bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of Solar Radiance Profiles With the Sun and Aureole Measurement System
Authors: Wilbert S. , Reinhardt B. , DeVore J. , Röger M. , Pitz-Paal R. , Gueymard C. , Buras R.
Published: June 2013

Due to forward scattering of direct sunlight in the atmosphere, the circumsolar region closely surrounding the solar disk looks very bright. The radiation coming from this region, the circumsolar radiation, is in large part included in common direct normal irradiance (DNI) measurements, but only partially intercepted by the receivers of focusing collectors. This effect has to be considered in the performance analysis of concentrating collectors in order to avoid overestimation of the intercepted irradiance. At times, the overestimation reaches more than 10% for highly concentrating systems even for sky conditions with relevant DNI above 200 W/m2. The amount of circumsolar radiation varies strongly with time, location and sky conditions. However, no representative sunshape measurements exist for locations that are now of particular interest for concentrating solar power (CSP) or concentrating photovoltaics (CPV). A new sunshape measurement system is developed and analyzed in this study. The system consists of the sun and aureole measurement instrument (SAM), an AERONET sun photometer and postprocessing software. A measurement network is being created with the presented system. The uncertainty of this system is significantly lower than what was obtained with previous devices. In addition, the spectral optical properties of circumsolar radiation are determined. As a result, the necessary information for CSP and CPV systems, and a basis for the development of modeling methods for circumsolar radiation, can now be achieved.
Stability and Stabilization for Discrete System With Probabilistic Nonlinearities
Authors: Zhao Xia , Tian Engang
Published: June 2013

This paper investigates stability and stabilization of discrete systems with probabilistic nonlinearities and time-varying delay. New characters of the nonlinearities, the probability of the nonlinearities happening between different bounds, are used to build new type of system model, which can help us make a full use of the inner variation information of the nonlinearities. With the help of the new characters, new system model is proposed. Then, sufficient conditions for the mean square stability of the system can be obtained by using the Lyapunov functional approach and linear matrix inequalities technique. An example is proposed to illustrate the efficiency of the proposed method.
Optimal Magnetorheological Damper Configuration Using the Taguchi Experimental Design Method
Authors: Parlak Zekeriya , Engin Tahsin , Şahin İsmail
Published: June 2013

Magnetorheological (MR) dampers have attracted the interest of suspension designers and researchers because of their variable damping feature, mechanical simplicity, robustness, low power consumption and fast response. This study deals with the optimal configuration of an MR damper using the Taguchi experimental design approach. The optimal solutions of the MR damper are evaluated for the maximum dynamic range and the maximum damper force separately. The MR dampers are constrained in a cylindrical container defined by radius and height. The optimal damper configurations obtained from this study are fabricated and tested for verification. The verification tests show that the dampers provide the specified damper force and dynamic range.
A Role for Platelet TRPC Channels in the Ca
2+
Response That Induces Procoagulant Activity
Authors: Mahaut-Smith Martyn P.
Published: June 2013

Multiple cation channels and an exchanger contribute to calcium signals that stimulate platelet phosphatidylserine exposure.
Two Endogenous Modulators in One
Authors: Gough Nancy R.
Published: June 2013

The
Dbi
gene encodes both positive and negative endogenous allosteric regulators of ionotropic GABA receptors.
Fitness Consequences of
Plasmodium falciparum pfmdr1
Polymorphisms Inferred from
Ex Vivo
Culture of Ugandan Parasites
Authors: Ochong Edwin , Tumwebaze Patrick K. , Byaruhanga Oswald , Greenhouse Bryan , Rosenthal Philip J.
Published: June 2013

Polymorphisms in the
Plasmodium falciparum
multidrug resistance 1 (
pfmdr1
) gene impact sensitivity to multiple antimalarials. In Africa, polymorphisms at N86Y and D1246Y are common and have various impacts on sensitivity to different drugs. To gain insight into the fitness consequences of these polymorphisms, we cultured parasites isolated from children with malaria in Tororo, Uganda, where the multiplicity of infection is high, and used pyrosequencing to follow polymorphism prevalences in culture over time. Of 71 cultures, parasites in 69 were successfully analyzed at N86Y and parasites in 68 were successfully analyzed at D1246Y over 3 to 36 days of culture. For position 86, the sequences of 39/69 (56.5%) parasites remained stable (>90% prevalence over 2 to 17 time points), with 82.1% of these being stable for the 86Y mutation. For position 1246, the sequences of 31/68 (45.6%) parasites remained stable, with 64.5% of these being stable for the wild-type D1246 sequence (
P
= 0.0002 for comparison of stable mutant genotypes for the two alleles). Defining allele selection as a ≥15% change in prevalence between the first and last samples assessed, for position 86, 11 samples showed selection, with selection toward 86Y occurring in 72.7% of alleles; for position 1246, 14 samples showed selection, with selection toward D1246 occurring in 64.3% of alleles (
P
= 0.11 for comparison of selection of mutations at the two alleles). Among the 7 samples with selection at both alleles, 5 showed selection for both 86Y and D1246. Overall, consistent trends in the direction of selection were seen, although differences were not statistically significant. Our results suggest fitness advantages for parasites with the
pfmdr1
86Y mutation and wild-type D1246, highlighting the complex interplay between drug resistance and fitness in malaria parasites. (This study has been registered at ClinicalTrials.gov under registration no. NCT00948896 and NCT00993031.)
Evaluation of Combinations of 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine with Clinically Used Antiretroviral Drugs
Authors: Hachiya Atsuko , Reeve Aaron B. , Marchand Bruno , Michailidis Eleftherios , Ong Yee Tsuey , Kirby Karen A. , Leslie Maxwell D. , Oka Shinichi , Kodama Eiichi N. , Rohan Lisa C. , Mitsuya Hiroaki , Parniak Michael A. , Sarafianos Stefan G.
Published: June 2013

Drug combination studies of 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) with FDA-approved drugs were evaluated by two different methods, MacSynergy II and CalcuSyn. Most of the combinations, including the combination of the two adenosine analogs EFdA and tenofovir, were essentially additive, without substantial antagonism or synergism. The combination of EFdA and rilpivirine showed apparent synergism. These studies provide information that may be useful for the design of EFdA combination regimens for initial and salvage therapy assessment.
Nasal Carriage of Epidemic Methicillin-Resistant Staphylococcus aureus 15 (EMRSA-15) Clone Observed in Three Chicago-Area Long-Term Care Facilities
Authors: Das Sanchita , Anderson Christopher J. , Grayes Althea , Mendoza Katherine , Harazin Maureen , Schora Donna M. , Peterson Lance R.
Published: June 2013

The spread of pandemic methicillin-resistant
Staphylococcus aureus
(MRSA) clones such as USA300 and EMRSA-15 is a global health concern. As a part of a surveillance study of three long-term care facilities in the Greater Chicago area, phenotypic and molecular characterization of nasal MRSA isolates was performed. We report a cluster of pandemic EMRSA-15, an MRSA clone rarely reported from the United States, detected during this study.
Amphiphilic Antimony(V) Complexes for Oral Treatment of Visceral Leishmaniasis
Authors: Fernandes Flaviana R. , Ferreira Weverson A. , Campos Mariana A. , Ramos Guilherme S. , Kato Kelly C. , Almeida Gregório G. , Corrêa José D. , Melo Maria N. , Demicheli Cynthia , Frézard Frédéric
Published: June 2013

The need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their potential for the oral treatment of visceral leishmaniasis (VL) was evaluated. Complexes of Sb and ligand at 1:3 (SbL8 and SbL10) were obtained from the reaction of antimony(V) with L8 and L10, as evidenced by elemental and electrospray ionization-tandem mass spectrometry (ESI-MS) analyses. Fluorescence probing of hydrophobic environment and negative-staining transmission electron microscopy showed that SbL8 forms kinetically stabilized nanoassemblies in water. Pharmacokinetic studies with mice in which the compound was administered by the oral route at 200 mg of Sb/kg of body weight indicated that the SbL8 complex promoted greater and more sustained Sb levels in serum and liver than the levels obtained for the conventional antimonial drug meglumine antimoniate (Glucantime [Glu]). The efficacy of SbL8 and SbL10 administered by the oral route was evaluated in BALB/c mice infected withLeishmania infantumafter a daily dose of 200 mg of Sb/kg for 20 days. Both complexes promoted significant reduction in the liver and spleen parasite burdens in relation to those in the saline-treated control group. The extent of parasite suppression (>99.96%) was similar to that achieved after Glu given intraperitoneally at 80 mg of Sb/kg/day. As expected, there was no significant reduction in the parasitic load in the group treated orally with Glu at 200 mg of Sb/(kg day). In conclusion, amphiphilic antimony(V) complexes emerge as an innovative and promising strategy for the oral treatment of VL.
Restrictive Streptomycin Resistance Mutations Decrease the Formation of Attaching and Effacing Lesions in Escherichia coli O157:H7 Strains
Authors: Chen Chun , Blumentritt Carla A. , Curtis Meredith M. , Sperandio Vanessa , Torres Alfredo G. , Dudley Edward G.
Published: June 2013

Streptomycin binds to the bacterial ribosome and disrupts protein synthesis by promoting misreading of mRNA. Restrictive mutations on the ribosomal subunit protein S12 confer a streptomycin resistance (Str
r
) phenotype and concomitantly increase the accuracy of the decoding process and decrease the rate of translation. Spontaneous Str
r
mutants of
Escherichia coli
O157:H7 have been generated for
in vivo
studies to promote colonization and to provide a selective marker for this pathogen. The locus of enterocyte effacement (LEE) of
E. coli
O157:H7 encodes a type III secretion system (T3SS), which is required for attaching and effacing to the intestinal epithelium. In this study, we observed decreases in both the expression and secretion levels of the T3SS translocated proteins EspA and EspB in
E. coli
O157:H7 Str
r
restrictive mutants, which have K42T or K42I mutations in S12. However, mildly restrictive (K87R) and nonrestrictive (K42R) mutants showed slight or indistinguishable changes in EspA and EspB secretion. Adherence and actin staining assays indicated that restrictive mutations compromised the formation of attaching and effacing lesions in
E. coli
O157:H7. Therefore, we suggest that
E. coli
O157:H7 strains selected for Str
r
should be thoroughly characterized before
in vivo
and
in vitro
experiments that assay for LEE-directed phenotypes and that strains carrying nonrestrictive mutations such as K42R make better surrogates of wild-type strains than those carrying restrictive mutations.
Species-Dependent Blood-Brain Barrier Disruption of Lipopolysaccharide: Amelioration by ColistinIn VitroandIn Vivo
Authors: Jin Liang , Nation Roger L. , Li Jian , Nicolazzo Joseph A.
Published: June 2013

The aim of this study was to usein vitroandin vivomodels to assess the impact of lipopolysaccharide (LPS) from two different bacterial species on blood-brain barrier (BBB) integrity and brain uptake of colistin. Following repeated administration of LPS fromPseudomonas aeruginosa, the brain-to-plasma ratio of [14C]sucrose in Swiss outbred mice was not significantly increased. Furthermore, while the brain uptake of colistin in mice increased 3-fold following administration of LPS fromSalmonella enterica, LPS fromP. aeruginosahad no significant effect on colistin brain uptake. This apparent species-dependent effect did not appear to correlate with differences in plasma cytokine levels, as the concentrations of tumor necrosis factor alpha and interleukin-6 following administration of each LPS were not different (P> 0.05). To clarify whether this species-specific effect of LPS was due to direct effects on the BBB, human brain capillary endothelial (hCMEC/D3) cells were treated with LPS fromP. aeruginosaorS. entericaand claudin-5 expression was measured by Western blotting.S. entericaLPS significantly (P< 0.05) reduced claudin-5 expression at a concentration of 7.5 μg/ml. In contrast,P. aeruginosaLPS decreased (P< 0.05) claudin-5 expression only at the highest concentration tested (i.e., 30 μg/ml). Coadministration of therapeutic concentrations of colistin ameliorated theS. entericaLPS-induced reduction in claudin-5 expression in hCMEC/D3 cells and the perturbation in BBB function in mice. This study demonstrates that BBB disruption induced by LPS is species dependent, at least betweenP. aeruginosaandS. enterica, and can be ameliorated by colistin.
In Vivo
Effects of Cefazolin, Daptomycin, and Nafcillin in Experimental Endocarditis with a Methicillin-Susceptible Staphylococcus aureus Strain Showing an Inoculum Effect against Cefazolin
Authors: Nannini Esteban C. , Singh Kavindra V. , Arias Cesar A. , Murray Barbara E.
Published: June 2013

Several reports have implicated the inoculum effect that some strains of type A beta-lactamase (Bla)-producing, methicillin-susceptible
Staphylococcus aureus
(MSSA) show against cefazolin as the cause for clinical failures in certain serious deep-seated infections. Here, using a previously reported MSSA strain displaying this phenotype (TX0117), we obtained a Bla-cured derivative (TX0117c) with a combination of novobiocin and high temperature. Both isolates were then used in a rat endocarditis model and treated with cefazolin, nafcillin, and daptomycin, given to simulate human dosing. Animals were treated for 3 days and either sacrificed at 24 h after the last antibiotic dose (standard group) or left untreated for an additional 3 days (relapse group). With TX0117 in the standard treatment group, daptomycin and nafcillin were both significantly better than cefazolin in reducing CFU/g of vegetations, achieving mean log
10
reductions compared to levels in untreated rats of 7.1, 5.3, and 1.8, respectively (cefazolin versus daptomycin,
P
< 0.0001; cefazolin versus nafcillin,
P
= 0.005; daptomycin versus nafcillin,
P
= 0.053). In addition, cefazolin was significantly more effective in reducing vegetation titers of TX0117c than of TX0117 (mean log
10
reduction of 1.4 versus 5.5, respectively;
P
= 0.0001). Similar results were observed with animals in the relapse group. Thus, these data show that there can be an
in vivo
consequence of the
in vitro
inoculum effect that some MSSA strains display against cefazolin and indicate a specific role for Bla production using a Bla-cured derivative strain against which cefazolin regained both
in vitro
and
in vivo
activity.
Synergistic and Additive Effects of Chromosomal and Plasmid-Encoded Hemolysins Contribute to Hemolysis and Virulence in Photobacterium damselae subsp. damselae
Authors: Rivas Amable J. , Balado Miguel , Lemos Manuel L. , Osorio Carlos R.
Published: June 2013

Photobacterium damselae
subsp.
damselae
causes infections and fatal disease in marine animals and in humans. Highly hemolytic strains produce damselysin (Dly) and plasmid-encoded HlyA (HlyA
pl
). These hemolysins are encoded by plasmid pPHDD1 and contribute to hemolysis and virulence for fish and mice. In this study, we report that all the hemolytic strains produce a hitherto uncharacterized chromosome-encoded HlyA (HlyA
ch
). Hemolysis was completely abolished in a single

hlyA
ch

mutant of a plasmidless strain and in a

dly hlyA
pl
hlyA
ch

triple mutant. We found that Dly, HlyA
pl
, and HlyA
ch
are needed for full hemolytic values in strains harboring pPHDD1, and these values are the result of the additive effects between HlyA
pl
and HlyA
ch
, on the one hand, and of the synergistic effect of Dly with HlyA
pl
and HlyA
ch
, on the other hand. Interestingly, Dly-producing strains produced synergistic effects with strains lacking Dly production but secreting HlyA, constituting a case of the CAMP (
C
hristie,
A
tkins, and
M
unch-
P
etersen) reaction. Environmental factors such as iron starvation and salt concentration were found to regulate the expression of the three hemolysins. We found that the contributions, in terms of the individual and combined effects, of the three hemolysins to hemolysis and virulence varied depending on the animal species tested. While Dly and HlyA
pl
were found to be main contributors in the virulence for mice, we observed that the contribution of hemolysins to virulence for fish was mainly based on the synergistic effects between Dly and either of the two HlyA hemolysins rather than on their individual effects.
Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli
Authors: Birchenough George M. H. , Johansson Malin E. V. , Stabler Richard A. , Dalgakiran Fatma , Hansson Gunnar C. , Wren Brendan W. , Luzio J. Paul , Taylor Peter W.
Published: June 2013

Two-day-old (P2), but not 9-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization by
Escherichia coli
K1. Age dependency reflects the capacity of colonizing K1 to translocate from gastrointestinal (GI) tract to blood. A complex GI microbiota developed by P2, showed little variation over P2 to P9, and did not prevent stable K1 colonization. Substantial developmental expression was observed over P2 to P9, including upregulation of genes encoding components of the small intestinal (α-defensins Defa24 and Defa-rs1) and colonic (trefoil factor Tff2) mucus barrier. K1 colonization modulated expression of these peptides: developmental expression of Tff2 was dysregulated in P2 tissues and was accompanied by a decrease in mucin Muc2. Conversely, α-defensin genes were upregulated in P9 tissues. We propose that incomplete development of the mucus barrier during early neonatal life and the capacity of colonizing K1 to interfere with mucus barrier maturation provide opportunities for neuropathogen translocation into the bloodstream.
Staphopains Modulate Staphylococcus aureus Biofilm Integrity
Authors: Mootz Joe M. , Malone Cheryl L. , Shaw Lindsey N. , Horswill Alexander R.
Published: June 2013

Staphylococcus aureus
is a known cause of chronic biofilm infections that can reside on medical implants or host tissue. Recent studies have demonstrated an important role for proteinaceous material in the biofilm structure. The
S. aureus
genome encodes many secreted proteases, and there is growing evidence that these enzymes have self-cleavage properties that alter biofilm integrity. However, the specific contribution of each protease and mechanism of biofilm modulation is not clear. To address this issue, we utilized a sigma factor B (Δ
sigB
) mutant where protease activity results in a biofilm-negative phenotype, thereby creating a condition where the protease(s) responsible for the phenotype could be identified. Using a plasma-coated microtiter assay, biofilm formation was restored to the Δ
sigB
mutant through the addition of the cysteine protease inhibitor E-64 or by using Staphostatin inhibitors that specifically target the extracellular cysteine proteases SspB and ScpA (called Staphopains). Through construction of gene deletion mutants, we determined that an
sspB scpA
double mutant restored Δ
sigB
biofilm formation, and this recovery could be replicated in plasma-coated flow cell biofilms. Staphopain levels were also found to be decreased under biofilm-forming conditions, possibly allowing biofilm establishment. The treatment of
S. aureus
biofilms with purified SspB or ScpA enzyme inhibited their formation, and ScpA was also able to disperse an established biofilm. The antibiofilm properties of ScpA were conserved across
S. aureus
strain lineages. These findings suggest an underappreciated role of the SspB and ScpA cysteine proteases in modulating
S. aureus
biofilm architecture.
Promotion of Colonization and Virulence by Cholera Toxin Is Dependent on Neutrophils
Authors: Queen Jessica , Satchell Karla J. F.
Published: June 2013

The innate immune response toVibrio choleraeinfection is poorly understood, but this knowledge is critical for the design of safe, effective vaccines. Using an adult mouse intestinal infection model, this study examines the contribution of neutrophils to host immunity, as well as the effect of cholera toxin and other secreted factors on this response. Depletion of neutrophils from mice with anti-Ly6G IA8 monoclonal antibody led to similar survival rates of mice infected with low or moderate doses of toxigenicV. choleraeEl Tor O1. At a high dose, neutropenic mice showed increased rates of survival compared to neutrophil-replete animals. Expression of cholera toxin was found to be protective to the neutropenic host, and this phenotype can be replicated by the administration of purified toxin. Neutrophils do not effectively clear colonizing bacteria from the small intestine, nor do they alter induction of early immune-modulating signals. In both neutropenic and neutrophil-replete animals, the local response to infection is characterized by expression of interleukin 6 (IL-6), IL-10, and macrophage inflammatory protein 2 alpha (MIP-2). Overall, these data indicate that the innate immune response to toxigenicV. choleraeinfection differs dramatically from the host response to nontoxigenic infection or vaccination, where neutrophils are protective to the host. In the absence of neutrophils, cholera toxin induces immunomodulatory effects that increase host survival. In cholera toxin-producing strains, similar to nontoxigenic infection, accessory toxins are critical to virulence, indicating that cholera toxin and the other secreted toxins modulate the host response by different mechanisms, with both contributing to bacterial persistence and virulence.
Immunization with the Yersiniabactin Receptor, FyuA, Protects against Pyelonephritis in a Murine Model of Urinary Tract Infection
Authors: Brumbaugh Ariel R. , Smith Sara N. , Mobley Harry L. T.
Published: June 2013

Urinary tract infections (UTI) are common and represent a substantial economic and public health burden. Roughly 80% of these infections are caused by a heterogeneous group of uropathogenic
Escherichia coli
(UPEC) strains. Antibiotics are standard therapy for UTI, but a rise in antibiotic resistance has complicated treatment, making the development of a UTI vaccine more urgent. Iron receptors are a promising new class of vaccine targets for UTI, as UPEC require iron to colonize the iron-limited host urinary tract and genes encoding iron acquisition systems are highly expressed during infection. Previously, three of six UPEC siderophore and heme receptors were identified as vaccine candidates by intranasal immunization in a murine model of ascending UTI. To complete the assessment of iron receptors as vaccine candidates, an additional six UPEC iron receptors were evaluated. Of the six vaccine candidates tested in this study (FyuA, FitA, IroN, the gene product of the CFT073 locus
c0294
, and two truncated derivatives of ChuA), only FyuA provided significant protection (
P
= 0.0018) against UPEC colonization. Intranasal immunization induced a robust and long-lived humoral immune response. In addition, the levels of FyuA-specific serum IgG correlated with bacterial loads in the kidneys [Spearman's rank correlation coefficient ρ(14) = −0.72,
P
= 0.0018], providing a surrogate of protection. FyuA is the fourth UPEC iron receptor to be identified from our screens, in addition to IutA, Hma, and IreA, which were previously demonstrated to elicit protection against UPEC challenge. Together, these iron receptor antigens will facilitate the development of a broadly protective, multivalent UTI vaccine to effectively target diverse strains of UPEC.
Adjuvant Activity of Naturally Occurring Monophosphoryl Lipopolysaccharide Preparations from Mucosa-Associated Bacteria
Authors: Chilton Paula M. , Hadel Diana M. , To Thao T. , Mitchell Thomas C. , Darveau Richard P.
Published: June 2013

Natural heterogeneity in the structure of the lipid A portion of lipopolysaccharide (LPS) produces differential effects on the innate immune response. Gram-negative bacterial species produce LPS structures that differ from the classic endotoxic LPS structures. These differences include hypoacylation and hypophosphorylation of the diglucosamine backbone, both differences known to decrease LPS toxicity. The effect of decreased toxicity on the adjuvant properties of many of these LPS structures has not been fully explored. Here we demonstrate that two naturally produced forms of monophosphorylated LPS, from the mucosa-associated bacteriaBacteroides thetaiotaomicronandPrevotella intermedia, function as immunological adjuvants for antigen-specific immune responses. Each form of mucosal LPS increased vaccination-initiated antigen-specific antibody titers in both quantity and quality when given simultaneously with vaccine antigen preparations. Interestingly, adjuvant effects on initial T cell clonal expansion were selective for CD4 T cells. No significant increase in CD8 T cell expansion was detected. MyD88/Toll-like receptor 4 (TLR4) and TRIF/TLR4 signaling pathways showed equally decreased signaling with the LPS forms studied here as with endotoxic LPS or detoxified monophosphorylated lipid A (MPLA). Natural monophosphorylated LPS from mucosa-associated bacteria functions as a weak but effective adjuvant for specific immune responses, with preferential effects on antibody and CD4 T cell responses over CD8 T cell responses.
Gender inequalities in the promptness of diagnosis of bladder and renal cancer after symptomatic presentation: evidence from secondary analysis of an English primary care audit survey
Authors: Lyratzopoulos Georgios , Abel Gary A , McPhail Sean , Neal Richard D , Rubin Gregory P
Published: June 2013

Objectives

To explore whether women experience greater delays in the diagnosis of bladder and renal cancer when first presenting to a general practitioner with symptoms caused by those cancers and potential reasons for such gender inequalities.

Design

Prospective national audit survey of cancer diagnosis.

Setting

English primary care (2009–2010).

Participants

920 patients with bladder and 398 patients with renal cancer (252 (27%) and 165 (42%), respectively, were women).

Primary and secondary outcome measures

Proportion of patients with three or more pre-referral consultations; number of days from first presentation to referral; proportion of patients who presented with haematuria and proportion of patients investigated in primary care.

Results

Women required three or more prereferral consultations more often than men (27% (95% CI 21% to 33%) vs 11% (9% to 14%) for bladder (p<0.001); and 30% (22% to 39%) vs 18% (13% to 25%) for renal cancer (p=0.025)) and had a greater number of days from presentation to referral. In multivariable analysis (adjusting for age, haematuria status and use of primary care-led investigations), being a woman was independently associated with higher odds of three or more pre-referral consultations (OR=3.29 (2.06 to 5.25, p<0.001) for bladder cancer; and OR=1.90 (1.06 to 3.42, p=0.031) for renal cancer). Although presentation with haematuria was associated with more timely diagnosis of bladder cancer, gender inequalities did not vary by haematuria status for either cancer (p=0.18 for bladder and p=0.27 for renal). Each year in the UK, approximately 700 women with either bladder or renal cancer experience a delayed diagnosis because of their gender, of whom more than a quarter (197, or 28%) present with haematuria.

Conclusions

There are notable gender inequalities in the timeliness of diagnosis of urological cancers. There is a need to both reinforce existing guidelines on haematuria investigation and develop new diagnostic decision aids and tests for patients who present without haematuria.
Proteomic study on the protective mechanism of fibroblast growth factor 21 to ischemia–reperfusion injury
Authors: Cong Wei-Tao , Ling Jin , Tian Hai-Shan , Ling Ren , Wang Yang , Huang Bin-Bin , Zhao Ting , Duan Yuan-Meng , Jin Li-Tai , Li Xiao Kun
Published: June 2013

Fibroblast growth factor (FGF)-21 is a novel regulator of insulin-independent glucose transport in 3T3-L1 adipocytes and has glucose and triglyceride lowering effects in rodent models of diabetes. In this study, we found that FGF-21 can significantly attenuate ischemia–reperfusion (I/R) induced damage in H9c2 cells (rat heart). However, it is unclear which signal transduction pathway is involved in the cardioprotective effect of FGF-21. Thus, this study was designed to investigate the potential mechanism induced by FGF-21. The results showed that FGF-21 treatment prevented the oxidative stress and apoptosis associated with I/R damage by reducing the levels of superoxide anions, inhibiting glycogen synthase kinase (GSK) 3β by activating Akt phosphorylation, and recovering the levels of ATP synthase pyruvate kinase isozymes M1 and protein kinase C, thereby improving energy supply. In summary, we conclude that FGF-21 protects H9c2 cells against I/R injury mainly through the Akt–GSK-3β–caspase-3 dependent pathway, preventing oxidative stress, and recovery of the energy supply.
WIENER MEASURE FOR H-TYPE GROUP
Authors: LIU HEPING , WANG YINGZHAN
Published: June 2013

In this paper, we build Wiener measure for the path space on H-type group by using the heat kernel corresponding to the sub-Laplacian and give the definition of the Wiener integral. Then we give the Feynman–Kac formula.
EFFECT OF PERIODICALLY MODULATED NOISE ON STOCHASTIC RESONANCE IN LASER SYSTEM
Authors: ZHANG LI , YUAN XIU-HUA
Published: June 2013

The output power and the signal-to-noise ratio (SNR) of a single-mode laser system are calculated in the case of the laser model with periodically modulated noise. The corresponding stochastic resonance (SR) phenomena are discussed and compared with the case without periodically modulated noise. It is shown that the main difference between the two noise laser models exists in the SNR as a function of signal period. There appears resonance and suppression coexisting phenomenon for the model with periodically modulated noise, which can be utilized to restrain or optimize the output SNR of the system. Whereas, SR is absent for the model without periodically modulated noise, and the SNR just increases monotonously with signal period.
HIGH FREQUENCY APPROXIMATION FOR THE MODAL ACOUSTIC IMPEDANCE COEFFICIENTS OF A CIRCULAR PLATE LOCATED AT THE BOUNDARY OF THE THREE-WALL CORNER REGION
Authors: SZEMELA KRZYSZTOF
Published: June 2013

The high frequency asymptotic formulas for the acoustic impedance modal coefficients of a clamped circular plate located at the boundary of the three-wall corner region have been obtained. The method of contour integral analysis, the series for the Bessel and Neumann functions and the stationary phase method have been used. Some sample modal coefficients of the acoustic resistance and reactance together with the absolute approximation error have been illustrated as the functions of a parameter proportional to the vibration frequency. The computational efficiency of the presented asymptotic formulas has been compared with the computational efficiency of the integral formulas. The cases, in which the asymptotic formulas allow to reduce the calculation time in comparison with the integral formulas, have been determined. The presented formulas can be used to decrease the computation time of the acoustics power radiated by a clamped circular plate located at the boundary of the three-wall corner region. Moreover, the sound pressure calculations can be performed much faster by using these formulas when the acoustic attenuation is included.
THE EFFECT OF CENTER OF MASS OFFSET ON THE DISTURBANCE REJECTION OF RUNNING ROBOTS
Authors: VAN OIJEN TIM P. , KARSSEN J. G. DANIËL , WISSE MARTIJN
Published: June 2013

Running robots often have their center-of-mass (CoM) of the torso located on the hip, to allow for simple control schemes. However, an offset between the CoM and the hip might increase a robot's ability to recover from disturbances. In this simulation study, we investigated the effect of the CoM-location on the largest disturbance that can be corrected within one or two steps. We found that, for one-step recovery strategies, the optimal CoM-location is above the hip for a step-down disturbance and below the hip for a push disturbance. For two-step recovery strategies, we found that the performance increases for increasing offset of the CoM. An offset of the CoM-location can increase the disturbance rejection up to a factor of 10 compared to the CoM at the hip.
A SHALLOW WATER MODEL BY FINITE POINT METHOD
Authors: BUACHART CHINAPAT , KANOK-NUKULCHAI WORSAK , ORTEGA ENRIQUE , OÑATE EUGENIO
Published: June 2013

In this paper, "finite point method" (FPM) is presented for modeling 2D shallow water flow problem. The method is based on the use of a weighted least-square approximation procedure, incorporating QR factorization and an iterative adjustment of local approximation parameters. The stabilization of the convective term in this present work is derived from the approximate Riemann solver proposed by Roe. The present method is shown to produce competitive accuracy in the comparisons with the analytical solutions and the well-known Galerkin characteristic-based split (CBS) algorithm.
ON SPHERICALLY SYMMETRIC FINSLER METRICS WITH ISOTROPIC BERWALD CURVATURE
Authors: GUO ENLI , LIU HUAIFU , MO XIAOHUAN
Published: June 2013

A Finsler metric F is said to be spherically symmetric if the orthogonal group O(n) acts as isometries of F. In this paper, we show that every spherically symmetric Finsler metric of isotropic Berwald curvature is a Randers metric. We also construct explicitly a lot of new isotropic Berwald spherically symmetric Finsler metrics.
NONLINEAR STABILITY OF PLANAR STATIONARY WAVES FOR GENERALIZED BENJAMIN–BONA–MAHONY–BURGERS EQUATIONS IN THE HALF-PLANE
Authors: XIAO QINGHUA , ZHAO HUIJIANG
Published: June 2013

This paper is concerned with the nonlinear stability of planar stationary waves of generalized Benjamin–Bona–Mahony–Burgers equations in half-plane. The planar stationary waves are shown to be globally nonlinear stable and then, by employing the space–time weighted energy method developed by Kawashima and Matsumura in 1995 and a generalized Hardy type inequality with the best possible constant introduced by Kawashima and Kurata in 2009, the corresponding convergence rates (both algebraic and exponential) of the global solutions to the stationary waves are also obtained for both the nondegenerate case and the degenerate case.
POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES
Authors: LI DONGZHI , HE HONGHUI , ZENG NAN , DU E , LIAO RAN , HE YONGHONG , MA HUI , LIU SHAOXIONG , LI MINGHUA
Published: June 2013

We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI), degree of polarization imaging (DOPI) and rotating linear polarization imaging (RLPI). Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.
MULTIFUNCTIONAL FULLERENE- AND METALLOFULLERENE-BASED NANOBIOMATERIALS
Authors: LALWANI GAURAV , SITHARAMAN BALAJI
Published: June 2013

Recent advances in nanotechnology have enabled the synthesis and characterization of nanomaterials suitable for applications in the field of biology and medicine. Due to their unique physico-chemical properties, carbon-based nanomaterials such as fullerenes, metallofullerenes, carbon nanotubes and graphene have been widely investigated as multifunctional materials for applications in tissue engineering, molecular imaging, therapeutics, drug delivery and biosensing. In this review, we focus on the multifunctional capabilities of fullerenes and metallofullerenes for diagnosis and therapy. Specifically, we review recent advances toward the development of fullerene- and metallofullerene-based magnetic resonance imaging (MRI) and X-ray imaging contrast agents, drug and gene delivery vehicles, and photodynamic therapy agents. We also discuss in vitro and in vivo toxicity, and biocompatibility issues associated with the use of fullerenes and metallofullerenes for biomedical applications.
Persistent Predecessor Search and Orthogonal Point Location on the Word RAM
Authors: Chan Timothy M.
Published: June 2013

We answer a basic data structuring question (e.g., raised by Dietz and Raman [1991]): Can van Emde Boas trees be made persistent, without changing their asymptotic query/update time? We present a (partially) persistent data structure that supports predecessor search in a set of integers in {1, ...,
U
} under an arbitrary sequence of
n
insertions and deletions, with
O
(log log
U
) expected query time and expected amortized update time, and
O
(
n
) space. The query bound is optimal in
U
for linear-space structures and improves previous near-
O
((log log
U
)
2
) methods.

The same method solves a fundamental problem from computational geometry: point location in orthogonal planar subdivisions (where edges are vertical or horizontal). We obtain the first static data structure achieving
O
(log log
U
) worst-case query time and linear space. This result is again optimal in
U
for linear-space structures and improves the previous
O
((log log
U
)
2
) method by de Berg et al. [1995]. The same result also holds for higher-dimensional subdivisions that are orthogonal binary space partitions, and for certain nonorthogonal planar subdivisions such as triangulations without small angles. Many geometric applications follow, including improved query times for orthogonal range reporting for dimensions ≥ 3 on the RAM.

Our key technique is an interesting new van-Emde-Boas--style recursion that alternates between two strategies, both quite simple.
Sparse Euclidean Spanners with Tiny Diameter
Authors: Solomon Shay
Published: June 2013

In STOC’95, Arya et al. [1995] showed that for any set of
n
points in R
d
, a (1 +
ε
)-spanner with diameter at most 2 (respectively, 3) and
O
(
n
log
n
) edges (respectively,
O
(
n
log log
n
) edges) can be built in
O
(
n
log
n
) time. Moreover, it was shown in Arya et al. [1995] and Narasimhan and Smid [2007] that for any
k
≥ 4, one can build in
O
(
n
(log
n
)2
k
α
k
(
n
)) time a (1 +
ε
)-spanner with diameter at most 2
k
and
O
(
n
2
k
α
k
(
n
)) edges. The function
α
k
is the inverse of a certain function at the
k
/2 th level of the primitive recursive hierarchy, where
α
0
(
n
) =
n
/2 ,
α
1
(
n
) = √
n
,
α
2
(
n
) = log
n
,
α
3
(
n
) = log log
n
,
α
4
(
n
) = log*
n
,
α
5
(
n
) = 12 log*
n
, ..., etc. It is also known [Narasimhan and Smid 2007] that if one allows quadratic time, then these bounds can be improved. Specifically, for any
k
 ≥ 4, a (1 + 
ε
)-spanner with diameter at most
k
and
O
(
nkα
k
(
n
)) edges can be constructed in
O
(
n
2
) time [Narasimhan and Smid 2007].

A major open question in this area is whether one can construct within time
O
(
n
log
n
 + 
nkα
k
(
n
)) a (1 + 
ε
)-spanner with diameter at most
k
and
O
(
nkα
k
(
n
)) edges. In this article, we answer this question in the affirmative. Moreover, in fact, we provide a stronger result. Specifically, we show that for any
k
 ≥ 4, a (1 + 
ε
)-spanner with diameter at most
k
and
O
(
nα
k
(
n
)) edges can be built in optimal time
O
(
n
log
n
).
Understanding SMS spam in a large cellular network
Authors: Jiang Nan , Jin Yu , Skudlark Ann , Zhang Zhi-Li
Published: June 2013

In this paper, we conduct a comprehensive study of SMS spam in a large cellular network in the US. Using one year of user reported spam messages to the network carrier, we devise text clustering techniques to group associated spam messages in order to identify SMS spam campaigns and spam activities. Our analysis shows that spam campaigns can last for months and have a wide impact on the cellular network. Combining with SMS network records collected during the same time, we find that spam numbers within the same activity often exhibit strong similarity in terms of their sending patterns, tenure and geolocations. Our analysis sheds light on the intentions and strategies of SMS spammers and provides unique insights in developing better method for detecting SMS spam.
Understanding internet video viewing behavior in the wild
Authors: Balachandran Athula , Sekar Vyas , Akella Aditya , Seshan Srinivasan
Published: June 2013

Over the past few years video viewership over the Internet has risen dramatically and market predictions suggest that video will account for more than 50% of the traffic over the Internet in the next few years. Unfortunately, there has been signs that the Content Delivery Network (CDN) infrastructure is being stressed with the increasing video viewership load. Our goal in this paper is to provide a first step towards a principled understanding of how the content delivery infrastructure must be designed and provisioned to handle the increasing workload by analyzing video viewing behaviors and patterns in the wild. We analyze various viewing behaviors using a dataset consisting of over 30 million video sessions spanning two months of viewership from two large Internet video providers. In these preliminary results, we observe viewing patterns that have significant impact on the design of the video delivery infrastructure.
Exact convex relaxation for optimal power flow in distribution networks
Authors: Gan Lingwen , Li Na , Low Steven , Topcu Ufuk
Published: June 2013

The optimal power flow (OPF) problem seeks to control the power generation/consumption to minimize the generation cost, and is becoming important for distribution networks. OPF is nonconvex and a second-order cone programming (SOCP) relaxation has been proposed to solve it. We prove that after a "small" modification to OPF, the SOCP relaxation is exact under a "mild" condition. Empirical studies demonstrate that the modification to OPF is "small" and that the "mild" condition holds for all test networks, including the IEEE 13-bus test network and practical networks with high penetration of distributed generation.
Stochastic modeling of large-scale solid-state storage systems
Authors: Li Yongkun , Lee Patrick P.C. , Lui John C.S.
Published: June 2013

Solid state drives (SSDs) have seen wide deployment in mobiles, desktops,and data centers due to their high I/O performance and low energy consumption. As SSDs write data out-of-place, garbage collection (GC) is required to erase and reclaim space with invalid data. However, GC poses additional writes that hinder the I/O performance, while SSD blocks can only endure a finite number of erasures. Thus, there is a performance-durability tradeoff on the design space of GC. To characterize the optimal tradeoff, this paper formulates an analytical model that explores the full optimal design space of any GC algorithm. We first present a stochastic Markov chain model that captures the I/O dynamics of large-scale SSDs, and adapt the mean-field approach to derive the asymptotic steady-state performance. We further prove the model convergence and generalize the model for all types of workload. Inspired by this model, we propose a randomized greedy algorithm (RGA) that can operate along the optimal tradeoff curve with a tunable parameter. Using trace-driven simulation on DiskSim with SSD add-ons, we demonstrate how RGA can be parameterized to realize the performance-durability tradeoff.
Revisiting widely held SSD expectations and rethinking system-level implications
Authors: Jung Myoungsoo , Kandemir Mahmut
Published: June 2013

Storage applications leveraging Solid State Disk (SSD) technology are being widely deployed in diverse computing systems. These applications accelerate system performance by exploiting several SSD-specific characteristics. However, modern SSDs have undergone a dramatic technology and architecture shift in the past few years, which makes widely held assumptions and expectations regarding them highly questionable. The main goal of this paper is to question popular assumptions and expectations regarding SSDs through an extensive experimental analysis using 6 state-of-the-art SSDs from different vendors. Our analysis leads to several conclusions which are either not reported in prior SSD literature, or contradict to current conceptions. For example, we found that SSDs are not biased toward read-intensive workloads in terms of performance and reliability. Specifically, random read performance of SSDs is worse than sequential and random write performance by 40% and 39% on average, and more importantly, the performance of sequential reads gets significantly worse over time. Further, we found that reads can shorten SSD lifetime more than writes, which is very unfortunate, given the fact that many existing systems/platforms already employ SSDs as read caches or in applications that are highly read intensive. We also performed a comprehensive study to understand the worst-case performance characteristics of our SSDs, and investigated the viability of recently proposed enhancements that are geared towards alleviating the worst-case performance challenges, such as TRIM commands and background-tasks. Lastly, we uncover the overheads of these enhancements and their limits, and discuss system-level implications.
Probabilistic optimal tree hopping for RFID identification
Authors: Shahzad Muhammad , Liu Alex X.
Published: June 2013

Radio Frequency Identification (RFID) systems are widely used in various applications such as supply chain management, inventory control, and object tracking. Identifying RFID tags in a given tag population is the most fundamental operation in RFID systems. While the Tree Walking (TW) protocol has become the industrial standard for identifying RFID tags, little is known about the mathematical nature of this protocol and only some ad-hoc heuristics exist for optimizing it. In this paper, first, we analytically model the TW protocol, and then using that model, propose the Tree Hopping (TH) protocol that optimizes TW both theoretically and practically. The key novelty of TH is to formulate tag identification as an optimization problem and find the optimal solution that ensures the minimal average number of queries. With this solid theoretical underpinning, for different tag population sizes ranging from 100 to 100K tags, TH significantly outperforms the best prior tag identification protocols on the metrics of the total number of queries per tag, the total identification time per tag, and the average number of responses per tag by an average of 50%, 10%, and 30%, respectively, when tag IDs are uniformly distributed in the ID space, and of 26%, 37%, and 26%, respectively, when tag IDs are non-uniformly distributed.