bluuebunny/crossref_metadata_2025 huggingface dataset:
MEASURING EARNINGS INEQUALITY: AN ECONOMIC ANALYSIS OF THE BONFERRONI INDEX
Authors: TUMEN SEMIH
Published: April 2011

This paper studies the economic content of the Bonferroni index. The most remarkable property of the Bonferroni index is that it overweights income transfers among the poor, and the weights are higher the lower the transfers occur on the income distribution. Hence, it is a good measure of inequality when changes in the living standards of the poor are concerned. There are many problems—especially in labor economics—that fall into this category. Using a version of the assignment model, we show that the Bonferroni index can be formulated endogenously within a mechanism featuring efficient assignment of workers to firms. This formulation is useful in evaluating the interactions between the distribution of skills and earnings inequality with a special emphasis on the lower tail of the earnings distribution. Moreover, it allows us to think about earnings inequality by separately analyzing the contribution of each economic parameter.
DOES SIZE MATTER? THE IMPACT OF CHANGES IN HOUSEHOLD STRUCTURE ON INCOME DISTRIBUTION IN GERMANY
Authors: PEICHL ANDREAS , PESTEL NICO , SCHNEIDER HILMAR
Published: April 2011

Income inequality in Germany has been continually increasing during the past 20 years. One cause of this development, among others, could be structural shifts in household formation due to long‐term societal trends. These affect per capita incomes, which has repercussions for the income distribution even if wages remain constant. The aim of this paper is to quantify the proportion of changing household structures in the increase in inequality. We find that the growth of the income gap in Germany (for both East and West from 1991 to 2007) is indeed strongly related to changes in household structure and employment behavior, and a large part of this increase is compensated by the welfare state.
A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxorubicin as an adjuvant therapy in dogs with splenic haemangiosarcoma
Authors: Teske E. , Rutteman G. R. , Kirpenstein J. , Hirschberger J.
Published: April 2011

Safety and efficacy of pegylated liposome encapsulated doxorubicin (PL‐DOX) was compared with free doxorubicin as an adjuvant monotherapy in dogs with splenic haemangiosarcoma after splenectomy in a randomized prospective clinical trial. A total of 17 dogs in each group were treated. No significant difference in survival between the two treatments was found. The calculated median overall survival time for the 34 dogs was 166 days [95% confidence interval (CI) 148–184]. The ½ year and one‐year survival was 41.2% (95% CI 24.8–56.9) and 22.7% (95% CI 9.9–37.4), respectively. In dogs treated with PL‐DOX, a desquamating dermatitis like palmar‐plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions. Cardiotoxicity was not seen in either treatment groups.
PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence
Authors: Falleti Edmondo , Fabris Carlo , Cmet Sara , Cussigh Annarosa , Bitetto Davide , Fontanini Elisabetta , Fornasiere Ezio , Bignulin Sara , Fumolo Elisa , Bignulin Eleonora , Pirisi Mario , Toniutto Pierluigi
Published: April 2011

Background and aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non‐alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown.

Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end‐stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism‐based assay.

Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over‐represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06–2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/* carriers), to 97/295 (32.9%; male C/*carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001).

Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.
Development and Characterization of a Full‐Thickness Acellular Porcine Cornea Matrix for Tissue Engineering
Authors: Du Liqun , Wu Xinyi
Published: April 2011

Our aim was to produce a natural, acellular matrix from porcine cornea for use as a scaffold in developing a tissue‐engineered cornea replacement. Full‐thickness, intact porcine corneas were decellularized by immersion in 0.5% (wt/vol) sodium dodecyl sulfate. The resulting acellular matrices were then characterized and examined specifically for completeness of the decellularization process. Histological analyses of decellularized corneal stromas showed that complete cell and α‐Gal removal was achieved, while the major structural proteins including collagen type I and IV, laminin, and fibronectin were retained. DAPI staining did not detect any residual DNA within the matrix, and the DNA contents, which reflect the presence of cellular materials, were significantly diminished in the decellularized cornea. The collagen content of the decellularized cornea was well maintained compared with native tissues. Uniaxial tensile testing indicated that decellularization did not significantly compromise the ultimate tensile strength of the tissue (P > 0.05). In vitro cytotoxicity assays using rabbit corneal fibroblast cultures excluded the presence of soluble toxins in the biomaterial. In vivo implantation to rabbit interlamellar stromal pockets showed good biocompability. In summary, a full‐thickness natural acellular matrix retaining the major structural components and strength of the cornea has been successfully developed. The matrix is biocompatible with cornea‐derived cells and has potential for use in corneal transplantation and tissue‐engineering applications.
Teicoplanin Pharmacokinetics During Albumin Dialysis
Authors: Weiler Stefan , Falkensammer Gerda , Seger Christoph , Joannidis Michael , Bellmann Romuald
Published: April 2011

Teicoplanin (TP) pharmacokinetics was assessed in a critically ill patient during albumin dialysis (AD), which was performed with the molecular adsorbent recirculating system. After a 1200‐mg loading dose (24 mg/kg), doses of 1200 and 1000 mg (20 mg/kg) on day 2 and 3, respectively, were administered during two cycles of AD. The mean TP peak and trough concentrations amounted to 99.3 and 21.4 µg/mL, respectively, during AD. A mean half‐life of 5.5 h, an apparent volume of distribution of 0.302 L/kg, and a mean total TP clearance of 39 mL/h/kg were calculated. Ninety minutes after the start of AD, the extracorporeal clearance was 3560 mL/h. Within 8 h of AD therapy, the serum concentrations decreased by about 75%. Despite a considerable elimination of TP by AD, therapeutic serum levels could be maintained during the entire treatment by administration of high doses and close monitoring of TP serum concentrations.
Restless legs syndrome in pregnancy is a frequent disorder with a good prognosis
Authors: UGLANE MARIT T. , WESTAD STIAN , BACKE BJØRN
Published: April 2011

The aim of this study was to assess the prevalence of restless legs syndrome in pregnancy. We distributed a questionnaire to 541 consecutive postpartum patients and received answers from 251 (46%) women. Of the participants, 34% reported restless legs syndrome in pregnancy. In 97% of the women in whom restless legs syndrome had started during the pregnancy, the symptoms disappeared within two to three days after delivery. There was no correlation between pregnancy‐related restless legs syndrome and low hemoglobin levels in the first trimester, and the incidence of restless legs syndrome was not affected by use of iron supplementation. We conclude that in our population, restless legs syndrome in pregnancy is both frequent and transient, occurring in approximately one in three pregnancies and typically resolving within a few days after delivery.
Control of nuclear receptor function by local chromatin structure
Authors: Wiench Malgorzata , Miranda Tina B. , Hager Gordon L.
Published: April 2011

Steroid hormone receptors regulate gene transcription in a highly tissue‐specific manner. The local chromatin structure underlying promoters and hormone response elements is a major component involved in controlling these highly restricted expression patterns. Chromatin remodeling complexes, as well as histone and DNA modifying enzymes, are directed to gene‐specific regions and create permissive or repressive chromatin environments. These structures further enable proper communication between transcription factors, co‐regulators and basic transcription machinery. The regulatory elements active at target genes can be either constitutively accessible to receptors or subject to rapid receptor‐dependent modification. The chromatin states responsible for these processes are in turn determined during development and differentiation. Thus access of regulatory factors to elements in chromatin provides a major level of cell selective regulation.
Urban Growth Management in Christchurch
Authors: MEMON P A
Published: April 2011

This article provides a critique of urban planning in the Christchurch metropolitan region. It is argued that pressure from land owners and developers in the urban fringe, self interest of constituent territorial local authorities, and inadequate national policy direction based on limited interpretation of the planning scope of the Resource Management Act 1991 have constrained a strategic approach to urban growth management in Christchurch. This situation stands in contrast to the apparent success of the Regional Growth Forum in Auckland.
Imaging characteristics following 90yttrium microsphere treatment for unresectable liver cancer
Authors: Bester Lourens , Hobbins Peter G , Wang Shih‐chang , Salem Riad
Published: April 2011

Selective internal radiation therapy (SIRT) with 90yttrium microspheres – also known as radioembolisation – is a relatively new interventional radiology technique offering symptomatic and survival advantages for patients with unresectable liver cancer. However, in delivering both beta‐particle brachytherapy and embolisation of tumour vasculature, SIRT produces biological sequelae and imaging characteristics distinct from other treatment modalities. Current CT interpretation criteria consistently under‐report pathological responses to radioembolisation, diminishing both the prognosis and subsequent treatment choices for responding patients. However, newer criteria incorporating both tumour dimensions and enhancement characteristics improve the correlation with histopathology and provide substantially earlier confirmation of response. CT following radioembolisation may also identify parenchymal features that are often benign but may be mistaken for tumour progression. This review outlines imaging criteria specific to SIRT, including assessment of tumour response and interpretation of both lesion and parenchymal characteristics. The adjunctive role of additional modalities such as positron emission tomography is also addressed.
An evaluation of a paediatric radiation oncology teaching programme incorporating a SCORPIO teaching model
Authors: Ahern Verity , Klein Linda , Bentvelzen Adam , Garlan Karen , Jeffery Heather
Published: April 2011

Introduction: Many radiation oncology registrars have no exposure to paediatrics during their training. To address this, the Paediatric Special Interest Group of the Royal Australian and New Zealand College of Radiologists has convened a biennial teaching course since 1997. The 2009 course incorporated the use of a Structured, Clinical, Objective‐Referenced, Problem‐orientated, Integrated and Organized (SCORPIO) teaching model for small group tutorials. This study evaluates whether the paediatric radiation oncology curriculum can be adapted to the SCORPIO teaching model and to evaluate the revised course from the registrars' perspective.

Methods: Teaching and learning resources included a pre‐course reading list, a lecture series programme and a SCORPIO workshop. Three evaluation instruments were developed: an overall Course Evaluation Survey for all participants, a SCORPIO Workshop Survey for registrars and a Teacher's SCORPIO Workshop Survey.

Results: Forty‐five radiation oncology registrars, 14 radiation therapists and five paediatric oncology registrars attended. Seventy‐three per cent (47/64) of all participants completed the Course Evaluation Survey and 95% (38/40) of registrars completed the SCORPIO Workshop Survey. All teachers completed the Teacher's SCORPIO Survey (10/10). The overall educational experience was rated as good or excellent by 93% (43/47) of respondents. Ratings of satisfaction with lecture sessions were predominantly good or excellent. Registrars gave the SCORPIO workshop high ratings on each of 10 aspects of quality, with 82% allocating an excellent rating overall for the SCORPIO activity. Both registrars and teachers recommended more time for the SCORPIO stations.

Conclusions: The 2009 course met the educational needs of the radiation oncology registrars and the SCORPIO workshop was a highly valued educational component.
Calcification of the Superior Glenoid Labrum
Authors: Dattani Rupen , Thompson Simon , Patel Vipul R.
Published: April 2011

Calcific tendonitis predominantly affects the rotator cuff tendons. Other reported sites of occurrence include the tendon of the long head of biceps, the trapezius and pectoralis major muscles. We report a rare case of calcification within the posterosuperior glenoid labrum of the shoulder.
Ergonomic Considerations for Shoulder Surgery in Combat Helicopter Pilots
Authors: Page Piers R. J. , Granville-Chapman Jeremy , Sykes Anna , Rosell Phillip A. E.
Published: April 2011

Background

Military aircrew have very high demands on their musculoskeletal system, requiring a combination of fine motor co-ordination, strength and endurance to fly combat missions. In common with the rest of the military, they also are at risk of developing shoulder pathology as a result of personal training or sporting injuries in addition to their main occupational risks. Such pathologies include rotator cuff tear, impingement and instability.

Methods

An observational study was undertaken to assess the functional demands placed on the shoulder when flying as captain (P1) or co-pilot (P2), aiming to guide postoperative instructions issued to the aviators undergoing surgery for these pathologies. The range of movement required of the shoulder to fly as P1 or P2 was recorded. Further notes were made of specific controls that presented additional difficulty as a result of the required control pressure, and that of certain special roles, for which equipping the cabin would alter the accessibility of controls.

Conclusion

This information has allowed the shoulder surgery team to formulate specific guidance to issue to pilots, their chain of command and their unit medical officer after their operation to ensure the earliest possible return to flying, at the same time as maintaining the safety of the pilot, their crew and those who depend on them in conflict.
A Novel Technique for Internal Fixation of a Complex Radial Head Fracture
Authors: Berber Onur , Pearse Eyiyemi O. , Tennent Thomas D.
Published: April 2011

The internal fixation of a transverse shear fracture through the radial head of a 31-year-old female is described. This unusual fracture pattern has not been previously described in the literature and presented an operative challenge. A novel technique was employed using suture anchors to securely re-attach the sheared fragment of bone without damaging the articular surface of the radial head. The patient made a full recovery with restoration of a full range of motion at the elbow, and radiological evidence of union with no signs of avascular necrosis at 6 months.
Epidermal growth factor receptor mutations and their correlation with epidermal growth factor receptor‐tyrosine kinase inhibitor therapy and association with the characteristics of patients with non‐small‐cell lung cancer: A meta‐analysis
Authors: Zhang Xiao‐Hang , Li Cheng , Dai Chen‐Fei , Zhou Bao‐Sen
Published: April 2011

Background:  Many studies have demonstrated that epidermal growth factor receptor (EGFR) mutation is associated with the response to therapy with single agent EGFR‐tyrosine kinase inhibitors (EGFR‐TKI) in non‐small cell lung cancer (NSCLC) patients, but the extent of the effect is varied. We carried out a meta‐analysis to assess the association between EGFR mutation and the efficacy of EGFR‐TKI therapy and the independent predictor of EGFR mutation in order to identify who would be likely to benefit from this kind of therapy.

Methods:  All literature relating to EGFR mutation and EGFR‐TKI therapy was researched and carefully selected. Related variables were abstracted and the pooled odds ratio calculated after a heterogeneity test with the software, State 10. Publication bias was evaluated at the same time.

Results:  Seventeen studies were included according to the selection criteria. We found a statistically significant higher probability of response in patients with an EGFR mutation versus wild‐type (19.33, 95% CI, 13.61–27.46, P < 0.0001). Furthermore, the pooled odds ration of susceptibility to EGFR mutation among female patients compared with male patients was 3.01 (95% confidence interval (CI), 2.34–3.88 P < 0.0001), adenocarcinoma patients compared with non‐adenocarcinoma patients was 5.40 (95% CI, 2.55–11.40 P < 0.0001), and non‐smoker patients compared smoker patients was 19.33 (95% CI:,13.61–27.46 P < 0.0001). The publication bias analysis had no statistically significant results.

Conclusion:  Female, adenocarcinoma and non‐smoker are independent predictors for the EGFR mutation. Efficacy of EGFR‐TKI therapy favors patients with an EGFR mutation. Without the gene mutational analysis, patients selected for EGFR‐TKI therapy should be female non‐smokers with adenocarcinoma.
Data mining reveals complex interactions of risk factors and clinical feature profiling associated with the staging of non‐hepatitis B virus/non‐hepatitis C virus‐related hepatocellular carcinoma
Authors: Kawaguchi Takumi , Kakuma Tatsuyuki , Yatsuhashi Hiroshi , Watanabe Hiroshi , Saitsu Hideki , Nakao Kazuhiko , Taketomi Akinobu , Ohta Satoshi , Tabaru Akinari , Takenaka Kenji , Mizuta Toshihiko , Nagata Kenji , Komorizono Yasuji , Fukuizumi Kunitaka , Seike Masataka , Matsumoto Shuichi , Maeshiro Tatsuji , Tsubouchi Hirohito , Muro Toyokichi , Inoue Osami , Akahoshi Motoo , Sata Michio
Published: April 2011

Aim:  Non‐hepatitis B virus/non‐hepatitis C virus‐related hepatocellular carcinoma (NBNC‐HCC) is often detected at an advanced stage, and the pathology associated with the staging of NBNC‐HCC remains unclear. Data mining is a set of statistical techniques which uncovers interactions and meaningful patterns of factors from a large data collection. The aims of this study were to reveal complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC‐HCC using data mining techniques.

Methods:  A database was created from 663 patients with NBNC‐HCC at 20 institutions. The Milan criteria were used as staging of HCC. Complex associations of variables and clinical feature profiling with the Milan criteria were analyzed by graphical modeling and decision tree algorithm methods, respectively.

Results:  Graphical modeling identified six factors independently associated with the Milan criteria: diagnostic year of HCC; diagnosis of liver cirrhosis; serum aspartate aminotransferase (AST); alanine aminotransferase (ALT); α‐fetoprotein (AFP); and des‐γ‐carboxy prothrombin (DCP) levels. The decision trees were created with five variables to classify six groups of patients. Sixty‐nine percent of the patients were within the Milan criteria, when patients showed an AFP level of 200 ng/mL or less, diagnosis of liver cirrhosis and an AST level of less than 93 IU/mL. On the other hand, 18% of the patients were within the Milan criteria, when patients showed an AFP level of more than 200 ng/mL and ALT level of 20 IU/mL or more.

Conclusion:  Data mining disclosed complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC‐HCC.
Effects of anodal transcranial direct current stimulation over the leg motor area on lumbar spinal network excitability in healthy subjects
Authors: Roche N. , Lackmy A. , Achache V. , Bussel B. , Katz R.
Published: April 2011

Non‐technical summary  Transcranial direct current stimulation (tDCS) induces modifications of motor cortex excitability depending on the polarity. However, the impact of tDCS applied to lower limb motor cortex on lumbar spinal network excitability has been unknown up to now. This study was performed in order to assess the effects of anodal tDCS compared to sham stimulation on three lumbar spinal circuits, namely reciprocal Ia inhibition, homonymous recurrent inhibition and presynaptic Ia inhibition, in healthy subjects. The results indicate that anodal tDCS modifies the behaviour of 2 of the 3 spinal circuits studied. Effects of anodal tDCS when applied over lower limb motor cortex should be considered with regard not only to cortical circuits but also to spinal motor circuits. The results also suggest that the effects of anodal tDCS on lumbar spinal circuits are similar to those observed during voluntary muscle co‐contractions.
Specific modulation of corticospinal and spinal excitabilities during maximal voluntary isometric, shortening and lengthening contractions in synergist muscles
Authors: Duclay Julien , Pasquet Benjamin , Martin Alain , Duchateau Jacques
Published: April 2011

Non‐technical summary  The neural control of muscle activity differs during voluntary shortening and lengthening contractions. In this paper, we show that the relative contribution of both cortical and spinal mechanisms to the modulation of neural activation is specific during lengthening contraction and differs between synergist muscles. Knowledge of spinal and corticospinal excitabilities modulations during shortening and lengthening muscle contraction improves our understanding of the processes that underlies the neural control of muscles during dynamic contractions.
Identification and Prediction of Force Coefficients in a Five-Pad and Four-Pad Tilting Pad Bearing for Load-on-Pad and Load-Between-Pad Configurations
Authors: Delgado Adolfo , Vannini Giuseppe , Ertas Bugra , Drexel Michael , Naldi Lorenzo
Published: April 2011

This paper presents the identification of the rotordynamic force coefficients for direct lubrication five-pad and four-pad tilting pad bearings. The bearing is 110 mm in diameter with a L/D of 0.4 pad axial length (44 mm). The experiments include load-on-pad and load-between-pad configurations, with 0.5 and 0.6 pivot offsets, for rotor speeds ranging from 7500 rpm to 15,000 rpm. The bearing force coefficients are identified from multiple frequency excitations (20–300 Hz) exerted on the bearing housing by a pair of hydraulic shakers and are presented as a function of the excitation frequency and rotor speed for a 300 kPa unit load. The experimental results also include temperatures at the trailing edge of three pads. The direct force coefficients, identified from curve-fits of the complex dynamic stiffness, are frequency independent if considering an added mass term much smaller than the test device modal mass. The force coefficients from the four-pad bearing load-between-pad configuration show similar coefficients in the loaded and orthogonal directions. On the other hand, as expected, the five-pad bearing load-on-pad shows larger coefficients (∼25%) in the loaded direction. The maximum pad temperature recorded for the 0.5 pivot offset configurations is up to 20°C higher than those associated to the 0.6 offset configuration. Results from a predictive code are within 50% of the experimental results for the direct stiffness coefficients and within 30% for the direct damping coefficients.
Heat Transfer and Pressure Losses of W-Shaped Small Ribs at High Reynolds Numbers for Combustor Liner
Authors: Hagari Tomoko , Ishida Katsuhiko , Oda Takeo , Douura Yasushi , Kinoshita Yasuhiro
Published: April 2011

The present study investigates the heat transfer performance of W-shaped ribs in a rectangular channel with typical geometries and flow conditions for a combustor liner cooling passage. In order to assess the Reynolds number dependence on heat transfer enhancement by the ribs for the combustor cooling passage, experiments were conducted with channel Reynolds number ranging from 40,000 to 550,000. The ribs were located on one side of the channel and the rib height-to-hydraulic diameter ratio (e/Dh) was 0.006–0.014, which simulate the combustor liner cooling configurations. Rib pitch-to-height ratio (P/e) was 10. Rib-roughened copper plates with constant temperature were used to measure the averaged heat transfer coefficients. Measured results show that the heat transfer enhancements of about 3 were obtained over that of a flat plate at high Reynolds numbers for all cases. The slope of heat transfer coefficient becomes constant with increasing Reynolds number because of the laminar-turbulent transition around the ribs, which is considered to occur at Reynolds number based on rib height of about 1000. Pressure loss measurements showed that the friction coefficients are constantly 3–4.5 times higher than those of a flat plate for a fully turbulent flow such as a combustor cooling passage. Pressure loss by ribs seems not to have a significant impact to the overall combustor performance. Numerical calculations were conducted additionally for all test cases. Predicted amount of heat released from the ribs contributes about 40% of the overall heat release even for low ribs. Heat transfer on the rib surface is essential in the evaluation of the rib-roughened cooling passage.
High In content InxGa1−xN grown by energetic neutral atom beam lithography and epitaxy under slightly N-rich conditions
Authors: Williamson Todd L. , Williams Joshua J. , Hubbard Jonathan C. D. , Hoffbauer Mark A.
Published: April 2011

Two series of In-rich InGaN films with compositions of ∼25% and ∼35% In, grown over a substrate temperature range from 490 to 620 °C, show how the film properties improve as the growth temperature is lowered below the InN decomposition temperature of ∼550 °C in vacuum. These InGaN films have been grown using a novel growth technique utilizing energetic N atoms as the active growth species. Under N-rich growth conditions, these InGaN films show how compositional uniformity, crystallinity, band edge photoluminescence, and surface morphology are improved as growth temperatures are reduced. The results emphasize the importance of energetic N atoms and lower substrate temperatures for overcoming difficulties associated with growing high-quality In-rich InxGa1−xN thin film materials. Utilizing energetic N atoms allows for the growth of high-quality, thick (>500 nm) InxGa1−xN films at temperatures below 500 °C.
How ITAMs Inhibit Signaling
Authors: Ivashkiv Lionel B.
Published: April 2011

ITAM-mediated inhibition recruits SHP-1 to membrane lipid rafts and diverts activated receptors to an inhibitory intracellular compartment.
pERKing Up the BLIMP in Plasma Cell Differentiation
Authors: Allman David M. , Cancro Michael P.
Published: April 2011

Extracellular signal–regulated kinase is critical for the generation of plasma cells.
One Channel for Pain and Smell
Authors: Gough Nancy R.
Published: April 2011

Without a functional Na
v
1.7 sodium channel, not only is the sense of pain lost, but so is the sense of smell.
No Receptor Necessary
Authors: Adler Elizabeth M.
Published: April 2011

Alum’s adjuvant action depends on signaling pathways initiated by its binding to dendritic cell membrane lipids.
Lipids Influence Hippo Signaling
Authors: VanHook Annalisa M.
Published: April 2011

A phosphatidylinositol 4-kinase is required for proper Merlin localization and Hippo signaling during fly oocyte polarization.
Sustained by Degradation
Authors: Wong Wei
Published: April 2011

A ubiquitin E3 ligase promotes degradation of the regulatory subunit of PKA and thus enhances PKA signaling.
Adenosine Receptor Activation
Authors: Vinson Valda
Published: April 2011

Changes associated with conformationally selective agonist binding shed light on G protein–coupled receptor activation.
Genetic Basis for Daptomycin Resistance in Enterococci
Authors: Palmer Kelli L. , Daniel Anu , Hardy Crystal , Silverman Jared , Gilmore Michael S.
Published: April 2011

The emergence of multidrug-resistant enterococci as a leading cause of hospital-acquired infection is an important public health concern. Little is known about the genetic mechanisms by which enterococci adapt to strong selective pressures, including the use of antibiotics. The lipopeptide antibiotic daptomycin is approved to treat Gram-positive bacterial infections, including those caused by enterococci. Since its introduction, resistance to daptomycin by strains of
Enterococcus faecalis
and
Enterococcus faecium
has been reported but is still rare. We evolved daptomycin-resistant strains of the multidrug-resistant
E. faecalis
strain V583. Based on the availability of a fully closed genome sequence for V583, we used whole-genome resequencing to identify the mutations that became fixed over short time scales (∼2 weeks) upon serial passage in the presence of daptomycin. By comparison of the genome sequences of the three adapted strains to that of parental V583, we identified seven candidate daptomycin resistance genes and three different mutational paths to daptomycin resistance in
E. faecalis
. Mutations in one of the seven candidate genes (EF0631), encoding a putative cardiolipin synthase, were found in each of the adapted
E. faecalis
V583 strains as well as in daptomycin-resistant
E. faecalis
and
E. faecium
clinical isolates. Alleles of EF0631 from daptomycin-resistant strains are dominant in
trans
and confer daptomycin resistance upon a susceptible host. These results demonstrate a mechanism of enterococcal daptomycin resistance that is genetically distinct from that occurring in staphylococci and indicate that enterococci possessing alternate EF0631 alleles are selected for during daptomycin therapy. However, our analysis of
E. faecalis
clinical isolates indicates that resistance pathways independent from mutant forms of EF0631 also exist.
Pharmacological Properties of the Marine Natural Product Marinopyrrole A against Methicillin-Resistant Staphylococcus aureus
Authors: Haste Nina M. , Hughes Chambers C. , Tran Dan N. , Fenical William , Jensen Paul R. , Nizet Victor , Hensler Mary E.
Published: April 2011

The ongoing spread of methicillin-resistant
Staphylococcus aureus
(MRSA) strains in hospital and community settings presents a great challenge to public health and illustrates the urgency of discovering new antibiotics. Marinopyrrole A is a member of a structurally novel class of compounds identified from a species of marine-derived streptomycetes with evidence of antistaphylococcal activity. We show that marinopyrrole A has potent concentration-dependent bactericidal activity against clinically relevant hospital- and community-acquired MRSA strains, a prolonged postantibiotic effect superior to that of the current first-line agents vancomycin and linezolid, and a favorable resistance profile. Marinopyrrole A showed limited toxicity to mammalian cell lines (at >20× MIC). However, its antibiotic activity against MRSA was effectively neutralized by 20% human serum. A variety of marinopyrrole analogs were isolated from culture or synthetically produced to try to overcome the inhibitory effect of serum. While many of these compounds retained potent bactericidal effect against MRSA, their activities were also inhibited by serum. Marinopyrrole A has significant affinity for plastic and may therefore have potential as a potent anti-MRSA agent in cutaneous, intracatheter, or antibiotic-lock applications.
β-Lactams Interfering with PBP1 Induce Panton-Valentine Leukocidin Expression by Triggering
sarA
and
rot
Global Regulators of Staphylococcus aureus
Authors: Dumitrescu Oana , Choudhury Priya , Boisset Sandrine , Badiou Cédric , Bes Michele , Benito Yvonne , Wolz Christiane , Vandenesch François , Etienne Jerome , Cheung Ambrose L. , Bowden Maria Gabriela , Lina Gerard
Published: April 2011

Previous articles reported that beta-lactam antibiotics increase the expression of
Staphylococcus aureus
Panton-Valentine leukocidin (PVL) by activating its transcription. We investigated the mechanisms underlying the inductor effect of beta-lactams on PVL expression by determining targets and regulatory pathways possibly implicated in this process. We measured PVL production in the presence of oxacillin (nonselective), imipenem (penicillin-binding protein 1 [PBP1] selective), cefotaxime (PBP2 selective), cefaclore (PBP3 selective), and cefoxitin (PBP4 selective).
In vitro
, we observed increased PVL production consistent with
luk
-PV mRNA levels that were 20 to 25 times higher for community-acquired methicillin-resistant
S. aureus
(CA-MRSA) cultures treated with PBP1-binding oxacillin and imipenem than for cultures treated with other beta-lactams or no antibiotic at all. This effect was also observed
in vivo
, with increased PVL mRNA levels in lung tissues from CA-MRSA-infected mice treated with imipenem but not cefoxitin. To confirm the involvement of PBP1 inhibition in this pathway, PBP1 depletion by use of an inducible
pbp1
antisense RNA showed a dose-dependent relationship between the level of
pbp1
antisense RNA and the
luk
-PV mRNA level. Upon imipenem treatment of exponential-phase cultures, we observed an increased
sarA
mRNA level after 30 min of incubation followed by a decreased
rot
mRNA level after 1 to 4 h of incubation. Unlike the
agr
and
saeRS
positive regulators, which were nonessential for PVL induction by beta-lactams, the
sarA
(positive) and
rot
(negative) PVL regulators were necessary for PVL induction by imipenem. Our results suggest that antibiotics binding to PBP1 increase PVL expression by modulating
sarA
and
rot
, which are essential mediators of the inductor effect of beta-lactams on PVL expression.
Preferential Emergence of Reduced Vancomycin Susceptibility in Health Care-Associated Methicillin-Resistant Staphylococcus aureus Isolates during Continuous-Infusion Vancomycin Therapy in an
In Vitro
Dynamic Model
Authors: Zelenitsky Sheryl , Alkurdi Noha , Weber Zhanni , Ariano Robert , Zhanel George
Published: April 2011

Bacterial killing and the development of reduced vancomycin susceptibility during continuous-infusion vancomycin (CIV) therapy were dependent on the area under the concentration-time curve over 24 h divided by the MIC (ƒAUC
24
/MIC), with values of ≥240 (equivalent total serum AUC
24
/MICs of ≥480) being bactericidal and suppressing emerging resistance in methicillin-resistant
Staphylococcus aureus
(MRSA). Also, vancomycin therapy was less likely to be bactericidal and 4.4 times more likely to lead to reduced vancomycin susceptibility in health care-associated MRSA than in community-associated MRSA.
Failure of Posaconazole Therapy in a Renal Transplant Patient with Invasive Aspergillosis Due to Aspergillus fumigatus with Attenuated Susceptibility to Posaconazole
Authors: Kuipers Saskia , Brüggemann Roger J. M. , de Sévaux Ruud G. L. , Heesakkers John P. F. A. , Melchers Willem J. G. , Mouton Johan W. , Verweij Paul E.
Published: April 2011

We report the case of a kidney transplant recipient with invasive aspergillosis due to
Aspergillus fumigatus
resistant to voriconazole and intermediately susceptible to posaconazole who failed posaconazole therapy. Plasma posaconazole concentrations indicated an unfavorable ratio of the area under the concentration-time curve over the MIC. Posaconazole should be used with caution for invasive aspergillosis caused by strains with attenuated posaconazole susceptibility, as drug exposure may be inadequate, resulting in therapeutic failure.
In Vivo
Pharmacodynamics of Torezolid Phosphate (TR-701), a New Oxazolidinone Antibiotic, against Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Strains in a Mouse Thigh Infection Model
Authors: Louie Arnold , Liu Weiguo , Kulawy Robert , Drusano G. L.
Published: April 2011

Torezolid phosphate (TR-701) is the phosphate monoester prodrug of the oxazolidinone TR-700 which demonstrates potent
in vitro
activity against Gram-positive bacteria, including methicillin-susceptible
Staphylococcus aureus
(MSSA) and methicillin-resistant
S. aureus
(MRSA). The pharmacodynamics of TR-701 or TR-700 (TR-701/700) against
S. aureus
is incompletely defined. Single-dose pharmacokinetic studies were conducted in mice for TR-701/700. Forty-eight-hour dose range and 24-hour dose fractionation studies were conducted in a neutropenic mouse thigh model of
S. aureus
infection using MRSA ATCC 33591 to identify the dose and schedule of administration of TR-701/700 that was linked with optimized antimicrobial effect. Additional dose range studies compared the efficacies of TR-701/700 and linezolid for one MSSA strain and one community-associated MRSA strain. In dose range studies, TR-701/700 was equally bactericidal against MSSA and MRSA. Mean doses of 37.6 and 66.9 mg/kg of body weight/day of TR-701/700 resulted in stasis and 1 log CFU/g decreases in bacterial densities, respectively, at 24 h, and mean doses of 35.3, 46.6, and 71.1 mg/kg/day resulted in stasis and 1 and 2 log CFU/g reductions, respectively, at 48 h. Linezolid administered at doses as high as 150 mg/kg/day did not achieve stasis at either time point. Dose fractionation studies demonstrated that the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the pharmacodynamic index for TR-701/700 that was linked with efficacy. TR-701/700 was highly active against MSSA and MRSA,
in vivo
, and was substantially more efficacious than linezolid, although linezolid's top exposure has half the human exposure. Dose fractionation studies showed that AUC/MIC was the pharmacodynamic index linked with efficacy, indicating that once-daily dosing in humans is feasible.
Synergistic Combination of Chitosan Acetate with Nanoparticle Silver as a Topical Antimicrobial: Efficacy against Bacterial Burn Infections
Authors: Huang Liyi , Dai Tianhong , Xuan Yi , Tegos George P. , Hamblin Michael R.
Published: April 2011

Chitosan and nanoparticle silver are both materials with demonstrated antimicrobial properties and have been proposed singly or in combination as constituents of antimicrobial burn dressings. Here, we show that they combine synergistically to inhibit the
in vitro
growth of Gram-positive methicillin-resistant
Staphylococcus aureus
(MRSA) and Gram-negative bacteria (
Pseudomonas aeruginosa
,
Proteus mirabilis
, and
Acinetobacter baumannii
), as judged by bioluminescence monitoring and isobolographic analysis, and also produce synergistic killing after 30 min of incubation, as measured by a CFU assay. The hypothesized explanation involves chitosan-mediated permeabilization of bacterial cells, allowing better penetration of silver ions into the cell. A dressing composed of freeze-dried chitosan acetate incorporating nanoparticle silver was compared with a dressing of chitosan acetate alone in an
in vivo
burn model infected with bioluminescent
P. aeruginosa
. The survival rates of mice treated with silver-chitosan or regular chitosan or left untreated were 64.3% (
P
= 0.0082 versus regular chitosan and
P
= 0.0003 versus the control), 21.4%, and 0%, respectively. Most of the fatalities occurred between 2 and 5 days postinfection. Silver-chitosan dressings effectively controlled the development of systemic sepsis, as shown by blood culture. These data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections.
Shift in Ribonucleotide Reductase Gene Expression in Pseudomonas aeruginosa during Infection
Authors: Sjöberg Britt-Marie , Torrents Eduard
Published: April 2011

The roles of different ribonucleotide reductases (RNRs) in bacterial pathogenesis have not been studied systematically. In this work we analyzed the importance of the different
Pseudomonas aeruginosa
RNRs in pathogenesis using the
Drosophila melanogaster
host-pathogen interaction model.
P. aeruginosa
codes for three different RNRs with different environmental requirements. Class II and III RNR chromosomal mutants exhibited reduced virulence in this model. Translational reporter fusions of RNR gene
nrdA
,
nrdJ
, or
nrdD
to the green fluorescent protein were constructed to measure the expression of each class during the infection process. Analysis of the
P. aeruginosa
infection by flow cytometry revealed increased expression of
nrdJ
and
nrdD
and decreased
nrdA
expression during the infection process. Expression of each RNR class fits with the pathogenicities of the chromosomal deletion mutants. An extended understanding of the pathogenicity and physiology of
P. aeruginosa
will be important for the development of novel drugs against infections in cystic fibrosis patients.
Smoke-free college campuses: no ifs, ands or toxic butts: Figure 1
Authors: Sawdey Michael , Lindsay Ryan P , Novotny Thomas E
Published: April 2011

Objective

To better estimate the burden of toxic cigarette butt waste and create awareness of the hazardous nature of cigarette butts on two large university campuses in San Diego by organizing and conducting student cigarette butt clean-up activities.

Methods

Two separate campus-wide clean-ups were conducted by student volunteers at San Diego State University (SDSU) and at University of California San Diego (UCSD) between April and July 2010.

Results

In 1 h, 63 volunteers at SDSU collected 23 885 butts; 6525 cigarette butts were collected in 1 h by 17 volunteers at UCSD. The average number of cigarette butts picked up per individual was 379.1 at SDSU and 383.8 at UCSD (range 25–1030 per volunteer).

Conclusions

The amount of cigarette waste on college campuses nationally may be quite substantial given the many thousands of cigarette butts gathered at each of the San Diego institutions. In just 10 s on average a volunteer could locate, walk to, pick up and put a cigarette butt in the collection bag and then begin looking for another discarded butt, indicating the saturation of cigarette butts on campus. Smoke-free policies on campus could have far-reaching effects not only in reducing smoking behaviour on campus and ground clean-up costs, but also on the environment. Campus cigarette waste clean-ups can be utilized to call attention to the issue of cigarette butt waste in the environment.
Toxicity of cigarette butts, and their chemical components, to marine and freshwater fish
Authors: Slaughter Elli , Gersberg Richard M , Watanabe Kayo , Rudolph John , Stransky Chris , Novotny Thomas E
Published: April 2011

Background

Cigarette butts are the most common form of litter, as an estimated 4.5 trillion cigarette butts are thrown away every year worldwide. Many chemical products are used during the course of growing tobacco and manufacturing cigarettes, the residues of which may be found in cigarettes prepared for consumption. Additionally, over 4000 chemicals may also be introduced to the environment via cigarette particulate matter (tar) and mainstream smoke.

Methods

Using US Environmental Protection Agency standard acute fish bioassays, cigarette butt-derived leachate was analysed for aquatic toxicity. Survival was the single endpoint and data were analysed using Comprehensive Environmental Toxicity Information System to identify the LC50 of cigarette butt leachate to fish.

Results

The LC50 for leachate from smoked cigarette butts (smoked filter + tobacco) was approximately one cigarette butt/l for both the marine topsmelt (Atherinops affinis) and the freshwater fathead minnow (Pimephales promelas). Leachate from smoked cigarette filters (no tobacco), was less toxic, with LC50 values of 1.8 and 4.3 cigarette butts/l, respectively for both fish species. Unsmoked cigarette filters (no tobacco) were also found to be toxic, with LC50 values of 5.1 and 13.5 cigarette butts/l, respectively, for both fish species.

Conclusion

Toxicity of cigarette butt leachate was found to increase from unsmoked cigarette filters (no tobacco) to smoked cigarette filters (no tobacco) to smoked cigarette butts (smoked filter + tobacco). This study represents the first in the literature to investigate and affirm the toxicity of cigarette butts to fish, and will assist in assessing the potential ecological risks of cigarette butts to the aquatic environment.
Analysis of metals leached from smoked cigarette litter
Authors: Moerman J W , Potts G E
Published: April 2011

Background

Littered cigarette butts represent potential point sources for environmental contamination. In areas with substantial amounts of cigarette litter, environmental hazards may arise as chemical components are leached from the filters and smoked tobacco.

Objective

The three main aims of this study were: (1) to quantify the amount of Al, Ba, Cd, Cr, Cu, Fe, Pb, Mn, Ni, Sr, Ti and Zn leached from cigarette butts, (2) to determine the relationship between the pH of the aqueous soaking solution and metal concentration leached and (3) to determine the relationship between the period of soaking in aqueous solution and metal concentration leached.

Methods

Smoked cigarette butts and unsmoked cigarettes were added to phials containing aqueous solutions of pH 4.00, 5.00 and 6.00 (±0.05). The metal concentration of the resultant leachates was measured via inductively coupled plasma optical emission spectroscopy (ICP-OES) 1 day, 7 days and 34 days after sample addition.

Results

All metals were detected in leachates 1 day after sample addition (with the exception of Cd) and were released at varying rates. No clear relationship between pH within the range typical of precipitation and metal concentration leached was observed.

Conclusions

Based on the gradual release of multiple metals over the full 34-day study period, cigarette litter was found to be a point source for metal contamination. The apparent rapid leaching of other metals may increase the risk of acute harm to local organisms.