bluuebunny/crossref_metadata_2025 huggingface dataset:
SUSTAINED COMOVING ACCELERATION OF OVERDENSE PLASMAS BY COLLIDING LASER PULSES
Authors: LIANG EDISON
Published: February 2007

We review recent PIC simulation results which show that double-sided irradiation of a thin over-dense plasma slab by ultra-intense laser pulses from both sides can lead to sustained comoving acceleration of surface electrons to energies much higher than the conventional ponderomotive limit. The acceleration stops only when the electrons drift transversely out of the laser beam. We show latest 2.5D results of parameter studies based on finite laser spot size and discuss future laser experiments that can be used to test these results.
A TEST OF THE REFRACTIVE INDEX IN A STRONG ELECTROMAGNETIC FIELD
Authors: HOMMA KENSUKE
Published: February 2007

A strong electromagnetic field may modify the refractive index of the normal vacuum due to nonlinear effects caused by photon-photon interactions. In order to test the increase of the refractive index, Cherenkov radiations associated with relativistic electrons into the strong electromagnetic field can be utilized as an experimental probe. We will present a result of the experimental search for the Cherenkov emissions with a laser intensity of 1017W/cm2 with the wavelength of 800nm and the electron beam of 35.4MeV/c, where photons with kinematically expected Compton energies and a symptom of visible ray emissions were observed.
DELAY-DEPENDENT AND DELAY-INDEPENDENT STABILITY CRITERIA FOR CELLULAR NEURAL NETWORKS WITH DELAYS
Authors: LI CHUANDONG , LIAO XIAOFENG , WONG KWOK-WO
Published: February 2007

The stability issues of the equilibrium points of the cellular neural networks (CNN) with single and multiple delays are further investigated. Several novel delay-dependent and delay-independent asymptotical/exponential stability criteria are established by employing parameterized first-order model transformation, Lyapunov–Krasovskii stability theorem and LMI technique in virtue of the linearization of considered model. The stability regions with respect to the delay parameters are formulated by applying the proposed results. To the best of the authors' knowledge, few (if any) reports about such "linearization" approach to stability analysis for delayed neural network models have been presented in the open literatures. Some numerical examples are also given to illustrate the effectiveness of our results and to compare with the recent results.
PERIODICITY AS CONDITION TO NOISE ROBUSTNESS FOR CHAOTIC MAPS WITH PIECEWISE CONSTANT INVARIANT DENSITY
Authors: PARESCHI FABIO , ROVATTI RICCARDO , SETTI GIANLUCA
Published: February 2007

Chaotic maps represent an effective method of generating random-like sequences, that combines the benefits of relying on simple, causal models with good unpredictability. However, since chaotic maps behavior is generally strongly dependent on unavoidable implementation errors and external perturbations, the possibility of guaranteeing map statistical robustness is of great practical concern. Here we present a technique to guarantee the independence of the first-order statistics of external perturbations, modeled as an additive, map-independent random variable. The developed criterion applies to a quite general class of maps.
ROBUST SYNCHRONIZATION OF CHAOTIC LUR'E SYSTEMS VIA REPLACING VARIABLES CONTROL
Authors: WU XIAOFENG , WANG MUHONG
Published: February 2007

The sufficient conditions for chaos synchronization of two nonidentical systems by replacing variables control have not been proposed until now. In this paper, synchronization of two chaotic Lur'e systems with parameter mismatch by replacing variables control is studied. First of all, we present a master-slave Lur'e systems synchronization scheme with both parameter mismatch and replacing variables control, and derive a responsive error system for the scheme. A new definition of synchronization with finite L 2-gain is then introduced. Based on the definition, the sufficient synchronization criteria which are in the form of linear matrix inequality (LMI) are proved using a quadratic Lyapunov function. By means of MKY lemma the frequency domain criteria are further derived from the obtained LMIs. These frequency domain criteria are illustrated on the master-slave Chua's circuits with parameter mismatch so that the ranges of the parameters of Chua's circuit are analytically solved in the sense of the synchronization with finite L 2-gain by replacing singe-variable control. The illustrative examples verify that within the ranges of the parameters it is possible to synchronize the master-slave Chua's circuits up to a small synchronization error bound, even the qualitative behaviors of the slave circuit are different from that of the master one, such as the trajectory of the master circuit is chaotic and that of the slave divergent. The relation between the synchronization error bound and parameter mismatch is shown.
Hypertension caused by prenatal testosterone excess in female sheep
Authors: King Andrew J. , Bari Olivier N. , Mohankumar P. S. , Lee James S. , Padmanabhan Vasantha , Fink Gregory D.
Published: February 2007

Polycystic ovary syndrome (PCOS), a leading cause of infertility, affects ∼10% of women of reproductive age. The etiology and pathophysiology of PCOS are poorly understood. PCOS is multifaceted and includes reproductive abnormalities and components of the metabolic syndrome such as insulin resistance, obesity, dyslipidemia, and hypertension. Exposure to excess testosterone (T) during the prenatal period may predispose individuals to PCOS phenotype. The goal of this study was to determine whether hypertension and dyslipidemia occur in a well-characterized model of PCOS produced by prenatal treatment of sheep with T. Radiotelemetry was used to measure blood pressure over a 24-h period in conscious, undisturbed animals. To normalize circulating estradiol levels across treatment, control ( n = 4) and prenatal T-treated (100 mg T propionate im twice weekly from days 30 to 90 of fetal life, n = 4) 2-yr-old females were ovariectomized, instrumented with a radiotelemetry transmitter, and clamped with early follicular phase levels of estrogen using an implant. Six days later, a 24-h recording period commenced. Prenatal T-treated sheep were hypertensive compared with control sheep, and heart rate tended to be higher. T-treated sheep had hyperglycemia, insulin resistance, hypernatremia, and hyperchloremia, and both total and LDL cholesterol tended to be higher. Plasma aldosterone and epinephrine were significantly lower in T-treated sheep, whereas norepinephrine was unchanged. This first-ever use of radiotelemetric blood pressure recordings in sheep demonstrates that mild hypertension, a risk factor reported in some women with PCOS, is also a feature of the sheep model of PCOS produced by prenatal T treatment.
IL-6 increases muscle insulin sensitivity only at superphysiological levels
Authors: Geiger Paige C. , Hancock Chad , Wright David C. , Han Dong-Ho , Holloszy John O.
Published: February 2007

Exercise induces an increase in glucose transport in muscle. As the acute increase in glucose transport reverses, it is replaced by an increase in insulin sensitivity. Interleukin-6 (IL-6) increases with exercise and has been reported to activate AMP-activated protein kinase (AMPK). Based on this information, we hypothesized that IL-6 would result in an increase in muscle insulin sensitivity. Rat epitrochlearis and soleus muscles were incubated with 120 ng/ml IL-6. Exposure to IL-6 induced a modest acute increase in glucose transport and was followed 3.5 h later by an increase in insulin sensitivity in epitrochlearis but not soleus muscles. IL-6 also brought about an increase in AMPK phosphorylation in epitrochlearis muscles. We conclude that exposure of fast-twitch muscle to 120 ng/ml IL-6 increases insulin sensitivity by activating AMPK. However, exposure of epitrochlearis muscles to 10 ng/ml IL-6, a concentration >100-fold higher than that attained in plasma during exercise, had no effect on glucose transport or insulin sensitivity. These findings provide evidence that the increases in glucose transport and insulin sensitivity induced by IL-6 are pharmacological rather than physiological effects. We interpret our results as evidence that the increase in IL-6 during exercise does not play a role in the exercise-induced increases in muscle glucose uptake and insulin sensitivity.
Quantitative transcriptome, proteome, and sulfur metabolite profiling of theSaccharomyces cerevisiaeresponse to arsenite
Authors: Thorsen Michael , Lagniel Gilles , Kristiansson Erik , Junot Christophe , Nerman Olle , Labarre Jean , Tamás Markus J.
Published: February 2007

Arsenic is ubiquitously present in nature, and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative transcriptome, proteome, and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance, and proteolytic activity. Importantly, we observed that nearly all components of the sulfate assimilation and glutathione biosynthesis pathways were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated cellular glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pinpointed transcription factors that mediate the core of the transcriptional response to arsenite. Taken together, our data reveal that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis, and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert.
The Global Ocean Mass Budget in 1993–2003 Estimated from Sea Level Change
Authors: Wenzel Manfred , Schröter Jens
Published: February 2007

The mass budget of the ocean in the period 1993–2003 is studied with a general circulation model. The model has a free surface and conserves mass rather than volume; that is, freshwater is exchanged with the atmosphere via precipitation and evaporation and inflow from land is taken into account. The mass is redistributed by the ocean circulation. Furthermore, the ocean’s volume changes by steric expansion with changing temperature and salinity. To estimate the mass changes, the ocean model is constrained by sea level measurements from the Ocean Topography Experiment (TOPEX)/Poseidon mission as well as by hydrographic data. The modeled ocean mass change within the years 2002–03 compares favorably to measurements from the Gravity Recovery and Climate Experiment (GRACE), and the evolution of the global mean sea level for the period 1993–2003 with annual and interannual variations can be reproduced to a 0.15-cm rms difference. Its trend has been measured as 3.37 mm yr−1 while the constrained model gives 3.34 mm yr−1 considering only the area covered by measurements (3.25 mm yr−1 for the total ocean). A steric rise of 2.50 mm yr−1 is estimated in this period, as is a gain in the ocean mass that is equivalent to an eustatic rise of 0.74 mm yr−1. The amplitude and phase (day of maximum value since 1 January) of the superimposed eustatic annual cycle are also estimated to be 4.6 mm and 278°, respectively. The corresponding values for the semiannual cycle are 0.42 mm and 120°. The trends in the eustatic sea level are not equally distributed. In the Atlantic Ocean (80°S–67°N) the eustatic sea level rises by 1.8 mm yr−1 and in the Indian Ocean (80°S–30°N) it rises by 1.4 mm yr−1, but it falls by −0.20 mm yr−1 in the Pacific Ocean (80°S–67°N). The latter is mainly caused by a loss of mass through transport divergence in the Pacific sector of the Antarctic Circumpolar Current (−0.42 Sv; Sv ≡ 109 kg s−1) that is not balanced by the net surface water supply. The consequence of this uneven eustatic rise is a shift of the oceanic center of mass toward the Atlantic Ocean and to the north.
Effects of Stratification on the Large-Scale Ocean Response to Barometric Pressure
Authors: Ponte Rui M. , Vinogradov Sergey V.
Published: February 2007

Single-layer (barotropic) models have been commonly used in studies of the inverted barometer effect and the oceanic response to atmospheric pressure loading. The potential effects of stratification on this response are explored here using a general circulation model in a near-global domain with realistic coasts and bathymetry. Periodic forcing by the diurnal and semidiurnal atmospheric tides and 6-hourly stochastic forcing from weather center analyses are both examined. A global dynamic response (i.e., departures from inverted barometer behavior) is clear in the response to atmospheric tides; for stochastic forcing, the largest dynamic signals occur in shallow and semienclosed regions and at mid- and high latitudes. The influence of stratification in the dynamics is assessed by comparing surface and bottom pressure signals. Baroclinic effects are generally weak, particularly in the response to the large-scale atmospheric tides. Under stochastic forcing, largest differences between surface and bottom pressure signals reach 10%–20% of the surface signals and tend to occur in regions of enhanced topographic gradients. Bottom-intensified, localized interactions with topography seem to be involved. Enhanced baroclinicity is also seen at low latitudes, where stratification effects are also felt in the upper ocean. General implications for modeling the ocean response to high-frequency atmospheric and tidal forcing are discussed.
Assimilation of Radiocarbon and Chlorofluorocarbon Data to Constrain Deep and Bottom Water Transports in the World Ocean
Authors: Schlitzer Reiner
Published: February 2007

A coarse-resolution global model with time-invariant circulation is fitted to hydrographic and tracer data by means of the adjoint method. Radiocarbon and chlorofluorocarbon (CFC-11 and CFC-12) data are included to constrain deep and bottom water transport rates and spreading pathways as well as the strength of the global overturning circulation. It is shown that realistic global ocean distributions of hydrographic parameters and tracers can be obtained simultaneously. The model correctly reproduces the deep ocean radiocarbon field and the concentrations gradients between different basins. The spreading of CFC plumes in the deep and bottom waters is simulated in a realistic way, and the spatial extent as well as the temporal evolution of these plumes agrees well with observations. Radiocarbon and CFC observations place upper bounds on the northward transports of Antarctic Bottom Water (AABW) into the Pacific, Atlantic, and Indian Oceans. Long-term mean AABW transports larger than 5 Sv (Sv ≡ 106 m3 s−1) through the Vema and Hunter Channels in the South Atlantic and net AABW transports across 30°S into the Indian Ocean larger than 10 Sv are found to be incompatible with CFC data. The rates of equatorward deep and bottom water transports from the North Atlantic and Southern Ocean are of similar magnitude (15.7 Sv at 50°N and 17.9 Sv at 50°S). Deep and bottom water formation in the Southern Ocean occurs at multiple sites around the Antarctic continent and is not confined to the Weddell Sea. A CFC forecast based on the assumption of unchanged abyssal transports shows that by 2030 the entire deep west Atlantic exhibits CFC-11 concentrations larger than 0.1 pmol kg−1, while most of the deep Indian and Pacific Oceans remain CFC free. By 2020 the predicted CFC concentrations in the deep western boundary current (DWBC) in the North Atlantic exceed surface water concentrations and the vertical CFC gradients start to reverse.
A Near-Uniform Basin-Wide Sea Level Fluctuation of the Mediterranean Sea
Authors: Fukumori Ichiro , Menemenlis Dimitris , Lee Tong
Published: February 2007

A new basin-wide oscillation of the Mediterranean Sea is identified and analyzed using sea level observations from the Ocean Topography Experiment (TOPEX)/Poseidon satellite altimeter and a numerical ocean circulation model. More than 50% of the large-scale, nontidal, and non-pressure-driven variance of sea level can be attributed to this oscillation, which is nearly uniform in phase and amplitude across the entire basin. The oscillation has periods ranging from 10 days to several years and has a magnitude as large as 10 cm. The model suggests that the fluctuations are driven by winds at the Strait of Gibraltar and its neighboring region, including the Alboran Sea and a part of the Atlantic Ocean immediately to the west of the strait. Winds in this region force a net mass flux through the Strait of Gibraltar to which the Mediterranean Sea adjusts almost uniformly across its entire basin with depth-independent pressure perturbations. The wind-driven response can be explained in part by wind setup; a near-stationary balance is established between the along-strait wind in this forcing region and the sea level difference between the Mediterranean Sea and the Atlantic Ocean. The amplitude of this basin-wide wind-driven sea level fluctuation is inversely proportional to the setup region’s depth but is insensitive to its width including that of Gibraltar Strait. The wind-driven fluctuation is coherent with atmospheric pressure over the basin and contributes to the apparent deviation of the Mediterranean Sea from an inverse barometer response.
Can Paleoceanographic Tracers Constrain Meridional Circulation Rates?
Authors: Huybers Peter , Gebbie Geoffrey , Marchal Olivier
Published: February 2007

The ability of paleoceanographic tracers to constrain rates of transport is examined using an inverse method to combine idealized observations with a geostrophic model. Considered are the spatial distribution, accuracy, and types of tracers required to constrain changes in meridional transport within an idealized single-hemisphere basin. Measurements of density and radioactive tracers each act to constrain rates of transport. Conservative tracers, while not of themselves able to inform regarding rates of transport, improve constraints when coupled with density or radioactive observations. It is found that the tracer data would require an accuracy one order of magnitude better than is presently available for paleo-observations to conclusively rule out factor-of-2 changes in meridional transport, even when assumed available over the entire model domain. When data are available only at the margins and bottom of the model, radiocarbon is unable to constrain transport while density remains effective only when a reference velocity level is assumed. The difficulty in constraining the circulation in this idealized model indicates that placing firm bounds on past meridional transport rates will prove challenging.
Boutique Multiculturalism and the Consumption of Repulsion: Re-Disseminating Food Fictions in Malaysian and Singaporean Diasporic Novels
Authors: Wagner Tamara S.
Published: February 2007

Food metaphors are among the most vexing clichés of postcolonial and diasporic fiction. But even as they help to promote the marketability of the multicultural, their renegotiation in more self-reflective writing has recently begun to engender new food fictions that capitalize on repulsion as a form of resistance to this demand for self-Orientalization. The curious retention of a marketable exoticizing of food that is indeed as often symbolic, to be rejected, as to be eaten, significantly articulates the growing unease caused by the commercial and ideological exploitation of “boutique multiculturalism” at large, as food symbolism itself acts as a metonym for the consumable exotic. In revaluating the literary potentials of self-irony in the representation of consumption and repulsion as two sides of the same coin, this article draws on diasporic fiction set in Malaysia, Singapore and Australia, including Hsu-Ming Teo’s Behind the Moon (2005), Vyvyanne Loh’s Breaking the Tongue (2004), and Josephine Chia’s growing list of autobiographical novels.
Finding The True Voice of Feeling: Kendrick Smithyman and New Criticism in New Zealand, 1961-1963
Authors: Smithies James
Published: February 2007

Kendrick Smithyman is one of New Zealand’s lesser-known poets and literary critics, but this article argues that he was instrumental in developing a globally oriented critique which provides a welcome line of sight towards both America and the postmodern age. His series of essays on “Post-War New Zealand Poetry”, written between 1961 and 1963 and published in the fringe journal Mate, employed the principles of New Criticism to suggest ways of looking at New Zealand literature that were almost totally at odds with dominant New Zealand critics like Allen Curnow, E. H. McCormick and Bill Pearson. The essays were eventually expanded into the only full-length treatment of New Zealand poetry written ( A Way of Saying, 1965), and represent a substantial contribution to the country’s literary critical tradition.
Venlafaxine—mirtazapine combination in the treatment of persistent depressive illness
Authors: Hannan Noel , Hamzah Zaf , Akinpeloye Henry Omoniyi , Meagher David
Published: February 2007

The combination of mirtazapine and venlafaxine has been suggested as a treatment option for difficult to treat depressive illness. We describe 32 patients with persistent depressive illness (44% male; mean age 42 years; mean 2.5 previous antidepressant trials) that received mirtazapine and venlafaxine in combination at some point over the 3 year period between 2002 and 2005. Clinical response rates (CGI-improvement score of two or less) were 44% at 4 weeks and 50% at 8 weeks. At 6 month review, 18 patients (56% of the original cohort and 75% of those still receiving treatment) had significantly responded. Clinical response typically occurred at moderate and high dose treatment with both agents. A total of 44% experienced some adverse effects with sedation (19%) and weight gain (19%) most frequent. Five patients discontinued treatment due to these effects. No serious adverse effects were linked to the combination treatment. We discuss the implications of these findings for the use of venlafaxine and mirtazapine in combination in more difficult to treat patients with depression.
Risperidone-to-methylphenidate switch reaction in children: three cases
Authors: Sabuncuoglu Osman
Published: February 2007

As atypical antipsychotics are increasingly used in the treatment of childhood behavioural disorders either as monotherapy or in combination with other medications, there is a need to know more about their safety, in particular during switching to and from methylphenidate treatment, as antipsychotics and methylphenidate have opposing effects on dopaminergic neurotransmission. This report is about three cases of children who developed severe adverse reactions during switching from risperidone to methylphenidate. The first patient was a 6-year-old boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). He developed severe hyperactivity and agitation on taking methylphenidate after the discontinuation of risperidone treatment. The second patient was a girl of 6, already on risperidone for ADHD and borderline intellectual functioning when referred. She displayed severe hyperactivity, agitation and irritability upon switching to methylphenidate medication. The third patient was a 15-year-old female adolescent with a similar clinical course as the previous patients. In all the cases described here, it is only with the discontinuation of methylphenidate that the adverse reactions resolved and readministration of methylphenidate in two patients did not produce any adverse effect after a drug-free interval. Functional regulation of certain neuroreceptors during risperidone treatment may lead to altered behavioural responses upon switching to methylphenidate. Thus, a drug-free interval is recommended in order to prevent adverse reactions.
Treatment and disposal alternatives for health-care waste in developing countries – a case study in Istanbul, Turkey
Authors: Alagöz B. Aylin Zeren , Kocasoy Günay
Published: February 2007

Efficient health-care waste management is crucial for the prevention of the exposure of health-care workers, patients, and the community to infections, toxic wastes and injuries as well as the protection of the environment ( Safe Management of Wastes from Health-care Activities. World Health Organization, Geneva). The amount of health-care waste produced in the İstanbul Metropolitan City in Turkey is 30 ton day–1 in total. The method used for the final disposal of most of the health-care waste of Istanbul is incineration. However, a great portion of the infectious waste is disposed of with the domestic waste into the sanitary landfill because of improper segregation practices applied in the health-care institutions. Therefore the alternatives for the treatment and disposal of health-care waste were evaluated. The technical information related to the available treatment technologies including incineration, microwave irradiation, mobile or stationary sterilization, etc. were also investigated. The capital investment cost, transportation/operational costs for each alternative method and the different locations for installation were compared. When the data collected were evaluated, it was found that separate handling and disposal of health-care waste generated on the European and the Asian sides of the city was the most economic and practicable solution. As a result, it was concluded that the capacity of the Kemerburgaz-Odayeri incineration plant is enough to incinerate the health-care waste generated on the European side of Istanbul, the construction of a new incineration plant or a stationary sterilization unit for the disposal of health-care waste generated on the Asian side was the most effective alternative.
Dense resistivity and induced polarization profiling for a landfill restoration project at Härlöv, Southern Sweden
Authors: Leroux Virginie , Dahlin Torleif , Svensson Mats
Published: February 2007

A resistivity and time-domain induced polarization (IP) survey was conducted at a landfill site under restoration at Härlöv in Southern Sweden. The covering of the landfill had begun some years ago, without keeping precise records of the work done, as is usual in such procedures. The survey was conducted in two steps, on two adjacent areas. First, a number of geoelectrical sections were made on a partly covered area that had been investigated earlier by auger drilling, in order to assist restoration. Then, a second area that should have received its final cover was imaged, and some defects in the cover could be detected and repaired. The resistivity and time-domain IP results were consistent with the results of the geotechnical drillings, and they enabled quasi-continuous mapping along the profiles. Three-dimensional visualization showed the overall consistency of the two-dimensional lines, and helped to generate a global view of the site. In spite of some ambiguities, cover and waste could be distinguished in most cases. In particular, fine-grained cover materials could be clearly distinguished from other cover materials.
Institutions and Trust
Authors: Bohnet Iris , Baytelman Yael
Published: February 2007

Institutions matter - but how? This article employs experiments to examine whether institutions only affect trust and trustworthiness behavior by changing constraints and thereby the beliefs people hold about others' behavior, as commonly assumed in a rational choice framework, or also by influencing preferences. In a within-subject design, we confront people with an anonymous one-shot trust game, a one-shot game with pre-play communication, post-play communication and a post-play punishment option and a finitely repeated game. Institutions increasing the cost of betrayal as compared to an anonymous one-shot game affect people's beliefs and enhance their willingness to trust and be trustworthy. However, all settings that offer tighter institutional constraints compared to the anonymous one-shot game decrease intrinsically motivated trust. They do not influence trustworthiness. Thus, institutions may also affect preferences. The ‘crowding-out’ of intrinsic trust is of concern as it has been found to be associated with economic performance and democracy.
Quantitative Assessment and Forecast for Structurally Deficient Bridge Diagnostics
Authors: Farhey Daniel N.
Published: February 2007

Diagnostic instrumentation and monitoring of bridges are essential for reliable structural condition assessment and performance evaluation. Particularly, structurally deficient bridges cannot be accurately evaluated by inspection and/or analysis alone. Reliable evaluation is an economic and engineering requirement before any decision-making for preventive action. Although structural health monitoring for bridge diagnostics appears to be accepted, it is not yet a typical field practice. This article assesses quantitatively the future needs for bridge diagnostics of structurally deficient bridges through structural health monitoring. Logistic components of bridge diagnostics are also discussed. The detailed aspects are intended to help, plan, and manage financial resources and implementation practices for bridge evaluation.
The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies
Authors: Traversari Catia , Marktel Sarah , Magnani Zulma , Mangia Patrizia , Russo Vincenzo , Ciceri Fabio , Bonini Chiara , Bordignon Claudio
Published: February 2007

Gene therapy is a promising therapeutic strategy for genetic and acquired hematologic diseases. With the improvements in gene transfer and expression, factors affecting safety and efficacy of gene therapy can now be evaluated to establish the best clinical benefit-to-risk ratio. The induction of immune responses against gene therapy components is one of the potential limitations. We studied the occurrence of such event in 23 patients treated with donor lymphocyte infusions (DLIs), with lymphocytes transduced to express the HSV-TK suicide gene for relapse of hematologic malignancies occurring after allogeneic hematopoietic stem cell transplantation (HSCT). The suicide gene was used to selectively control graft-versus-host disease (GvHD). Seven patients given infusions late after HSCT developed an immune response against the transgene. Immunization involved appearance of thymidine kinase (TK)–specific CD8+ effectors and required a level of immunocompetence at the time of TK-DLI that can be achieved only several months after transplantation. This did not prevent graft-versus-leukemia (GvL) effect of the TK-DLI, since 5 of 7 immunized patients maintained the complete remission achieved prior to immunization. We suggest that appropriate study designs taking into account the immune suppression of the patient and time-kinetics of GvL mediated by TK-transduced donor lymphocytes may allow the full exploitation of TK-DLI.
Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells
Authors: Bowie Michelle B. , Kent David G. , Copley Michael R. , Eaves Connie J.
Published: February 2007

Fetal hematopoietic stem cells (HSCs) regenerate daughter HSCs in irradiated recipients more rapidly than do adult HSCs. However, both types of HSCs divide in vitro with the same cell-cycle transit times, suggesting different intrinsically determined self-renewal activities. To investigate the mechanism(s) underlying these differences, we compared fetal and adult HSC responses to Steel factor (SF) stimulation in vitro and in vivo. These experiments were undertaken with both wild-type cells and W41/W41 cells, which have a functionally deficient c-kit kinase. In vitro, fetal HSC self-renewal divisions, like those of adult HSCs, were found to be strongly dependent on c-kit activation, but the fetal HSCs responded to much lower SF concentrations in spite of indistinguishable levels of c-kit expression. Fetal W41/W41 HSCs also mimicked adult wild-type HSCs in showing the same reduced rate of amplification in irradiated adult hosts (relative to fetal wild-type HSCs). Assessment of various proliferation and signaling gene transcripts in fetal and adult HSCs self-renewing in vitro revealed a singular difference in Ink4c expression. We conclude that the ability of fetal HSCs to execute symmetric self-renewal divisions more efficiently than adult HSCs in vivo may be dependent on specific developmentally regulated signals that act downstream of the c-kit kinase.
Kit is essential for PMA-inflammation–induced mast-cell accumulation in the skin
Authors: Waskow Claudia , Bartels Susanne , Schlenner Susan M. , Costa Celine , Rodewald Hans-Reimer
Published: February 2007

Cutaneous mast cells have important pathogenic roles in skin inflammation, but the signals regulating mast-cell numbers in healthy and inflamed skin are not fully understood. Mast-cell development depends on the receptor tyrosine kinase Kit as shown by a greater than 95% reduction of mast-cell numbers in hypomorphic (KitW/Wv) mutant mice that are widely used as a mast-cell deficiency model. Mast-cell numbers are normally very low in KitW/Wv mice, but numbers can strongly increase under inflammatory conditions. It remains elusive whether this inflammation-driven mast-cell accumulation is mediated by signals transmitted via the KitWv receptor or by other, Kit-independent stimuli. We show here, using viable Kit- null mice (KitW/W), that Kit is essential for mast-cell accumulation in phorbol-12-myristate-13-acetate (PMA)–treated, chronically inflamed skin. This increase in mast- cell numbers is strongly attenuated in KitW/Wv mice lacking mature lymphocytes (T, B, and natural killer [NK] cells). These data, together with reconstitution experiments, point at a role for lymphocytes in the regulation of mast-cell compartments under limiting Kit signaling. We conclude that inflammation-induced cutaneous mast-cell accumulation is dependent on Kit signaling strength, and, under limiting Kit signals, on cells of the adaptive immune system.
Migratory path of definitive hematopoietic stem/progenitor cells during zebrafish development
Authors: Jin Hao , Xu Jin , Wen Zilong
Published: February 2007

The development of vertebrate definitive hematopoiesis is featured by temporally and spatially dynamic distribution of hematopoietic stem/progenitor cells (HSPCs). It is proposed that the migration of definitive HSPCs, at least in part, accounts for this unique characteristic; however, compelling in vivo lineage evidence is still lacking. Here we present an in vivo analysis to delineate the migration route of definitive HSPCs in the early zebrafish embryo. Cell-marking analysis was able to first map definitive HSPCs to the ventral wall of dorsal aorta (DA). These cells were subsequently found to migrate to a previously unappreciated organ, posterior blood island (PBI), located between the caudal artery and caudal vein, and finally populate the kidney, the adult hematopoietic organ. These findings demonstrate that the PBI acts as an intermediate hematopoietic organ in a manner analogous to the mammalian fetal liver to sustain definitive hematopoiesis before adult kidney hematopoiesis occurs. Thus our study unambiguously documents the in vivo trafficking of definitive HSPCs among developmentally successive hematopoietic compartments and underscores the ontogenic conservation of definitive hematopoiesis between zebrafish and mammals.
The evolutionary history of mitochondrial porins
Authors: Young Matthew J , Bay Denice C , Hausner Georg , Court Deborah A
Published: February 2007

Background

Mitochondrial porins, or voltage-dependent anion-selective channels (VDAC) allow the passage of small molecules across the mitochondrial outer membrane, and are involved in complex interactions regulating organellar and cellular metabolism. Numerous organisms possess multiple porin isoforms, and initial studies indicated an intriguing evolutionary history for these proteins and the genes that encode them.

Results

In this work, the wealth of recent sequence information was used to perform a comprehensive analysis of the evolutionary history of mitochondrial porins. Fungal porin sequences were well represented, and newly-released sequences from stramenopiles, alveolates, and seed and flowering plants were analyzed. A combination of Neighbour-Joining and Bayesian methods was used to determine phylogenetic relationships among the proteins. The aligned sequences were also used to reassess the validity of previously described eukaryotic porin motifs and to search for signature sequences characteristic of VDACs from plants, animals and fungi. Secondary structure predictions were performed on the aligned VDAC primary sequences and were used to evaluate the sites of intron insertion in a representative set of the corresponding VDAC genes.

Conclusion

Our phylogenetic analysis clearly shows that paralogs have appeared several times during the evolution of VDACs from the plants, metazoans, and even the fungi, suggesting that there are no "ancient" paralogs within the gene family. Sequence motifs characteristic of the members of the crown groups of organisms were identified. Secondary structure predictions suggest a common 16 β-strand framework for the transmembrane arrangement of all porin isoforms. The GLK (and homologous or analogous motifs) and the eukaryotic porin motifs in the four representative Chordates tend to be in exons that appear to have changed little during the evolution of these metazoans. In fact there is phase correlation among the introns in these genes. Finally, our preliminary data support the notion that introns usually do not interrupt structural protein motifs, namely the predicted β-strands. These observations concur with the concept of exon shuffling, wherein exons encode structural modules of proteins and the loss and gain of introns and the shuffling of exons via recombination events contribute to the complexity of modern day proteomes.
Availability and quality of paraffin blocks identified in pathology archives: A multi-institutional study by the Shared Pathology Informatics Network (SPIN)
Authors: Patel Ashokkumar A , Gupta Dilipkumar , Seligson David , Hattab Eyas M , Balis Ulysses J , Ulbright Thomas M , Kohane Isaac S , Berman Jules J , Gilbertson John R , Dry Sarah , Schirripa Osvaldo , Yu Hong , Becich Michael J , Parwani Anil V ,   the Shared Pathology Informatics Network
Published: February 2007

Background

Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that utilizes clinical reports of the vast amount of paraffin-embedded tissues routinely stored by medical centers. SPIN has an informatics component (sending tissue-related queries to multiple institutions via the internet) and a service component (providing histopathologically annotated tissue specimens for medical research). This paper examines if tissue blocks, identified by localized computer searches at participating institutions, can be retrieved in adequate quantity and quality to support medical researchers.

Methods

Four centers evaluated pathology reports (1990–2005) for common and rare tumors to determine the percentage of cases where suitable tissue blocks with tumor were available. Each site generated a list of 100 common tumor cases (25 cases each of breast adenocarcinoma, colonic adenocarcinoma, lung squamous carcinoma, and prostate adenocarcinoma) and 100 rare tumor cases (25 cases each of adrenal cortical carcinoma, gastro-intestinal stromal tumor [GIST], adenoid cystic carcinoma, and mycosis fungoides) using a combination of Tumor Registry, laboratory information system (LIS) and/or SPIN-related tools. Pathologists identified the slides/blocks with tumor and noted first 3 slides with largest tumor and availability of the corresponding block.

Results

Common tumors cases (n = 400), the institutional retrieval rates (all blocks) were 83% (A), 95% (B), 80% (C), and 98% (D). Retrieval rate (tumor blocks) from all centers for common tumors was 73% with mean largest tumor size of 1.49 cm; retrieval (tumor blocks) was highest-lung (84%) and lowest-prostate (54%).

Rare tumors cases (n = 400), each institution's retrieval rates (all blocks) were 78% (A), 73% (B), 67% (C), and 84% (D). Retrieval rate (tumor blocks) from all centers for rare tumors was 66% with mean largest tumor size of 1.56 cm; retrieval (tumor blocks) was highest for GIST (72%) and lowest for adenoid cystic carcinoma (58%).

Conclusion

Assessment shows availability and quality of archival tissue blocks that are retrievable and associated electronic data that can be of value for researchers. This study serves to compliment the data from which uniform use of the SPIN query tools by all four centers will be measured to assure and highlight the usefulness of archival material for obtaining tumor tissues for research.
Understanding and modifying the impact of parents' substance
misuse on children
Authors: Velleman Richard , Templeton Lorna
Published: February 2007

We outline the huge literature on the potentially negative impact on
children of growing up with a parent who has an alcohol or drug problem, the
risk factors that can exacerbate this effect, and resilience and the
protective factors that can reduce it. Clear ways that practitioners can
intervene to reduce risk and to increase resilience are discussed. All
practitioners have a responsibility to work in holistic ways if damage to
children and families is to be avoided, and we summarise the key common
skills needed to work with individuals (children as well as adults) and
families. The differences between a resilience and a deficit approach are
outlined.
Why, when and how to ask about childhood abuse
Authors: Read John , Hammersley Paul , Rudegeair Thom
Published: February 2007

Subscribers to the medical model of the causation of madness and distress
emphasise the role of genes and can severely underestimate the impact of
traumatic events on the development of the human mind. This bias persists
despite the worldwide popular wisdom that mental illness arises when bad
things happen to people. Childhood physical and sexual abuse and neglect are
extremely common experiences among those who develop serious mental health
problems. Unfortunately, victims are typically reluctant to disclose their
histories of abuse and practitioners are often reluctant to seek it. We
explore the nature and extent of the problem and the apparent reasons for
the pervasive neglect of this important area of care. Then, on the basis of
our experience in New Zealand, we provide guidelines on asking patients
about childhood abuse and describe an ongoing initiative in the UK to
further advance our understanding of the impact of abuse and our skills to
detect it and treat survivors.
Service innovation: transitional attention-deficit hyperactivity disorder clinic
Authors: Verity Robert , Coates John
Published: February 2007

Attention-deficit hyperactivity disorder (ADHD) affects 3–7% of school-age children (Goldman et al, 1998) and causes symptoms of inattention, hyperactivity and impulsivity (DSM–IV; American Psychiatric Association, 1994). In the UK, many adolescents are currently being treated for ADHD; the prevalence of treated ADHD among boys aged 5–14 years was estimated at 5.3 per 1000 in 1999 (Jick et al, 2004). This means that over 40 000 boys aged 5–14 years are currently treated in the UK (2001 Census; http://www.Statistics.gov.uk/census2001/census2001.asp).
Clinical attachments in psychiatry
Authors: O'Shea Rory , Nimmagadda Srikanth
Published: February 2007

This article discusses the history of clinical attachments in psychiatry and recent changes in this area, including work permit regulations, which can make it increasingly difficult to obtain an attachment. The advantages and disadvantages of clinical attachments are considered for both the clinical attache and the UK health service. Good practice points for clinical attaches and their supervisors are presented. The future of the scheme is discussed and potential solutions to difficulties are suggested.
Teaching psychiatrists to teach: qualifications in clinical education for psychiatrists
Authors: Dinniss Stephen , Bowers Richard , Christopher Antony
Published: February 2007

The education and training of medical students and trainees is a key role of senior clinicians, and the General Medical Council states we ‘must develop the skills, attitudes and practices of a competent teacher’ (General Medical Council, 2005). The Royal College of Psychiatrists places the role of educator as a core competency for psychiatrists (Bhugra, 2005) and believes we should understand ‘the principles of education and use teaching methods appropriate to educational objectives' (Royal College of Psychiatrists, 2004).
The ADMA/DDAH pathway is a critical regulator of endothelial cell motility
Authors: Wojciak-Stothard Beata , Torondel Belen , Tsang Lillian Yen Fen , Fleming Ingrid , Fisslthaler Beate , Leiper James M. , Vallance Patrick
Published: February 2007

Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide production associated with abnormal blood vessel growth and repair, however, the mechanism of action of ADMA is not well understood. We studied the role of exogenous and endogenous ADMA in the regulation of cell motility and actin cytoskeleton in porcine pulmonary endothelial cells (PAECs) and pulmonary microvascular endothelial cells (PMECs) from knockout mice that lack one of the enzyme metabolising ADMA, dimethylarginine dimethylaminohydrolase I (DDAHI) as well as endothelial cells overexpressing DDAH in vitro.

We show that ADMA induced stress fibre and focal adhesion formation and inhibited cell motility in primary pulmonary endothelial cells. The effects of ADMA depended on the activity of RhoA and Rho kinase and were reversed by overexpression of DDAH, nitric oxide donors and protein kinase G activator, 8-bromo-cGMP. ADMA also inhibited the activities of Rac1 and Cdc42 in cells but these changes had a minor effect on cell motility. Endogenous ADMA increased RhoA activity and inhibited cell motility in PMECs from DDAHI knockout mice and inhibited angiogenesis in vitro. These results are the first demonstration that metabolism of cardiovascular risk factor ADMA regulates endothelial cell motility, an important factor in angiogenesis and vascular repair.
Square deployable frames for space applications. Part 2: Realization
Authors: Chen Y , You Z
Published: February 2007

In a sister paper, the authors have proved mathematically that the three-dimensional 4 R overconstrained Bennett linkage has an alternative form allowing it to be folded up completely. In this paper, the ways of building such structures are shown. For design purposes, a set of design parameters is introduced that could be used for rapid prototyping because they are closely linked with the final expanded configuration. The relationships between the design and geometrical parameters, commonly used to describe the Bennett linkages by kinematicians, have been derived. Moreover, the concept of a single compact folding Bennett linkage has been extended to a grid in which the Bennett linkages are nested within each other. The new assembly retains all the common features of the single linkage. A series of physical models were made, which successfully demonstrate the concept.