bluuebunny/crossref_metadata_2025 huggingface dataset:
ENERGETIC PROTON ACCELERATION BY ULTRAINTENSE LASER PULSES IN INHOMOGENEOUS PLASMA TARGETS
Authors: ABUDUREXITI A. , MIKADO Y. , OKADA T.
Published: February 2007

Particle-in-Cell (PIC) simulations of fast particles produced by a short laser pulse with duration of 40 fs and an intensity of 1020W/cm2 interacting with a foil target are performed. The experimental process is numerically simulated by considering a triangular concave target illuminated by an ultraintense laser. We have demonstrated increased acceleration and higher proton energies for triangular concave targets. We also determined the optimum target plasma conditions for maximum proton acceleration. The results indicated that a change in the plasma target shape directly affects the degree of contraction accelerated proton bunch.
THE GEOMETRY OF QUADRATIC DIFFERENTIAL SYSTEMS WITH A WEAK FOCUS OF SECOND ORDER
Authors: ARTÉS JOAN C. , LLIBRE JAUME , SCHLOMIUK DANA
Published: February 2007

Planar quadratic differential systems occur in many areas of applied mathematics. Although more than one thousand papers were written on these systems, a complete understanding of this class is still missing. Classical problems, and in particular, Hilbert's 16th problem [Hilbert, 1900, 1902], are still open for this class. In this article we make an interdisciplinary global study of the subclass [Formula: see text] which is the closure within real quadratic differential systems, of the family QW2 of all such systems which have a weak focus of second order. This class [Formula: see text] also includes the family of all quadratic differential systems possessing a weak focus of third order and topological equivalents of all quadratic systems with a center.

The bifurcation diagram for this class, done in the adequate parameter space which is the three-dimensional real projective space, is quite rich in its complexity and yields 373 subsets with 126 phase portraits for [Formula: see text], 95 for QW2, 20 having limit cycles but only three with the maximum number of limit cycles (two) within this class. The phase portraits are always represented in the Poincaré disc. The bifurcation set is formed by an algebraic set of bifurcations of singularities, finite or infinite and by a set of points which we suspect to be analytic corresponding to global separatrices which have connections.

Algebraic invariants were needed to construct the algebraic part of the bifurcation set, symbolic computations to deal with some quite complex invariants and numerical calculations to determine the position of the analytic bifurcation set of connections.

The global geometry of this class [Formula: see text] reveals interesting bifurcations phenomena; for example, all phase portraits with limit cycles in this class can be produced by perturbations of symmetric (reversible) quadratic systems with a center. Many other nonlinear phenomena displayed here form material for further studies.
A NEW TWO-DIMENSIONAL COMPLEXITY MEASURE
Authors: CAI ZHIJIE , SHEN ENHUA , GU FANJI , XU ZHENGJIE , RUAN JIONG , CAO YANG
Published: February 2007

In this paper, a new two-dimensional complexity measure, 2D C0 complexity, which is shown to be a reasonable measure under the meaning of randomness finding complexity, is presented and its mathematical properties are proved. This complexity measure is robust for short data and it is calculated easily. An application to characterize the optical imaging orientation functional map in cat visual cortex is also shown.
HIGH AND LOW FREQUENCY OSCILLATIONS IN DRUG EPIDEMICS
Authors: CAULKINS JONATHAN P. , GRAGNANI ALESSANDRA , FEICHTINGER GUSTAV , TRAGLER GERNOT
Published: February 2007

We extend the two-dimensional model of drug use introduced in [Behrens et al., 1999, 2000, 2002] by considering two additional states that represent in more detail newly initiated ("light") users' response to the drug experience. Those who dislike the drug quickly "quit" and briefly suppress initiation by others. Those who like the drug progress to ongoing ("moderate") use, from which they may or may not escalate to "heavy" or dependent use. Initiation is spread contagiously by light and moderate users, but is moderated by the drug's reputation, which is a function of the number of unhappy users (recent quitters + heavy users). The model reproduces recent prevalence data reasonably well from the U.S. cocaine epidemic, with one pronounced peak followed by decay toward a steady state. However, minor variation in parameter values yields both long-run periodicity with a period akin to the gap between the first U.S. cocaine epidemic (peak ~1910) and the current one (peak ~1980), as well as short-run periodicity akin to that observed in data on youthful use for a variety of substances. The combination of short- and long-run periodicity is reminiscent of the elliptical burstors described by Rubin and Terman [2002]. The existence of such complex behavior including cycles, quasi periodic solutions, and chaos is proven by means of bifurcation analysis.
BIOLOGICALLY INSPIRED CIRCUITS: COALITION FORMATION IN AGGREGATES
Authors: HOPPENSTEADT FRANK
Published: February 2007

Knowledge of how a hippocampal brain structure works is informative for the design of circuits and architectures of practical use in pattern recognition. A new model for neural membrane dynamics is derived here that is consistent with micro- and nano-circuits, and it is employed to analyze the response of an aggregate of oscillators to common forcing. The result is a pattern of resonant responses that can serve as a basis for comparison in pattern recognition methodologies that we are investigating elsewhere.
Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy
Authors: Hassoun Heitham T. , Grigoryev Dmitry N. , Lie Mihaela L. , Liu Manchang , Cheadle Chris , Tuder Rubin M. , Rabb Hamid
Published: February 2007

Acute kidney injury (AKI) is associated with significant mortality, which increases further when combined with acute lung injury. Experiments in rodents have shown that kidney ischemia-reperfusion injury (IRI) facilitates lung injury and inflammation. To identify potential ischemia-specific lung molecular pathways involved, we conducted global gene expression profiling of lung 6 or 36 h following 1) bilateral kidney IRI, 2) bilateral nephrectomy (BNx), and 3) sham laparotomy in C57BL/6J mice. Bronchoalveolar lavage fluid analysis revealed increased total protein, and lung histology revealed increased cellular inflammation following IRI, but not BNx, compared with sham controls. Total RNA from whole lung was isolated and hybridized to 430MOEA (22,626 genes) GeneChips ( n = 3/group), which were analyzed by robust multichip average and significance analysis of microarrays and linked to gene ontology (GO) terms using MAPPFinder. The microarray power analysis predicted that the false discovery rate ( q < 1%) and ≥50%-fold change compared with sham would represent significant changes in gene expression. Analysis identified 266 and 455 ischemia-specific, AKI-associated lung genes with increased expression and 615 and 204 with decreased expression at 6 and 36 h, respectively, compared with sham controls. Real-time PCR analysis validated select array changes in lung serum amyloid A3 and endothelin-1. GO analysis revealed significant activation ( Z > 1.95) of several proinflammatory and proapoptotic biological processes. Ischemic AKI induces functional and transcriptional changes in the lung distinct from those induced by uremia alone. Further investigation using this lung molecular signature induced by kidney IRI will provide mechanistic insights and new therapies for critically ill patients with AKI.
Albumin overload induces adaptive responses in human proximal tubular cells through oxidative stress but not via angiotensin II type 1 receptor
Authors: Shalamanova Liliana , McArdle Frank , Amara Alieu B. , Jackson Malcolm J. , Rustom Rana
Published: February 2007

Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.
Evidence that renal arterial-venous oxygen shunting contributes to dynamic regulation of renal oxygenation
Authors: Leong Chai-Ling , Anderson Warwick P. , O'Connor Paul M. , Evans Roger G.
Published: February 2007

Renal blood flow (RBF) can be reduced in rats and rabbits by up to 40% without significant changes in renal tissue Po2. We determined whether this occurs because renal oxygen consumption changes with RBF or due to some other mechanism. The relationships between RBF and renal cortical and medullary tissue Po2 and renal oxygen metabolism were determined in the denervated kidneys of anesthetized rabbits under hypoxic, normoxic, and hyperoxic conditions. During artificial ventilation with 21% oxygen (normoxia), RBF increased 32 ± 8% during renal arterial infusion of acetylcholine and reduced 31 ± 5% during ANG II infusion. Neither infusion significantly altered arterial pressure, tissue Po2 in the renal cortex or medulla, nor renal oxygen consumption. However, fractional oxygen extraction fell as RBF increased and the ratio of oxygen consumption to sodium reabsorption increased during ANG II infusion. Ventilation with 10% oxygen (hypoxia) significantly reduced both cortical and medullary Po2 (60–70%), whereas ventilation with 50% and 100% oxygen (hyperoxia) increased cortical and medullary Po2 (by 62–298 and 30–56%, respectively). However, responses to altered RBF under hypoxic and hyperoxic conditions were similar to those under normoxic conditions. Thus renal tissue Po2 was relatively independent of RBF within a physiological range (±30%). This was not due to RBF-dependent changes in renal oxygen consumption. The observation that fractional extraction of oxygen fell with increased RBF, yet renal parenchymal Po2 remained unchanged, supports the hypothesis that preglomerular diffusional shunting of oxygen from arteries to veins increases with increasing RBF, and so contributes to dynamic regulation of intrarenal oxygenation.
Hungary, Suez, and Hannah Arendt
Authors: Hitchens Christopher
Published: February 2007

This essay is adapted from the keynote lecture at Thinking in Dark Times, A Conference in Honor of Hannah Arendt on the 100th Anniversary of Her Birth, sponsored by Bard College in October 2006.
Statistical Parameterization of Heterogeneous Oceanic Convection
Authors: Pasquero Claudia , Tziperman Eli
Published: February 2007

A statistical convective adjustment scheme is proposed that attempts to account for the effects of mesoscale and submesoscale variability of temperature and salinity typically observed in the oceanic convective regions. Temperature and salinity in each model grid box are defined in terms of their mean, variance, and mutual correlations. Subgrid-scale instabilities lead to partial mixing between different layers in the water column. This allows for a smooth transition between the only two states (convection on and convection off) allowed in standard convective adjustment schemes. The advantage of the statistical parameterization is that possible instabilities associated with the sharp transition between the two states, which are known to occasionally affect the large-scale model solution, are eliminated. The procedure also predicts the generation of correlations between temperature and salinity and the presence of convectively induced upgradient fluxes that have been obtained in numerical simulations of heterogeneous convection and that cannot be represented by standard convective adjustment schemes.
Regional Dynamic and Steric Sea Level Change in Response to the IPCC-A1B Scenario
Authors: Landerer Felix W. , Jungclaus Johann H. , Marotzke Jochem
Published: February 2007

This paper analyzes regional sea level changes in a climate change simulation using the Max Planck Institute for Meteorology (MPI) coupled atmosphere–ocean general circulation model ECHAM5/MPI-OM. The climate change scenario builds on observed atmospheric greenhouse gas (GHG) concentrations from 1860 to 2000, followed by the International Panel on Climate Change (IPCC) A1B climate change scenario until 2100; from 2100 to 2199, GHG concentrations are fixed at the 2100 level. As compared with the unperturbed control climate, global sea level rises 0.26 m by 2100, and 0.56 m by 2199 through steric expansion; eustatic changes are not included in this simulation. The model’s sea level evolves substantially differently among ocean basins. Sea level rise is strongest in the Arctic Ocean, from enhanced freshwater input from precipitation and continental runoff, and weakest in the Southern Ocean, because of compensation of steric changes through dynamic sea surface height (SSH) adjustments. In the North Atlantic Ocean (NA), a complex tripole SSH pattern across the subtropical to subpolar gyre front evolves, which is consistent with a northward shift of the NA current. On interannual to decadal time scales, the SSH difference between Bermuda and the Labrador Sea correlates highly with the combined baroclinic gyre transport in the NA but only weakly with the meridional overturning circulation (MOC) and, thus, does not allow for estimates of the MOC on these time scales. Bottom pressure increases over shelf areas by up to 0.45 m (water column equivalent) and decreases over the Atlantic section in the Southern Ocean by up to 0.20 m. The separate evaluation of thermosteric and halosteric sea level changes shows that thermosteric anomalies are positive over most of the World Ocean. Because of increased atmospheric moisture transport from low to high latitudes, halosteric anomalies are negative in the subtropical NA and partly compensate thermosteric anomalies, but are positive in the Arctic Ocean and add to thermosteric anomalies. The vertical distribution of thermosteric and halosteric anomalies is highly nonuniform among ocean basins, reaching deeper than 3000 m in the Southern Ocean, down to 2200 m in the North Atlantic, and only to depths of 500 m in the Pacific Ocean by the end of the twenty-first century.
New Labours, Older Nativisms? Australian Critical Whiteness Studies, Indigeneity and David Malouf’s Harland’s Half Acre
Authors: Mullaney Julie
Published: February 2007

This article assesses the “new” labours of Australian critical whiteness studies and “older” fantasies of white indigeneity. Nativist “turns” on the creation of a white indigeneity, exemplified in David Malouf’s Harland’s Half Acre, are revisited in the language and rhetorical gestures of whiteness studies, which may suggest both the debt and stranglehold of nativism. Whiteness studies’ preoccupation with an ever more self-questioning and constantly shifting whiteness, are prefigured in Malouf’s novel and his quest for a settled white indigene. If an embodied white indigeneity represents, for Malouf, relief from ghostly non-belongings associated with an unsettled settler culture, for whiteness studies it represents the possible derailment of its ethical intentions, destabilized by the prospect of an embodied, uncontrolled and monstrously reproducing whiteness. However, recognition of the incommensurability of indigenous and non-indigenous understandings of sovereignty in whiteness studies and the commitment to reworking the grounds of non-indigenous investments in sovereignty suggests departure from earlier nativisms.
Identification of feigned maximal shoulder external rotation effort
Authors: Chaler Joaquim , Dvir Zeevi , Díaz Urko , Quintana Salvador , Abril Àngels , Unyó Carme , Garreta Roser
Published: February 2007

Objective: To examine the efficiency of the difference between the isokinetic eccentric to concentric strength ratios at high and low velocities (DEC) for identifying feigned maximal shoulder external rotation effort.

Background: Previous studies have indicated that the DEC is a powerful identifier of feigned maximal effort. However comparison of maximal versus feigned maximal shoulder external rotation effort has not been undertaken. Due to the high prevalence of rotational shoulder disorders and their chronic ramifications in terms of occupational disability such a study is of specific interest.

Design: Maximal and feigned maximal shoulder external rotation isokinetic efforts were compared.

Setting: Functional evaluation unit at an occupational rehabilitation centre.

Subjects: Seventeen healthy male volunteers aged between 20 and 40 years old.

Main measure: Concentric and eccentric isokinetic tests at 30°/s and 120°/s in maximal and feigned maximal experimental conditions. DEC was calculated by subtracting the 30°/s eccentric/concentric peak torque ratios from the 120°/s ones for both experimental conditions.

Results: A case-by-case analysis revealed that the DEC scores derived from the feigned effort were significantly greater than their maximal counterparts in all cases, leading to a cut-off value (0.81) which could distinguish between maximal and feigned performances.

Conclusions: The findings indicate that the DEC is highly effective in identifying feigned shoulder external rotation effort in normal subjects.
Perceptions of self-efficacy and rehabilitation among neurologically disabled adults
Authors: Dixon Guy , Thornton Everard W , Young Carolyn A
Published: February 2007

Objective: To explore constructs relevant to self-efficacy in neurological rehabilitation.

Design: Qualitative methods using semi-structured interviews.

Setting: Specialist neurological rehabilitation unit, Liverpool, UK.

Subjects: Twenty-four patients (12 male) with experience of inpatient rehabilitation, aged 17-59 (mean 38.1) years at onset, with diagnoses of stroke ( n = 8), traumatic brain injury ( n = 6) or other monophasic neurological impairment ( n = 10).

Results: Eleven themes emerged from the data that reflect self-efficacy beliefs: self-reliance and independence were deemed important and many patients recognized the importance of determination, making time to take an active role and working in partnership with the multidisciplinary team. Patients had complex information needs but were able to use goal setting and the vicarious experiences of other inpatients to map out the stages of their own recovery. It was important for patients to be able to recognize for themselves that they were making progress and they valued external reassurance on this from other patients, staff and visitors. A number of difficulties were identified that interfered with their developing self-efficacy in rehabilitation, such as structuring their time. Two different models for rehabilitation emerged from the data, ‘recovery’ and ‘adaptation’.

Conclusions: Patients consistently identified 11 factors falling in the supraordinate themes of self, others and process, and these influenced their self-efficacy to participate in neurological rehabilitation. Patients consider rehabilitation in terms of either an ‘adaptation’ or ‘recovery’ model.
Sinterability study of ceramic bodies made from a mixture of mineral coal bottom ash and soda-lime glass cullet
Authors: Villanova Daniela L. , Bergmann Carlos P.
Published: February 2007

The aim of this study was to investigate the sinterability to improve the technical properties of ceramic bodies made from coal bottom ash and soda-lime glass cullet. Different mixtures of bottom ash and glass cullet were formulated. The amount of bottom ash was 100, 70, 50 and 30 wt.%. The particle size distribution was the same for all formulations. The mixture containing 50 wt.% bottom ash also had its particle size distribution changed. Samples were formed by dry pressing and then fired at 950, 1050 and 1150°C. Samples were evaluated for linear shrinkage, water absorption, flexural mechanical resistance, scanning electronic microscopy, pyroplastic deformation and thermodilatometric analysis. The higher firing temperature led to a decrease in water absorption and increased linear shrinkage, mechanical resistance and pyroplastic deformation. This effect was also observed for addition of glass up to 50 wt.%. The effect of smaller particles of bottom ash was more significant for linear shrinkage and mechanical resistance of ceramic bodies fired at 1150°C. The use of a finer powder contributed to increase these properties. The influence of finer particles on water absorption and mechanical resistance of ceramic bodies fired at 950 and 1050°C was not significant.
Optimization of anaerobic digestion of municipal solid waste in combined process and sequential staging
Authors: Juanga Jeanger P. , Visvanathan Chettiyappen , Tränkler Josef
Published: February 2007

The optimization of anaerobic digestion aims to maximize organic waste stabilization after a short digestion period. This paper presents the optimization performance of the combined anaerobic digestion and sequential staging concept in a thermophilic, solid-state batch system as a treatment technology prior to landfill. The former involves enhanced pre-stage flushing with the addition of microaeration and inoculum in the methane phase. The latter involves leachate cross-recirculation between the mature and fresh waste reactors without conducting a pre-stage operation. The optimized process for combined anaerobic digestion showed that reducing the pre- stage operation with the maximum removal of organics from the waste bed is beneficial. Moreover, the sequential staging concept offers an improved process over the combined anaerobic digestion wherein the specific methane yield of 11.9 and 7.2 L CH4 kg-1 volatile solids (VS) per day was achieved, respectively. After 28 days of operation, the sequential staging process showed an improved waste stabilization with 86 and 79% mass and volume reduction, respectively. A higher methane yield of 334 L CH4 kg-1 VS with 86% VS reduction, which is equivalent to 84% process efficiency was obtained.
Working your Way in
Authors: de Ruijter Esther , Weesie Jeroen
Published: February 2007

This article studies the influence of trust problems and social embeddedness on the behavior of home maintenance suppliers, especially (1) their efforts to convince households of their trustworthiness, and (2) whether or not they will behave opportunistically. Data were collected by means of a vignette experiment among 83 home maintenance suppliers, with a total of 165 vignettes. To some extent, the problem potential increases the efforts suppliers make to convince the household of their trustworthiness; a large transaction volume increases the amount of time spent on drawing up a quotation. Suppliers are more likely to behave opportunistically if more complex jobs are involved. Network embeddedness prevents opportunism and decreases the investments made in commitments, while dyadic embeddedness has no effect. Apparently, it is less important for suppliers to invest in dyadic relations than staying on good terms with people who can spread negative information about them to others.
Determination of Railway Vertical Wheel Impact Magnitudes: Field Trials
Authors: Lee M. L. , Chiu W. K.
Published: February 2007

The authors utilized both experimental and finite element modeling methods earlier to develop both a classical inverse approach as well as a root mean square (RMS) method to estimate the magnitude of wheel impact forces on railway track-like structures. This study presents some results from the field trials of the techniques developed in (Lee, M.L., Chiu, W.K. and Koss, L.L (2005). A numerical study into the reconstruction of impact forces on railway track-like structures. Structural Health Monitoring: An International Journal, 4(1), 19–45. Lee, M.L. and Chiu, W.K (2005). The reconstruction of dynamic impact forces on a railway track-like structure by using an inverse analysis technique. In: Proceedings of the 4th Australasian Congress of Applied Mechanics, pp. 605–610, Melbourne, Australia. Lee, M.L. and Chiu, W.K. (2005). A comparative study on impact force prediction on a railway track-like structure. Structural Health Monitoring: An International Journal, 4(4), 355–376.). A length of track carrying freight rail traffic and situated along the Melbourne–Geelong line (Victoria, Australia) is instrumented with accelerometers and shear-bridges. The instrumentation consists of five rail cribs instrumented with a shear-bridge and an accelerometer on the rail foot at the midspan of each crib. Using the shear-bridge instrumentation as a check, it is found that the proposed inverse analysis method (IAM) shows potential in not only reconstructing clean impact strikes but also in reconstructing strikes occurring outside of the shear-bridge effective zone within a single crib. Furthermore, based on the principle of superposition governing linear systems, multiple impact strikes within a single crib of rail are also able to be reconstructed. Regarding the RMS method, it is found that while a good correlation (R ≈ 0.8) existed between wheel impact force and track response RMS, a significant spread existed in the data.
Antitumor effects of HSV-TK–engineered donor lymphocytes after allogeneic stem-cell transplantation
Authors: Ciceri Fabio , Bonini Chiara , Marktel Sarah , Zappone Elisabetta , Servida Paolo , Bernardi Massimo , Pescarollo Alessandra , Bondanza Attilio , Peccatori Jacopo , Rossini Silvano , Magnani Zulma , Salomoni Monica , Benati Claudia , Ponzoni Maurilio , Callegaro Luciano , Corradini Paolo , Bregni Marco , Traversari Catia , Bordignon Claudio
Published: February 2007

The extensive exploitation of the antitumor effect of donor lymphocytes infused after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is limited by the risk of graft-versus-host disease (GvHD). To overcome this limitation, we investigated the therapeutic potential of donor lymphocytes engineered with the suicide gene thymidine kinase of herpes simplex virus (TK) in 23 patients experiencing recurrence of hematologic malignancies after allo-HSCT. Long-term follow-up of infused patients included analysis of engraftment of genetically engineered lymphocytes, in vivo assessment of antitumor effect, and control of GvHD by ganciclovir. All 17 patients evaluable for engraftment and graft-versus-leukemia (GvL) had circulating TK+ cells detectable beginning at a median time of 18 days. Eleven patients (65%) experienced a substantial clinical benefit resulting in 6 (35%) complete remissions and 5 (29%) partial responses. The antitumor effect tightly correlated with the in vivo expansion of TK+ cells. Seven patients received ganciclovir, resulting in elimination of TK+ cells and effective and selective treatment of GvHD. Immunization against HSV-TK was observed in 7 patients but did not preclude an effective GvL. These data validate the feasibility, safety, and efficacy of TK+ cells in the context of allografting and represent the basis for a broader application of this technology.
CD4 cells can be more efficient at tumor rejection than CD8 cells
Authors: Perez-Diez Ainhoa , Joncker Nathalie T. , Choi Kyungho , Chan William F. N. , Anderson Colin C. , Lantz Olivier , Matzinger Polly
Published: February 2007

Researchers designing antitumor treatments have long focused on eliciting tumor-specific CD8 cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T “helper” cells might also serve as antitumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study, we compared monoclonal populations of tumor-specific CD4 and CD8 T cells as effectors against several different tumors, and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed major histocompatibility complex (MHC) class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with NK cells to obtain the maximal antitumor effect. These findings suggest that CD4 T cells can be powerful antitumor effector cells that can, in some cases, outperform CD8 T cells, which are the current “gold standard” effector cell in tumor immunotherapy.
Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist
Authors: Jenkins Julian M. , Williams Daphne , Deng Yanli , Uhl Joanne , Kitchen Valerie , Collins David , Erickson-Miller Connie L.
Published: February 2007

Eltrombopag (SB-497 115) is a first-in-class, oral, small-molecule, nonpeptide agonist of the thrombopoietin receptor (TpoR), being developed as a treatment for thrombocytopenia of various etiologies. In this phase 1 placebo-controlled clinical trial in 73 healthy male subjects, eltrombopag was administered as once-daily oral capsules for 10 days at doses of 5, 10, 25, 30, 50, and 75 mg. The pharmacokinetics of eltrombopag were dose dependent and linear, and eltrombopag increased platelet counts in a dose-dependent manner. There were no apparent differences in the incidence or severity of adverse events in subjects receiving active or placebo study medication. These observations indicate that eltrombopag is a once-daily, oral TpoR agonist with demonstrated thrombopoietic activity in human subjects, encouraging further studies in patients with thrombocytopenia.
Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival
Authors: Cerhan James R. , Wang Sophia , Maurer Matthew J. , Ansell Stephen M. , Geyer Susan M. , Cozen Wendy , Morton Lindsay M. , Davis Scott , Severson Richard K. , Rothman Nathaniel , Lynch Charles F. , Wacholder Sholom , Chanock Stephen J. , Habermann Thomas M. , Hartge Patricia
Published: February 2007

Recent gene-expression data have suggested that host immune genetic signatures may predict outcomes in patients with follicular lymphoma. We evaluated the hypothesis that germ line common variation in candidate immune genes is associated with survival. Cox models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for individual SNPs after accounting for age, clinical, and other demographic factors. The median age at diagnosis of the 278 patients was 57 years, and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27-78 months) for surviving patients. SNPs in IL8 (rs4073; HRTT = 2.14, 1.26-3.63), IL2 (rs2069762; HRGT/TT = 1.80, 1.06-3.05), IL12B (rs3212227; HRAC/CC = 1.83, 1.06-3.06), and IL1RN (rs454078; HRAA = 1.93, 1.11-3.34) were the most robust predictors of survival. A summary score of the number of deleterious genotypes from these genes was strongly associated with survival (P = .001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (P < .001); the 5-year Kaplan-Meier survival estimates were 96% (93%-100%), 72% (62%-83%), and 58% (48%-72%) for groups at low, intermediate, and high risk, respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.
Dynamic regulation of Gata factor levels is more important than their identity
Authors: Ferreira Rita , Wai Albert , Shimizu Ritsuko , Gillemans Nynke , Rottier Robbert , von Lindern Marieke , Ohneda Kinuko , Grosveld Frank , Yamamoto Masayuki , Philipsen Sjaak
Published: February 2007

Three Gata transcription factors (Gata1, -2, and -3) are essential for hematopoiesis. These factors are thought to play distinct roles because they do not functionally replace each other. For instance, Gata2 messenger RNA (mRNA) expression is highly elevated in Gata1-null erythroid cells, yet this does not rescue the defect. Here, we test whether Gata2 and -3 transgenes rescue the erythroid defect of Gata1-null mice, if expressed in the appropriate spatiotemporal pattern. Gata1, -2, and -3 transgenes driven by β-globin regulatory elements, directing expression to late stages of differentiation, fail to rescue erythropoiesis in Gata1-null mutants. In contrast, when controlled by Gata1 regulatory elements, directing expression to the early stages of differentiation, Gata1, -2, and -3 do rescue the Gata1-null phenotype. The dramatic increase of endogenous Gata2 mRNA in Gata1-null progenitors is not reflected in Gata2 protein levels, invoking translational regulation. Our data show that the dynamic spatiotemporal regulation of Gata factor levels is more important than their identity and provide a paradigm for developmental control mechanisms that are hard-wired in cis-regulatory elements.
In vivo vasculogenic potential of human blood-derived endothelial progenitor cells
Authors: Melero-Martin Juan M. , Khan Zia A. , Picard Arnaud , Wu Xiao , Paruchuri Sailaja , Bischoff Joyce
Published: February 2007

Vascularization of tissues is a major challenge of tissue engineering (TE). We hypothesize that blood-derived endothelial progenitor cells (EPCs) have the required proliferative and vasculogenic activity to create vascular networks in vivo. To test this, EPCs isolated from human umbilical cord blood or from adult peripheral blood, and human saphenous vein smooth muscle cells (HSVSMCs) as a source of perivascular cells, were combined in Matrigel and implanted subcutaneously into immunodeficient mice. Evaluation of implants at one week revealed an extensive network of human-specific lumenal structures containing erythrocytes, indicating formation of functional anastomoses with the host vasculature. Quantitative analyses showed the microvessel density was significantly superior to that generated by human dermal microvascular endothelial cells (HDMECs) but similar to that generated by human umbilical vein endothelial cells (HUVECs). We also found that as EPCs were expanded in culture, their morphology, growth kinetics, and proliferative responses toward angiogenic factors progressively resembled those of HDMECs, indicating a process of in vitro maturation. This maturation correlated with a decrease in the degree of vascularization in vivo, which could be compensated for by increasing the number of EPCs seeded into the implants. Our findings strongly support the use of human EPCs to form vascular networks in engineered organs and tissues.
Tools used to measure airway remodelling in research
Authors: Bergeron C. , Tulic M. K. , Hamid Q.
Published: February 2007

Airway remodelling refers to changes in the airway structure and includes subepithelial fibrosis, increased smooth muscle mass, submucosal gland enlargement, neovascularisation and epithelial alterations. Remodelling is observed in response to chronic injury and is seen not only in asthma but in all airway diseases.

Remodelling is associated with more severe airflow obstruction and airway hyperresponsiveness in asthma; however, the clinical significance of this is still a matter of debate. Research should be pursued to better understand the accurate implication of airway remodelling in disease and its therapeutic modulation.

To allow research in this field, accurate and standardised methods should be utilised to measure airway alterations in disease and following therapy. The standard detection of structural alterations is through direct analyses of airway tissues obtained during apost mortem, surgically or by flexible bronchoscopy. To avoid invasive techniques, other tools have been developed to indirectly measure remodelling, including induced sputum, bronchoalveolar lavage fluid, blood and urine analyses, physiological and radiological assessments, as well asin vitrotechniques.

Although of great interest, the exact significance of airway remodelling measurements gained through such indirect techniques is uncertain and further research is needed. Despite their invasive nature, direct methods should be favoured to adequately measure airway remodelling in disease and its modulation by therapy.
1α,25-Dihydroxycholecalciferol activates binding of CREB to a CRE site in theCD14promoter and drives promoter activity in a phosphatidylinositol-3 kinase-dependent manner
Authors: Moeenrezakhanlou Alireza , Nandan Devki , Shephard Lindsay , Reiner Neil E
Published: February 2007

1,25-Dihydroxycholecalciferol, also known as 1α,25-dihydroxyvitamin D3 or calcitriol, regulates the differentiation and functional properties of mononuclear phagocytes. Many of these effects involve nongenomic signaling pathways, which are not fully understood. Activation of CD14 expression, a monocyte differentiation marker and coreceptor with TLR-2 for bacterial LPS, by calcitriol was shown previously to be PI-3K-dependent [1]; however, the mechanism of gene activation remained undefined. Using a transcription factor-binding array screen coupled with EMSA, we found evidence for PI-3K-dependent activation of CREB in THP-1 cells incubated with calcitriol. Furthermore, analysis of the proximal promoter of human CD14 identified regions that contained up to seven sequences, which showed significant similarity to a canonical CRE sequence, 5′-TGACGTCA-3′. Treatment of THP-1 cells with calcitriol activated CREB binding to one of these regions at Positions −37 to −55, relative to the transcription start site in a PI-3K-dependent manner. This 19-mer region also became transcriptionally active in a reporter assay in response to calcitriol, again dependent on PI-3K. Mutation of the CRE within the 19-mer abolished this activity. Taken together, these results show that calcitriol signaling, leading to activation of the CD14 promoter, involves CREB activation downstream of PI-3K.
Working with people with personality disorder: utilising service users' views
Authors: Barlow Kimberley , Miller Stephen , Norton Kingsley
Published: February 2007

Aims and Method

To ascertain the views of people with personality disorder on their clinical interactions with professionals, to identify potential solutions to problematic interactions and to compile guidelines on how professionals could improve their interactions with these service users. Qualitative methodology was employed, comprising a modified nominal group technique with two iterative groups and ranking by importance the issues and themes raised.

Results

There were 13 service users from three separate personality disorder services who actively participated in a group discussion and iterative process. Collectively they indicated considerable areas of deficiency in the quality of their interaction and communication with professionals. These deficits were defined clearly enough to allow the construction of guidelines aimed at preventing or remedying such deficiencies.

Conclusions

The contribution of those people with personality disorder who took part in this study was sufficiently thoughtful to allow the development of guidelines that might help staff improve their interactions with such service users. From these guidelines, further training tools are being developed, which will be evaluated in the future. However, because not all those approached chose to participate, the views expressed might not be representative of this group as a whole.
A new buprenorphine prescribing service for opiate detoxification
Authors: Littlewood Claire
Published: February 2007

Aims and Method

A buprenorphine prescribing service was set up for opiate-dependent patients and the initiative was then audited using 11 standards.

Results

Thirty-three patients met inclusion criteria for opiate detoxification and 7 successfully completed detoxification, equating to a number needed to treat of 5. However, 2-year follow-up data showed no clear advantage for these 7 patients compared with 9 patients who had failed detoxification at the outset. Only 5 of the 11 audit standards were satisfied.

Clinical Implications

The results suggest that a buprenorphine prescribing service may be of benefit to opiate-dependent patients in the short term. However, the audit standards identified may be unrealistic because of the likely lack of adherence of this patient group. Further work is needed to establish the feasibility of this treatment modality in ‘real-world’ settings.
Compulsory psychiatric detention and treatment in Finland
Authors: Putkonen Hanna , Vollm Birgit
Published: February 2007

Despite efforts to integrate and harmonise legislation across the member states of the European Union (EU), mental health legislation, including legislation for the detention and treatment of offenders with mental disorders, differs widely across Europe. With changes to the Mental Health Act 1983 in the UK currently underway, investigating the different approaches to compulsory psychiatric care in other countries can be a stimulating and worthwhile exercise. We explored the Finnish mental health law with regard to compulsory admission and treatment and forensic care. Relevant differences between the Finnish approach and legislation in other European countries will be discussed.
Psychiatrists' views and experiences of the Mental Health (Care and Treatment) (Scotland) Act 2003
Authors: Carswell Christine , Donaldson Andrew , Brown Keith
Published: February 2007

Aims and Method

This study assesses the views and experiences of psychiatrists of the Mental Health (Care and Treatment) (Scotland) Act 2003. A postal questionnaire was sent to 340 consultant psychiatrists and specialist registrars throughout Scotland.

Results

A response rate of 76% was achieved (n=257); 31 respondents (12%) felt patient care had improved with the newAct; 167 (65%) felt that informal patients' care had suffered; 135 (52%) did not consider that tribunals were better than the previous court system; 151 (59%) felt that the out-of-hours workload had increased.

Clinical Implications

An early indication of psychiatrists' views and experiences of the new Mental Health (Care and Treatment) (Scotland) Act 2003 is given.
Epigenetic regulation of facultative heterochromatinisation inPlanococcus citrivia the Me(3)K9H3-HP1-Me(3)K20H4 pathway
Authors: Bongiorni Silvia , Pasqualini Barbara , Taranta Monia , Singh Prim B. , Prantera Giorgio
Published: February 2007

Using RNA interference (RNAi) we have conducted a functional analysis of the HP1-like chromobox gene pchet2 during embryogenesis of the mealybug Planococcus citri. Knocking down pchet2 expression results in decondensation of the male-specific chromocenter that normally arises from the developmentally-regulated facultative heterochromatinisation of the paternal chromosome complement. Together with the disappearance of the chromocenter the staining levels of two associated histone modifications, tri-methylated lysine 9 of histone H3 [Me(3)K9H3] and tri-methylated lysine 20 of histone H4 [Me(3)K20H4], are reduced to undetectable levels. Embryos treated with double-stranded RNA (dsRNA) targeting pchet2 also exhibit chromosome abnormalities, such as aberrant chromosome condensation, and also the presence of metaphases that contain `lagging' chromosomes. We conclude that PCHET2 regulates chromosome behavior during metaphase and is a crucial component of a Me(3)K9H3-HP1-Me(3)K20H4 pathway involved in the facultative heterochromatinisation of the (imprinted) paternal chromosome set.
Prediction of relative efficiency reduction of centrifugal slurry pumps: Empirical- and artificial-neural network-based methods
Authors: Engin T
Published: February 2007

This paper has focused on the predictive methods for relative efficiency reduction of centrifugal pumps handling slurries based on empirical- and artificial-neural network (ANN) approaches. A new correlation has been developed to predict the relative efficiency reduction of the centrifugal slurry pumps, and the range of validity of the present correlation has been verified using the data available in the literature. Then, the applicability of ANNs for the same purpose has been investigated using a total of 315 data. The comparisons of both methods showed that the present correlation produced the lowest deviation among some recent correlations in the literature, and, if properly constructed, ANNs could be used as a predictive tool with higher accuracy than the conventional empirical methods.
Time series analysis-based adaptive tuning techniques for a heaving wave energy converter in irregular seas
Authors: Yavuz H , Stallard T. J. , McCabe A. P. , Aggidis G. A.
Published: February 2007

The paper presents a time domain model of a heaving buoy wave-energy converter and investigates the tuning problem in irregular seas. The tuning issue is addressed by employing both fixed (passive) and adaptive (active) power-take-off settings. The fixed power-take-off tuning approach includes models based on tuning the device natural frequency to either the energy frequency or peak frequency of the sea-state or a weighted average of several peak frequencies. The adaptive tuning approaches employ a sliding discrete Fourier transform frequency analysis, or a time-series analysis of the measured wave elevation and device velocity to estimate a localized dominant wave frequency and hence calculate power-take-off settings. The paper presents details of these tuning techniques by discussing issues related to the modelling, simulation, and predicted power captures for each method. A comparative study of each method along with practical implications of the results and recommendations are also presented.
Metal-metal friction characteristics and the transmission efficiency of a metal V-belt-type continuously variable transmission
Authors: Narita K , Priest M
Published: February 2007

The influence of metal-metal friction characteristics on the efficiency of a continuously variable transmission (CVT) of a metal pushing V-belt type was experimentally investigated using a commercial CVT unit of a metal belt assembly and pulley design. The experiments for transmission efficiency were carried out, varying the clamping force on the secondary pulley from 10.5 to 34.6 kN and the speed ratio from 2.36 (reduction ratio) to 0.44 (overdrive ratio). In order to analyse the metal-metal friction characteristics of each contact pair, a ring-on-disc tribometer was developed. Fluids giving a higher transmittable CVT torque capacity of CVT were found to have the potential for decreasing the maximum required pulley clamping force, resulting in the reduction of overall power loss in the CVT unit. The transmission efficiency of the CVT decreased under an overdrive speed ratio and lower load condition. The maximum difference in the efficiency between all the commercial automatic transmission and CVT fluids tested at the same pulley clamping force condition reached 3 per cent. This number depends on the friction losses caused by slipping behaviour between the belt segments and pulley, the segments and band, and between the bands. Furthermore, mathematical modelling of the friction loss in the belt was developed. Results calculated by this model were similar to those obtained experimentally.