bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of the critical current of a balanced superconducting quantum interference device
Authors: Kemppinen Antti , Manninen Antti J. , Möttönen Mikko , Vartiainen Juha J. , Peltonen Joonas T. , Pekola Jukka P.
Published: February 2008

We present an experimental study of the magnetic flux dependence of the critical current of a balanced superconducting quantum interference device (SQUID) with three Josephson junctions in parallel. Unlike for ordinary direct current (dc) SQUIDs, the suppression of the critical current does not depend on the exact parameters of the Josephson junctions. The suppression is essentially limited only by the inductances of the SQUID loops. We demonstrate a critical current suppression ratio of higher than 300 in a balanced SQUID with a maximum critical current 30nA.
Legal battle over sonar testing heats up
Authors: Ouellette Jennifer
Published: February 2008

Does the mid-frequency active sonar used by the US Navy adversely affect marine mammals? The scientific evidence is incomplete, but the courts find environmentalists’ arguments persuasive.
Physics meets biology at new HIV structural biology centers
Authors: Kramer David
Published: February 2008

Biophysicists play a major role in the attempt to unravel the molecular processes the human immunodeficiency virus uses to infect and hijack the immune system.
Urban Form, Everyday Life, and Ideology: Support for Privatization in Three Toronto Neighbourhoods
Authors: Walks R Alan
Published: February 2008

One of the trends marking neoliberalism and the attack on the welfare state from the right is the move toward the privatization of public services. Recent research in both the United States and Canada suggests that residents of the suburbs of large urban regions are more likely to vote for political parties on the right and to support neoliberal policies such as privatization, while the opposite is true for inner-city dwellers. However, the reasons why such a spatial division should occur have received little academic attention. This paper seeks to fill this gap in the literature by analyzing the relationship between residential location, spatial factors, and attitudes toward privatization, using survey data collected in the Toronto region. Results suggest that the way urban space influences residents' daily routines and personal experiences may then mediate their perception of the uses of public services and the efficacy of government spending, factors which are found to affect spatial disparities in support of and/or in opposition to privatization. Thus, there is some evidence that urban spatial form is important for understanding the geographic unevenness of support for neoliberalism, and thus ultimately for the production of ideology.
Regulating the Social Impacts of Studentification: A Loughborough Case Study
Authors: Hubbard Phil
Published: February 2008

Now a recognised phenomenon in many British cities, studentification is the process by which specific neighbourhoods become dominated by student residential occupation. Outlining the causes and consequences of this process, this paper suggests that studentification raises important questions about community cohesiveness and that intervention may be required by local authorities if social and cultural conflicts are to be avoided. Detailing the social impacts of studentification in Loughborough, a market town in the English East Midlands, the paper accordingly considers recent housing policies designed to prevent the formation of exclusive ‘student ghettos’. The paper concludes by suggesting that the type of ‘threshold analysis’ utilised in Loughborough may well spread students more thinly across a city, but that the relationship between students and the wider community requires other forms of regulation if town–university tensions are to be effectively managed. Throughout, comparison is made between the Loughborough and other UK university towns where the challenges and opportunities associated with studentification have been differently addressed.
Absorption of gypsum solution by a potassic soil: a data set
Authors: Smiles D. E. , Smith C. J.
Published: February 2008

Reliable experimental data required to test hydrodynamic dispersion/chemical reaction models are scarce. This paper provides such a dataset based on absorption of gypsum solution by horizontal columns of relatively dry soil with an initially high exchangeable potassium ratio. Initial and boundary conditions are well defined. Water and cation concentration profiles measured after 200 and 400 min lay on single curves when graphed in terms of distance divided by the square root of time. Cation exchange occurred close to the intake surface and calcium derived from the gypsum was confined to a narrow band well behind the notional piston front that separates the absorbed solution from that originally present. Anion exchange was negligible and the solution concentration up to the piston front approximated the anion concentration of the invading solution. The interval between the region of cation exchange and the piston front maintained the original cation adsorption ratios but at a total cation solution concentration approximating that of saturated gypsum (~25 mmolc/L). Some implications of this phenomenon are discussed. Comparison of cation exchange isotherms observed when the virgin soil absorbs effluent-like solutions and when effluent-irrigated soil absorbs saturated gypsum suggest that, operationally, these isotherms may be considered to be unaffected by hysteresis in the exchange reactions.
Patterns of movement in the small dasyurid (Ningaui yvonneae)
Authors: Bos Darren G. , Carthew Susan M.
Published: February 2008

The movement behaviour of a small dasyurid (Ningaui yvonneae) was investigated using mark–recapture data collected over 28 months from a population in the Middleback Ranges, South Australia. We were particularly interested in assessing variability in patterns of movement between the sexes and across seasons, as this has potentially important implications for population composition and dynamics. The species was found to be fairly mobile, with frequent and sometimes large movements relative to the size of the animal (up to 900+ m). Average distances moved between recaptures within and between trap sessions were 84 m and 160 m respectively, with nearly half of all recorded movements being between trapping grids (i.e. >80 m). Relatively high recapture rates (many separated by more than 100 days) and measures of site fidelity indicated that the species was not particularly transitory, but probably establishes large and/or drifting home ranges. However, patterns of movement varied considerably according to sex and the time of year. Female N. yvonneae were generally more sedentary than males, with few females moving between trapping grids, and most short-term movements (<100 days apart) being less than 70 m. Movements of females for which the records were separated by more than 100 days tended to be larger, with an average between-capture distance >200 m. In contrast, males often moved between trapping grids, even over short periods. Some short-term movements were more than 600 m in length, and the average distance moved within trapping sessions was >100 m. During the breeding season, males more than doubled the average distances moved between recaptures, when they were presumably roaming in search of females. For females, movement distances were similar during the prebreeding and breeding seasons, but were significantly smaller in the postbreeding season, when they were caring for young.
Growth and development of the southern hairy-nosed wombat, Lasiorhinus latifrons (Vombatidae)
Authors: Taggart David A. , Finlayson Graeme R. , Shimmin Glenn , Gover Clare , Dibben Ron , White Craig R. , Steele Vernon , Temple-Smith Peter D.
Published: February 2008

There are few published studies on breeding and reproduction in hairy-nosed wombats and little information available on growth and development of pouch young. At a field site near Swan Reach in the Murraylands of South Australia morphometric measurements of 353 young southern hairy-nosed wombats and notes on their development were recorded. These data were combined with growth data collected from repeat measures of 10 mother-reared and 5 hand-reared joeys in order to establish information for aging young of this species and to plot developmental changes. Young weighed ~0.4 g at birth and had a head length (HL) of ~5.2 mm. Head length was the most accurate body parameter from which to assess age. Growth of pouch young was linear between birth and ~Day 310 with head length growing at ~0.4 mm HL per day. After Day 300 growth slowed, represented by a polynomial equation. Eyes were open at 5 months and pouch young started to develop fur at 5–6 months of age. Most young were permanently out of pouch at 9 months of age, and were weaned between 11 and 13 months, when they weighed 6–7 kg. Young remained in the burrow for 1–2 months following pouch exit before venturing above ground at night.
Emergent decision-making in biological signal transduction networks
Authors: Helikar Tomáš , Konvalina John , Heidel Jack , Rogers Jim A.
Published: February 2008

The complexity of biochemical intracellular signal transduction networks has led to speculation that the high degree of interconnectivity that exists in these networks transforms them into an information processing network. To test this hypothesis directly, a large scale model was created with the logical mechanism of each node described completely to allow simulation and dynamical analysis. Exposing the network to tens of thousands of random combinations of inputs and analyzing the combined dynamics of multiple outputs revealed a robust system capable of clustering widely varying input combinations into equivalence classes of biologically relevant cellular responses. This capability was nontrivial in that the network performed sharp, nonfuzzy classifications even in the face of added noise, a hallmark of real-world decision-making.
Orai1 and STIM1 move to the immunological synapse and are up-regulated during T cell activation
Authors: Lioudyno Maria I. , Kozak J. Ashot , Penna Aubin , Safrina Olga , Zhang Shenyuan L. , Sen Debasish , Roos Jack , Stauderman Kenneth A. , Cahalan Michael D.
Published: February 2008

For efficient development of an immune response, T lymphocytes require long-lasting calcium influx through calcium release-activated calcium (CRAC) channels and the formation of a stable immunological synapse (IS) with the antigen-presenting cell (APC). Recent RNAi screens have identified Stim and Orai in
Drosophila
cells, and their corresponding mammalian homologs STIM1 and Orai1 in T cells, as essential for CRAC channel activation. Here, we show that STIM1 and Orai1 are recruited to the immunological synapse between primary human T cells and autologous dendritic cells. Both STIM1 and Orai1 accumulated in the area of contact between either resting or super-antigen (SEB)-pretreated T cells and SEB-pulsed dendritic cells, where they were colocalized with T cell receptor (TCR) and costimulatory molecules. In addition, imaging of intracellular calcium signaling in T cells loaded with EGTA revealed significantly higher Ca
2+
concentration near the interface, indicating Ca
2+
influx localized at the T cell/dendritic cell contact area. Expression of a dominant-negative Orai1 mutant blocked T cell Ca
2+
signaling but did not interfere with the initial accumulation of STIM1, Orai1, and CD3 in the contact zone. In activated T cell blasts, mRNA expression for endogenous STIM1 and all three human homologs of Orai was up-regulated, accompanied by a marked increase in Ca
2+
influx through CRAC channels. These results imply a positive feedback loop in which an initial TCR signal favors up-regulation of STIM1 and Orai proteins that would augment Ca
2+
signaling during subsequent antigen encounter.
Structural insight into the reaction mechanism and evolution of cytokinin biosynthesis
Authors: Sugawara Hajime , Ueda Nanae , Kojima Mikiko , Makita Nobue , Yamaya Tomoyuki , Sakakibara Hitoshi
Published: February 2008

The phytohormone cytokinin regulates plant growth and development. This hormone is also synthesized by some phytopathogenic bacteria, such as
Agrobacterium tumefaciens
, and is as a key factor in the formation of plant tumors. The rate-limiting step of cytokinin biosynthesis is catalyzed by adenosine phosphate-isopentenyltransferase (IPT).
Agrobacterium
IPT has a unique substrate specificity that enables it to increase
trans
-zeatin production by recruiting a metabolic intermediate of the host plant's biosynthetic pathway. Here, we show the crystal structures of Tzs, an IPT from
A. tumefaciens
, complexed with AMP and a prenyl-donor analogue, dimethylallyl
S
-thiodiphosphate. The structures reveal that the carbon-nitrogen-based prenylation proceeds by the SN2-reaction mechanism. Site-directed mutagenesis was used to determine the amino acid residues, Asp-173 and His-214, which are responsible for differences in prenyl-donor substrate specificity between plant and bacterial IPTs. IPT and the
p
loop-containing nucleoside triphosphate hydrolases likely evolved from a common ancestral protein. Despite structural similarities, IPT has evolved a distinct role in which the
p
loop transfers a prenyl moiety in cytokinin biosynthesis.
Pupil dilation reflects perceptual selection and predicts subsequent stability in perceptual rivalry
Authors: Einhäuser Wolfgang , Stout James , Koch Christof , Carter Olivia
Published: February 2008

During sustained viewing of an ambiguous stimulus, an individual's perceptual experience will generally switch between the different possible alternatives rather than stay fixed on one interpretation (perceptual rivalry). Here, we measured pupil diameter while subjects viewed different ambiguous visual and auditory stimuli. For all stimuli tested, pupil diameter increased just before the reported perceptual switch and the relative amount of dilation before this switch was a significant predictor of the subsequent duration of perceptual stability. These results could not be explained by blink or eye-movement effects, the motor response or stimulus driven changes in retinal input. Because pupil dilation reflects levels of norepinephrine (NE) released from the locus coeruleus (LC), we interpret these results as suggestive that the LC–NE complex may play the same role in perceptual selection as in behavioral decision making.
Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms
Authors: Puri Niti , Roche Paul A.
Published: February 2008

Mast cells degranulate and release the contents of intracellular secretory granules in response to the cross-linking of FcεRI by multivalent antigens. These granules contain a variety of biologically active inflammatory mediators; however, it is not clear whether these granules are homogenous or whether there is heterogeneity within the secretory granule population in mast cells. By using genetically altered mice lacking specific vesicle-associated SNARE membrane fusion proteins, we found that VAMP-8-deficient mast cells exhibited defects in FcεRI-regulated exocytosis, whereas synaptobrevin 2- or VAMP-3-deficient mast cells did not. Surprisingly, the defect in secretion in VAMP-8-deficient mice was limited to the subpopulation of mast cell secretory granules containing serotonin and cathepsin D, whereas regulated exocytosis of secretory granules containing histamine and TNF-α was normal. Confocal microscopy confirmed that serotonin and histamine were present in distinct intracellular granules and that most serotonin-containing granules were VAMP-8-positive. Thus, this study demonstrates that mast cells do indeed possess distinct subsets of secretory granules and that these subsets use different SNARE isoforms for exocytosis.
Biosynthetic origin of natural products isolated from marine microorganism–invertebrate assemblages
Authors: Simmons T. Luke , Coates R. Cameron , Clark Benjamin R. , Engene Niclas , Gonzalez David , Esquenazi Eduardo , Dorrestein Pieter C. , Gerwick William H.
Published: February 2008

In all probability, natural selection began as ancient marine microorganisms were required to compete for limited resources. These pressures resulted in the evolution of diverse genetically encoded small molecules with a variety of ecological and metabolic roles. Remarkably, many of these same biologically active molecules have potential utility in modern medicine and biomedical research. The most promising of these natural products often derive from organisms richly populated by associated microorganisms (e.g., marine sponges and ascidians), and often there is great uncertainty about which organism in these assemblages is making these intriguing metabolites. To use the molecular machinery responsible for the biosynthesis of potential drug-lead natural products, new tools must be applied to delineate their genetic and enzymatic origins. The aim of this perspective is to highlight both traditional and emerging techniques for the localization of metabolic pathways within complex marine environments. Examples are given from the literature as well as recent proof-of-concept experiments from the authors' laboratories.
The kernel energy method of quantum mechanical approximation carried to fourth-order terms
Authors: Huang Lulu , Massa Lou , Karle Jerome
Published: February 2008

It is now possible to calculate the
ab initio
quantum mechanics of very large biological molecules. Two things lead to this perspective, namely, (
i
) the advances of parallel supercomputers, and (
ii
) the discovery of a quantum formalism called quantum crystallography and the use of quantum kernels, a method that is well suited for parallel computation. The kernel energy method (KEM) carried to second order has been used to calculate the quantum mechanical
ab initio
molecular energy of peptides, protein (insulin and collagen), DNA, and RNA and the interaction of drugs with their biochemical molecular targets. The results were found to have good accuracy. In this article, the accuracy of the KEM is investigated up to an approximation including fourth-order interactions among kernels. Remarkable accuracy is achieved in the calculation of the energy of the ground state of the important biological molecule Leu
1
-zervamicin, whose crystal structure is known and used in the calculations.
Controlling energy transfer between multiple dopants within a single nanoparticle
Authors: DiMaio Jeffrey R. , Sabatier Clément , Kokuoz Baris , Ballato John
Published: February 2008

Complex core-shell architectures are implemented within LaF
3
nanoparticles to allow for a tailored degree of energy transfer (ET) between different rare earth dopants. By constraining specific dopants to individual shells, their relative distance to one another can be carefully controlled. Core-shell LaF
3
nanoparticles doped with Tb
3+
and Eu
3+
and consisting of up to four layers were synthesized with an outer diameter of ≈10 nm. It is found that by varying the thicknesses of an undoped layer between a Tb
3+
-doped layer and a Eu
3+
-doped layer, the degree of ET can be engineered to allow for zero, partial, or total ET from a donor ion to an acceptor ion. More specifically, the ratio of the intensities of the 541-nm Tb
3+
and 590 nm Eu
3+
peaks was tailored from <0.2 to ≈2.4 without changing the overall composition of the particles but only by changing the internal structure. Further, the emission spectrum of a blend of singly doped nanoparticles is shown to be equivalent to the spectra of co-doped particles when a core-shell configuration that restricts ET is used. Beyond simply controlling ET, which can be limiting when designing materials for optical applications, this approach can be used to obtain truly engineered spectral features from nanoparticles and composites made from them. Further, it allows for a single excitation source to yield multiple discrete emissions from numerous lanthanide dopants that heretofore would have been quenched in a more conventional active optical material.
Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase
Authors: Blakeley Matthew P. , Ruiz Federico , Cachau Raul , Hazemann Isabelle , Meilleur Flora , Mitschler Andre , Ginell Stephan , Afonine Pavel , Ventura Oscar N. , Cousido-Siah Alexandra , Haertlein Michael , Joachimiak Andrzej , Myles Dean , Podjarny Alberto
Published: February 2008

We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 Å, 100K; 0.80 Å, 15K; 1.75 Å, 293K), neutron Laue data (2.2 Å, 293K), and quantum mechanical modeling. These complementary techniques unveil the internal organization and mobility of the hydrogen bond network that defines the properties of the catalytic engine, explaining how this promiscuous enzyme overcomes the simultaneous requirements of efficiency and promiscuity offering a general mechanistic view for this class of enzymes.
Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain-dependent process
Authors: Pfau Raymond , Tzatsos Alexandros , Kampranis Sotirios C. , Serebrennikova Oksana B. , Bear Susan E. , Tsichlis Philip N.
Published: February 2008

A common integration site, cloned from MoMuLV-induced rat T cell lymphomas, was mapped immediately upstream of
Not dead yet-1
(
Ndy1
)/
KDM2B
, a gene expressed primarily in testis, spleen, and thymus, that is also known as
FBXL10
or
JHDM1B. Ndy1
encodes a nuclear, chromatin-associated protein that harbors Jumonji C (JmjC), CXXC, PHD, proline-rich, F-box, and leucine-rich repeat domains.
Ndy1
and its homolog
Ndy2/KDM2A
(
FBXL11
or
JHDM1A
), which is also a target of provirus integration in retrovirus-induced lymphomas, encode proteins that were recently shown to possess Jumonji C-dependent histone H3 K36 dimethyl-demethylase or histone H3 K4 trimethyl-demethylase activities. Here, we show that mouse embryo fibroblasts engineered to express
Ndy1
or
Ndy2
undergo immortalization in the absence of replicative senescence via a JmjC domain-dependent process that targets the Rb and p53 pathways. Knockdown of endogenous
Ndy1
or expression of JmjC domain mutants of
Ndy1
promote senescence, suggesting that
Ndy1
is a physiological inhibitor of senescence in dividing cells and that inhibition of senescence depends on histone H3 demethylation.
Perceptual learning depends on perceptual constancy
Authors: Garrigan Patrick , Kellman Philip J.
Published: February 2008

Perceptual learning refers to experience-induced improvements in the pick-up of information. Perceptual constancy describes the fact that, despite variable sensory input, perceptual representations typically correspond to stable properties of objects. Here, we show evidence of a strong link between perceptual learning and perceptual constancy: Perceptual learning depends on constancy-based perceptual representations. Perceptual learning may involve changes in early sensory analyzers, but such changes may in general be constrained by categorical distinctions among the high-level perceptual representations to which they contribute. Using established relations of perceptual constancy and sensory inputs, we tested the ability to discover regularities in tasks that dissociated perceptual and sensory invariants. We found that human subjects could learn to classify based on a perceptual invariant that depended on an underlying sensory invariant but could not learn the identical sensory invariant when it did not correlate with a perceptual invariant. These results suggest that constancy-based representations, known to be important for thought and action, also guide learning and plasticity.
A role for leptin in sustaining lymphopoiesis and myelopoiesis
Authors: Claycombe Kate , King Louis E. , Fraker Pamela J.
Published: February 2008

Although leptin is known for its regulation of food intake, it has many emerging roles in immune function. To better define the role of leptin in hematopoietic processes, a leptin-deficient obese mouse (ob/ob) and C57BL/6 lean wild-type controls were compared. Despite their large size and consumption of substantial amounts of nutrients, theob/obmice had only 60% as many nucleated cells in their marrow as controls. The greatest impact of leptin deficiency was on the B cell compartment that had 70% fewer cells, reducing the absolute number of pre-B and immature B cells to 21% and 12% of normal, respectively, and indicating a significant reduction in lymphopoiesis inob/obmice. Whereas the proportion of myeloids remained nearly normal in the obese mice, they also exhibited a reduction of 40% and 25%, respectively, in absolute numbers of granulocytes and monocytes. Seven days of provision of recombinant leptin promoted substantial lymphopoiesis, increasing the numbers of B cells in the marrow of the obese mice twofold, while doubling and tripling, respectively, the numbers of pre-B and immature B cells. Twelve days of supplementation brought these subpopulations to near-normal proportions. Leptin treatment also facilitated myelopoiesis such that the marrow of the obese mice contained normal numbers of monocytes and granulocytes after 7 days. Taken together, the data support an important role for leptin in sustaining lymphopoiesis and myelopoiesis.
Molecular basis for LDL receptor recognition by PCSK9
Authors: Kwon Hyock Joo , Lagace Thomas A. , McNutt Markey C. , Horton Jay D. , Deisenhofer Johann
Published: February 2008

Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation. The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. Here, we describe the crystal structure of a complex between PCSK9 and the EGF-A domain of the LDLR. The binding site for the LDLR EGF-A domain resides on the surface of PCSK9's subtilisin-like catalytic domain containing Asp-374, a residue for which a gain-of-function mutation (Asp-374–Tyr) increases the affinity of PCSK9 toward LDLR and increases plasma LDL-cholesterol (LDL-C) levels in humans. The binding surface on PCSK9 is distant from its catalytic site, and the EGF-A domain makes no contact with either the C-terminal domain or the prodomain. Point mutations in PCSK9 that altered key residues contributing to EGF-A binding (Arg-194 and Phe-379) greatly diminished binding to the LDLR's extracellular domain. The structure of PCSK9 in complex with the LDLR EGF-A domain defines potential therapeutic target sites for blocking agents that could interfere with this interaction
in vivo
, thereby increasing LDLR function and reducing plasma LDL-C levels.
The development of peer educator‐based harm reduction programmes in northern Vietnam
Authors: WALSH NICK , GIBBIE TANIA M. , HIGGS PETER
Published: February 2008

Introduction. Injecting drug use remains an important risk factor for transmission in Vietnam, with an estimated 50% of the 290 000 people living with HIV/AIDS reporting injecting drug use as a risk factor. Despite this, effective harm reduction interventions are generally lacking. This paper describes the implementation of peer‐based harm reduction programmes in two rural provinces of Vietnam. Design and Methods. Peer educators were trained in basic HIV prevention, including harm reduction. After significant preparation work with the Provincial AIDS Committees of Bac Giang and Thanh Hoa and other relevant national, provincial and local authorities, the interventions were commenced. Harm reduction interventions were delivered through outreach as well as on‐site. This included needle and syringe distribution and collection. Results. Community advocacy occurred throughout the life of the project. Local authorities and peers believed that while there was a general reduction in stigma and discrimination, legal barriers associated particularly with the carrying of injecting equipment remained. This impacted upon the ability of peer educators to work with their clients. Conclusion. Peer‐based delivery of harm reduction intervention is acceptable. Harm reduction interventions, including needle and syringe programmes, are feasible and acceptable in these two rural Vietnamese provinces. Community acceptance and uptake of these interventions is key to successful expansion across the region. Active participation by families of drug users seems crucial. This initiative demonstrates that despite a difficult policy environment, peer‐delivered needle and syringe programmes are feasible within a rural Asian environment as long as there is adequate local political and community support.
Consumer participation in the planning and delivery of drug treatment services: the current arrangements
Authors: BRYANT JOANNE , SAXTON MELISSA , MADDEN ANNIE , BATH NICKY , ROBINSON SUZANNE
Published: February 2008

Introduction and Aims. Consumer participation in decision‐making about service planning is common in certain health services in Australia but is thought to be largely underdeveloped in drug treatment services. This paper (1) describes the current practices within Australian drug treatment services that aim to include consumers in service planning and provision; and (2) determines how much consumers know about the existing opportunities for involvement. Design and Method. Sixty‐four randomly selected service providers (representing 64 separate services) completed interviews about the current arrangements for consumer participation within their services (response rate = 82%). A total of 179 consumers completed interviews assessing their knowledge of the consumer participation activities available at the service they attended. Results. Consumer participation activities were not uncommon in drug treatment services, although the existing activities were concerned largely with providing information to or receiving information from consumers. Activities that included consumers in higher forms of involvement, such as those in which consumers took part in decision‐making, were largely uncommon. Consumers had a considerable lack of knowledge about the participation activities available to them, revealing a lack of communication between providers and consumers. Conclusions. While service providers were making efforts to engage consumers in service planning and provision (despite the general lack of State or Commonwealth policy directives and extra funding to do so), these appear ineffectual because of poor communication between providers and consumers. As a starting point, a critical part of any meaningful consumer participation initiative must include systems to ensure that consumers know about available opportunities.
Consumers' and providers' perspectives about consumer participation in drug treatment services: is there support to do more? What are the obstacles?
Authors: BRYANT JOANNE , SAXTON MELISSA , MADDEN ANNIE , BATH NICKY , ROBINSON SUZANNE
Published: February 2008

Introduction and Aims. Implementing consumer participation initiatives in Australian drug treatment services successfully is predicated on the support of those most centrally involved. This paper describes service providers' and consumers' (1) beliefs about and commitment to consumer participation; and (2) perceived barriers to conducting or participating in consumer participation. Design and Methods. Data were collected from 64 providers and 179 consumers of drug treatment services. Results. The data showed that almost all consumers (89.9%, n = 161) and providers (84.4%, n = 54) believed in the principle of consumer participation (that consumers' views should be included in service planning and delivery) and a large proportion would be willing to conduct or participate in consumer participation activities in future. Providers were less supportive of activities in which consumers would be involved in decision‐making that relates directly to staff (such as staff training, recruitment and performance appraisal), and expressed concerns about the practicality of operationalising such activities, the inadequacy of consumers' skills, consumers' lack of interest and the appropriateness of having consumers involved in such decision‐making. A small proportion of consumers also indicated that they did not want to participate, expressing beliefs that it was not their place to be involved and that they lacked the required skills. Conclusions. Overall, these findings revealed that there was considerable support for the further development of consumer participation in drug treatment services, but the predominant obstacle was the view that it is not consumers' place to take part, and that they lack the interest and skills to do so.
Issues with recruitment to randomised controlled trials in the drug and alcohol field: a literature review and Australian case study
Authors: THOMSON CLARE L. , MORLEY KIRSTEN C. , TEESSON MAREE , SANNIBALE CLAUDIA , HABER PAUL S.
Published: February 2008

Issues. The randomised control trial (RCT) is a widely used tool for measuring the effectiveness of health treatments and services. However, subject recruitment is an ongoing challenge for those conducting RCTs and may have a serious impact on the success of the study and the reliability of the outcomes. Approach. In this review we present an examination of the problems and strategies associated with recruitment to RCTs, with particular reference to studies conducted in the drug and alcohol field. A case study of recruitment to an RCT for the treatment of alcohol dependence is presented, supplemented by PubMed, Current Contents and Medline searches to identify relevant publications. Key Findings. The literature suggests that the most common barriers to patient participation involve fears of assignment to placebo treatment, insufficient compensation and poor attendance at initial appointments. Moreover, subject referrals from staff may be a greater problem than reluctance of patients. Referrals are inhibited by complicated entry criteria, time constraints due to busy work schedules or a limited research culture. Implications. Subject recruitment may be promoted by financial reimbursement, close partnerships between research and referral staff; increasing the treatment group ratio in multi‐drug trials to minimise randomisation to placebo; addressing negative staff attitudes; and simplifying the referral process. Conclusion. The need for multi‐centre sites in Australian drug and alcohol treatment studies is highlighted.
Leukocyte Adhesion in Capillary‐Sized, P‐Selectin‐Coated Micropipettes
Authors: Sundd Prithu , Zou Xiaoyan , Goetz Douglas J. , Tees David F. J.
Published: February 2008

Objective:Leukocyte retention in lung capillaries is observed in normal physiology and following a bacterial infection. It has been hypothesized that cells either become mechanically trapped or adhere to capillary endothelial cells via adhesion molecules. We propose that retention involves both mechanical and adhesive forces and that the biochemical adhesive force is modulated by mechanical forces that alter the area of contact between leukocytes and endothelium.

Methods:To probe this hypothesis, an adhesion assay has been developed in which individual HL‐60 cells were aspirated into micropipettes pre‐coated with P‐selectin. Following aspiration, cells were exposed to physiological pressure differences.

Results:Little adhesion was seen in micropipettes coated with BSA, whereas significant adhesion was observed in micropipettes coated with P‐selectin. The frequency of cell arrest on P‐selectin in the micropipette was much greater than on P‐selectin in a parallel plate flow chamber even though the disruptive force in the micropipette assay exceeds that in the parallel plate flow chamber. These results demonstrate that receptor–ligand interactions can enhance adhesion in a capillary geometry and that differences in capillary geometry vs. venule geometry can significantly influence the adhesive phenotype.

Conclusions:Taken together, these observations support the hypothesis that an interplay between mechanical and biochemical adhesive forces can play a major role in retention.
Hydrogen Peroxide Emerges as a Regulator of Tone in Skeletal Muscle Arterioles During Juvenile Growth
Authors: Samora Julie Balch , Frisbee Jefferson C. , Boegehold Matthew A.
Published: February 2008

Objective: The endothelium‐dependent dilation of skeletal muscle arterioles is mediated by factors that have not been identified in young rats, and partly mediated by an unidentified hyperpolarizing factor in maturing rats. This study was designed to determine if endogenous hydrogen peroxide (H2O2) contributes to this arteriolar dilation at either of these growth stages.

Methods: Gracilis muscle arterioles were isolated from rats at ages 24–26 days (“weanlings”) and 46–48 days (“juveniles”). We investigated the effects of catalase treatment on the endothelium‐dependent dilation of these vessels to simvastatin and acetylcholine (ACh). Catalase‐sensitive 2′,7′‐dichlorofluorescein (DCF) fluorescence also was measured as an index of H2O2 formation, and arteriolar dilation to exogenous H2O2 was pharmacologically probed in each age group.

Results: Responses to simvastatin and ACh were attenuated by catalase in juvenile, but not weanling, arterioles. Juvenile, but not weanling, arterioles also displayed catalase‐sensitive DCF fluorescence that was increased by ACh. Exogenous H2O2 could induce dilation in juvenile, but not weanling, arterioles. In juvenile arterioles, this dilation was abolished by the K+ channel inhibitors TEA and glibenclamide, and attenuated by NOS inhibition or endothelial removal.

Conclusions: These findings suggest that endogenous H2O2 contributes to endothelium‐dependent arteriolar dilation in juvenile rats, but not in younger rats, and that H2O2 acts in juvenile rats by stimulating endothelial NO release and activating smooth muscle K+ channels.
Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast
Authors: Fei Weihua , Shui Guanghou , Gaeta Bruno , Du Ximing , Kuerschner Lars , Li Peng , Brown Andrew J. , Wenk Markus R. , Parton Robert G. , Yang Hongyuan
Published: February 2008

Lipid droplets (LDs) are emerging cellular organelles that are of crucial importance in cell biology and human diseases. In this study, we present our screen of ∼4,700 Saccharomyces cerevisiae mutants for abnormalities in the number and morphology of LDs; we identify 17 fld (few LDs) and 116 mld (many LDs) mutants. One of the fld mutants (fld1) is caused by the deletion of YLR404W, a previously uncharacterized open reading frame. Cells lacking FLD1 contain strikingly enlarged (supersized) LDs, and LDs from fld1Δ cells demonstrate significantly enhanced fusion activities both in vivo and in vitro. Interestingly, the expression of human seipin, whose mutant forms are associated with Berardinelli-Seip congenital lipodystrophy and motoneuron disorders, rescues LD-associated defects in fld1Δ cells. Lipid profiling reveals alterations in acyl chain compositions of major phospholipids in fld1Δ cells. These results suggest that an evolutionally conserved function of seipin in phospholipid metabolism and LD formation may be functionally important in human adipogenesis.
Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases
Authors: Armaka Maria , Apostolaki Maria , Jacques Peggy , Kontoyiannis Dimitris L. , Elewaut Dirk , Kollias George
Published: February 2008

Tumor necrosis factor (TNF) is key to the pathogenesis of various arthritic diseases and inflammatory bowel disease (IBD). Anti-TNF therapies have proved successful in the clinical treatment of these diseases, but a mechanistic understanding of TNF function is still lacking. We have investigated early cellular mechanisms of TNF function in these diseases using an established TNF transgenic model, which develops a spondyloarthritis-like disease characterized by peripheral joint arthritis, sacroiliitis, enthesitis, and Crohn's-like IBD. Bone marrow grafting experiments demonstrated that development of arthritis requires TNF receptor I (TNFRI) expression in the radiation-resistant compartment, which is also known to be a sufficient target of TNF in the development of Crohn's-like IBD in the same model. Early activation of synovial fibroblasts and intestinal myofibroblasts could also be demonstrated by perturbed expression of matrix metalloproteases and their inhibitors. Notably, selective Cre/loxP-mediated TNFRI expression in mesenchymal cells resulted in a fully arthritic–spondyloarthritic and intestinal phenotype, indicating that mesenchymal cells are primary and sufficient targets of TNF in these pathologies. Our results offer a novel mechanistic perspective for TNF function in gut and joint pathologies and indicate early common cellular pathways that may also explain the often observed synovial–gut axis in human disease.
Deuterium removal during thermo-oxidation of Be-containing codeposits from JET divertor tiles
Authors: Tsui C.K. , Haasz A.A. , Davis J.W. , Coad J.P. , Likonen J.
Published: February 2008

This study focuses on the removal of trapped D from thick codeposits on JET divertor tiles via thermo-oxidation. The tiles were removed from the JET Mark II Gas Box divertor after the 1998–2001 campaign. These codeposits have Be concentrations of up to ∼60% Be/(Be + C) and their thicknesses range from 10 to 270 µm. Laser thermal desorption spectroscopy was used to determine the D removal rates and final remaining D concentrations following oxidation. Estimates of the carbon removed during oxidation were obtained from mass-loss measurements. The initial rate of D removal was found to be much higher for the thick codeposits of this study than for the previously studied codeposits with thicknesses in the range 1–5 µm (from TFTR, DIII-D and JET). This is despite the large Be concentrations. For oxidation performed at 623 K (350 °C) and 21 kPa (160 Torr) O2pressure the initial D removal rates were found to increase linearly with increasing ‘inherent’ D content; about 50% of the inherent D was removed from all specimens in the first 15 min—independent of Be content and codeposit thickness. Following 8 h of oxidation, the fraction of D removed was >85% for all specimens, again, independent of Be content and thickness.
Prototype of an adaptive disruption predictor for JET based on fuzzy logic and regression trees
Authors: Murari A. , Vagliasindi G. , Arena P. , Fortuna L. , Barana O. , Johnson M.
Published: February 2008

Disruptions remain one of the most hazardous events in the operation of a tokamak device, since they can cause damage to the vacuum vessel and surrounding structures. Their potential danger increases with the plasma volume and energy content and therefore they will constitute an even more serious issue for the next generation of machines. For these reasons, in the recent years a lot of attention has been devoted to devise predictors, capable of foreseeing the imminence of a disruption sufficiently in advance, to allow time for undertaking remedial actions. In this paper, the results of applying fuzzy logic and classification and regression trees (CART) to the problem of predicting disruptions at JET are reported. The conceptual tools of fuzzy logic, in addition to being well suited to accommodate the opinion of experts even if not formulated in mathematical but linguistic terms, are also fully transparent, since their governing rules are human defined. They can therefore help not only in forecasting disruptions but also in studying their behaviour. The analysis leading to the rules of the fuzzy predictor has been complemented with a systematic investigation of the correlation between the various experimental signals and the imminence of a disruption. This has been performed with an exhaustive, non-linear and unbiased method based on decision trees. This investigation has confirmed that the relative importance of various signals can change significantly depending on the plasma conditions. On the basis of the results provided by CART on the information content of the various quantities, the prototype of an adaptive fuzzy logic predictor was trained and tested on JET database. Its performance is significantly better than the previous static one, proving that more flexible prediction strategies, not uniform over the whole discharge but tuned to the operational region of the plasma at any given time, can be very competitive and should be investigated systematically.
Lipid Lowering Activity of Anthocephalus indicus Root in Hyperlipidemic Rats
Authors: Kumar Vishnu , Khan Mohammad Mubin , Khanna Ashok Kumar , Singh Ranjana , Singh Sushma , Chander Ramesh , Mahdi Farzana , Mahdi Abbas Ali , Saxena Jitendra Kumar , Singh Raj Kumar
Published: February 2008

The lipid lowering activity of Anthocephalus indicus (family Rubiaceae; Hindi name Kadamba) root extract has been studied in triton WR‐1339 induced hyperlipidemia in rats. In this model, feeding with root extract (500 mg kg−1 b.w.) lowered plasma lipids and reactivated post‐heparin lipolytic activity in hyperlipidemic rats. Furthermore, the root extract (50–500 μM) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non‐enzymic systems, in vitro. The results of the present study demonstrated both lipid lowering and antioxidant activities in root extract of A. indicus, which could help prevention of hyperlipidemia and related diseases.
Parentage testing in alpacas (Vicugna pacos) using semi‐automated fluorescent multiplex PCRs with 10 microsatellite markers
Authors: Agapito J. , Rodríguez J. , Herrera‐Velit P. , Timoteo O. , Rojas P. , Boettcher P. J. , García F. , Espinoza J. R.
Published: February 2008

The aim of this study was to assess and apply a microsatellite multiplex system for parentage determination in alpacas. An approach for parentage testing based on 10 microsatellites was evaluated in a population of 329 unrelated alpacas from different geographical zones in Perú. All microsatellite markers, which amplified in two multiplex reactions, were highly polymorphic with a mean of 14.5 alleles per locus (six to 28 alleles per locus) and an average expected heterozygosity (HE) of 0.8185 (range of 0.698–0.946). The total parentage exclusion probability was 0.999456 for excluding a candidate parent from parentage of an arbitrary offspring, given only the genotype of the offspring, and 0.999991 for excluding a candidate parent from parentage of an arbitrary offspring, given the genotype of the offspring and the other parent. In a case test of parentage assignment, the microsatellite panel assigned 38 (from 45 cases) offspring parentage to 10 sires with LOD scores ranging from 2.19 × 10+13 to 1.34 × 10+15 and Δ values ranging from 2.80 × 10+12 to 1.34 × 10+15 with an estimated pedigree error rate of 15.5%. The performance of this multiplex panel of markers suggests that it will be useful in parentage testing of alpacas.
Domatia reduce larval cannibalism in predatory mites
Authors: FERREIRA JOÃO A. M. , ESHUIS BRECHTJE , JANSSEN ARNE , SABELIS MAURICE W.
Published: February 2008

Abstract1. Acarodomatia are small structures on the underside of leaves of many plant species, which are mainly inhabited by carnivorous and fungivorous mites.

2. Domatia are thought to protect these mites against adverse environmental conditions and against predation. They are considered as an indirect plant defence; they provide shelter to predators and fungivores and these in turn protect the plants against herbivores and fungi.

3. We studied the possible role of domatia of coffee (Coffea arabicaL.) (Rubiaceae) and sweet pepper (Capsicum annumL.) (Solanaceae) in reducing cannibalism in the mites inhabiting the domatia. We measured cannibalism of larvae by adults of the predatory mitesIphiseiodes zuluagaiDenmark & Muma andAmblyseius herbicolusChant on coffee leaf discs and of the predatory miteIphiseius degenerans(Berl.) on sweet pepper leaf. Domatia were closed with glue or left open.

4. Cannibalism in all three species increased when domatia were closed. WithI. degenerans, moreover, we found that the previous diet of the cannibal attenuated the effect of domatia on cannibalism.

5. We conclude that domatia can protect young predatory mites against cannibalism by adults and that the diet of cannibals affects the rate of cannibalism.