to HIT was present in 39.4a%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder, and 351 major operations were performed. Clinical outcomes were assessed during danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the danaparoid-treated patients 83.8a% survived; 63.7a% had no or minor adverse events and 20.1a% suffered serious non-fatal adverse events. New thromboses occurred during 9.7a% of treatment episodes, and 16.4a% of treatment episodes had an inadequate treatment response (i. e. developed one or more of the following: new/extended thrombosis, persistent/new platelet count reduction, unplanned amputation during treatment and follow-up). Major bleeding was reported in 8.1a% of treatment episodes. Clinical cross-reactivity of danaparoid (new/persistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event, i. e. a total of 45 patients (3.2a%). Clinical outcomes of these case reports of patients given danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors, especially when a sufficient danaparoid dosing intensity was used in patients with isolated HIT. Post-operative bleeding limits danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.
Activation of human polymorphonuclear neutrophils by streptolysin O from Streptococcus pyogenes leads to the release of proinflammatory mediators
Authors: Nilsson Maria , Sørensen Ole , Mörgelin Matthias , Weineisen Maria , Sjöbring Ulf , Herwald Heiko
Published: May 2006

Streptococcus pyogenes is an important Gram-positive pathogen that is strictly limited to infections in humans. Here we report that streptolysin O (SLO),a cytolytic exotoxin secreted by S. pyogenes, activates human polymorphonuclear neutrophils (PMNs) by perforating these cells. This appears to be followed by an influx of Ca2+ and p38 MAPK activation. As a consequence, PMNs secrete heparin-binding protein, a potent inducer of vascular leakage, and neutrophil-borne proteins, including LL-37, α-defensins, and elastase. The results of the present work therefore suggest that the interaction between SLO and PMNs evokes an exaggerated host response which may contribute to the pathogenesis of local and generalized S. pyogenes infections.
Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in mice does not affect adipogenesis or adipose tissue development
Authors: Demeulemeester Diego , Scroyen Ilse , Voros Gabor , Snoeys Jan , De Geest Bart , Collen Désiré , Lijnen H.
Published: May 2006

In order to evaluate a potential functional role of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in development of obesity, we studied the effect of overexpression of human TIMP-1 (hTIMP-1) in C57Bl/6J mice in vivo and in 3T3-F442A preadipocytes in vitro. Stable long-term overexpression of hTIMP-1 in mice was achieved by adenoviral gene transfer, yielding plasma levels exceeding 250 ng/ml at eight weeks after injection. Mice overexpressing hTIMP-1 and kept on a high fat diet for 14 weeks had body weights, adipose tissue weights, and adipocyte diameters that were somewhat, but not significantly, lower than those of control mice. Similar observations were made after overexpression of hTIMP-1 in mice with lipectomy of the subcutaneous adipose tissue, kept on a high fat diet for 20 weeks. In both in vivo models, blood vessels in the adipose tissues were significantly smaller after hTIMP-1 gene transfer than in control mice. Overexpression of hTIMP-1 in 3T3-F442A preadipocytes had no effect on their subsequent differentiation into mature adipocytes. Thus, overexpression of hTIMP-1 in mice had no significant effect on ongoing adipogenesis or adipose tissue development, although the blood vessel size in adipose tissues was reduced.
Haplotypes encoding the factor VIII 1241Glu variation, factor VIII levels and the risk of venous thrombosis
Authors: Eikenboom Jeroen , Vos Hans , Bakker Egbert , Tanis Bea , Doggen Carine , Bertina Rogier , Rosendaal Frits , Nossent A.
Published: May 2006

Levels of factorVIII (FVIII) are associated with the risk of venous thrombosis.The FVIII variation D1241E has been reported to be associated with decreased levels of FVIII. Our objective was to study whether D1241E is associated with levels of FVIII and the risk of venous thrombosis and whether this association is caused by D1241E or another linked variation.We analyzed the association of three FVIII gene haplotypes encoding 1241E (further denoted as HT1, HT3, and HT5) with FVIII levels and thrombosis risk. This analysis was performed in the Leiden Thrombophilia Study (LETS). The control populations of two case-controls studies on arterial thrombosis in men and women, respectively, were used to confirm the effects observed on FVIII:C in the LETS.In men,HT1 was associated with a 6% reduction in FVIII:C and witha reduced risk of venous thrombosis [odds ratio 0.4 (CI95 0.2–0.8)]. Logistic regression showed that the risk reduction was only partially dependent of the reduction in FVIII levels. HT1 showed no effects in women on either FVIII:C or risk of thrombosis.The number of carriers of HT3 and HT5 was too low to make an accurate estimate of the risk of venous thrombosis. Neither HT3 nor HT5 showed effects on levels of FVIII:C.When we consider that all three haplotypes encoding 1241E show different effects on FVIII:C and thrombosis risk, it is possible that D1241E is not the functional variation. However, FVIII gene variations do contribute to both levels of FVIII and the risk of thrombosis.
Vitamin K antagonists and pregnancy outcome
Authors: Hannemann Doreen , Meister Reinhard , Eléfant Elisabeth , Paulus Wolfgang , Vial Thierry , Reuvers Minke , Robert-Gnansia Elisabeth , Arnon Judy , De Santis Marco , Clementi Maurizio , Rodriguez-Pinilla Elvira , Dolivo Alla , Merlob Paul , Schaefer Christof
Published: May 2006

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n=12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n=280), acenocoumarol (n=226), fluindione (n=99), warfarin (n=63) and phenindione (n=2) to a non-exposed control group (n=1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86–8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76–3.86), mean gestational age at delivery (37.9 vs. 39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p<0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28–4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes.The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1st trimester did not take place later than week 8 after the 1st day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.
Plasma levels of bradykinin are suppressed in factor XII-deficient mice
Authors: Iwaki Takayuki , Castellino Francis
Published: May 2006

A genetically-transmissible factor (F) XII-inactivated allele has been produced in mice by targeted replacement of exons 3–8 of the FXII gene with the neomycin resistance gene. Interbreeding of these mice provided offspring homozygous for two inactivated FXII alleles (FXII−/−). Male and female FXII-deficient mice bred normally in all genotypic combinations of the heterozygous and homozygous states, and the offspring survived to adulthood, suggesting that a total FXII deficiency does not affect embryonic development and survival. Neither FXII transcripts nor FXII antigen was found in various tissues of adult FXII−/−mice. No obvious unchallenged coagulopathies were present in FXII−/−adult mice, despite greatly prolonged activated partial thromboplastin times in this mouse cohort. FXII−/−mice were then used to assess the in vivo importance of the plasma FXII/prekallikrein/kininogen pathway in provision of resting plasma bradykinin (BK) levels and in generation of plasma BK stimulated by contact with an artificial surface, using a new and greatly improved plasma BK assay developed during these studies. It was found that approximately 50% of resting BK, and all of the contact-stimulated plasma BK, was provided by this FXII-dependent pathway, without a requirement for FXI. These results provide clear evidence that surface-stimulated BK production, in mice, is dependent on the activation of FXII.