bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic cell fate regulation of hepatic stellate cells
Authors: Tsukamoto Hidekazu , Zhu Nian‐Ling , Asahina Kinji , Mann Derek A. , Mann Jelena
Published: April 2011

Research in the past three decades has identified key mediators and signaling mechanisms responsible for myofibroblastic transdifferentiation (MTD) of hepatic stellate cells (HSC), the pivotal event in liver fibrogenesis. Yet, fundamental understanding of the MTD from the viewpoint of cell fate or lineage regulation has been elusive. Recent studies using genetic cell fate mapping techniques demonstrate HSC are derived from mesoderm and at least in part via septum transversum and mesothelium. HSC express markers for different cell types derived from multipotent mesenchymal progenitors. A regulatory commonality between differentiation of adipocytes and that of HSC is shown, and a shift from adipogenic to myogenic or neuronal phenotype characterizes HSC MTD. Central to this shift is a loss of expression of the master adipogenic regulator peroxisome proliferator activated receptor‐γ (PPAR‐γ). Restored expression of PPAR‐γ and/or other adipogenic transcription factors reverses myofibroblastic HSC to differentiated cells. In MTD, Pparγ is epigenetically repressed by induction of methyl‐CpG binding protein 2 and its enrichment to the promoter and polycomb repressive complex‐facilitated histone H3 lysine 27 di/tri‐methylation at the 3′ exons. Blocking canonical wingless‐related MMTV integration site (Wnt) signaling in myofibroblastic HSC with the co‐receptor antagonist Dickkopf‐1, abrogates these epigenetic mechanisms, restores PPAR‐γ expression and HSC differentiation. Necdin, a melanoma antigen family protein, is identified as an upstream mediator for induction of the canonical Wnt10b and consequent Pparγ repression and HSC MTD. The identified morphogen‐induced epigenetic regulation of Pparγ and HSC fate may serve as a novel target for manipulation of liver fibrosis and mesenchymal–epithelial interactions in liver regeneration.
Nociceptin/orphanin FQ suppresses the excitability of neurons in the ventromedial nucleus of the hypothalamus
Authors: Chee Melissa J. , Price Christopher J. , Statnick Michael A. , Colmers William F.
Published: April 2011

Non‐technical summary  Feeding behaviour is controlled in part by activity within brain hypothalamic nuclei. The ventromedial nucleus of the hypothalamus (VMN) contains a population of neurons that inhibit feeding when they are active. The neuropeptide nociceptin or orphanin FQ (N/OFQ) acts within the VMN to stimulate food intake. We show that N/OFQ, through its receptor, directly inhibits these VMN neurons. We think that by inhibiting anorexigenic VMN neurons, N/OFQ thereby allows the stimulation of food intake. These studies increase our knowledge of how VMN neurons participate in regulating food intake and maintain energy homeostasis in the body.
A Probabilistic Secondary Flow System Design Process for Gas Turbine Engines
Authors: Ramerth Douglas L. , MirzaMoghadam Alexander V. , Kiratsingh Ashish , Banda Gaurav
Published: April 2011

Gas turbine engine secondary flow systems are sensitive to variation in part dimensions, clearances, flow coefficients, swirl ratios, head loss factors, tolerances, boundary conditions, etc. This paper reveals a process and software application, which embodies the process, wherein both offer a measurable contribution to secondary airflow system reliability. The probabilistic methodology is empirically validated by (1) applying it to an engine component that failed in a validation test and (2) demonstrating that a multiple order sensitivity analysis performed during detailed design was unable to detect a failure mode while a probabilistic analysis revealed a small yet significant risk of failure. Therefore, a secondary flow analyst does not have a justifiable reason to be highly confident of a design qualified by a first, second, or higher order sensitivity analysis. The last example empirically demonstrates the compatibility of optimization techniques with probabilistic methods (as part of the process) to quantify the likelihood of failure and reveal an optimized design space of key characteristics, where risk is eliminated and the effects of variation are controlled. Trade study analysis is more valuable if it includes a quantitative evaluation of the effects of variation on alternate designs and the response to failure modes. A key feature of the software application is a relational database with the capability to configure and effectively manage flow networks in many forms including a status model, failure modes of the status model, multiple alternative designs, as well as failure modes specific to an alternative design.
The Effect of the Combustor-Turbine Slot and Midpassage Gap on Vane Endwall Heat Transfer
Authors: Lynch Stephen P. , Thole Karen A.
Published: April 2011

Turbine vanes are generally manufactured as single- or double-airfoil sections that are assembled into a full turbine disk. The gaps between the individual sections, as well as a gap between the turbine disk and the combustor upstream, provide leakage paths for relatively higher-pressure coolant flows. This leakage is intended to prevent ingestion of the hot combustion flow in the primary gas path. At the vane endwall, this leakage flow can interfere with the complex vortical flow present there and thus affect the heat transfer to that surface. To determine the effect of leakage flow through the gaps, heat transfer coefficients were measured along a first-stage vane endwall and inside the midpassage gap for a large-scale cascade with a simulated combustor-turbine interface slot and a midpassage gap. For increasing combustor-turbine leakage flows, endwall surface heat transfer coefficients showed a slight increase in heat transfer. The presence of the midpassage gap, however, resulted in high heat transfer near the passage throat where flow is ejected from that gap. Computational simulations indicated that a small vortex created at the gap flow ejection location contributed to the high heat transfer. The measured differences in heat transfer for the various midpassage gap flowrates tested did not appear to have a significant effect.
Electric potential of a metallic nanowall between cathode and anode planes
Authors: Qin Xizhou , Wang Weiliang , Li Zhibing
Published: April 2011

The electric field around a nanowall that is vertically mounted on a planar cathode is studied. The system is designed as a cold field electron emitter or an electron tunneling line scanner. Exact expressions for the electric potential and the edge field enhancement factor are obtained for arbitrary cathode-anode distances. It is found that the finite distance correction is significant for the cathode-anode distances less than twice the height of the nanowall. The angle-dependent transmission probability implies that the forward emission is dominant.
Inhibitory ITAM Signaling Traps Activating Receptors with the Phosphatase SHP-1 to Form Polarized “Inhibisome” Clusters
Authors: Pfirsch-Maisonnas Séverine , Aloulou Meryem , Xu Ting , Claver Julien , Kanamaru Yutaka , Tiwari Meetu , Launay Pierre , Monteiro Renato C. , Blank Ulrich
Published: April 2011

Receptors with activating motifs are captured in inhibitory intracellular compartments and thereby prevented from signaling.
Assessing Filopodia Form and Function
Authors: Ray L. Bryan
Published: April 2011

Signaling protein receptors are segregated into different cell protrusions in
Drosophila
cells.
Just the Right Amount (of Activation)
Authors: Gough Nancy R.
Published: April 2011

New structures for the energy-sensing kinase AMPK suggest a potential mechanism for adjusting the amount of activation to suit the cell’s energy status.
Seeking the Right Pathway
Authors: Kiberstis Paula A.
Published: April 2011

Transforming growth factor–β promotes aortic aneurysm formation through activation of its “noncanonical” signaling pathway.
Precise Null Deletion Mutations of the Mycothiol Synthesis Genes Reveal Their Role in Isoniazid and Ethionamide Resistance in Mycobacterium smegmatis
Authors: Xu Xia , Vilchèze Catherine , Av-Gay Yossef , Gómez-Velasco Anaximandro , Jacobs William R.
Published: April 2011

Mycothiol (MSH; AcCys-GlcN-Ins) is the glutathione analogue for mycobacteria. Mutations in MSH biosynthetic genes have been associated with resistance to isoniazid (INH) and ethionamide (ETH) in mycobacteria, but rigorous genetic studies are lacking, and those that have been conducted have yielded different results. In this study, we constructed independent null deletion mutants for all four genes involved in the MSH biosynthesis pathway (
mshA
,
mshB
,
mshC
, and
mshD
) in
Mycobacterium smegmatis
and made complementing constructs in integrating plasmids. The resulting set of strains was analyzed for levels of MSH, INH resistance, and ETH resistance. The
mshA
and
mshC
single deletion mutants were devoid of MSH production and resistant to INH, whereas the
mshB
deletion mutant produced decreased levels of MSH yet was sensitive to INH, suggesting that MSH biosynthesis is essential for INH susceptibility in
M. smegmatis
. Further evidence supporting this conclusion was generated by deleting the gene encoding the MSH S-conjugate amidase (
mca
) from the Δ
mshB
null mutant. This double mutant, Δ
mshB
Δ
mca
, completely abolished MSH production and was resistant to INH. The
mshA
,
mshC
, and
mshB
single deletion mutants were also resistant to ETH, indicating that ETH resistance is modulated by the level of MSH in
M. smegmatis
. Surprisingly, the
mshD
deletion mutant lacked MSH production but was sensitive to both INH and ETH. The drug sensitivity was likely mediated by the compensated synthesis of
N
-formyl-Cys-GlcN-Ins, previously demonstrated to substitute for MSH in an
mshD
mutant of
M. smegmatis
. We conclude that MSH or
N
-formyl-Cys-GlcN-Ins is required for susceptibility to INH or ETH in
M. smegmatis
.
Danoprevir Monotherapy Decreases Inflammatory Markers in Patients with Chronic Hepatitis C Virus Infection
Authors: Schaefer Caralee J. , Kossen Karl , Lim Sharlene R. , Lin Jiing-Huey , Pan Lin , Bradford Williamson , Smith Patrick F. , Seiwert Scott D.
Published: April 2011

Danoprevir is a potent and selective direct-acting antiviral agent that targets the protease activity of hepatitis C virus (HCV) NS3/4A. This agent results in a significant rapid decline in HCV RNA levels when it is used in monotherapy. The present study evaluated whether plasma concentrations of the inflammatory markers gamma interferon-inducible protein 10 (IP-10) and neopterin or the interferon-stimulated gene product 2′-5′-oligoadenylate synthetase (OAS-1) were correlated with the plasma HCV RNA concentration before or during 14-day danoprevir monotherapy. In contrast to pegylated interferon and ribavirin treatment, a higher baseline IP-10 concentration was positively correlated with a greater first-phase HCV RNA decline upon danoprevir administration. Changes in the IP-10 plasma concentration during danoprevir administration were also associated with categorical changes in HCV RNA concentration at days 7 and 14. The neopterin concentration appeared to be moderately decreased during danoprevir administration, although these changes were not statistically significant. However, changes in neopterin concentration showed a statistically significant correlation with changes in IP-10 concentration. Considerable variation in the OAS-1 concentration was observed before and during treatment, including in patients treated with placebo and/or patients with minimal virologic response. Overall, these results suggest that effective treatment with a direct-acting antiviral agent may reduce hepatic inflammation and that first-phase HCV RNA decline during treatment with an NS3/4A protease inhibitor is more robust in patients with high baseline IP-10 concentrations.
A Single Polymorphism in HIV-1 Subtype C SP1 Is Sufficient To Confer Natural Resistance to the Maturation Inhibitor Bevirimat
Authors: Lu Wuxun , Salzwedel Karl , Wang Dan , Chakravarty Suvobrata , Freed Eric O. , Wild Carl T. , Li Feng
Published: April 2011

3-
O
-(3′,3′-Dimethylsuccinyl) betulinic acid (DSB), also known as PA-457, bevirimat (BVM), or MPC-4326, is a novel HIV-1 maturation inhibitor. Unlike protease inhibitors, BVM blocks the cleavage of the Gag capsid precursor (CA-SP1) to mature capsid (CA) protein, resulting in the release of immature, noninfectious viral particles. Despite the novel mechanism of action and initial progress made in small-scale clinical trials, further development of bevirimat has encountered unexpected challenges, because patients whose viruses contain genetic polymorphisms in the Gag SP1 (positions 6 to 8) protein do not generally respond well to BVM treatment. To better define the role of amino acid residues in the HIV-1 Gag SP1 protein that are involved in natural polymorphisms to confer resistance to the HIV-1 maturation inhibitor BVM, a series of Gag SP1 chimeras involving BVM-sensitive (subtype B) and BVM-resistant (subtype C) viruses was generated and characterized for sensitivity to BVM. We show that SP1 residue 7 of the Gag protein is a primary determinant of SP1 polymorphism-associated drug resistance to BVM.
Disseminated Candidiasis Caused by Candida albicans with Amino Acid Substitutions in Fks1 at Position Ser645 Cannot Be Successfully Treated with Micafungin
Authors: Slater J. L. , Howard S. J. , Sharp A. , Goodwin J. , Gregson L. M. , Alastruey-Izquierdo A. , Arendrup M. C. , Warn P. A. , Perlin D. S. , Hope W. W.
Published: April 2011

The clinical utility of the echinocandins is potentially compromised by the emergence of drug resistance. We investigated whether
Candida albicans
with amino acid substitutions at position Ser645 in Fks1 can be treated with either a conventional or an elevated dosage of micafungin. We studied
Candida albicans
(wild-type SC5314; MIC, 0.06 mg/liter) and four
fks1
mutants (one
FKS1
/
fks1
heterozygote mutant [MIC, 0.5 mg/liter] and three
fks1
/
fks1
homozygous mutants [MICs for all, 2 mg/liter]) with a variety of amino acid substitutions at Ser645. The pharmacokinetic and pharmacodynamic relationships were characterized in a persistently neutropenic murine model of disseminated candidiasis. A mathematical model was fitted to all pharmacokinetic and pharmacodynamic data. This mathematical model was then used to “humanize” the murine pharmacokinetics, and the predicted antifungal effect was determined. The estimated maximal rate of growth and ultimate fungal densities in the kidney for each of the strains were similar. The administration of micafungin at 1 mg/kg of body weight to the wild type resulted in moderate antifungal activity, whereas the administration of 5 and 20 mg/kg resulted in rapid fungicidal activity. In contrast, the
FKS1
/
fks
heterozygote was killed only with 20 mg/kg, and the homozygous
fks1
mutants failed to respond to any dosage. The bridging study revealed that human dosages of 100 and 400 mg/day were active only against the wild type, with no activity against either the heterozygote or the homozygote mutants. Ser645 Fks1
Candida albicans
mutants cannot be treated with either conventional or elevated dosages of micafungin and should be deemed resistant.
Pharmacokinetics of Single-Dose Daptomycin in Patients with Suspected or Confirmed Neurological Infections
Authors: Kullar Ravina , Chin Judy N. , Edwards David J. , Parker Dennis , Coplin William M. , Rybak Michael J.
Published: April 2011

There are currently few or no published data on the amount of cerebrospinal fluid (CSF) penetration of daptomycin in patients with suspected or documented neurosurgical infections. We conducted a prospective study, assessing the pharmacokinetics and CSF penetration of a single intravenous daptomycin dose administered at 10 mg/kg, based on total body weight (TBW), in six neurosurgical patients with indwelling external CSF shunts with suspected or documented meningitis or ventriculitis. Each patient had four blood and CSF samples drawn simultaneously at specific times after the end of infusion: 30 min, 6 h, 12 h, and 24 h. Pharmacokinetic parameters of daptomycin in serum were calculated using standard noncompartmental methods, and daptomycin was assayed using high-performance liquid chromatography (for serum) or liquid chromatography with mass spectrometry (for CSF). The mean (± standard deviation [SD]) maximum measured daptomycin concentrations were 93.7 ± 17.3 mg/liter in serum at 0.5 h postinfusion and 0.461 ± 0.51 mg/liter in CSF at 6 h postinfusion. The mean (± SD) daptomycin minimum concentrations were 13.8 ± 4.8 mg/liter in serum at 24 h postinfusion and 0.126 ± 0.12 mg/liter in CSF at 0.5 h postinfusion. The mean daptomycin penetration, determined by the area under the concentration-time curve in CSF (AUC
CSF
)/(AUC
serum
ratio), was 0.8%. Corrected for protein binding, the overall CSF penetration was 11.5%. Additional pharmacokinetic studies evaluating multiple and/or higher dosages of daptomycin are necessary in human subjects to better characterize the CSF penetration of daptomycin in neurosurgical patients.
Caspofungin Dose Escalation for Invasive Candidiasis Due to Resistant Candida albicans
Authors: Wiederhold Nathan P. , Najvar Laura K. , Bocanegra Rosie A. , Kirkpatrick William R. , Patterson Thomas F.
Published: April 2011

Previous
in vivo
studies have reported caspofungin dose escalation to be effective against
Candida glabrata
with reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent species
Candida albicans
, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of three
C. albicans
isolates, including one susceptible and two resistant isolates with different
FKS1
hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1→3)-β-
d
-glucan were measured. Significant differences in virulence were observed among the three
C. albicans
isolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1→3)-β-
d
-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1→3)-β-
d
-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistant
C. albicans
isolates, and this may be associated with the virulence of the strain.
Effect of Moxifloxacin Combined with Cefotaxime Compared to Cefotaxime-Gentamicin Combination on Prevention of White Matter Damage Associated with Escherichia coli Sepsis in Neonatal Rats
Authors: Le Saché Nolwenn , Baud Olivier , Pansiot Julien , Pham Hoa , Biran Valérie , Brunel-Meunier Nadège , Bidet Philippe , Kitzis Marie-Dominique , Gressens Pierre , Bingen Edouard , Charriaut-Marlangue Christiane , Bonacorsi Stéphane
Published: April 2011

Relative to the cefotaxime-gentamicin combination, the moxifloxacin-cefotaxime combination significantly reduced microglial activation and immature oligodendrocyte cell death and delayed myelination in the developing white matter of neonatal rats with experimental
Escherichia coli
sepsis. These neuroprotective effects were not due to differences in
in vivo
bactericidal activities or in the systemic inflammatory responses and could be related to the intrinsic immunomodulatory properties of moxifloxacin. Molecular mechanisms underlying the neuroprotective effect of moxifloxacin remain to be elucidated.
Conservation of Ebp-Type Pilus Genes among Enterococci and Demonstration of Their Role in Adherence of Enterococcus faecalis to Human Platelets
Authors: Nallapareddy Sreedhar R. , Sillanpää Jouko , Mitchell Jennifer , Singh Kavindra V. , Chowdhury Shahreen A. , Weinstock George M. , Sullam Paul M. , Murray Barbara E.
Published: April 2011

Ebp are
e
ndocarditis- and
b
iofilm-associated
p
ili of
Enterococcus faecalis
that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the
ebp
locus is unique to enterococci. In
E. faecalis
, the
ebp
locus is very highly conserved and only 1/473
E. faecalis
isolates tested lacked
ebpABC
, while only 1.2% had the
bee
pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of
E. faecalis
strains (unlike
Enterococcus faecium
and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced
in vitro
by 91/91 brain heart infusion (BHI) plus serum-grown
E. faecalis
isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of
E. faecalis
cells, consistent with a bistability mode of expression. We also evaluated
E. faecalis
interactions with human platelets and found that growth of
E. faecalis
in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the Δ
srtA
, Δ
bps
, and Δ
bps
Δ
srtA
mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of
E. faecalis
to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species.
Sialidase and Sialoglycoproteases Can Modulate Virulence in Porphyromonas gingivalis
Authors: Aruni Wilson , Vanterpool Elaine , Osbourne Devon , Roy Francis , Muthiah Arun , Dou Yuetan , Fletcher Hansel M.
Published: April 2011

The
Porphyromonas gingivalis
recombinant VimA can interact with the gingipains and several other proteins, including a sialidase. Sialylation can be involved in protein maturation; however, its role in virulence regulation in
P. gingivalis
is unknown. The three sialidase-related proteins in
P. gingivalis
showed the characteristic sialidase Asp signature motif (SXDXGXTW) and other unique domains. To evaluate the roles of the associated genes, randomly chosen
P. gingivalis
isogenic mutants created by allelic exchange and designated FLL401 (
PG0778
::
ermF
), FLL402 (
PG1724
::
ermF
), and FLL403 (
PG0352
::
ermF-ermAM
) were characterized. Similar to the wild-type strain, FLL402 and FLL403 displayed a black-pigmented phenotype in contrast to FLL401, which was not black pigmented. Sialidase activity in
P. gingivalis
FLL401 was reduced by approximately 70% in comparison to those in FLL402 and FLL403, which were reduced by approximately 42% and 5%, respectively. Although there were no changes in the expression of the gingipain genes, their activities were reduced by 60 to 90% in all the isogenic mutants compared to that for the wild type. Immunoreactive bands representing the catalytic domains for RgpA, RgpB, and Kgp were present in FLL402 and FLL403 but were missing in FLL401. While adhesion was decreased, the capacity for invasion of epithelial cells by the isogenic mutants was increased by 11 to 16% over that of the wild-type strain. Isogenic mutants defective in
PG0778
and
PG0352
were more sensitive to hydrogen peroxide than the wild type. Taken together, these results suggest that the
P. gingivalis
sialidase activity may be involved in regulating gingipain activity and other virulence factors and may be important in the pathogenesis of this organism.
Essential Role of Factor B of the Alternative Complement Pathway in Complement Activation and Opsonophagocytosis during Acute Pneumococcal Otitis Media in Mice
Authors: Li Qian , Li Yong Xing , Stahl Gregory L. , Thurman Joshua M. , He Yujuan , Tong Hua Hua
Published: April 2011

We recently reported that the complement system plays a pivotal role in innate immune defense againstStreptococcus pneumoniaeduring acute otitis media (OM) in mice. The current study was designed to determine which of the complement pathways are activated during acute pneumococcal OM and whether components of complement are expressed in the middle ear epithelium. Gene expression was determined by quantitative PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. We found thatS. pneumoniaeinduced increased gene expression of factor B of the alternative complement pathway and C3 in mouse middle ear epithelium. Activation of factor B and C3 in the middle ear lavage fluids was significantly greater than in simultaneously obtained serum samples as determined by Western blotting. Using mice deficient in complement C1qa, factor B, and factor B/C2, we found that complement C3 activation and opsonophagocytosis ofS. pneumoniaewere greatly attenuated in factor B- and factor B/C2-deficient mice. These findings support the concept that local complement activation is an important host innate immune response and that activation of the alternative complement pathway represents one of the innate immune defense mechanisms against pneumococcal infection during the early stage of acute OM.
Whose butt is it? tobacco industry research about smokers and cigarette butt waste: Table 1
Authors: Smith Elizabeth A , Novotny Thomas E
Published: April 2011

Background

Cigarette filters are made of non-biodegradable cellulose acetate. As much as 766 571 metric tons of butts wind up as litter worldwide per year. Numerous proposals have been made to prevent or mitigate cigarette butt pollution, but none has been effective; cigarette butts are consistently found to be the single most collected item in beach clean-ups and litter surveys.

Methods

We searched the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) and http://tobaccodocuments.org using a snowball strategy beginning with keywords (eg, ‘filter’, ‘biodegradable’, ‘butts’). Data from approximately 680 documents, dated 1959–2006, were analysed using an interpretive approach.

Results

The tobacco industry has feared being held responsible for cigarette litter for more than 20 years. Their efforts to avoid this responsibility included developing biodegradable filters, creating anti-litter campaigns, and distributing portable and permanent ashtrays. They concluded that biodegradable filters would probably encourage littering and would not be marketable, and that smokers were defensive about discarding their tobacco butts and not amenable to anti-litter efforts.

Conclusions

Tobacco control and environmental advocates should develop partnerships to compel the industry to take financial and practical responsibility for cigarette butt waste.
Regulating the disposal of cigarette butts as toxic hazardous waste
Authors: Barnes Richard L
Published: April 2011

The trillions of cigarette butts generated each year throughout the world pose a significant challenge for disposal regulations, primarily because there are millions of points of disposal, along with the necessity to segregate, collect and dispose of the butts in a safe manner, and cigarette butts are toxic, hazardous waste. There are some hazardous waste laws, such as those covering used tyres and automobile batteries, in which the retailer is responsible for the proper disposal of the waste, but most post-consumer waste disposal is the responsibility of the consumer. Concepts such as extended producer responsibility (EPR) are being used for some post-consumer waste to pass the responsibility and cost for recycling or disposal to the manufacturer of the product. In total, 32 states in the US have passed EPR laws covering auto switches, batteries, carpet, cell phones, electronics, fluorescent lighting, mercury thermostats, paint and pesticide containers, and these could be models for cigarette waste legislation. A broader concept of producer stewardship includes EPR, but adds the consumer and the retailer into the regulation. The State of Maine considered a comprehensive product stewardship law in 2010 that is a much better model than EPR. By using either EPR or the Maine model, the tobacco industry will be required to cover the cost of collecting and disposing of cigarette butt waste. Additional requirements included in the Maine model are needed for consumers and businesses to complete the network that will be necessary to maximise the segregation and collection of cigarette butts to protect the environment.
Tobacco documents research methodology
Authors: Anderson Stacey J , McCandless Phyra M , Klausner Kim , Taketa Rachel , Yerger Valerie B
Published: April 2011

Tobacco documents research has developed into a thriving academic enterprise since its inception in 1995. The technology supporting tobacco documents archiving, searching and retrieval has improved greatly since that time, and consequently tobacco documents researchers have considerably more access to resources than was the case when researchers had to travel to physical archives and/or electronically search poorly and incompletely indexed documents. The authors of the papers presented in this supplement all followed the same basic research methodology. Rather than leave the reader of the supplement to read the same discussion of methods in each individual paper, presented here is an overview of the methods all authors followed. In the individual articles that follow in this supplement, the authors present the additional methodological information specific to their topics. This brief discussion also highlights technological capabilities in the Legacy Tobacco Documents Library and updates methods for organising internal tobacco documents data and findings.
Marketing of menthol cigarettes and consumer perceptions: a review of tobacco industry documents
Authors: Anderson Stacey J
Published: April 2011

Objective

To examine tobacco industry marketing of menthol cigarettes and to determine what the tobacco industry knew about consumer perceptions of menthol.

Methods

A snowball sampling design was used to systematically search the Legacy Tobacco Documents Library (LTDL) (http://legacy.library.ucsf.edu) between 28 February and 27 April 2010. Of the approximately 11 million documents available in the LTDL, the iterative searches returned tens of thousands of results from the major US tobacco companies and affiliated organisations. A collection of 953 documents from the 1930s to the first decade of the 21st century relevant to 1 or more of the research questions were qualitatively analysed, as follows: (1) are/were menthol cigarettes marketed with health reassurance messages? (2) What other messages come from menthol cigarette advertising? (3) How do smokers view menthol cigarettes? (4) Were menthol cigarettes marketed to specific populations?

Results

Menthol cigarettes were marketed as, and are perceived by consumers to be, healthier than non-menthol cigarettes. Menthol cigarettes are also marketed to specific social and demographic groups, including African–Americans, young people and women, and are perceived by consumers to signal social group belonging.

Conclusions

The tobacco industry knew consumers perceived menthol as healthier than non-menthol cigarettes, and this was the intent behind marketing. Marketing emphasising menthol attracts consumers who may not otherwise progress to regular smoking, including young, inexperienced users and those who find ‘regular’ cigarettes undesirable. Such marketing may also appeal to health-concerned smokers who might otherwise quit.
Menthol cigarettes and smoking cessation behaviour: a review of tobacco industry documents
Authors: Anderson Stacey J
Published: April 2011

Objective

To determine what the tobacco industry knew about menthol's relation to smoking cessation behaviour.

Methods

A snowball sampling design was used to systematically search the Legacy Tobacco Documents Library (LTDL) (http://legacy.library.ucsf.edu) between 15 May to 1 August 2010. Of the approximately 11 million documents available in the LTDL, the iterative searches returned tens of thousands of results. A final collection of 509 documents relevant to 1 or more of the research questions were qualitatively analysed, as follows: (1) perceived sensory and taste rewards of menthol and potential relation to quitting; and (2) motivation to quit among menthol users.

Results

Menthol's cooling and anaesthetic effects mask the short-term negative physiological effects of smoking such as throat pain, burning and cough. This provides superficial physical relief as well as psychological assurance against concerns about the health dangers of smoking that would otherwise motivate smokers to quit. Menthol smokers, particularly women, perceive the minty aroma of menthol cigarettes to be more socially acceptable than non-menthol cigarettes.

Discussion

Consumers believe menthol's sensory effects equate to health protections and that menthol cigarettes are more socially acceptable than non-menthol cigarettes. Menthol in cigarettes may encourage experimenters who find non-mentholated cigarettes too harsh, including young or inexperienced users, to progress to regular smoking rather than quitting, and may lessen the motivation to quit among established menthol smokers. The perception of menthol cigarettes as more socially acceptable lessens the impact of smoking denormalisation on quitting motivation. Menthol makes cigarettes easier and more palatable to smoke and less desirable to quit among established smokers. Fewer smokers quitting contributes to the incidence of tobacco-related diseases.
ON THE PERFORMANCE OF STATIC AND DYNAMIC LOCATION MANAGEMENT STRATEGIES IN MOBILE COMPUTING
Authors: TAHERI JAVID , ZOMAYA ALBERT Y.
Published: April 2011

This work reviews a number of algorithms to solve the location management problem in mobile networks for both static and dynamic scenarios. In the static mode, results of five algorithms are used to highlight the pros and cons for each algorithm. These results provide new insight into the mobility management problem that can influence the design of future wireless networks. In the dynamic mode in which mobile users' past movement patterns are used in making future paging decisions by the network, the performance of an online location management algorithm is examined under different deployment setups. Performance results of this algorithm show its advantages over the currently implemented and/or proposed static location management systems (including GSM).
POPULATION SIZE MODELING FOR GA IN TIME-CRITICAL TASK SCHEDULING
Authors: SUN WEI
Published: April 2011

Genetic algorithms (GAs) have been well applied in solving scheduling problems and their performance advantages have also been recognized. However, practitioners are often troubled by parameters setting when they are tuning GAs. Population Size (PS) has been shown to greatly affect the efficiency of GAs. Although some population sizing models exist in the literature, reasonable population sizing for task scheduling is rarely observed. In this paper, based on the PS deciding model proposed by Harik, we present a model to represent the relation between the success ratio and the PS for the GA applied in time-critical task scheduling, in which the efficiency of GAs is more necessitated than in solving other kinds of problems. Our model only needs some parameters easy to know through proper simplifications and approximations. Hence, our model is applicable. Finally, our model is verified through experiments.
ELLIPTIC FLOW IN pp-COLLISIONS AT THE LHC
Authors: TROSHIN S. M. , TYURIN N. E.
Published: April 2011

We consider collective effects in pp-collisions at the LHC energies related to presence of the large orbital angular momentum in the initial state and role of this orbital momentum in the elliptic flow behavior.
SCALE FACTOR DUALITY WITH MATTER
Authors: LEE SUNGGEUN
Published: April 2011

We investigate the scale factor duality of the scalar–tensor theory in four and ten dimensions with matter. It is shown that when the pressure of the matter vanishes (γ = 0 for the equation of state p = γρ), the action is invariant under the duality. In addition, the action is invariant again under the change of the sign of the pressure (p→-p or γ→-γ). In higher dimensions, we distinguish the matter, e.g., in four dimensions px = γxρ and for extra six dimensions py = γy ρ. The scale factor duality in this case is that when γx = 0 the duality transformation acts on the four-dimensional scale factor and the dilaton with the extra dimensions intact while when γy = 0 it acts on the extra six dimensions and the dilaton with four dimensions intact.
THE EXISTENCE OF TIME
Authors: SPENCER JOSEPH A. , WHEELER JAMES T.
Published: April 2011

Of those gauge theories of gravity known to be equivalent to general relativity, only the biconformal gauging introduces new structures — the quotient of the conformal group of any pseudo-Euclidean space by its Weyl subgroup always has natural symplectic and metric structures. Using this metric and symplectic form, we show that there exist canonically conjugate, orthogonal, metric submanifolds if and only if the original gauged space is Euclidean or signature 0. In the Euclidean cases, the resultant configuration space must be Lorentzian. Therefore, in this context, time may be viewed as a derived property of general relativity.
SEIBERG–WITTEN EQUATIONS FROM FEDOSOV DEFORMATION QUANTIZATION OF ENDOMORPHISM BUNDLE
Authors: DOBRSKI MICHAŁ
Published: April 2011

It is shown how Seiberg–Witten equations can be obtained by means of Fedosov deformation quantization of endomorphism bundle and the corresponding theory of equivalences of star products. In such setting, Seiberg–Witten map can be iteratively computed for arbitrary gauge group up to any given degree with recursive methods of Fedosov construction. Presented approach can be also considered as a generalization of Seiberg–Witten equations to Fedosov type of noncommutativity.
HOLONOMY IN ROGERS SUPERMANIFOLDS WITH APPLICATIONS TO SUPER YANG–MILLS THEORY
Authors: COOK JAMES S. , FULP RONALD
Published: April 2011

The present paper focuses on a certain class of Banach manifolds we call Rogers supermanifolds since they are indeed supermanifolds modeled on graded Banach spaces. Although the subject of holonomy is well-developed for superanalytic supermanifolds utilizing local ring formulations of supermanifolds this seems not to be the case for supermanifolds modeled on graded Banach manifolds in the sense of Rogers. The proof of our main result requires a partial development of these concepts for such supermanifolds. Our main result determines conditions under which a super connection on a superprincipal bundle [Formula: see text] induces a connection on a quotient superprincipal bundle [Formula: see text] where [Formula: see text] is a foliation of [Formula: see text] and [Formula: see text] is the induced foliation on [Formula: see text]. We also show how such a quotient formulation may be used to describe in a fully geometric fashion the so-called "conventional constraints" of super Yang–Mills theory. One consequence of our development is that instead of requiring two superconnections to describe Yang–Mills theory as is the case in some formulations, we describe the relevant concepts using a single superconnection and moreover we show that the "pregauge transformations" are simply ordinary gauge transformations on the appropriate quotient bundles.
Visualizing the Variance of a Random Variable
Authors: Cacciafesta Fabrizio
Published: April 2011

We provide a simple way to visualize the variance and the mean absolute error of a random variable with finite mean. Some application to options theory and to second order stochastic dominance is given: we show, among other, that the "call-put parity" may be seen as a Taylor formula.
A GENERALIZED HYBRID GENERATION SCHEME OF DIFFERENTIAL EVOLUTION FOR GLOBAL NUMERICAL OPTIMIZATION
Authors: GONG WENYIN , CAI ZHIHUA , JIA LIYUAN , LI HUI
Published: April 2011

Differential evolution (DE) is a simple yet powerful evolutionary algorithm for global numerical optimization over continuous domain, which has been widely used in many areas. Although DE is good at exploring the search space, it is slow at the exploitation of the solutions. To alleviate this drawback, in this paper, we propose a generalized hybrid generation scheme, which attempts to enhance the exploitation and accelerate the convergence velocity of the original DE algorithm. In the hybrid generation scheme the operator with powerful exploitation is hybridized with the original DE operator. In addition, a self-adaptive exploitation factor is introduced to control the frequency of the exploitation operation. In order to evaluate the performance of our proposed generation scheme, two operators, the migration operator of biogeography-based optimization and the "DE/best/1" mutation operator, are employed as the exploitation operator. Moreover, 23 benchmark functions (including 10 test functions provided by CEC2005 special session) are chosen from the literature as the test suite. Experimental results confirm that the new hybrid generation scheme is able to enhance the exploitation of the original DE algorithm and speed up its convergence rate.
Health Problem Solving by Older Persons Using a Complex Government Web Site
Authors: Sharit Joseph , Hernandez Mario A. , Nair Sankaran N. , Kuhn Thomas , Czaja Sara J.
Published: April 2011

A large number of health-related Web sites currently exist that offer consumers a wealth of information that can be used to enhance the quality of their lives. Much less attention has been given to Web sites that can support complex health-related problem solving, as opposed to more general information search activities, of user populations such as older adults. In this article, we expand on a prior usability study that examined the performance of 112 older adults who were asked to solve two problems using the U. S. government’s Medicare.gov Web site. The indications from that study were that older adults had difficulty carrying out these problem-solving tasks.

This article illustrates, in the context of a case study, the use of a structured methodology for obtaining insights into Web site design issues that could make it difficult for healthcare consumers such as older adults to solve health-related problems. Initially, a number of Web design guidelines that have been developed for older users are presented. The argument is made that such checklist-type guidelines, though essential, are difficult to apply to complex Web-based problem-solving activities. Following a review of research in the area of Web-based health information seeking and problem-solving by older adults, the description and implementation of a methodology for aiding designers in anticipating cognitive demands that older users might confront during their problem-solving activities is presented. Detailed analysis of task performance is then presented to demonstrate that very few of the study participants were able to successfully negotiate the solution to the problem. The use of the methodology for identifying a number user-Web site interaction issues and for proposing recommendations particularly relevant to older users, and ultimately for enhancing the accessibility of health Web sites, is highlighted. Finally, a detailed framework is presented that is intended for guiding designers in the application of this methodology.
Virtual network embedding through topology-aware node ranking
Authors: Cheng Xiang , Su Sen , Zhang Zhongbao , Wang Hanchi , Yang Fangchun , Luo Yan , Wang Jie
Published: April 2011

Virtualizing and sharing networked resources have become a growing trend that reshapes the computing and networking architectures. Embedding multiple virtual networks (VNs) on a shared substrate is a challenging problem on cloud computing platforms and large-scale sliceable network testbeds. In this paper we apply the Markov Random Walk (RW) model to rank a network node based on its resource and topological attributes. This novel topology-aware node ranking measure reflects the relative importance of the node. Using node ranking we devise two VN embedding algorithms. The first algorithm maps virtual nodes to substrate nodes according to their ranks, then embeds the virtual links between the mapped nodes by finding shortest paths with unsplittable paths and solving the multi-commodity flow problem with splittable paths. The second algorithm is a backtracking VN embedding algorithm based on breadth-first search, which embeds the virtual nodes and links during the same stage using node ranks. Extensive simulation experiments show that the topology-aware node rank is a better resource measure and the proposed RW-based algorithms increase the long-term average revenue and acceptance ratio compared to the existing embedding algorithms.
Volume Expansion Factor and Growth Efficiency of Anodic Alumina Formed in Sulphuric Acid
Authors: Zhou F. , Mohamed Al-Zenati A. K. , Baron-Wiecheć A. , Curioni M. , Garcia-Vergara S. J. , Habazaki H. , Skeldon P. , Thompson G. E.
Published: April 2011

The growth of anodic alumina in sulphuric acid is investigated at constant current on bulk and sputtering-deposited aluminium. The ratio of the thickness of the film to the thickness of oxidized aluminium is shown to increase with increase of the current density (from 0.5 to 50 mA cm−2) and with decrease of the electrolyte temperature (from 20 to 0°C). In addition, the sulphur content of the films and the efficiency of film formation increase. It is suggested that pores are generated primarily by dissolution at current densities below ∼2 mA cm−2, with flow of film material dominating at higher current densities.
Detection of EpCAM-Negative and Cytokeratin-Negative Circulating Tumor Cells in Peripheral Blood
Authors: Mikolajczyk Stephen D. , Millar Lisa S. , Tsinberg Pavel , Coutts Stephen M. , Zomorrodi Maryam , Pham Tam , Bischoff Farideh Z. , Pircher Tony J.
Published: April 2011

Enrichment of rare circulating tumor cells (CTCs) in blood is typically achieved using antibodies to epithelial cell adhesion molecule (EpCAM), with detection using cytokeratin (CK) antibodies. However, EpCAM and CK are not expressed in some tumors and can be downregulated during epithelial-to-mesenchymal transition. A micro-fluidic system, not limited to EpCAM or CK, was developed to use multiple antibodies for capture followed by detection using CEE-Enhanced (CE), a novelin situstaining method that fluorescently labels the capture antibodies bound to CTCs. Higher recovery of CTCs was demonstrated using antibody mixtures compared to anti-EpCAM. In addition, CK-positive breast cancer cells were found in 15 of 24 samples (63%; range 1–60 CTCs), while all samples contained additional CE-positive cells (range 1–41; median = 11; ). Thus, antibody mixtures against a range of cell surface antigens enables capture of more CTCs than anti-EpCAM alone and CE staining enables the detection of CK-negative CTCs.