bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Watch us Wander’: Mobile Surveillance and the Surveillance of Mobility
Authors: Molz Jennie Germann
Published: February 2006

Social relations between geographically distant and mobile individuals are increasingly mediated through new information and communication technologies. In this paper I argue that the configuration of these mobile social relations can be understood through a model of interpersonal surveillance that, unlike hierarchical state structures of surveillance, constitutes a decentralised social relation between individuals. This shift may be characterised in the writings of Foucault as a move from the panopticon model of surveillance that mediates the relation between the state and the individual to his later writings on technologies of the self, which emphasise interaction between individuals as a source of self-discipline. Like the panopticon, this second form of surveillance also constitutes a power/knowledge regime that produces certain ways of seeing and certain objects of the ‘surveilling’ gaze. Drawing on empirical material from research on round-the-world travel websites, in this paper I outline the way metaphors of surveillance such as ‘watching’ and ‘following’ configure the mobile social relations that occur between travellers and their on-line audience.
Vision in Motion
Authors: Büscher Monika
Published: February 2006

Mobility and materiality are pervasive and revealing features of professional vision. In this paper I examine how landscape architects assess visual and landscape effects of proposed urban or rural developments. A focus on mobility and materiality reveals a struggle for objectivity and transparency, and the lived reality of Latour's observation that “we have never been modern”. But it also highlights the emergence of new forms of perception and epistemic practice. Based on work with landscape architects and computer scientists in participatory technology research and design projects, I present an analysis of current practices and some observations on emerging future practices of appreciating and shaping places.
Aeromobility and Work
Authors: Lassen Claus
Published: February 2006

In this paper, the hypothesis is that there is a connection between international aeromobility, knowledge organisations, and environmental impacts. The object is therefore to examine the driving forces, mechanisms, and patterns of meaning behind the increase in international long-distance work mobility. The author will draw on a case study which involves two Danish examples of ‘knowledge organisations’. He argues that it is necessary to rethink central concepts of travel, tourism, and working life, in order to understand and describe this kind of international mobility in these organisations. The boundary between work and tourism is not distinct and there is a very complex connection between travel, work, tourism, and play. He shows that actually, there is a strong ‘material’ impact from supposedly ‘immaterial’ organisations and this ‘materiality’ is particularly linked to the extension of forms of mobility. This has implications for understanding the possibilities of replacing physical work mobility with virtual mobility as a tool in order to ensure a more ‘sustainable transport system’ in the future.
Tending to Mobility: Intensities of Staying at the Petrol Station
Authors: Normark Daniel
Published: February 2006

This paper reports a study of ongoing social activities at a petrol station. Petrol stations constitute a nexus for mobility. Through ethnographic observations the author tests how the continuous flow of vehicles, commodities, money, and people are sustained and made accountable. The fieldwork demonstrates that, despite its transitory character, the petrol station offers a wide spectrum of ‘duration of stay’. The station was used while being-on-the-way as well as providing a possibility to disembark from automobility, that is, being-off-the-way. However, the most important finding is that the station tends to mobility, from the production and recognition of fluency, the constant negotiation and articulation work of situations, to continuous maintenance and repair of movement. Accomplishing a flow of people, vehicles, money, and commodities is a complex and delicate task requiring subtle negotiation between staff and visitors as well as among visitors themselves. A negotiation supported and hampered by available materialities of the place.
Mobility and War: The Cosmic View of US ‘Air Power’
Authors: Kaplan Caren
Published: February 2006

Air power was a contested military strategy during the first half of the 20th century. During World War 2, the doctrine of air power became a dominant part of US national defence contributing to the nationalisation of air space. In this paper I raise parallels between the rise of the doctrine of air power in the US during World War 2 and the concerns about national security following the attacks on September 11, 2001. The visual and spatial logics of air power generate a ‘cosmic view’ that unifies and fixes targets from the air. Yet, this articulation of nationalism is challenged by the current practices and conditions of warfare.
Regulating activation of transplanted cells controls tissue regeneration
Authors: Hill Elliott , Boontheekul Tanyarut , Mooney David J.
Published: February 2006

Current approaches to tissue regeneration are limited by the death of most transplanted cells and/or resultant poor integration of transplanted cells with host tissue. We hypothesized that transplanting progenitor cells within synthetic microenvironments that maintain viability, prevent terminal differentiation, and promote outward migration would significantly enhance their repopulation and regeneration of damaged host tissue. This hypothesis was addressed in the context of muscle regeneration by transplanting satellite cells to muscle laceration sites on a delivery vehicle releasing factors that induce cell activation and migration (hepatocyte growth factor and fibroblast growth factor 2) or transplantation on materials lacking factor release. Controls included direct cell injection into muscle, the implantation of blank scaffolds, and scaffolds releasing factors without cells. Injected cells demonstrated a limited repopulation of damaged muscle and led to a slight improvement in muscle regeneration, as expected. Delivery of cells on scaffolds that did not promote migration resulted in no improvement in muscle regeneration. Strikingly, delivery of cells on scaffolds that promoted myoblast activation and migration led to extensive repopulation of host muscle tissue and increased the regeneration of muscle fibers at the wound and the mass of the injured muscle. This previously undescribed strategy for cell transplantation significantly enhances muscle regeneration from transplanted cells and may be broadly applicable to the various tissues and organ systems in which provision and instruction of a cell population competent to participate in regeneration may be clinically useful.
Microscale technologies for tissue engineering and biology
Authors: Khademhosseini Ali , Langer Robert , Borenstein Jeffrey , Vacanti Joseph P.
Published: February 2006

Microscale technologies are emerging as powerful tools for tissue engineering and biological studies. In this review, we present an overview of these technologies in various tissue engineering applications, such as for fabricating 3D microfabricated scaffolds, as templates for cell aggregate formation, or for fabricating materials in a spatially regulated manner. In addition, we give examples of the use of microscale technologies for controlling the cellular microenvironment
in vitro
and for performing high-throughput assays. The use of microfluidics, surface patterning, and patterned cocultures in regulating various aspects of cellular microenvironment is discussed, as well as the application of these technologies in directing cell fate and elucidating the underlying biology. Throughout this review, we will use specific examples where available and will provide trends and future directions in the field.
Relevance and safety of telomerase for human tissue engineering
Authors: Klinger Rebecca Y. , Blum Juliana L. , Hearn Bevin , Lebow Benjamin , Niklason Laura E.
Published: February 2006

Tissue engineering holds the promise of replacing damaged or diseased tissues and organs. The use of autologous donor cells is often not feasible because of the limited replicative lifespan of cells, particularly those derived from elderly patients. Proliferative arrest can be overcome by the ectopic expression of telomerase via human telomerase reverse transcriptase (hTERT) gene transfection. To study the efficacy and safety of this potentially valuable technology, we used differentiated vascular smooth muscle cells (SMC) and vascular tissue engineering as a model system. Although we previously demonstrated that vessels engineered with telomerase-expressing SMC had improved mechanics over those grown with control cells, it is critical to assess the phenotypic impact of telomerase expression in donor cells, because telomerase up-regulation is observed in >95% of human malignancies. To study the impact of telomerase in tissue engineering, expression of hTERT was retrovirally induced in SMC from eight elderly patients and one young donor. In hTERT SMC, significant lifespan extension beyond that of control was achieved without population doubling time acceleration. Karyotype changes were seen in both control and hTERT SMC but were not clonal nor representative of cancerous change. hTERT cells also failed to show evidence of neoplastic transformation in functional assays of tumorigenicity. In addition, the impact of donor age on cellular behavior, particularly the synthetic capability of SMC, was not affected by hTERT expression. Hence, this tissue engineering model system highlights the impact of donor age on cellular synthetic function that appears to be independent of lifespan extension by hTERT.
Crystal structure of human indoleamine 2,3-dioxygenase: Catalytic mechanism of O
2
incorporation by a heme-containing dioxygenase
Authors: Sugimoto Hiroshi , Oda Shun-ichiro , Otsuki Takashi , Hino Tomoya , Yoshida Tadashi , Shiro Yoshitsugu
Published: February 2006

Human indoleamine 2,3-dioxygenase (IDO) catalyzes the cleavage of the pyrrol ring of
l
-Trp and incorporates both atoms of a molecule of oxygen (O
2
). Here we report on the x-ray crystal structure of human IDO, complexed with the ligand inhibitor 4-phenylimidazole and cyanide. The overall structure of IDO shows two α-helical domains with the heme between them. A264 of the flexible loop in the heme distal side is in close proximity to the iron. A mutant analysis shows that none of the polar amino acid residues in the distal heme pocket are essential for activity, suggesting that, unlike the heme-containing monooxygenases (i.e., peroxidase and cytochrome P450), no protein group of IDO is essential in dioxygen activation or proton abstraction. These characteristics of the IDO structure provide support for a reaction mechanism involving the abstraction of a proton from the substrate by iron-bound dioxygen. Inactive mutants (F226A, F227A, and R231A) retain substrate-binding affinity, and an electron density map reveals that 2-(
N
-cyclohexylamino)ethane sulfonic acid is bound to these residues, mimicking the substrate. These findings suggest that strict shape complementarities between the indole ring of the substrate and the protein side chains are required, not for binding, but, rather, to permit the interaction between the substrate and iron-bound dioxygen in the first step of the reaction. This study provides the structural basis for a heme-containing dioxygenase mechanism, a missing piece in our understanding of heme chemistry.
Association of brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) with recycling endosomes during transferrin uptake
Authors: Shen Xiaoyan , Xu Kai-Feng , Fan Qingyuan , Pacheco-Rodriguez Gustavo , Moss Joel , Vaughan Martha
Published: February 2006

ADP-ribosylation factors (ARFs) are critical in vesicular trafficking. Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG)1 and BIG2 activate ARFs by accelerating replacement of bound GDP with GTP. Additional and differing functions of these ≈200-kDa proteins are now being recognized, as are their independent intracellular movements. Here, we describe the localization in COS7 cells by immunofluorescence microscopy of BIG2, but not BIG1, with structures that have characteristics of recycling endosomes during transferrin (Tfn) uptake and Tfn receptor (TfnR) recycling. Cell content of BIG2 and Rab11, but not TfnR, BIG1, Rab4, or Exo70, was increased after 60 min of Tfn uptake. BIG2, but not BIG1, appeared in density-gradient fractions containing TfnR, Rab11, and Exo70 after 60 min of Tfn uptake. Treatment of cells with BIG2 small interfering RNA (siRNA), but not BIG1 or control siRNAs, decreased BIG2 protein >90% without affecting BIG1, ARF, or actin content, whereas TfnR was significantly increased as was its accumulation in perinuclear recycling endosomes. Tfn release appeared unaffected by BIG1 siRNA but was significantly slowed from cells treated with BIG2 siRNA alone or plus BIG1 siRNA. We suggest that BIG2 has an important role in Tfn uptake and TfnR recycling, perhaps through its demonstrated interaction with Exo70 and the exocyst complex.
Directly observed reversible shape changes and hemoglobin stratification during centrifugation of human and
Amphiuma
red blood cells
Authors: Hoffman Joseph F. , Inoué Shinya
Published: February 2006

This paper describes changes that occur in human and
Amphiuma
red blood cells observed during centrifugation with a special microscope. Dilute suspensions of cells were layered, in a centrifuge chamber, above an osmotically matched dense solution, containing Nycodenz, Ficoll, or Percoll (Pharmacia) that formed a density gradient that allowed the cells to slowly settle to an equilibrium position. Biconcave human red blood cells moved downward at low forces with minimum wobble. The cells oriented vertically when the force field was increased and Hb sedimented as the lower part of each cell became bulged and assumed a “bag-like” shape. The upper centripetal portion of the cell became thinner and remained biconcave. These changes occurred rapidly and were completely reversible upon lowering the centrifugal force. Bag-shaped cells, upon touching red cells in rouleau, immediately reverted to biconcave disks as they flipped onto a stack.
Amphiuma
red cells displayed a different type of reversible stratification and deformation at high force fields. Here the cells became stretched, with the nucleus now moving centrifugally, the Hb moving centripetally, and the bottom of the cells becoming thinner and clear. Nevertheless, the distribution of the marginal bands at the cells' rim was unchanged. We conclude that centrifugation,
per se
, while changing a red cell's shape and the distribution of its intracellular constituents, does so in a completely reversible manner. Centrifugation of red cells harboring altered or missing structural elements could provide information on shape determinants that are still unexplained.
IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-κB activation
Authors: Song Yoon-Jae , Jen Kai-Yu , Soni Vishal , Kieff Elliott , Cahir-McFarland Ellen
Published: February 2006

Epstein–Barr virus latent infection integral membrane protein 1 (LMP1) mimics a constitutively active TNF receptor (TNFR). LMP1 has two C-terminal cytosolic domains, transformation effector sites (TES)1 and -2, that engage TNFR-associated factors (TRAFs) and the TNFR-associated death domain protein, respectively, and activate NF-κB. NF-κB activation is critical for Epstein–Barr virus-infected lymphoblast survival. TES1- and TES2-mediated NF-κB activations are IL-1 receptor-associated kinase 1 (IRAK1)-dependent. Because IRAK1 is upstream of TRAF6 in IL-1 activation of NF-κB, the potential role of IRAK1 in LMP1-mediated NF-κB activation through TRAF6 and inhibitor of κB (IκB) kinase (IKK) was initially investigated. Surprisingly, LMP1 expression activated TRAF6 ubiquitination, IKKβ induction of IκBα phosphorylation, and p65 nuclear translocation in both WT and IRAK1-deficient I1A 293 cells. LMP1 also induced IKKα-mediated p100 processing and p52 nuclear localization in WT and IRAK1-deficient I1A 293 cells. Further, LMP1 TES1 and TES2 induced p65, p50, and p52 NF-κB DNA binding in WT and IRAK1-deficient I1A 293 cells. However, LMP1 induced p65/RelA S536 phosphorylation only in WT 293 cells or in IRAK1 kinase point mutant reconstituted I1A 293 cells but not in IRAK1-deficient I1A 293 cells. IRAK1 was also required for LMP1 activation of p38, one of the kinases that can mediate p65/RelA S536 phosphorylation and activate NF-κB-dependent transcription. Thus, the critical IRAK1 role in LMP1-induced NF-κB activation is in mediating p65/RelA S536 phosphorylation through an effect on p38 or other p65 S536 kinases.
Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins
Authors: Gaspar Miguel , Shenk Thomas
Published: February 2006

The DNA damage checkpoint pathway responds to DNA damage and induces a cell cycle arrest to allow time for DNA repair. Several viruses are known to activate or modulate this cellular response. Here we show that the ataxia-telangiectasia mutated checkpoint pathway, which responds to double-strand breaks in DNA, is activated in response to human cytomegalovirus DNA replication. However, this activation does not propagate through the pathway; it is blocked at the level of the effector kinase, checkpoint kinase 2 (Chk2). Late after infection, several checkpoint proteins, including ataxia-telangiectasia mutated and Chk2, are mislocalized to a cytoplasmic virus assembly zone, where they are colocalized with virion structural proteins. This colocalization was confirmed by immunoprecipitation of virion proteins with an antibody that recognizes Chk2. Virus replication was resistant to ionizing radiation, which causes double-strand breaks in DNA. We propose that human CMV DNA replication activates the checkpoint response to DNA double-strand breaks, and the virus responds by altering the localization of checkpoint proteins to the cytoplasm and thereby inhibiting the signaling pathway.
Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype
Authors: Martinat Cecile , Bacci Jean-Jacques , Leete Thomas , Kim Jongpil , Vanti William B. , Newman Amy H. , Cha Joo H. , Gether Ulrik , Wang Honggang , Abeliovich Asa
Published: February 2006

Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson’s disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson’s disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures
in vitro
, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.
κ opioids selectively control dopaminergic neurons projecting to the prefrontal cortex
Authors: Margolis Elyssa B. , Lock Hagar , Chefer Vladimir I. , Shippenberg Toni S. , Hjelmstad Gregory O. , Fields Howard L.
Published: February 2006

Dopaminergic afferents arising from the ventral tegmental area (VTA) are crucial elements in the neural circuits that mediate arousal, motivation, and reinforcement. Two major targets of these afferents are the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). Whereas dopamine (DA) in the mPFC has been implicated in working memory and attentional processes, DA in the NAc is required for responding to reward predictive cues. These distinct functions suggest a role for independent firing patterns of dopaminergic neurons projecting to these brain regions. In fact, DA release in mPFC and NAc can be differentially modulated. However, to date, electrophysiological studies have largely overlooked heterogeneity among VTA neurons. Here, we provide direct evidence for differential neurotransmitter control of DA neural activity and corresponding DA release based on projection target. κ opioid receptor agonists inhibit VTA DA neurons that project to the mPFC but not those that project to the NAc. Moreover, DA levels in the mPFC, but not the NAc, are reduced after local infusion of κ opioid receptor agonists into the VTA. These findings demonstrate that DA release in specific brain regions can be independently regulated by opioid targeting of a subpopulation of VTA DA neurons. Selective control of VTA DA neurons projecting to the mPFC has important implications for understanding addiction, attention disorders, and schizophrenia, all of which are associated with DA dysfunction in the mPFC.
Liddle’s syndrome mutations increase Na
+
transport through dual effects on epithelial Na
+
channel surface expression and proteolytic cleavage
Authors: Knight Kristin K. , Olson Diane R. , Zhou Ruifeng , Snyder Peter M.
Published: February 2006

Liddle’s syndrome, an inherited form of hypertension, is caused by mutations that delete or disrupt a C-terminal PY motif in the epithelial Na
+
channel (ENaC). Previous work indicates that these mutations increase expression of ENaC at the cell surface by disrupting its binding to Nedd4-2, an E3 ubiquitin–protein ligase that targets ENaC for degradation. However, it remains uncertain whether this mechanism alone is responsible; increased activity of ENaC channels could also contribute to excessive Na
+
transport in Liddle’s syndrome. ENaC activity is controlled in part by its cleavage state; proteolytic cleavage produces channels with a high open-state probability, whereas uncleaved channels are inactive. Here, we found that Liddle’s syndrome mutations have two distinct effects of ENaC surface expression, both of which contribute to increased Na
+
transport. First, these mutations increased ENaC expression at the cell surface; second, they increased the fraction of ENaC at the cell surface that was cleaved (active). This disproportionate increase in cleavage was reproduced by expression of a dominant-negative Nedd4-2 or mutation of ENaC ubiquitination sites, interventions that disrupt ENaC endocytosis and lysosomal degradation. Conversely, overexpression of Nedd4-2 had the opposite effect, decreasing the fraction of cleaved ENaC at the cell surface. Thus, the data not only suggest that Nedd4-2 regulates epithelial Na
+
transport in part by controlling the relative expression of cleaved and uncleaved ENaC at the cell surface but also provide a mechanism by which Liddle’s syndrome mutations alter ENaC activity.
DNA conformation on surfaces measured by fluorescence self-interference
Authors: Moiseev Lev , Ünlü M. Selim , Swan Anna K. , Goldberg Bennett B. , Cantor Charles R.
Published: February 2006

The conformation of DNA molecules tethered to the surface of a microarray may significantly affect the efficiency of hybridization. Although a number of methods have been applied to determine the structure of the DNA layer, they are not very sensitive to variations in the shape of DNA molecules. Here we describe the application of an interferometric technique called spectral self-interference fluorescence microscopy to the precise measurement of the average location of a fluorescent label in a DNA layer relative to the surface and thus determine specific information on the conformation of the surface-bound DNA molecules. Using spectral self-interference fluorescence microscopy, we have estimated the shape of coiled single-stranded DNA, the average tilt of double-stranded DNA of different lengths, and the amount of hybridization. The data provide important proofs of concept for the capabilities of novel optical surface analytical methods of the molecular disposition of DNA on surfaces. The determination of DNA conformations on surfaces and hybridization behavior provide information required to move DNA interfacial applications forward and thus impact emerging clinical and biotechnological fields.
Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds
Authors: Pilch Jan , Brown Darren M. , Komatsu Masanobu , Järvinen Tero A. H. , Yang Meng , Peters David , Hoffman Robert M. , Ruoslahti Erkki
Published: February 2006

Screening of a phage library for peptides that bind to clotted plasma in the presence of liquid plasma yielded two cyclic decapeptides, CGLIIQKNEC (CLT1) and CNAGESSKNC (CLT2). When injected intravenously into mice bearing various types of tumors, fluorescein-conjugated CLT peptides accumulated in a fibrillar meshwork in the extracellular compartment of the tumors, but were not detectable in other tissues of the tumor-bearing mice. The tumor homing of both peptides was strongly reduced after coinjection with unlabeled CLT2, indicating that the two peptides recognize the same binding site. The CLT peptide fluorescence colocalized with staining for fibrin(ogen) present in the extravascular compartment of tumors, but not in other tissues. The CLT peptides did not home to tumors grown in fibrinogen-null mice or in mice that lack plasma fibronectin. The CLT peptides also accumulated at the sites of injury in arteries, skeletal muscle, and skin. We conclude that the CLT peptides recognize fibrin–fibronectin complexes formed by clotting of plasma proteins that have leaked into the extravascular space in tumors and other lesions. These peptides may be useful in targeting diagnostic and therapeutic materials into tumors and injured tissues.
Role for calcium/calmodulin-dependent protein kinase II in the p75-mediated regulation of sympathetic cholinergic transmission
Authors: Slonimsky John D. , Mattaliano Mark D. , Moon Jung-il , Griffith Leslie C. , Birren Susan J.
Published: February 2006

Neurotrophins regulate sympathetic neuron cotransmission by modulating the activity-dependent release of norepinephrine and acetylcholine. Nerve growth factor promotes excitatory noradrenergic transmission, whereas brain-derived neurotrophic factor (BDNF), acting through the p75 receptor, increases inhibitory cholinergic transmission. This regulation of corelease by target-derived factors leads to the functional modulation of myocyte beat rate in neuron–myocyte cocultures. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the control of both pre- and postsynaptic mechanisms of synaptic plasticity. We demonstrate that CaMKII acts in conjunction with p75 signaling to regulate cholinergic transmission between sympathetic neurons and heart cells. Inhibition of presynaptic CaMKII prevents the BDNF-dependent shift to inhibitory neurotransmission, whereas presynaptic expression of a constitutively active CaMKII results in inhibitory neurotransmission in the absence of added BDNF, suggesting that activation of presynaptic CaMKII is both necessary and sufficient for a shift from excitatory to inhibitory transmission. Several isozymes of CaMKII are expressed in sympathetic neurons, with the δ-CaMKII being activated by BDNF and nerve growth factor. Activated CaMKII is less effective at promoting cholinergic transmission in the absence of p75 signaling, demonstrating that p75 and CaMKII act to coordinate neurotransmitter selection in sympathetic neurons.
Self-Stabilizing Global Optimization Algorithms for Large Network Graphs
Authors: Goddard Wayne , Hedetniemi Stephen T. , Jacobs David P. , Srimani Pradip K.
Published: February 2006

The paradigm of self-stabilization provides a mechanism to design efficient localized distributed algorithms that are proving to be essential for modern day large networks of sensors. We provide self-stabilizing algorithms (in the shared-variable ID-based model) for three graph optimization problems: a minimal total dominating set (where every node must be adjacent to a node in the set) and its generalizations, a maximal k-packing (a set of nodes where every pair of nodes are more than distance k apart), and a maximal strong matching (a collection of totally disjoint edges).
An Architecture for Robust Sensor Network Communications
Authors: Younis Ossama , Fahmy Sonia , Santi Paolo
Published: February 2006

Node clustering in sensor networks increases scalability, robustness, and energy-efficiency. In hostile environments, unexpected failures or attacks on cluster heads (through which communication takes place) may partition the network or degrade application performance. We propose REED (Robust Energy-Efficient Distributed clustering), for clustering sensors deployed in hostile environments in an interleaved manner with low complexity. Our primary objective is to construct a k-fault-tolerant (i.e., k-connected) clustered network, where k is a constant determined by the application. Fault tolerance is achieved by selecting k independent sets of cluster heads (i.e., cluster head overlays) on top of the physical network, so that each node can quickly switch to other cluster heads in case of failures. The independent cluster head overlays also give multiple vertex-disjoint routing paths for load balancing and security. Network lifetime is prolonged by selecting cluster heads with high residual energy and low communication cost, and periodically re-clustering the network. We prove that REED asymptotically achieves k-connectivity if certain conditions on node density are met. We also discuss inter-cluster routing and MAC layer considerations, and investigate REED clustering properties via extensive simulations.
Impaired response to Listeria in H2-M3–deficient mice reveals a nonredundant role of MHC class Ib–specific T cells in host defense
Authors: Xu Honglin , Chun Taehoon , Choi Hak-Jong , Wang Bin , Wang Chyung-Ru
Published: February 2006

The major histocompatibility complex (MHC) class Ib molecule H2-M3 primes the rapid expansion of CD8+ T cells by presenting N-formylated bacterial peptides. However, the significance of H2-M3–restricted T cells in host defense against bacteria is unclear. We generated H2-M3–deficient mice to investigate the role of H2-M3 in immunity against Listeria monocytogenes (LM), a model intracellular bacterial pathogen. H2-M3–deficient mice are impaired in early bacterial clearance during primary infection, with diminished LM-specific CD8+ T cell responses and compromised innate immune functions. Although H2-M3–restricted CD8+ T cells constitute a significant proportion of the anti-listerial CD8+ T cell repertoire, the kinetics and magnitude of MHC class Ia–restricted T cell responses are not altered in H2-M3–deficient mice. The fact that MHC class Ia–restricted responses cannot compensate for the H2-M3–mediated immunity suggests a nonredundant role of H2-M3 in the protective immunity against LM. Thus, the early H2-M3–restricted response temporally bridges the gap between innate and adaptive immune responses, subsequently affecting the function of both branches of the immune system.
T-independent type II immune responses generate memory B cells
Authors: Obukhanych Tetyana V. , Nussenzweig Michel C.
Published: February 2006

Unlike T-dependent immune responses against protein antigens, T-independent responses against polysaccharides confer long-lasting humoral immunity in the absence of recall responses and are not known to generate memory B cells. Here we report that polysaccharide antigens elicit memory B cells that are phenotypically distinct from those elicited by protein antigens. Furthermore, memory B cell responses against polysaccharides are regulated by antigen-specific immunoglobulin G antibodies. As the generation and regulation of immunologic memory is central to vaccination, our findings help explain the mode of action of the few existing polysaccharide vaccines and provide a rationale for a wider application of polysaccharide-based strategies in vaccination.
Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis
Authors: Noorbakhsh Farshid , Tsutsui Shigeki , Vergnolle Nathalie , Boven Leonie A. , Shariat Neda , Vodjgani Mohammed , Warren Kenneth G. , Andrade-Gordon Patricia , Hollenberg Morley D. , Power Christopher
Published: February 2006

The proteinase-activated receptors (PARs) are widely recognized for their modulatory properties of inflammation and neurodegeneration. We investigated the role of PAR2 in the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in mice. PAR2 expression was increased on astrocytes and infiltrating macrophages in human MS and murine EAE central nervous system (CNS) white matter (P < 0.05). Macrophages and astrocytes from PAR2 wild-type (WT) and knockout (KO) mice exhibited differential immune gene expression with PAR2 KO macrophages showing significantly higher interleukin 10 production after lipopolysaccharide stimulation (P < 0.001). PAR2 activation in macrophages resulted in the release of soluble oligodendrocyte cytotoxins (P < 0.01). Myelin oligodendrocyte glycoprotein–induced EAE caused more severe inflammatory gene expression in the CNS of PAR2 WT animals (P < 0.05), together with enhanced T cell proliferation and interferon γ production (P < 0.05), compared with KO littermates. Indeed, PAR2 WT animals showed markedly greater microglial activation and T lymphocyte infiltration accompanied by worsened demyelination and axonal injury in the CNS compared with their PAR2 KO littermates. Enhanced neuropathological changes were associated with a more severe progressive relapsing disease phenotype (P < 0.001) in WT animals. These findings reveal previously unreported pathogenic interactions between CNS PAR2 expression and neuroinflammation with ensuing demyelination and axonal injury.
Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice
Authors: Jansen Jacob G. , Langerak Petra , Tsaalbi-Shtylik Anastasia , van den Berk Paul , Jacobs Heinz , de Wind Niels
Published: February 2006

Somatic hypermutation of Ig genes enables B cells of the germinal center to generate high-affinity immunoglobulin variants. Key intermediates in somatic hypermutation are deoxyuridine lesions, introduced by activation-induced cytidine deaminase. These lesions can be processed further to abasic sites by uracil DNA glycosylase. Mutagenic replication of deoxyuridine, or of its abasic derivative, by translesion synthesis polymerases is hypothesized to underlie somatic hypermutation.

Rev1 is a translesion synthesis polymerase that in vitro incorporates uniquely deoxycytidine opposite deoxyuridine and abasic residues. To investigate a role of Rev1 in mammalian somatic hypermutation we have generated mice deficient for Rev1. Although Rev1−/− mice display transient growth retardation, proliferation of Rev1−/− LPS-stimulated B cells is indistinguishable from wild-type cells. In mutated Ig genes from Rev1−/− mice, C to G transversions were virtually absent in the nontranscribed (coding) strand and reduced in the transcribed strand. This defect is associated with an increase of A to T, C to A, and T to C substitutions. These results indicate that Rev1 incorporates deoxycytidine residues, most likely opposite abasic nucleotides, during somatic hypermutation. In addition, loss of Rev1 causes compensatory increase in mutagenesis by other translesion synthesis polymerases.
EGFR Kinase Regulates Volume-sensitive Chloride Current Elicited by Integrin Stretch via PI-3K and NADPH Oxidase in Ventricular Myocytes
Authors: Browe David M. , Baumgarten Clive M.
Published: February 2006

Stretch of β1 integrins activates an outwardly rectifying, tamoxifen-sensitive Cl− current (Cl− SAC) via AT1 receptors, NADPH oxidase, and reactive oxygen species, and Cl− SAC resembles the volume-sensitive Cl− current (ICl,swell). Epidermal growth factor receptor (EGFR) kinase undergoes transactivation upon stretch, integrin engagement, and AT1 receptor activation and, in turn, stimulates NADPH oxidase. Therefore, we tested whether Cl− SAC is regulated by EGFR kinase signaling and is volume sensitive. Paramagnetic beads coated with mAb for β1 integrin were attached to myocytes and pulled with an electromagnet. Stretch activated a Cl− SAC that was 1.13 ± 0.10 pA/pF at +40 mV. AG1478 (10 μM), an EGFR kinase blocker, inhibited 93 ± 13% of Cl− SAC, and intracellular pretreatment with 1 μM AG1478 markedly suppressed Cl− SAC activation. EGF (3.3 nM) directly activated an outwardly rectifying Cl− current (0.81 ± 0.05 pA/pF at +40 mV) that was fully blocked by 10 μM tamoxifen, an ICl,swell blocker. Phosphatidylinositol 3-kinase (PI-3K) is downstream of EGFR kinase. Wortmannin (500 nM) and LY294002 (100 μM), blockers of PI-3K, inhibited Cl− SAC by 67 ± 6% and 91 ± 25% respectively, and the EGF-induced Cl− current also was fully blocked by LY294002. Furthermore, gp91ds-tat (500 nM), a cell-permeable, chimeric peptide that specifically blocks NADPH oxidase assembly, profoundly inhibited the EGF-induced Cl− current. Inactive permeant and active impermeant control peptides had no effect. Myocyte shrinkage with hyperosmotic bathing media inhibited the Cl− SAC and EGF-induced Cl− current by 88 ± 9% and 127 ± 11%, respectively. These results suggest that β1 integrin stretch activates Cl− SAC via EGFR, PI-3K, and NADPH oxidase, and that both the Cl− SAC and the EGF-induced Cl− currents are likely to be the volume-sensitive Cl− current, ICl,swell.
Differential Sialylation Modulates Voltage-gated Na+ Channel Gating throughout the Developing Myocardium
Authors: Stocker Patrick J. , Bennett Eric S.
Published: February 2006

Voltage-gated sodium channel function from neonatal and adult rat cardiomyocytes was measured and compared. Channels from neonatal ventricles required an ∼10 mV greater depolarization for voltage-dependent gating events than did channels from neonatal atria and adult atria and ventricles. We questioned whether such gating shifts were due to developmental and/or chamber-dependent changes in channel-associated functional sialic acids. Thus, all gating characteristics for channels from neonatal atria and adult atria and ventricles shifted significantly to more depolarized potentials after removal of surface sialic acids. Desialylation of channels from neonatal ventricles did not affect channel gating. After removal of the complete surface N-glycosylation structures, gating of channels from neonatal atria and adult atria and ventricles shifted to depolarized potentials nearly identical to those measured for channels from neonatal ventricles. Gating of channels from neonatal ventricles were unaffected by such deglycosylation. Immunoblot gel shift analyses indicated that voltage-gated sodium channel α subunits from neonatal atria and adult atria and ventricles are more heavily sialylated than α subunits from neonatal ventricles. The data are consistent with approximately 15 more sialic acid residues attached to each α subunit from neonatal atria and adult atria and ventricles. The data indicate that differential sialylation of myocyte voltage-gated sodium channel α subunits is responsible for much of the developmental and chamber-specific remodeling of channel gating observed here. Further, cardiac excitability is likely impacted by these sialic acid–dependent gating effects, such as modulation of the rate of recovery from inactivation. A novel mechanism is described by which cardiac voltage-gated sodium channel gating and subsequently cardiac rhythms are modulated by changes in channel-associated sialic acids.
A cultural‐conceptual approach and world Englishes: the case of Aboriginal English
Authors: Sharifian Farzad
Published: February 2006

Abstract: Studies of world Englishes have traditionally fallen within the scope of sociolinguistics, applied linguistics, English studies, lexicography and critical linguistics. This paper is an attempt to show how these studies can be complemented by an emerging approach that employs the analytic tools and frameworks developed in cognitive and cultural linguistics to explore various features of world Englishes. The fundamental premise in this approach is that world Englishes should not be examined exclusively in terms of their linguistic features but rather as emergent systems that are largely adopted and explored to encode and express thecultural conceptualisationsof their speakers. The paper focuses on Aboriginal English and shows how various features of this indigenised dialect of Australia reflect cultural schemas, categories, and metaphors that embody cultural beliefs and experiences of Aboriginal people.
The politics of code‐switching: English vs. Nigerian languages
Authors: Bamiro Edmund O.
Published: February 2006

Abstract:  The present study explores the politics of code‐switching with reference to the novels of two prominent Nigerian authors, Wole Soyinka and Chinua Achebe. In addition to drawing a theoretical distinction between overt and covert modes of code alternation, the study points out that at the primary degree of delicacy, code‐switching not only reveals the tensions and conflicts in the Nigerian social structure, but this linguistic phenomenon is also used to mark identity, solidarity, exclusion from an in‐group membership, status manipulation, and social and communicative distance. At the secondary degree of delicacy, the politics of code‐switching reveal that in the sociolinguistic balance of power, English dominates the local languages identified in the study. The sociolinguistic situation described in the study is thus symptomatic of the linguistic situation in Nigeria generally where the local languages are in a subtractive polyglossic relationship with English. Subtractive polyglossia, in turn, results in the Nigerian English users’ subtractive bilingualism and linguistic schizophrenia. And unless urgent steps are taken to redress the geolinguistic imbalance between English and Nigeria's minority languages in the hierarchy of code functions, Nigeria's local dialects – except Hausa, Igbo, and Yoruba – face continuous decline and degeneration, if not possible death.
The Comparability of New‐Dialect Formation and Creole Development
Authors: Mufwene Salikoko S.
Published: February 2006

Book reviewed:

New‐Dialect Formation: The Inevitability of Colonial Englishes. Peter Trudgill.
Effect of the introduction of minimum lesion size on interobserver reproducibility using RECIST guidelines in non‐small cell lung cancer patients
Authors: Watanabe Hirokazu , Kunitoh Hideo , Yamamoto Seiichiro , Kawasaki Shin , Inoue Akira , Hotta Katsuyuki , Shiomi Kazu , Kusumoto Masahiko , Sugimura Kazuro , Saijo Nagahiro
Published: February 2006

We evaluated interobserver reproducibility for the response evaluation criteria in solid tumors (RECIST) guidelines and the influence of minimum lesion size (MLS) on reproducibility. The 110 consecutive patients with non‐small cell lung cancer were treated with platinum‐based chemotherapy. Five observers measured target lesions according to both the World Health Organization (WHO) criteria and RECIST. The percentage changes for unidimensional measurements (UD; RECIST type) and bidimensional measurements (BD; WHO type) were calculated for each patient. Interobserver reproducibility among five observers, that is 10 pairs, was expressed as the Spearman's correlation coefficient for the percentage changes, the proportion of agreement and the kappa statistics for response categories. The same analysis was carried out using MLS. BD was more reproducible than UD (Spearman rank correlation coefficient, 0.84 vs 0.81; proportion of agreement, 84.4% vs 82.5%; kappa value, 0.69 vs 0.61). When MLS was applied to UD, eligible cases decreased by 6.4% and the number of target lesions by 44.6%, whereas interobserver reproducibility for UD improved (Spearman rank correlation coefficient, 0.81–0.84; proportion of agreement, 82.5–84.2%; kappa value, 0.61–0.65). The introduction of MLS to UD could also improve intercriteria reproducibility between WHO and RECIST. It is important to apply the MLS when using RECIST for the comparable interobserver reproducibility attained with WHO. (Cancer Sci 2006; 97: 214–218)
Marital status, social support and survival after curative resection in non‐small‐cell lung cancer
Authors: Saito‐Nakaya Kumi , Nakaya Naoki , Fujimori Maiko , Akizuki Nobuya , Yoshikawa Eisho , Kobayakawa Makoto , Nagai Kanji , Nishiwaki Yutaka , Tsubono Yoshitaka , Uchitomi Yosuke
Published: February 2006

It has been suggested that marital status and social support are associated with survival in cases of lung cancer, and that such an association may be mediated by several factors. In this prospective cohort study, we investigated the effect of marital status and social support on survival after curative resection for non‐small cell lung carcinoma (NSCLC) in Japan. From June 1996 to April 1999, a total of 238 patients with resectable NSCLC were enrolled. Marital status and social support were assessed. The presence and absence of confidants and the satisfaction level with the confidants were used as factors reflecting social support. During the follow‐up period, 57 deaths from all causes were identified through January 2004. For the statistical analysis, Cox proportional hazards regression analyses were used. With regard to marital status, the multivariable adjusted hazard ratio (HR) of unmarried patients versus married patients was 0.8 (95% confidence interval, 0.3–1.8) (P‐value = 0.53) after controlling for potential confounding factors, including age, sex, occasion of cancer diagnosis, pathological stage, smoking status, smoking status after surgery and serum albumin level. Similarly, the multivariable adjusted HR of patients without confidants versus those with confidants was 1.0 (0.5–2.2) (P‐value = 0.90), whereas the multivariable adjusted HR of the dissatisfied‐with‐confidants group versus the satisfied‐with‐confidants group was 0.7 (0.4–1.3) (P‐value = 0.28). The present data do not support the hypothesis that marital status and social support are associated with survival in NSCLC. (Cancer Sci 2006; 97: 206–213)
A framework for reporting outcomes in problem gambling treatment research: the Banff, Alberta Consensus
Authors: Walker Michael , Toneatto Tony , Potenza Marc N. , Petry Nancy , Ladouceur Robert , Hodgins David C. , El‐Guebaly Nady , Echeburua Enrique , Blaszczynski Alex
Published: February 2006

Objective  The objective is provide a framework concerning the minimum features of reporting efficacy of treatment in the problem gambling field. Research to date has not used uniform outcome measures and it is, therefore, difficult to compare the relative efficacy of various approaches. Some studies emphasize self‐reported behavioural measures such as frequency and intensity of gambling whereas others emphasise change with respect to the criteria used to diagnose problem gambling or use composite measures of symptom severity in multiple domains involving gambling‐related thoughts, urges, and behaviours.

Methods  An expert panel consensus.

Results  The proposed minimum features of reporting the efficacy of treatment outcome studies are: measures of gambling behaviour ‐ the net expenditure each month, the frequency (in days per month) with which gambling takes place, and the time spent thinking about or engaged in the pursuit of gambling each month; measures of the problems caused by gambling ‐ especially problems in the areas of personal health, relationships, financial, and legal; these measures can be complemented by additional measures of quality of life. measures of the processes of change ‐ whatever mechanisms of change are assumed to occur.

Conclusions  We believe that these guidelines are broad enough to allow clinical research conducted from diverse perspectives to allow valid cross study evaluations of intervention studies. Such conditions will facilitate the development of empirically validated best practice guidelines for use by clinicians in the management of problem gambling.