bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoscale plastic deformation and fracture of polymers studied by in situ nanoindentation in a transmission electron microscope
Authors: Zhou J. , Komvopoulos K. , Minor A. M.
Published: May 2006

Nanoscale plasticity and fracture of polymers were studied by in situ nanoindentation in a transmission electron microscope. The indentation-induced plasticity during loading and the significant recovery of the deformed polymer upon unloading provide insight into the nanoscale viscoelastic and plastic behavior. Crack initiation and growth from a preexisting surface nanodefect due to adjacent nanoindentation was found to lead to localized delamination. The in situ observations of this study provide information for the evolution of nanoscale viscoelastic-plastic deformation and fracture (delamination) processes at polymer surfaces during the loading and unloading phases of a nanoindentation cycle.
Pulse-width selective all-optical switching
Authors: Wang Youfa , Wang Wenfeng
Published: May 2006

The coupled nonlinear Schrödinger equations governing the optical pulse coupling in a nonlinear directional coupler are solved numerically. The numerical results show that the optical pulse can be coupled back and forth efficiently between the two-coupled waveguides by varying the input pulse duration. The energy transfer efficiency between the two-coupled waveguide can be greater than 90%. It implies that the pulse-width dependent all-optical switching can be realized in a nonlinear directional coupler.
Three-dimensional metallic photonic crystals fabricated by soft lithography for midinfrared applications
Authors: Lee Jae-Hwang , Kim Chang-Hwan , Kim Yong-Sung , Ho Kai-Ming , Constant Kristen , Oh Cha Hwan
Published: May 2006

We present an efficient method of fabricating freestanding three-dimensional metallic photonic crystals using soft lithography. Low cost and ease of fabrication are achieved through gold sputter deposition on a freestanding woodpile polymer template. We compare experimental results to theoretical calculations for tetragonal and face-centered-tetragonal structures as a function of the number of layers. The photonic crystals behave like full metallic structures with a photonic band edge at a wavelength of 3.5μm. The rejection rates of the structures are about 10dB/layer.
Industrial Ecology and Planning: Assessing and Socially Embedding Green Technological Systems
Authors: Tansey James
Published: May 2006

The notion that industrial systems can be redesigned to reflect ‘lessons from nature’ has led to the emergence of a new discipline known as ‘industrial ecology’. In this paper I provide a brief overview of the principles that underpin the discipline, and provide a critical evaluation of the extent to which it is guided by ecology or simply uses the label for rhetorical support. I suggest that simply appealing to ecological analogies is not sufficient to ensure that the impacts of industrial activities are reduced. Further, I propose that the technical process of industrial design needs to be embedded in legitimate social processes if social acceptability is to be attained.
Decision Models for the Location of Community Corrections Centers
Authors: Johnson Michael P
Published: May 2006

Community corrections centers (CCCs, or ‘halfway houses’) represent a community-based justice strategy intended to reintegrate offenders into civil society. Site selection for these facilities is complicated by negative perceptions of CCC impacts on the part of potential host communities. I solve the CCC-location problem through the use of a framework based on value-focused thinking and quantitative decision models. The first of two mathematical models for CCC location is a novel integer programming formulation that incorporates neighborhood characteristics and equity considerations; the second is a straightforward application of the analytic hierarchy process. These models are applied to a case study in the city of Pittsburgh, PA. In contrast to traditional dispersion models, the mathematical programming model identifies sites in high-amenity neighborhoods which are argued to be associated with beneficial CCC client outcomes. Also, I find that sites selected using multicriteria decision models are relatively easy to generate and are competitive with mathematical programming models in terms of objective function measures.
Internet Reliability with Realistic Peering
Authors: O'Kelly Morton E , Kim Hyun , Kim Changjoo
Published: May 2006

Peering between network providers is modeled as a set of interconnections at hub nodes. The paper employs probabilistic methods to determine the likelihood of a path between nodes, under a variety of simulated disruptions or failures of parts of a network. Reliability is measured as the probability of withstanding failure of network components such as nodes or linkages. A reliability envelope is devised in order to define a range of impacts—with the recognition that the damage to subsets of the network can vary from a relatively benign effect to a much more critical or lethal impact. Thus, we describe a range of scenarios from best to worst, within the same level of infrastructure loss. With the use of simulation data for the United States, results show the critical role of major hubs in sustaining communication among cities. In the paper we highlight especially reliable nodes (for example, Chicago and Atlanta) and those that are most susceptible (for example, Birmingham, Alabama, and Nashville, Tennessee). Failure in major hub cities such as Chicago, Dallas, and San Francisco would significantly influence adjacent areas and could cause severe degradation for the entire network with a loss of resiliency to below tolerable levels. An important finding is that various patterns in the reliability envelope can be influenced by factors such as network structures, hub structures, and geographical locations.
Supporting Group Work in Crisis Management: Visually Mediated Human — GIS — Human Dialogue
Authors: MacEachren Alan M , Cai Guoray
Published: May 2006

Geospatial information is a fundamental component of many crisis management activities. However, current geospatial technologies do not support work by crisis management personnel, most of whom are not technology specialists—a key impediment is that the technologies require the user to learn the system's language. In addition, geospatial technologies are not ‘collaboration friendly’—they impede rather than facilitate group work. In this paper we address both issues by presenting (1) a theoretical framework for understanding the roles of visual mediation in map-supported human–human dialogues, and (2) a computational approach for enabling such roles in collaborative spatial decisionmaking contexts. Building upon our initial implementation of a map-mediated collaborative environment, the DAVE_G system [a natural, multimodal, dialogue-enabled interface to geographical information systems (GIS)], we model human–GIS and human–GIS–human dialogues as complex visual-cognitive signification processes in which maps become dynamic facilitators. Using a scenario simulating two crisis managers dealing with a major nuclear release event, we demonstrate how visual display (in DAVE_G) actively mediates human–human dialogue directed to situation assessment and action planning in real applications.
15N partitioning in tomato: vascular constraints versus tissue demand
Authors: Zanne Amy E. , Lower Steven S. , Cardon Zoe G. , Orians Colin M.
Published: May 2006

Allocation of root-derived resources is influenced by tissue demand; however, vascular pathways mediate resource flow from roots to shoots. In vascularly constrained plants (i.e. sectored plants), effects of vascular connections likely limit homogenous resource delivery, especially when environmental resource distribution is patchy. Here, we quantify relative roles of vascular connections, demands by different leaves (i.e. by leaf age and size), and molecule size of transported N compounds (effective sectoriality: nitrate v. ammonium) on allocation of 15N in the sectored tomato (Solanum lycopersicum L.). Vascular connections were the strongest predictor of both accumulation (amount per leaf; P<0.0001) and δ (estimate of concentration; P<0.0001) 15N values in mature leaves, but young expanding leaves did not show such dramatically sectored uptake (accumulation: P=0.0685; δ: P=0.0455), suggesting that sectoriality is less strong in young expanding tissue, especially in the youngest leaf. In patchy environments sectoriality, then, should have large consequences for the ability of a plant to allocate resources in mature tissue; however, young leaves do not appear to experience such strong vascular constraints when building new tissue.
Progestin is an essential factor for the initiation of the meiosis in spermatogenetic cells of the eel
Authors: Miura Takeshi , Higuchi Masato , Ozaki Yuichi , Ohta Takashi , Miura Chiemi
Published: May 2006

Meiosis is an indispensable process of sexual reproduction. However, detailed information on the regulatory mechanisms that initiate meiosis is not available. Progestins are important steroids regulating final maturation in male and female vertebrates. In male teleosts, it is known that progestin induces spermiation and sperm maturation. However, a role for progestin in early spermatogenesis or meiosis has not yet been described. In this study, we examined the functions of progestin on the initiation of meiosis in male Japanese eel. A natural progestin in teleost fish 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and its receptors were present in the testis at an early stage of spermatogenesis. By using an eel testicular culture system, DHP was shown to induce DNA replication in spermatogonia. Although 11-ketotestosterone, a known initiator of spermatogenesis, also stimulated DNA synthesis in spermatogonia, antibodies against DHP prevented DNA replication when added during the period in which meiosis was initiated. DHP treatment also induced the expression of meiosis-specific markers, such as DmcI and Spo11. Furthermore, Spo11 expression and synaptonemal complexes, specific features of the meiotic prophase, were detected in testicular fragments cultured with DHP in some germ cells that showed morphological characteristics of undifferentiated spermatogonia. We conclude that DHP, a progestin, is an essential factor for the initiation of meiosis.
Stat3 activation of NF-κB p100 processing involves CBP/p300-mediated acetylation
Authors: Nadiminty Nagalakshmi , Lou Wei , Lee Soo Ok , Lin Xin , Trump Donald L. , Gao Allen C.
Published: May 2006

Activation of the noncanonical NF-κB signaling pathway involved in the proteolytic processing of NF-κB p100 to p52 is tightly regulated, and overproduction of p52 leads to lymphocyte hyperplasia and transformation. We have demonstrated that active but not latent Stat3, expressed in many types of human cancers involved in cell proliferation and survival, induces p100 processing to p52 by activation of IKKα and subsequent phosphorylation of p100. The Stat3-mediated p100 processing to p52 requires activation of Stat3 by the acetyltransferase activity of cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300. A mutant of Stat3 defective in acetylation blocked Stat3-mediated p100 processing to p52 and acted as a dominant negative in blocking the production of p52. Furthermore, overexpression of p52 protected cells from apoptotic cell death. Thus, activation of the processing of p100 to p52 by Stat3 may represent one of the common pathways used by cancer cells to survive and escape therapy.
There is no universal molecular clock for invertebrates, but rate variation does not scale with body size
Authors: Thomas Jessica A. , Welch John J. , Woolfit Megan , Bromham Lindell
Published: May 2006

The existence of a universal molecular clock has been called into question by observations that substitution rates vary widely between lineages. However, increasing empirical evidence for the systematic effects of different life history traits on the rate of molecular evolution has raised hopes that rate variation may be predictable, potentially allowing the “correction” of the molecular clock. One such example is the body size trend observed in vertebrates; smaller species tend to have faster rates of molecular evolution. This effect has led to the proposal of general predictive models correcting for rate heterogeneity and has also been invoked to explain discrepancies between molecular and paleontological dates for explosive radiations in the fossil record. Yet, there have been no tests of an effect in any nonvertebrate taxa. In this study, we have tested the generality of the body size effect by surveying a wide range of invertebrate metazoan lineages. DNA sequences and body size data were collected from the literature for 330 species across five phyla. Phylogenetic comparative methods were used to investigate a relationship between average body size and substitution rate at both interspecies and interfamily comparison levels. We demonstrate significant rate variation in all phyla and most genes examined, implying a strict molecular clock cannot be assumed for the Metazoa. Furthermore, we find no evidence of any influence of body size on invertebrate substitution rates. We conclude that the vertebrate body size effect is a special case, which cannot be simply extrapolated to the rest of the animal kingdom.
Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6
Authors: Ohtaki Hirokazu , Nakamachi Tomoya , Dohi Kenji , Aizawa Yoichi , Takaki Atsushi , Hodoyama Kei , Yofu Sachiko , Hashimoto Hitoshi , Shintani Norihito , Baba Akemichi , Kopf Manfred , Iwakura Yoichiro , Matsuda Kouhei , Arimura Akira , Shioda Seiji
Published: May 2006

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to decrease ischemic neuronal damage and increase IL-6 secretion in rats. However, the mechanisms underlying neuroprotection are still to be fully elucidated. The present study was designed to investigate the role played by PACAP and IL-6 in mediating neuroprotection after ischemia in a null mouse. Infarct volume, neurological deficits, and cytochrome
c
in cytoplasm were higher in PACAP
+/−
and PACAP
−/−
mice than in PACAP
+/+
animals after focal ischemia, although the severity of response was ameliorated by the injection of PACAP38. A decrease in mitochondrial bcl-2 was also accentuated in PACAP
+/−
and PACAP
−/−
mice, but the decrease could be prevented by PACAP38 injection. PACAP receptor 1 (PAC1R) immunoreactivity was colocalized with IL-6 immunoreactivity in neurons, although the intensity of IL-6 immunoreactivity in PACAP
+/−
mice was less than that in PACAP
+/+
animals. IL-6 levels increased in response to PACAP38 injection, an effect that was canceled by cotreatment with the PAC1R antagonist. However, unlike in wild-type controls, PACAP38 treatment did not reduce the infarction in IL-6 null mice. To clarify the signaling pathway associated with the activity of PACAP and IL-6, phosphorylated STAT (signal transducer and activator of transcription) 3, ERK (extracellular signal-regulated kinase), and AKT levels were examined in PACAP
+/−
and IL-6 null mice after ischemia. Lower levels of pSTAT3 and pERK were observed in the PACAP
+/−
mice, whereas a reduction in pSTAT3 was recorded in the IL-6 null mice. These results suggest that PACAP prevents neuronal cell death after ischemia via a signaling mechanism involving IL-6.
Basic requirements for a metal-binding site in a protein: The influence of loop shortening on the cupredoxin azurin
Authors: Li Chan , Yanagisawa Sachiko , Martins Berta M. , Messerschmidt Albrecht , Banfield Mark J. , Dennison Christopher
Published: May 2006

The main active-site loop of the copper-binding protein azurin (a cupredoxin) has been shortened from C
112
TFPGH
117
SALM
121
to C
112
TPH
115
PFM
118
(the native loop from the cupredoxin amicyanin) and also to C
112
TPH
115
PM
117
. The Cu(II) site structure is almost unaffected by shortening, as is that of the Cu(I) center at alkaline pH in the variant with the C
112
TPH
115
PM
117
loop sequence. Subtle spectroscopic differences due to alterations in the spin density distribution at the Cu(II) site can be attributed mainly to changes in the hydrogen-bonding pattern. Electron transfer is almost unaffected by the introduction of the C
112
TPH
115
PFM
118
loop, but removal of the Phe residue has a sizable effect on reactivity, probably because of diminished homodimer formation. At mildly acidic pH values, the His-115 ligand protonates and dissociates from the cuprous ion, an effect that has a dramatic influence on the reactivity of cupredoxins. These studies demonstrate that the amicyanin loop adopts a conformation identical to that found in the native protein when introduced into azurin, that a shorter than naturally occurring C-terminal active-site loop can support a functional T1 copper site, that CTPHPM is the minimal loop length required for binding this ubiquitous electron transfer center, and that the length and sequence of a metal-binding loop regulates a range of structural and functional features of the active site of a metalloprotein.
CO
2
signaling in guard cells: Calcium sensitivity response modulation, a Ca
2+
-independent phase, and CO
2
insensitivity of the
gca2
mutant
Authors: Young Jared J. , Mehta Samar , Israelsson Maria , Godoski Jan , Grill Erwin , Schroeder Julian I.
Published: May 2006

Leaf stomata close in response to high carbon dioxide levels and open at low CO
2
. CO
2
concentrations in leaves are altered by daily dark/light cycles, as well as the continuing rise in atmospheric CO
2
. Relative to abscisic acid and blue light signaling, little is known about the molecular, cellular, and genetic mechanisms of CO
2
signaling in guard cells. Interestingly, we report that repetitive Ca
2+
transients were observed during the stomatal opening stimulus, low [CO
2
]. Furthermore, low/high [CO
2
] transitions modulated the cytosolic Ca
2+
transient pattern in

Arabidopsis

guard cells (Landsberg

erecta

). Inhibition of cytosolic Ca
2+
transients, achieved by loading guard cells with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-

N,N,N′,N′

-tetraacetic acid and not adding external Ca
2+
, attenuated both high CO
2
-induced stomatal closing and low CO
2
-induced stomatal opening, and also revealed a Ca
2+
-independent phase of the CO
2
response. Furthermore, the mutant,
growth controlled by abscisic acid
(

gca2

) shows impairment in [CO
2
] modulation of the cytosolic Ca
2+
transient rate and strong impairment in high CO
2
-induced stomatal closing. Our findings provide insights into guard cell CO
2
signaling mechanisms, reveal Ca
2+
-independent events, and demonstrate that calcium elevations can participate in opposed signaling events during stomatal opening and closing. A model is proposed in which CO
2
concentrations prime Ca
2+
sensors, which could mediate specificity in Ca
2+
signaling.
Loss of
p53
impedes the antileukemic response to BCR-ABL inhibition
Authors: Wendel Hans-Guido , de Stanchina Elisa , Cepero Enriqué , Ray Sagarika , Emig Michael , Fridman Jordan S. , Veach Darren R. , Bornmann William G. , Clarkson Bayard , McCombie W. Richard , Kogan Scott C. , Hochhaus Andreas , Lowe Scott W.
Published: May 2006

Targeted cancer therapies exploit the continued dependence of cancer cells on oncogenic mutations. Such agents can have remarkable activity against some cancers, although antitumor responses are often heterogeneous, and resistance remains a clinical problem. To gain insight into factors that influence the action of a prototypical targeted drug, we studied the action of imatinib (STI-571, Gleevec) against murine cells and leukemias expressing BCR-ABL, an imatinib target and the initiating oncogene for human chronic myelogenous leukemia (CML). We show that the tumor suppressor p53 is selectively activated by imatinib in BCR-ABL-expressing cells as a result of BCR-ABL kinase inhibition. Inactivation of p53, which can accompany disease progression in human CML, impedes the response to imatinib
in vitro
and
in vivo
without preventing BCR-ABL kinase inhibition. Concordantly, p53 mutations are associated with progression to imatinib resistance in some human CMLs. Our results identify p53 as a determinant of the response to oncogene inhibition and suggest one way in which resistance to targeted therapy can emerge during the course of tumor evolution.
Persistent soil seed banks of the globally significant invasive species, Eupatorium adenophorum, in Yunnan Province, south-western China
Authors: Shen Youxin , Liu Wenyao , Baskin Jerry M. , Baskin Carol C. , Cao Min
Published: May 2006

Soil cores were collected at different times between the seed germination and dispersal seasons of Eupatorium adenophorum from 19 sites at five stations with different kinds of vegetation in Yunnan, south-western China. Mother plants of E. adenophorum were absent from eight of the sites, and their frequency was low at nine other sites. However, persistent soil seed banks were present at all 19 sites. Seed density in the 0–10 cm soil layer varied from 47 to 13,806 seeds m−2, and averaged 2199 seeds m−2. Fifty-seven percent of the seeds of E. adenophorum were in the 0–2 cm soil layer, 24% in the 2–5 cm layer and 19% in the 5–10 cm layer. The percentage of cores from which seedlings emerged ranged from 33–100% across all sites. Seed density and seedling emergence percentages varied significantly among the five stations, and both were positively correlated with abundance of mother plants.
Changes in lipoxygenase isoforms during germination and early seedling growth of Pisum sativum L.
Authors: Mo Bing , Koster Karen L.
Published: May 2006

Investigations of physiological functions of seed lipoxygenase during germination and early seedling growth are complicated by the presence of multiple isoforms with different product specificity. The combination of isoelectric focusing, lipoxygenase in-gel activity staining and mass spectrometry showed that only two seed lipoxygenases, LOX-2 and LOX-3, were active at neutral pH in protein extracts from dry and germinating pea seeds (Pisum sativum L.), with LOX-3 more abundant than LOX-2. Each active seed LOX appeared at multiple pIs, probably resulting from post-translational modifications. The abundance of pea seed lipoxygenases was lower in embryonic shoots than in other parts of the axis. After radicle emergence, seed LOXs were degraded, as revealed by Western blotting using antibodies specific to pea seed LOXs. Two new vegetative isoforms, LOX-N3 and LOX-g, appeared in the shoot and gradually replaced the pea seed lipoxygenases as the principal contributors to LOX enzyme activity during early seedling growth. Activities of LOX-N3 and LOX-g were abundant in shoot tips, but not root tips, in pea seedlings. Thus, during germination, there is a shift of LOX activity from radicles to shoots that accompanies the transition from seed LOXs to vegetative LOXs. These results confirmed that identification of pea LOXs based solely on pI may be misleading; however, mass spectrometry enabled more accurate identification of these highly homologous proteins to be made.
Distinct mechanisms regulate hemocyte chemotaxis during development and wound healing in Drosophila melanogaster
Authors: Wood Will , Faria Celia , Jacinto Antonio
Published: May 2006

Drosophila melanogaster hemocytes are highly motile macrophage-like cells that undergo a stereotypic pattern of migration to populate the whole embryo by late embryogenesis. We demonstrate that the migratory patterns of hemocytes at the embryonic ventral midline are orchestrated by chemotactic signals from the PDGF/VEGF ligands Pvf2 and -3 and that these directed migrations occur independently of phosphoinositide 3-kinase (PI3K) signaling. In contrast, using both laser ablation and a novel wounding assay that allows localized treatment with inhibitory drugs, we show that PI3K is essential for hemocyte chemotaxis toward wounds and that Pvf signals and PDGF/VEGF receptor expression are not required for this rapid chemotactic response. Our results demonstrate that at least two separate mechanisms operate in D. melanogaster embryos to direct hemocyte migration and show that although PI3K is crucial for hemocytes to sense a chemotactic gradient from a wound, it is not required to sense the growth factor signals that coordinate their developmental migrations along the ventral midline during embryogenesis.
Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells
Authors: Moriyama Mariko , Osawa Masatake , Mak Siu-Shan , Ohtsuka Toshiyuki , Yamamoto Norio , Han Hua , Delmas Véronique , Kageyama Ryoichiro , Beermann Friedrich , Larue Lionel , Nishikawa Shin-Ichi
Published: May 2006

Melanoblasts (Mbs) are thought to be strictly regulated by cell–cell interactions with epidermal keratinocytes, although the precise molecular mechanism of the regulation has been elusive. Notch signaling, whose activation is mediated by cell–cell interactions, is implicated in a broad range of developmental processes. We demonstrate the vital role of Notch signaling in the maintenance of Mbs, as well as melanocyte stem cells (MSCs). Conditional ablation of Notch signaling in the melanocyte lineage leads to a severe defect in hair pigmentation, followed by intensive hair graying. The defect is caused by a dramatic elimination of Mbs and MSCs. Furthermore, targeted overexpression of Hes1 is sufficient to protect Mbs from the elimination by apoptosis. Thus, these data provide evidence that Notch signaling, acting through Hes1, plays a crucial role in the survival of immature Mbs by preventing initiation of apoptosis.
Bax does not have to adopt its final form to drive T cell death
Authors: Zhu Yanan , Liu Xinqi , Hildeman David , Peyerl Fred W. , White Janice , Kushnir Elenora , Kappler John , Marrack Philippa
Published: May 2006

The introduction of antigen into animals causes antigen-specific T cells to divide and then die. Activated T cell death requires either of the death effector molecules, Bak or Bax. When T cells die, Bak and Bax change their conformations, a phenomenon that is thought to be required for Bak or Bax to drive cell death. Here we show that Bak changes conformation before activated T cells die, as detected by an antibody specific for a peptide near the NH2 terminus of Bak, but Bax does not change its shape markedly until after the cells are dead, as detected by an antibody specific for a peptide near the NH2 terminus of Bax. This latter finding is also true in activated T cells that lack Bak and are therefore dependent on Bax to die. This result suggests that Bax does not have to adopt its final, completely unfolded form until after the cells are dead.
A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis
Authors: Trapp Sascha , Parcells Mark S. , Kamil Jeremy P. , Schumacher Daniel , Tischer B. Karsten , Kumar Pankaj M. , Nair Venugopal K. , Osterrieder Nikolaus
Published: May 2006

Telomerase is a ribonucleoprotein complex consisting of two essential core components: a reverse transcriptase and an RNA subunit (telomerase RNA [TR]). Dysregulation of telomerase has been associated with cell immortalization and oncogenesis. Marek's disease herpesvirus (MDV) induces a malignant T cell lymphoma in chickens and harbors in its genome two identical copies of a viral TR (vTR) with 88% sequence identity to chicken TR. MDV mutants lacking both copies of vTR were significantly impaired in their ability to induce T cell lymphomas, although lytic replication in vivo was unaffected. Tumor incidences were reduced by >60% in chickens infected with vTR− viruses compared with animals inoculated with MDV harboring at least one intact copy of vTR. Lymphomas in animals infected with the vTR− viruses were also significantly smaller in size and less disseminated. Constitutive expression of vTR in the chicken fibroblast cell line DF-1 resulted in a phenotype consistent with transformation as indicated by morphological alteration, enhanced anchorage-independent cell growth, cell growth beyond saturation density, and increased expression levels of integrin αv. We concluded that vTR plays a critical role in MDV-induced T cell lymphomagenesis. Furthermore, our results provide the first description of tumor-promoting effects of TR in a natural virus–host infection model.
Protective immune responses against West Nile virus are primed by distinct complement activation pathways
Authors: Mehlhop Erin , Diamond Michael S.
Published: May 2006

West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3−/− and complement receptor 1/2−/− mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8+ T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.
Why Healthcare Workers Don't Wash Their Hands: A Behavioral Explanation
Authors: Whitby Michael , McLaws Mary-Louise , Ross Michael W.
Published: May 2006

Objective.

To elucidate behavioral determinants of handwashing among nurses.

Design.

Statistical modeling using the Theory of Planned Behavior and relevant components to handwashing behavior by nurses that were derived from focus-group discussions and literature review.

Setting.

The community and 3 tertiary care hospitals.

Participants.

Children aged 9-10 years, mothers, and nurses.

Results.

Responses from 754 nurses were analyzed using backward linear regression for handwashing intention. We reasoned that handwashing results in 2 distinct behavioral practices—inherent handwashing and elective handwashing—with our model explaining 64% and 76%, respectively, of the variance in behavioral intention. Translation of community handwashing behavior to healthcare settings is the predominant driver of all handwashing, both inherent (weightedβ= 2.92) and elective (weightedβ= 4.1). Intended elective in-hospital handwashing behavior is further significantly predicted by nurses' beliefs in the benefits of the activity (weightedβ= 3.12), peer pressure of senior physicians (weightedβ= 3.0) and administrators (weightedβ= 2.2), and role modeling (weightedβ= 3.0) but only to a minimal extent by reduction in effort (weightedβ= 1.13). Inherent community behavior (weightedβ= 2.92), attitudes (weightedβ= 0.84), and peer behavior (weightedβ= 1.08) were strongly predictive of inherent handwashing intent.

Conclusions.

A small increase in handwashing adherence may be seen after implementing the use of alcoholic hand rubs, to decrease the effort required to wash hands. However, the facilitation of compliance is not simply related to effort but is highly dependent on altering behavioral perceptions. Thus, introduction of hand rub alone without an associated behavioral modification program is unlikely to induce a sustained increase in hand hygiene compliance.
Screening of Hospital Workers for Pulmonary Tuberculosis in a Medical Center in Taiwan
Authors: Wang Fu-Der , Chang Chi-Hwar , Su Wei-Juin , Shih Jen-Fu , Hsiao Kuang-Ming , Chern Ming-Sheng , Chen Te-Li , Lin Ming-Yin , Chen Yin-Yin , Lee Chen-Hsen
Published: May 2006

At a medical center in Taiwan, all workers were examined by chest radiography, to determine the prevalence of pulmonary tuberculosis. The prevalence of tuberculosis among all hospital workers was 0.12%, that among nurses was 0.35%, and that among externally contracted cleaners was 0.57%. All of the Mycobacterium tuberculosis isolates recovered from 2 nurses and from a patient with pulmonary tuberculosis were the Beijing strain, but the strains had different serotypes.
Lack of Association Between the Increased Incidence ofClostridium difficile–Associated Disease and the Increasing Use of Alcohol-Based Hand Rubs
Authors: Boyce John M. , Ligi Cathy , Kohan Cindy , Dumigan Diane , Havill Nancy L.
Published: May 2006

Objective.

To determine whether there is an association between the increasing use of alcohol-based hand rubs (ABHRs) and the increased incidence ofClostridium difficile–associated disease (CDAD).

Setting.

A 500-bed university-affiliated community teaching hospital.

Methods.

Use of ABHRs during the period 2000-2003 was expressed as the number of liters of ABHR used per 1000 patient-days. The proportion of hand hygiene episodes performed by using an ABHR was determined by periodic observational surveys. CDAD was defined as a physician-ordered stool assay positive forC. difficiletoxin A or A/B. The incidence of CDAD was expressed as the number of unique patients who had 1 or more positive CDAD test results per 1,000 patient-days.

Results.

During 2000-2003, the use of ABHR increased 10-fold, from 3 to greater than 30 L/1,000 patient-days (P< .001). The proportion of hand hygiene episodes performed using an ABHR increased from 10% to 85% (P< .001). The incidence of CDAD in 2000, 2001, 2002, and 2003 was 1.74, 2.33, 1.14, and 1.18 cases/1,000 patient-days, respectively.

Conclusion.

Despite a significant and progressive increase in the use of ABHRs in our facility during a 3-year period, there was no evidence that the incidence of CDAD increased. These findings suggest that factors other than the increased use of ABHRs are responsible for the increasing incidence of CDAD noted since 2000 in other facilities.
Discontinuation of Respiratory Isolation for Possible Tuberculosis: Do Two Negative Sputum Smear Results Suffice?
Authors: Bryan Charles S. , Rapp Deborah J. , Brown Cynthia A.
Published: May 2006

Analysis of acid-fast bacillus smear results at a hospital with a mod-erate incidence of tuberculosis confirms recent recommendations that 2 negative smear results suffice for discontinuation of respiratory isolation. Use of polymerase chain reaction analysis further increases the confidence with which the diagnosis of active tuberculosis likely to be transmitted to others can be excluded.
Epidemiologic Study and Containment of a Nosocomial Outbreak of Severe Acute Respiratory Syndrome in a Medical Center in Kaohsiung, Taiwan
Authors: Liu Jien-Wei , Lu Sheng-Nan , Chen Shun-Sheng , Yang Kuender D. , Lin Meng-Chih , Wu Chao-Chien , Bloland Peter B. , Park Sarah Y. , Wong William , Tsao Kuo-Chien , Lin Tzou-Yien , Chen Chao-Long
Published: May 2006

Objective.

We conducted an epidemiologic investigation at the beginning of a nosocomial outbreak of severe acute respiratory syndrome (SARS) to clarify the dynamics of SARS transmission, the magnitude of the SARS outbreak, and the impact of the outbreak on the community.

Methods.

We identified all potential cases of nosocomially acquired SARS, linked them to the most likely infection source, and described the hospital containment measures.

Setting.

A 2,300-bed medical center in Kaohsiung, Taiwan.

Results.

A total of 55 cases of SARS were identified, and 227 hospital workers were quarantined. The index patient and neighboring patients were isolated. A chest physician team reviewed medical charts and chest radiographs and monitored the development of SARS in patients staying in the ward. The presence of underlying lung disease and immunocompromise in some patients made the diagnosis of SARS difficult. Some cases of SARS were diagnosed after the patients had died. Medical personnel were infected only if they cared for patients with unrecognized SARS, and caretakers played important roles in transmission of SARS to family members. As the number of cases of nosocomial SARS increased, the hospital closed the affected ward and expedited construction of negative-pressure rooms on other vacated floors for patient cohorting, and the last case in the hospital was identified 1 week later.

Conclusions.

Timely recognition of SARS is extremely important. However, given the limitations of SARS testing, possible loss of epidemic links, and the nonspecific clinical presentations in hospitalized patients, it is very important to establish cohorts of persons with low, medium, and high likelihoods of SARS acquisition. Rapid closure of affected wards may minimize the impact on hospital operations. Establishment of hospitals dedicated to appropriate treatment of patients with SARS might minimize the impact of the disease in future epidemics.
Infection Control Practices to Reduce Airborne Bacteria During Total Knee Replacement: A Hospital Survey in Four States
Authors: Miner Andrew L. , Losina Elena , Katz Jeffrey N. , Fossel Anne H. , Piatt Richard
Published: May 2006

Objective:

To describe the use of laminar airflow, body exhaust, and ultraviolet lights during total knee replacement (TKR) in four U.S. states.

Design:

Survey of healthcare facilities.

Setting:

Hospitals in Illinois, North Carolina, Ohio, and Tennessee that performed TKR during 2000 as identified by Medicare claims data.

Participants:

Hospitals responding to a mailed questionnaire.

Results:

Two hundred ninety-five (73%) of 405 eligible hospitals that performed 18,374 primary and revision TKR procedures responded to the questionnaire. Among responding hospitals, 30% reported regular use (for > 75% of procedures) of laminar airflow, 42% reported regular use of body exhaust, and 5% reported regular use of ultraviolet lights. Among hospitals providing complete data, 150 (58%) performing 66% of procedures reported regular use of at least one of these techniques. On regression analyses, laminar airflow was used more often by hospitals with a TKR volume greater than 25 procedures per year (odds ratio [OR], 2.0; 95% confidence interval [CI95], 1.1-3.7) and orthopedic residency programs (OR,2.8;CI95,1.3-6.3), but its use was not significantly related to hospital setting or ownership status.

Conclusions:

Although these clean air practices are not recommended by any U.S. governmental or professional organization, they are used in nearly two-thirds of TKR procedures. Better information about their impact on current practice and more explicit guidelines may aid decisions about the use of these resource-intensive infection control practices.
‘Dare the boist’rous main': The role of the Belfast News Letter in the process of emigration from Ulster to North America, 1760–1800
Authors: Royle Stephen A. , Laoire Caitríona Ní
Published: May 2006

Before the mass migrations from Ireland in the nineteenth century, earlier waves of migration in the eighteenth century saw significant numbers of people leave Ireland, predominantly from Ulster, to settle in North America. This article, using as its principal data source the Belfast News Letter ( BNL), its letters, advertisements and reports, focuses firstly on reconstructing the late eighteenth‐century migration process and voyage, highlighting the barriers represented by the Atlantic Ocean. In addition to the challenges of the sea, there were problems with the ships, the ever‐present danger of disease and also threats from other vessels, from privateers to press gangs. The voyage was recognized as a ‘universal dread’, and the risks taken to ‘dare the boist’rous main' were perhaps not minimized in the pages of the BNL, whose editorial stance was antipathetic to the migration for the potential harm it caused to Ulster by removing so many of its industrious young. The second part of this article goes on to consider the newspaper's and others' vested interests in the emigration process, demonstrates how these were manifested in the press and sets the coverage of this very significant early emigration flow within the context of contemporary religious and colonial discourses at a period of very lively transatlantic interactions.
The UNESCO Biosphere Reserve Program in Australia: constraints and opportunities for localized sustainable development
Authors: Matysek Kate A. , Stratford Elaine , Kriwoken Lorne K.
Published: May 2006

Since their creation under the auspices of the United Nations Educational, Scientific and Cultural Organization (UNESCO) Man and the Biosphere (MAB) Program in 1976, biosphere reserves have provided an international framework for linking protected areas with their associated working landscapes. In Australia, twelve biosphere reserves were added to the World Network between 1977 and 1982. That initial flurry of activity has been followed by twenty‐five years of limited interest and development in biosphere reserves in this country, although evidence suggests that new energies are being directed to it. After sketching the origins of the biosphere reserve concept and its central tenets, we explore those environmental, cultural and institutional factors that may be promoting renewed interest in the program. We then review the initial implementation and current status of the Australian Biosphere Reserve Program. Factors supporting the limited success that exists in the program in Australia are highlighted, and the new form of biosphere reserve is illustrated with reference to Australia's recent and only urban biosphere reserve, at the Mornington Peninsula, in the state of Victoria. We speculate that prospects for biosphere reserves in Australia are brighter because of the provision for biosphere reserves under the Commonwealth of Australia's Environment Protection and Biodiversity Conservation Act (DEH 1999), the conceptual relevance of the biosphere reserve to bioregional and catchment management more generally and the continued success of existing model biosphere reserves.
Measuring the effectiveness of Parks Canada's environmental management system: a case study of Riding Mountain National Park
Authors: Bronson Jackie , Noble Bram
Published: May 2006

In 1996, the Geneva‐based International Organization for Standardization released its ISO 14001 guidelines for environmental management systems (EMSs). By implementing an EMS, an organization is better situated to manage the environmental effects of its operations which, in turn, should lead to better environmental performance. However, research on EMS performance has only recently begun to emerge, and the relation between EMSs and genuine improvement in environmental performance has not been clearly established, particularly for organizations such as Parks Canada, whose principal mandate is to protect the natural environment. While EMSs are gaining recognition amongst parks as a systematic approach for dealing with the environmental aspects of park operations, there has been very little investigation as to the effectiveness of EMSs in improving the environmental performance of park operations. This paper presents the results of a case study of the effectiveness of Riding Mountain National Park's (RMNP's) EMS and its contribution to environmental improvement. The results confirm EMS experience elsewhere in that RMNP's EMS has been only moderately successful at best and that there exists no clear link between the EMS and the environmental improvement of park operations.
Surgical vs wire‐guided cricothyroidotomy: a randomised crossover study of cuffed and uncuffed tracheal tube insertion
Authors: Sulaiman L. , Tighe S. Q. M. , Nelson R. A.
Published: May 2006

Using an airway mannequin and artificial lung model, we compared surgical cricothyroidotomy with a 6.0‐mm cuffed Portex tracheostomy tube with wire‐guided cricothyroidotomy using a 5.0‐mm cuffed Melker or 6.0‐mm uncuffed Melker tube. The trial was carried out by 27 anaesthetists using a randomised, crossover design. Surgical cricothyroidotomy proved significantly faster (mean (SD) time to first breath 44.3 (12.5) s for Portex surgical, 87.2 (21.6) s for cuffed Melker, 87.8 (19.2) s for uncuffed Melker, p < 0.001). With a standardised ventilator model, the cuffed tubes provided more effective ventilation (mean (SD) tidal volume 446 (41) ml Portex, 436 (52) ml cuffed Melker, 19 (5) ml uncuffed Melker, p < 0.001). Fourteen of the participants preferred the wire‐guided system. We conclude that, in this model, a cuffed device is preferable when cricothyroidotomy is needed. In addition, the surgical method is quicker than a wire‐guided approach.
Poor correlation between 6β‐hydroxycortisol:cortisol molar ratios and midazolam clearance as measure of hepatic CYP3A activity
Authors: Chen Ya‐Chi , Gotzkowsky S. Karl. , Nafziger Anne N. , Kulawy Robert W. , Rocci Mario L. , Bertino Joseph S. , Kashuba Angela D. M.
Published: May 2006

Aims

A non‐invasive proposed method for measuring CYP3A activity is the urinary 6β‐hydroxycortisol:cortisol ratio. This ratio has been used as an indicator of CYP3A induction and inhibition, with mixed results. This investigation evaluated the relationship between a validated, biomarker, intravenous midazolam clearance and the urinary cortisol ratio under constitutive conditions and with the influence of a moderate CYP3A inhibitor.

Methods

This was a sequential, cross‐over study design. Intravenous midazolam 0.025 mg kg−1 was administered to 10 male and 10 female subjects once every 14 days for 4 months. Fluvoxamine 150 mg day−1 was given to all subjects during the last two visits. Total body clearance of midazolam and urinary 6β‐hydroxycortisol:cortisol molar ratio were used as biomarkers of hepatic CYP3A activity.

Results

No significant correlations were found between these two markers (r2 < 0.5, P > 0.05). Larger interindividual and intra‐individual variability in CYP3A activity was observed in 6β‐hydroxycortisol:cortisol ratios compared with midazolam clearances. With fluvoxamine therapy, midazolam clearance values decreased approximately 1.5‐fold and cortisol ratios decreased approximately 1.9‐fold.

Conclusions

The high intra‐individual variability of the urinary cortisol ratio, compared with midazolam, makes this a suboptimal CYP3A phenotyping tool.
Effect of widely used combinations of antiretroviral therapy on liver CYP3A4 activity in HIV‐infected patients
Authors: Mouly Stéphane , Rizzo‐Padoin Nathalie , Simoneau Guy , Verstuyft Céline , Aymard Guy , Salvat Cécile , Mahé Isabelle , Bergmann Jean‐François
Published: May 2006

Aims

To evaluate the effects of combined antiretroviral drugs (HAART) on liver CYP3A4 activity using the [14C‐N‐methyl]‐erythromycin breath test (ERMBT).

Methods

HIV‐infected patients (31 women, 30 men) with mean (± SD) age of 38 ± 9 years were enrolled and underwent complete clinical and laboratory evaluation. Patients were divided into five groups and were treated with two nucleoside analogues (NAs) and one of the following: nelfinavir alone (n = 13), any ritonavir‐boosted protease inhibitor with (n = 8) or without (n = 13) nevirapine, nevirapine alone (n = 15), or a third NA (n = 12). Three or four ERMBTs were performed 7 days prior to (D−7) and at the beginning of treatment (D0), D14 (only for patients taking nevirapine) and on D28.

Results

Mean baseline liver CYP3A4 activity displayed high interindividual variability (47%) but low intraindividual variability (15%). Women had 30% higher ERMBT values than men [2.7 ± 1.3vs.1.9 ± 0.7; 95% confidence interval (CI) 20.5, 49.5;P = 0.003]. The ERMBT data correlated with body weight, α‐ and β‐globulins and alanin aminotransferases (0.10 < rs < 0.20;P < 0.01). Whereas nevirapine had no effect on liver CYP3A4 activity, nelfinavir‐based and ritonavir‐boosted drug regimens inhibited it by 69% (95% CI 64.7, 72.9;P = 0.005) and by 95% (95% CI 93.3, 96.7;P = 0.001), respectively.

Conclusion

Evaluation of the effect of HAART on liver CYP3A4 activity may aid in preventing inappropriate treatment regimens in HIV‐infected patients.