bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasmodium falciparum-Infected Erythrocytes and β-Hematin Induce Partial Maturation of Human Dendritic Cells and Increase Their Migratory Ability in Response to Lymphoid Chemokines
Authors: Giusti Pablo , Urban Britta C. , Frascaroli Giada , Albrecht Letusa , Tinti Anna , Troye-Blomberg Marita , Varani Stefania
Published: April 2011

Acute and chronicPlasmodium falciparuminfections alter the immune competence of the host possibly through changes in dendritic cell (DC) functionality. DCs are the most potent activators of T cells, and migration is integral to their function. Mature DCs express lymphoid chemokine receptors (CCRs), expression of which enables them to migrate to the lymph nodes, where they encounter naïve T cells. The present study aimed to investigate the impact of the synthetic analog to malaria parasite pigment hemozoin, i.e., β-hematin, or infected erythrocytes (iRBCs) on the activation status of human monocyte-derived DCs and on their expression of CCRs. Human monocyte-derived DCs partially matured upon incubation with β-hematin as indicated by an increased expression of CD80 and CD83. Both β-hematin and iRBCs provoked the release of proinflammatory and anti-inflammatory cytokines, such as interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha, but not IL-12, and induced upregulation of the lymphoid chemokine receptor CXCR4, which was coupled to an increased migration to lymphoid ligands. Taken together, these results suggest that the partial and transient maturation of human myeloid DCs upon stimulation with malaria parasite-derived products and the increased IL-10 but lack of IL-12 secretion may lead to suboptimal activation of T cells. This may in turn lead to impaired adaptive immune responses and therefore insufficient clearance of the parasites.
TOPOLOGY PROPERTY AND DYNAMIC BEHAVIOR OF A GROWING SPATIAL NETWORK
Authors: CAO XIAN-BIN , DU WEN-BO , HU MAO-BIN , RONG ZHI-HAI , SUN PENG , CHEN CAI-LONG
Published: April 2011

In this paper, we propose a growing spatial network (GSN) model and investigate its topology properties and dynamical behaviors. The model is generated by adding one node i with m links into a square lattice at each time step and the new node i is connected to the existing nodes with probabilities proportional to: [Formula: see text], where kj is the degree of node j, α is the tunable parameter and dij is the Euclidean distance between i and j. It is found that both the degree heterogeneity and the clustering coefficient monotonously increase with the increment of α, while the average shortest path length monotonously decreases. Moreover, the evolutionary game dynamics and network traffic dynamics are investigated. Simulation results show that the value of α can also greatly influence the dynamic behaviors.
TRANSPORT EFFICIENCY OF PASSIVE DIFFUSION OF VIRAL CARGOS IN BIOLOGICAL CELLS
Authors: PASTOR MARISSA G. , BANTANG JOHNROB Y.
Published: April 2011

Using in silico experiments, we isolate the effects of geometry on the efficiency of passive diffusion transport, PS, of viral cargos to the nuclear region. We model the cell as an elliptical 2D structure (eccentricity e) containing a circular nucleus with radii R (semi-minor) and r, respectively. The cargos move in isotropic random walk inside the cell. PS is estimated as the ratio of the number of cargos that reach the nuclear region and of cargos released. We show that PS decreases with the total distance traveled but increases with r/R. Shifting the nuclear position inside circular cells (e = 0) produce probability distribution functions of total distance traveled that shifts to shorter modes as one side becomes closer to the cell membrane. On the contrary, cargos in more elongated cells (e = 0) have preserved PS-values even for longer distances of travel inside the cell. Finally, an optimum r/R exists due to a trade-off between increased efficiency of transport to the nucleus and high cytoplasmic area. This work could contribute in elucidating the reason why some viruses induce asymmetry in their host cells.
STOCHASTIC TIME DELAYS IN REGULATORY NETWORKS AND MODEL REDUCTION
Authors: DIAZ OCHOA JUAN G.
Published: April 2011

Stochastic time delays and asynchronism in regulatory networks is an ubiquitous phenomena in biology, in particular in regulatory networks. However, this phenomena is poorly understood. In particular, variable-stochastic time intervals in the realization of chemical reactions have a crucial effect in the dynamics of the system. I analyze the effect that different time delays in feedback loops can have in the transient behavior of a regulatory network. Using a simple toy model for a regulatory network with forcing I show that such time delays introduce an oscillatory behavior that can alternatively be explained if additional loops are defined. The results suggest that the introduction of time delays is a mechanism that is helpful to theoretically reduce the number of elements, in particular the number of feedback loops, in competing network models.
UNIVERSAL MASS MATRIX AND LEPTONIC θ13 ANGLE
Authors: NISHIURA HIROYUKI , FUKUYAMA TAKESHI
Published: April 2011

We propose a universal mixing hypothesis between quark and lepton sectors at high energy scale (probably GUT scale) where quark–lepton universality holds. Namely in the charged lepton diagonal base, all the other mass matrices for up and down quarks and neutrinos are diagonalized by the same unitary matrix except for the phase elements. Thanks to this hypothesis, the observed values of the Cabibbo–Kobayashi–Maskawa (CKM) quark mixing matrix and the mixing angles θ12 and θ23 in the Maki–Nakagawa–Sakata (MNS) lepton mixing matrix can predict the unknown magnitudes of the mixing angle θ13 and of the CP violating Dirac phase δ in the MNS matrix. Their allowed regions are rather narrow, 0.036 < sin θ13 < 0.048 and 6° < δ < 12°.
MODELING AND PARAMETER ESTIMATION OF TUBERCULOSIS WITH APPLICATION TO CAMEROON
Authors: BOWONG SAMUEL , KURTHS JURGEN
Published: April 2011

This paper deals with the problem of modeling and parameter estimation of a deterministic model of tuberculosis (abbreviated as TB for tubercle bacillus). We first propose and analyze a tuberculosis model without seasonality that incorporates the essential biological and epidemiological features of the disease. The model is shown to exhibit the phenomenon of backward bifurcation, where a stable disease-free equilibrium coexists with one or more stable endemic equilibria when the associated basic reproduction number is less than unity. The statistical data of new TB cases show seasonal fluctuations in many countries. Then, we extend the proposed TB model by incorporating seasonality. We propose a numerical study to estimate unknown parameters according to demographic and epidemiological data in Cameroon. Simulation results are in good accordance with the seasonal variation of the reported new cases of active TB in Cameroon.
A TABULATION OF PRIME KNOTS UP TO ARC INDEX 11
Authors: JIN GYO TAEK , PARK WANG KEUN
Published: April 2011

As a supplement to the paper [Prime knots with arc index up to 11 and an upper bound of arc index for non-alternating knots, J. Knot Theory Ramifications19(12) (2010) 1655–1672], we present minimal arc presentations of the prime knots up to arc index 11.
BOUNDARY COMPONENT PRESERVING SYMMETRIES OF GRAPH LINK EXTERIORS
Authors: IKEDA TORU
Published: April 2011

We consider a graph link L in S3which admits a symmetry of the exterior given by a boundary component preserving periodic homeomorphism f (orientation-preserving or not). This paper shows that L is obtained by a specific construction method if f is not a strong inversion. As an application, we provide a complete classification of 2-component graph links with symmetries of the exteriors which are not extendable to symmetries of S3.
INVARIANTS OF FLAT VIRTUAL LINKS INDUCED FROM VASSILIEV INVARIANTS OF DEGREE ONE FOR VIRTUAL LINKS
Authors: IM YOUNG HO , KIM SERA , LEE KYEONGHUI
Published: April 2011

We introduce invariants of flat virtual links which are induced from Vassiliev invariants of degree one for virtual links. Also we give several properties of these invariants for flat virtual links and examples. In particular, if the value of some invariants of flat virtual knots F are non-zero, then F is non-invertible so that every virtual knot overlying F is non-invertible.
ENERGY SYSTEMATICS OF HEAVY NUCLEI — MEAN FIELD MODELS IN COMPARISON
Authors: REINHARD P.-G. , AGRAWAL B. K.
Published: April 2011

We compare the systematics of binding energies computed within the standard and extended versions of the relativistic mean-field (RMF) model and the Skyrme–Hartree–Fock (SHF) model. The general trends for the binding energies for super-heavy nuclei are significantly different for these models. The SHF models tend to underbind the superheavy nuclei, while RMF models show just the opposite trend. The extended RMF model seems to provide remarkable improvements over the results obtained for the standard RMF model.
The Effect of Knowledge Management, Technological Capability and Innovation on the Enterprise Performance: A Comprehensive Emperical Study of the Turkish Textile Sector
Authors: Gökmen Aytaç , Hamşioğlu Ahmet Buğra
Published: April 2011

This study aims to analyse the correlation among enterprise performance, knowledge management, technological capability and innovation. The sample of the study comprised 96 textile enterprises among the 500 largest companies in Turkey. Among those 96 companies, 45 of them responded to the research proposal and 225 questionnaires were assessed. The data acquired was analysed with factor analysis, correlation analysis, regression analysis and descriptive analysis. As a result of the research, a high level and significant correlation among the variables was established and the positive effect of knowledge management and technological capability on innovation was detected. Moreover, innovation was found to have a positive effect on performance as well.
Effect of hydrogen bonding on catalytic activity of some manganese porphyrins in epoxidation reactions
Authors: Alemohammad Tahereh , Safari Nasser , Osati Samira
Published: April 2011

Mn (III)-tetra phenyl porphyrin-acetate (MnTPPOAc) and some kinds of meso-phenyl substituted porphyrins by hydroxyl groups and their Mn (III) complexes were synthesized. These Mn -porphyrins were used as catalyst in the epoxidation of various alkenes with tetra-n-butylammonium hydrogen monopersulfate (n- Bu4NHSO5 ) as oxidant and tetra-n-butylammonium acetate (n- Bu4NOAc ) as the axial ligand. The following order of catalytic activity was observed for cyclooctene: T(2,3-OHP)PMnOAc ≫ T(2,4,6-OHP)PMnOAc ≥ T(4-OHP)PMnOAc ≥ T(2,6-OHP)PMnOAc ≥ TPPMnOAc and T(2,3-OHP)PMnOAc ≫ TPPMnOAc > T(4-OHP)PMnOAc > T(2,4,6-OHP)PMnOAc > T(2,6-OHP)PMnOAc for other alkenes. Different activity and stability of the catalysts were interpreted based on the hydrogen bonding between hydroxyl groups with appropriate orientation on the meso-position of the phenyl groups and axial bases or oxidant. T(2,3-OHP)PMnOAc catalyst has shown optimal condition for effective hydrogen bonding. In the case of other catalysts, electronic and steric factors overcome the hydrogen bonding effect.
Short-Term Exposure to Tobacco Toxins Alters Expression of Multiple Proliferation Gene Markers in Primary Human Bronchial Epithelial Cell Cultures
Authors: Chaudhry Imran S. , El-Meanawy Ashraf , Khiyami Amer , Tomashefski Joseph F. , Machekano Rhoderick N. , Kass Lawrence
Published: April 2011

The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(b)fluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). After a 24-hour exposure,EGFRwas expressed in cell membrane and cytoplasm,BCL-2was expressed only in the irregular nuclei of large atypical cells,MKI67was expressed in nuclei with no staining in larger cells, cytoplasmicBIRC5with stronger nuclear staining was seen in large atypical cells, and nuclearTP53was strongly expressed in all cells. After only a 24-hour exposure, cells exhibited atypical nuclear and cytoplasmic features. After a 48-hour exposure,EGFRstaining was localized to the nucleus,BCL-2was slightly decreased in intensity,BIRC5was localized to the cytoplasm, andTP53staining was increased in small and large cells.BCL2L1was expressed in both the cytoplasm and nuclei of cells at 24- and 48-hour exposures. We illustrate that short-termexposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens alters the expression of key proliferation regulatory genes,EGFR, BCL-2, BCL2L1, BIRC5, TP53, andMKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions.
Maximizing the Mean Exit Time of a Brownian Motion from an Interval
Authors: Lefebvre Mario
Published: April 2011

Let X(t) be a controlled one-dimensional standard Brownian motion starting from x∈(−d,d). The problem of optimally controlling X(t) until |X(t)|=d for the first time is solved explicitly in a particular case. The maximal value that the instantaneous reward given for survival in (−d,d) can take is determined.
A New Era in Mental Health Care in Vanuatu
Authors: Benson Jill , Pond Dimity , Funk Michelle , Hughes Frances , Wang Xiangdong , Tarivonda Len
Published: April 2011

Inequity in health-care delivery for those with mental illness is widespread throughout low- and middle-income countries. In the Pacific Island countries there are many barriers to addressing the growing mental health burden. In an effort to address this problem, the WHO is coordinating the Pacific Islands Mental Health Network involving 18 countries in the Pacific region with the financial support of New Zealand Aid (NZAid). JB and DP have developed and presented mental health training to health professionals, community leaders, and social service personnel in an environment in Vanuatu that is very different from that of their usual Australian-based general practices. They discuss evidence for their work, an outline of the programme, some difficulties working across different cultures, and the enthusiasm with which the training has been greeted. Vanuatu is now well on its way to addressing the inequity of access to mental health care with a culturally appropriate and self-sustaining mental health workforce.
Increased Adiposity and Altered Adipocyte Function in Female Survivors of Childhood Acute Lymphoblastic Leukaemia Treated without Cranial Radiation
Authors: Kohler J.A. , Moon R.J. , Wright S. , Willows E. , Davies J.H.
Published: April 2011

Background: Excess adiposity is a complication of childhood acute lymphoblastic leukaemia (ALL) and is commonly attributed to cranial radiation (CRT) administration. Hyperleptinaemia also occurs during ALL treatment, but there are no data on long-term alterations to adipocytokines following treatment without CRT. Methods: Fifty-four survivors (50% female) and 51 controls (59% female) were recruited. Body composition assessment was by BMI, air displacement plethysmography (BODPOD), bioelectrical impedance analysis (BIA) and skinfold thickness (SFT). Fasting blood samples were analysed for adipocytokines (leptin, adiponectin, resistin, tumour necrosis factor-α, interleukin-6). Results: The BMI standard deviation score (0.71 vs. 0.04, p < 0.05) and fat percentage measured by BIA (29.8% vs. 24.6%, p = 0.01) and SFT (31.7% vs. 28.2%, p = 0.007) were greater in female survivors compared with controls. Adiposity was similar in male survivors and controls. Absolute leptin (17.8 vs. 7.8 ng/ml, p = 0.01) and fat-adjusted leptin concentrations (p < 0.05) were higher in female survivors compared to controls. Female survivors were less insulin sensitive than controls (p = 0.02). These findings were not observed in males. There were no differences in the other adipocytokines between survivors and controls. Conclusions: Long-term unfavourable alterations to body composition and adipocyte function are observed in female, but not male, survivors of ALL treatment without CRT.
High-Resolution Ultrasound Combined with Power Doppler Sonography Can Reduce the Number of Sentinel Lymph Node Biopsies in Cutaneous Melanoma
Authors: Hinz Torsten , Wilsmann-Theis Dagmar , Buchner Andrea , Wenzel Joerg , Wendtner Clemens-M. , Bieber Thomas , Reinhard Guenter , Baumert Jens , Schmid-Wendtner Monika-H.
Published: April 2011

Background: Sentinel lymph node biopsy (SLNB) is a widely accepted procedure to accurately stage patients with cutaneous melanoma. Disadvantages of the SLNB procedure are the overall costs and potential side effects of the operation [J Dtsch Dermatol Ges 2009;7:318–327; J Am Dermatol 2010;62:737–748]. Objective: The purpose of our study was to evaluate whether high-resolution ultrasound combined with power Doppler sonography (PDS) is an appropriate tool for preoperative identification and characterization of sentinel lymph nodes (SLNs) in patients with cutaneous melanoma. Methods: In a prospective study eighty-one consecutive patients with cutaneous melanoma (33 females and 48 males) in whom dissection of SLNs was indicated underwent ultrasound examinations before and after the preoperative lymphoscintigraphy. Results: A total of 170 SLNs (mean 2.1 per patient) were removed and examined by histopathology. High resolution ultrasound combined with PDS correctly identified 2 of 9 positive SLNs. The sensitivity, specifity, positive predictive value, and negative predictive values of ultrasound were 22.2% (95% confidence interval (CI) = 2.8–60.0), 100% (95% CI = 97.7–100.0), 100.0% (95% CI = 15.8–100.0), and 95.8% (95% CI = 91.6–98.3), respectively. Conclusions: Although high-resolution ultrasound combined with PDS cannot substitute SLNB, this technique offers earlier diagnosis of lymph node involvement in a small subgroup of patients (with subcapsular location of metastases), and introduces the possibility to exclude those patients from SLN procedure and directly prepare them for complete lymph node dissection (CLND).
Normative Values for Testicular Volume Measured by Ultrasonography in a Normal Population from Infancy to Adolescence
Authors: Goede J. , Hack W.W.M. , Sijstermans K. , van der Voort-Doedens L.M. , Van der Ploeg T. , Meij-de Vries A. , Delemarre-van de Waal H.A.
Published: April 2011

Background/Aims: We obtained reference data for testicular volume measured by ultrasound in asymptomatic boys aged 0.5–18 years. In addition, we assessed the validity of the Prader orchidometer per age group by correlating it with the volume measurement by ultrasound. Methods: The study only included healthy boys with two scrotal testes at birth and at the time of the examination. For each boy the testicular volume of both testes was measured by ultrasound and the Prader orchidometer. Testicular volumes were measured for boys aged from 1 to 18 years. The boys’ ages were rounded down to the last birthday if it had occurred less than 6 months previously or rounded up to the next birthday if it was going to be within 6 months. Results: The volume measurement by the Prader orchidometer according to reference curves showed a statistically significant correlation. Moreover, the testicular volumes measured by the Prader orchidometer showed an accurate goodness of fit with US measurements (R2 = 0.956). Conclusion: Normative values are provided for testicular volume measured by ultrasound in boys aged 0.5–18 years. An accurate correlation was found between volume measurements by ultrasound and by the Prader orchidometer (R2 = 0.956). Therefore, volume measurement by the Prader orchidometer, as generally used in the practice by doctors, can be used as a valid parameter for monitoring testicular growth.
Hairy Pinnae after Orchiectomy and Chemotherapy for Testicular Cancer: Acquired Localized Hypertrichosis of the Ears
Authors: Sänger C.F.E. , Dietrich N. , Pelivani N. , Borradori L. , de Viragh P.A.
Published: April 2011

Acquired localized hypertrichosis has rarely been reported. Here, we describe a patient with localized hypertrichosis of the pinnae that occurred 4 months after orchiectomy and chemotherapy for a testicular carcinoma. To our knowledge, this is the first case of an acquired hypertrichosis of the pinnae after cancer therapy. We propose that in our patient either hypogonadism or the hormonal imbalance caused by the cancer therapy led to the development of the hairy pinnae, perhaps alongside a genetic predisposition for hairy ears.
Mortality Associated With Atrial Fibrillation in Patients With Myocardial Infarction
Authors: Jabre Patricia , Roger Véronique L. , Murad Mohammad H. , Chamberlain Alanna M. , Prokop Larry , Adnet Frédéric , Jouven Xavier
Published: April 2011

Background—

Atrial fibrillation (AF) is a common finding in patients with myocardial infarction (MI). Atrial fibrillation is not generally perceived by clinicians as a critical event during the acute phase of MI; however, its prognostic influence in MI remains controversial. Furthermore, contradictory data exist concerning the risk of death according to AF timing. This article, a systematic review and first meta-analysis, aims to quantify the mortality risk associated with AF in MI patients and its timing.

Methods and Results—

A comprehensive search of several electronic databases (1970 to 2010; adults, any language) identified MI studies that evaluated mortality related to AF. Evidence was reviewed by 2 blinded reviewers with a formal assessment of the methodological quality of the studies. Adjusted odds ratios were pooled across studies using the random-effects model. The I
2
statistic was used to assess heterogeneity. In the 43 included studies (278 854 subjects), the mortality odds ratio associated with AF was 1.46 (95% confidence interval, 1.35 to 1.58; I
2
=76%; 23 studies). This worse prognosis persisted regardless of the timing of AF; the odds ratio of mortality for new AF with no prior history of AF was 1.37 (95% confidence interval, 1.26 to 1.49), I
2
=28%, 9 studies), and for prior AF was 1.28 (95% confidence interval, 1.16 to 1.40; I
2
=24%; 4 studies). The sensitivity analysis of new AF studies adjusting for confounding factors did not show a decrease in risk of death.

Conclusions—

Atrial fibrillation is associated with increased risk of mortality in MI patients. New AF with no history of AF before MI remained associated with an increased risk of mortality even after adjustment for several important AF risk factors. These subsequent increases in mortality suggest that AF can no longer be considered a nonsevere event during MI.
Inhibition of the AMP-Activated Protein Kinase-α2 Accentuates Agonist-Induced Vascular Smooth Muscle Contraction and High Blood Pressure in Mice
Authors: Wang Shuangxi , Liang Bin , Viollet Benoit , Zou Ming-Hui
Published: April 2011

The aim of the present study was to determine the effects and molecular mechanisms by which AMP-activated protein kinase (AMPK) regulates smooth muscle contraction and blood pressure in mice. In cultured human vascular smooth muscle cells, we observed that activation of AMPK by 5-aminoimidazole-4-carboxamide 1-β-
d
-ribofuranoside inhibited agonist-induced phosphorylation of myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1). Conversely, AMPK inhibition with pharmacological or genetic means potentiated agonist-induced the phosphorylation of MLC and MYPT1, whereas it inhibited both Ras homolog gene family member A and Rho-associated kinase activity. In addition, AMPK activation or Rho-associated kinase inhibition with Y27632 abolished agonist-induced phosphorylation of MLC and MYPT1. Gene silencing of p190-guanosine triphosphatase-activating protein abolished the effects of AMPK activation on MLC, MYPT1, and Ras homolog gene family member A in human smooth muscle cells. Ex vivo analyses revealed that agonist-induced contractions of the mesenteric artery and aortas were stronger in both AMPKα1
−/−
and AMPKα2
−/−
knockout mice than in wild-type mice. Inhibition of Rho-associated kinase with Y27632 normalized agonist-induced contractions of AMPKα1
−/−
and AMPKα2
−/−
vessels. AMPKα2
−/−
mice had higher blood pressure along with decreased serine phosphorylation of p190-guanosine triphosphatase–activating protein. Finally, inhibition of the Ras homolog gene family member A/Rho-associated kinase pathway with Y27632, which suppressed MYPT1 and MLC phosphorylation, lowered blood pressure in AMPKα2
−/−
mice. In conclusion, AMPK decreases vascular smooth muscle cell contractility by inhibiting p190-GTP-activating protein–dependent Ras homolog gene family member A activation, indicating that AMPK may be a new therapeutic target in lowering high blood pressure.
Prognostic value of demographic factors, pre-test probability scoring, exercise test diagnosis, and inability to exercise in patients with recent onset suspected cardiac chest pain
Authors: Khattar Rajdeep S , Nair Satheesh B , Hamid Tahir , Chacko Sanoj , Mamas Mamas , Turkie Wajdi , Arumugam Parthiban
Published: April 2011

Aims: To assess the prognostic value of an inconclusive exercise test or inability to exercise in patients with recent onset suspected cardiac chest pain and to determine the independent predictors of events in these patients.

Methods: This was an observational follow-up study of patients presenting to a rapid access chest pain clinic with a history of recent-onset suspected cardiac chest pain as referred by the family practitioner. The main outcome measure was a composite endpoint of death and acute coronary syndrome hospital admission.

Results: The study cohort consisted of 1851 patients in whom a total of 147 events were recorded during a mean follow-up period of 4.1 ± 1.1 years. Those with events were significantly older (65.1 ± 12.5 years versus 56.4 ± 13.2 years, p < 0.001), had higher mean pre-test probability of coronary artery disease (CAD), and had higher prevalence of diabetes (18.4% vs. 13.6%, p < 0.001), hypertension (55.8% vs. 38.7%, p < 0.001), and smoking (36.7% vs. 25.4%, p = 0.03) than those without events. These patients were also more likely to have a positive exercise electrocardiogram (ECG) (15.6% vs. 8.6%, p < 0.001) or not have a diagnostic exercise test because of an inconclusive result or inability to exercise (60.5% vs. 28.6%, p < 0.001). Cox multivariate regression analysis showed that age (hazard ratio, HR 1.03, p < 0.001), pre-test probability of CAD (HR 1.08, p = 0.04), positive exercise ECG (HR 2.94, p < 0.001), and an inconclusive test or inability to exercise (HR 3.45, p < 0.001) were independent predictors of events.

Conclusions: In patients with recent onset suspected cardiac chest pain, not having a diagnostic exercise ECG because of an inconclusive test or inability to exercise is an independent predictor of events and has similar prognostic implications to a positive exercise ECG. In addition, pre-test probability estimation at baseline is a robust indicator of clinical outcome. Future models of care need to incorporate early and increased access to non-exercise cardiac imaging techniques in order to meet the needs of this high-risk subgroup of patients.
Residues within a lipid-associated segment of the PECAM-1 cytoplasmic domain are susceptible to inducible, sequential phosphorylation
Authors: Paddock Cathy , Lytle Betsy L. , Peterson Francis C. , Holyst Trudy , Newman Peter J. , Volkman Brian F. , Newman Debra K.
Published: April 2011

Immunoreceptor tyrosine-based inhibitory motif (ITIM)–containing receptors inhibit cellular responsiveness to immunoreceptor tyrosine-based activation motif (ITAM)–linked receptors. Although tyrosine phosphorylation is central to the initiation of both inhibitory ITIM and stimulatory ITAM signaling, the events that regulate receptor phosphorylation are incompletely understood. Previous studies have shown that ITAM tyrosines engage in structure-inducing interactions with the plasma membrane that must be relieved for phosphorylation to occur. Whether ITIM phosphorylation is similarly regulated and the mechanisms responsible for release from plasma membrane interactions to enable phosphorylation, however, have not been defined. PECAM-1 is a dual ITIM-containing receptor that inhibits ITAM-dependent responses in hematopoietic cells. We found that the PECAM-1 cytoplasmic domain is unstructured in an aqueous environment but adopts an α-helical conformation within a localized region on interaction with lipid vesicles that mimic the plasma membrane. The lipid-interacting segment contains the C-terminal ITIM tyrosine and a serine residue that undergo activation-dependent phosphorylation. The N-terminal ITIM is excluded from the lipid-interacting segment, and its phosphorylation is secondary to phosphorylation of the membrane-interacting C-terminal ITIM. On the basis of these findings, we propose a novel model for regulation of inhibitory signaling by ITIM-containing receptors that relies on reversible plasma membrane interactions and sequential ITIM phosphorylation.
Joint analysis of transcriptional and post- transcriptional brain tumor data: searching for emergent properties of cellular systems
Authors: Fronza Raffaele , Tramonti Michele , Atchley William R , Nardini Christine
Published: April 2011

Background

Advances in biotechnology offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. However, to date, most computational and algorithmic efforts have been directed at mining data from each of these molecular levels (genomic, transcriptional, etc.) separately. In view of the rapid advances in technology (new generation sequencing, high-throughput proteomics) it is important to address the problem of analyzing these data as a whole, i.e. preserving the emergent properties that appear in the cellular system when all molecular levels are interacting. We analyzed one of the (currently) few datasets that provide both transcriptional and post-transcriptional data of the same samples to investigate the possibility to extract more information, using a joint analysis approach.

Results

We use Factor Analysis coupled with pre-established knowledge as a theoretical base to achieve this goal. Our intention is to identify structures that contain information from both mRNAs and miRNAs, and that can explain the complexity of the data. Despite the small sample available, we can show that this approach permits identification of meaningful structures, in particular two polycistronic miRNA genes related to transcriptional activity and likely to be relevant in the discrimination between gliosarcomas and other brain tumors.

Conclusions

This suggests the need to develop methodologies to simultaneously mine information from different levels of biological organization, rather than linking separate analyses performed in parallel.
Long term culture of mesenchymal stem cells in hypoxia promotes a genetic program maintaining their undifferentiated and multipotent status
Authors: Basciano Leticia , Nemos Christophe , Foliguet Bernard , de Isla Natalia , de Carvalho Marcelo , Tran Nguyen , Dalloul Ali
Published: April 2011

Background

In the bone marrow, hematopietic and mesenchymal stem cells form a unique niche in which the oxygen tension is low. Hypoxia may have a role in maintaining stem cell fate, self renewal and multipotency. However, whereas most studies addressed the effect of transientin vitroexposure of MSC to hypoxia, permanent culture under hypoxia should reflect the better physiological conditions.

Results

Morphologic studies, differentiation and transcriptional profiling experiments were performed on MSC cultured in normoxia (21% O2) versus hypoxia (5% O2) for up to passage 2. Cells at passage 0 and at passage 2 were compared, and those at passage 0 in hypoxia generated fewer and smaller colonies than in normoxia. In parallel, MSC displayed (>4 fold) inhibition of genes involved in DNA metabolism, cell cycle progression and chromosome cohesion whereas transcripts involved in adhesion and metabolism (CD93, ESAM, VWF, PLVAP, ANGPT2, LEP, TCF1) were stimulated. Compared to normoxic cells, hypoxic cells were morphologically undifferentiated and contained less mitochondrias. After this lag phase, cells at passage 2 in hypoxia outgrew the cells cultured in normoxia and displayed an enhanced expression of genes (4-60 fold) involved in extracellular matrix assembly (SMOC2), neural and muscle development (NOG, GPR56, SNTG2, LAMA) and epithelial development (DMKN). This group described herein for the first time was assigned by the Gene Ontology program to "plasticity".

Conclusion

The duration of hypoxemia is a critical parameter in the differentiation capacity of MSC. Even in growth promoting conditions, hypoxia enhanced a genetic program that maintained the cells undifferentiated and multipotent. This condition may better reflect thein vivogene signature of MSC, with potential implications in regenerative medicine.
Expression ratio of CCND1 to CDKN2A mRNA predicts RB1 status of cultured cancer cell lines and clinical tumor samples
Authors: Mizuarai Shinji , Machida Takumitsu , Kobayashi Tsutomu , Komatani Hideya , Itadani Hiraku , Kotani Hidehito
Published: April 2011

Background

The retinoblastoma product (RB1) is frequently deregulated in various types of tumors by mutation, deletion, or inactivation through association with viral oncoproteins. The functional loss of RB1 is recognized to be one of the hallmarks that differentiate cancer cells from normal cells. Many researchers are attempting to develop anti-tumor agents that are preferentially effective against RB1-negative tumors. However, to identify patients with RB1-negative cancers, it is imperative to develop predictive biomarkers to classify RB1-positive and -negative tumors.

Results

Expression profiling of 30 cancer cell lines composed of 16 RB1-positive and 14 RB1-negative cancers was performed to find genes that are differentially expressed between the two groups, resulting in the identification of an RB1 signature with 194 genes. Among them, critical RB1 pathway components CDKN2A and CCND1 were included. We found that microarray data of the expression ratio of CCND1 and CDKN2A clearly distinguished the RB1 status of 30 cells lines. Measurement of the CCND1/CDKN2A mRNA expression ratio in additional cell lines by RT-PCR accurately predicted RB1 status (12/12 cells lines). The expression of CCND1/CDKN2A also correlated with RB1 status in xenograft tumors in vivo. Lastly, a CCND1/CDKN2A assay with clinical samples showed that uterine cervical and small cell lung cancers known to have a high prevalence of RB1-decifiency were predicted to be 100% RB1-negative, while uterine endometrial or gastric cancers were predicted to be 5-22% negative. All clinically normal tissues were 100% RB1-positive.

Conclusions

We report here that the CCND1/CDKN2A mRNA expression ratio predicts the RB1 status of cell lines in vitro and xenograft tumors and clinical tumor samples in vivo. Given the high predictive accuracy and quantitative nature of the CCND1/CDKN2A expression assay, the assay could be utilized to stratify patients for anti-tumor agents with preferential effects on either RB1-positive or -negative tumors.
Health-Related Quality of Life in Non–Small-Cell Lung Cancer: An Update of a Systematic Review on Methodologic Issues in Randomized Controlled Trials
Authors: Claassens Lily , van Meerbeeck Jan , Coens Corneel , Quinten Chantal , Ghislain Irina , Sloan Elizabeth K. , Wang Xin Shelly , Velikova Galina , Bottomley Andrew
Published: April 2011

Purpose

This study is an update of a systematic review of health-related quality-of-life (HRQOL) methodology reporting in non–small-cell lung cancer (NSCLC) randomized controlled trials (RCTs). The objective was to evaluate HRQOL methodology reporting over the last decade and its benefit for clinical decision making.

Methods

A MEDLINE systematic literature review was performed. Eligible RCTs implemented patient-reported HRQOL assessments and regular oncology treatments for newly diagnosed adult patients with NSCLC. Included studies were published in English from August 2002 to July 2010. Two independent reviewers evaluated all included RCTs.

Results

Fifty-three RCTs were assessed. Of the 53 RCTs, 81% reported that there was no significant difference in overall survival (OS). However, 50% of RCTs that were unable to find OS differences reported a significant difference in HRQOL scores. The quality of HRQOL reporting has improved; both reporting of clinically significant differences and statistical testing of HRQOL have improved. A European Organisation for Research and Treatment of Cancer HRQOL questionnaire was used in 57% of the studies. However, reporting of HRQOL hypotheses and rationales for choosing HRQOL instruments were significantly less than before 2002 (P < .05).

Conclusion

The number of NSCLC RCTs incorporating HRQOL assessments has considerably increased. HRQOL continues to demonstrate its importance in RCTs, especially in those studies in which no OS difference is found. Despite the improved quality of HRQOL methodology reporting, certain aspects remain underrepresented. Our findings suggest need for an international standardization of HRQOL reporting similar to the CONSORT guidelines for clinical findings.
Prediction of Venous Thromboembolism in Patients With Cancer by Measuring Thrombin Generation: Results From the Vienna Cancer and Thrombosis Study
Authors: Ay Cihan , Dunkler Daniela , Simanek Ralph , Thaler Johannes , Koder Silvia , Marosi Christine , Zielinski Christoph , Pabinger Ingrid
Published: April 2011

Purpose

Patients with cancer are at increased risk of venous thromboembolism (VTE). Laboratory tests measuring the overall thrombophilic tendency might be useful to assess VTE risk. The aim of this study was to investigate thrombin generation, a key process in hemostasis, as predictor of cancer-associated VTE.

Patients and Methods

The Vienna Cancer and Thrombosis Study (CATS) is a prospective observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. The study end point is occurrence of objectively confirmed symptomatic or fatal VTE within a follow-up period of 2 years. Thrombin generation was measured with a commercially available assay.

Results

One thousand thirty-three patients with malignancies of the breast (n = 151), lung (n = 148), upper (n = 44) and lower gastrointestinal tract (n = 125), pancreas (n = 67), kidney (n = 34), prostate (n = 122), and brain (n = 134) or lymphoma (n = 126), multiple myeloma (n = 26), and other tumor types (n = 56) were observed for a median observation period of 517 days. VTE occurred in 77 patients (7.5%). Patients with elevated peak thrombin (defined as values ≥ 611 nM thrombin, representing the 75th percentile of the total study population) had an increased risk of VTE with a hazard ratio of 2.1 (95% CI, 1.3 to 3.3, P = .002) in multivariable analysis including age, sex, surgery, chemotherapy, and radiotherapy. The cumulative probability of developing VTE after 6 months was significantly higher in patients with elevated peak thrombin than in those with lower peak thrombin (11% v 4%; log-rank test: P = .002).

Conclusion

Measurement of thrombin generation may help identify patients with cancer at high risk of VTE.
Hydrogen Atom Adsorption on Aluminum Clusters: An Electronic Structures Density Functional Study
Authors: Viet Bac Phung Thi , Ogawa Hiroshi
Published: April 2011

Properties of hydrogenated icosahedral aluminum clusters were investigated using density functional theory in comparison with those of aluminum bulk systems. Two surface models simulating f.c.c. and icosahedral (111) surfaces were introduced. Results show that the H atom interacts weakly with surface of clusters when the cluster size is increased. The migration energy of H atom between neighboring T and O sites becomes smaller for icosahedral subsurface than for either bulk material or the f.c.c. subsurface. The results indicate that the icosahedral surface is more favored for H atom to adsorp than f.c.c. surface, the icosahedral surface increases the migration barriers of H atom from the surface to the subsurface.
Characterization on the Electrical Properties of PDMS Nanocomposites by Conducting Polymer Nanowires
Authors: Du Ping , Lin Xi , Zhang Xin
Published: April 2011

Polydimethylsiloxane (PDMS) is one of the most used materials in bio-applications. However, previous works were mainly focus on the mechanical aspect. In this paper we presented a practical and efficient approach to enhance the electrical properties of PDMS by using conducting polymer nanowires (CPNWs). The nanowires were synthesized using template method and added in PDMS to form nanocomposites. The dielectric constants of the composites were characterized by impedance measurements, and the dielectric relaxation behavior and the volume fraction of CPNWs was investigated. Based on the percolation theory a much lower threshold (5.3 vol%) was achieved.
Development of Bacterial Cellulose Nanocomposites
Authors: Benson Roberto , O’Neill Hugh M. , Evans B.R. , Hutchens S. , Stephens C.P. , Hammonds R.
Published: April 2011

The development of synthetic materials with inherent bone properties would allow the safe restoration of bone function and reduce current risks associated with the use of grafts. This study investigated the development of bacterial cellulose–hydroxyapatite composite (CdHA-BC) as a potential bone substitute material. Composites of bacterial cellulose (BC) and oxidized, degradable, cellulose (OBC) were mineralized by sequential incubation in calcium chloride and aqueous sodium phosphate to form a calcium deficient hydroxyapatite (CdHA). The CdHA produced in BC and OBC is similar in morphology and chemistry to the hydroxyapatite found in natural bone. The formation of CdHA is supported by XRD, and EDS results. The CdHA-BC and CdHA-OBC composites degrade in a simulated aqueous physiological environment.
Self-Assembled Nano-Needles of Polyaniline, Efficient Structures in Controlling Electrical Conductivity
Authors: Ibrahim Michael I. , Bassil Maria J. , Demirci Umit B. , El Haj Moussa Georges , El Tahchi Mario R. , Miele Philippe
Published: April 2011

Polyaniline (PANI) is one of the most interesting conducting polymers with a wide and controllable conductivity range, synthesized easily via chemical or electrical route, stable chemically and environmentally, having high absorption in the visible range and high mobility of charge carriers. Under different conditions, PANI morphology can be controlled yielding to the creation of nano-tubes, belts, rods, fibers and particles.

In this study, the chemical oxidative polymerization which consists of mixing aniline hydrochloride (A-HCl) with ammonium peroxydisulfate (APS) was used to synthesize HCl doped PANI. Fixing the weight ratio A-HCl/APS defined by the IUPAC while varying their quantities leads to the formation of PANI nanoparticles with variable diameters. In addition, PANI nano-needles of 60 nm average diameter at the center are also obtained. Different methods are used to investigate of 1-D morphologies. The electrical conductivity of bulk PANI pellets is measured using the four-point probe technique. The absorption in the visible range of PANI particles and nano-needles is determined by UV-Vis spectroscopy. XRD analysis was performed to study the effect of PANI particle size and morphology on the crystallinity of the powder. Such structures could be used in hybrid solar cells for higher conversion efficiencies.
Photo-polymerizable gold nanorods / methyl methacrylate composite for plasmonic optical application
Authors: Masui Kyoko , Shoji Satoru , Duan Xuan-Ming , Kawata Satoshi
Published: April 2011

We prepared a photo-polymerizable compound of Au nanorods and methyl methacrylate (MMA). An irradiation of ultraviolet (UV) light onto the compound induces photo-polymerization of MMA, resulting in a formation of an Au nanorods/PMMA composite. Au nanorods were synthesized by seed-mediated growth method in aqueous solution. Hydrophobically functionalized Au nanorods were dispersed into MMA with a small amount of photosensitizer and initiator. We investigated the stability and the uniformity of the dispersion of Au nanorods during the photo-polymerization process through VIS-NIR absorption spectroscopy. We also demonstrated the use of the compound for two-photon micro/nanolithography.
Rheological Behavior of Nanoclay Containing Nanofluids
Authors: Munro Jeffrey C. , Rao YuanQiao
Published: April 2011

A synthetic hectorite nanoclay, Laponite®, with a disc shape (20 – 30 nm in diameter and 1 nm in thickness) was used as a model nanoparticle to prepare dispersions in water and different organic solvents. Although up to 20 wt% of nanoclay can be dispersed in water to form a low-viscosity stable colloidal sol, dispersions in organic solvents behave differently. The effect of the dielectric constant of the medium on the viscosity of the dispersion was studied systematically using two series of water-organic solvent miscible blends. Changes in the rheological behavior of the dispersions suggest that the dielectric constant of the organic solvent is a determining factor in the sol-gel transition of a nanoclay-containing nanofluid.
Image Analysis Optimization for Quantifying Nanoparticle Dispersions in Polymer-based Nanocomposites Using Transmission Electron Microscopy (TEM)
Authors: Badami Anand S. , Beach Mark W. , Wood Stewart P. , Rozeveld Steven J. , Heeschen William A.
Published: April 2011

When comparing large numbers of TEM micrographs of insoluble additives in polymer-based nanocomposite systems, the ability to determine or estimate the dispersion quality (i.e. uniformity of size and/or spatial distribution) is often difficult. The objective of this study was to develop a method to quantify dispersions observed in TEM micrographs that enables both a numerical “ranking” to be assigned to individual dispersions as well as tabulation a multitude of images acquired over time. Several methods were reviewed and applied to a set of TEM dispersion images of an insoluble additive in polystyrene. Projected area diameter, particle area, and Euclidean distance between particle centroids were chosen from all the particle size distribution and spatial distribution parameters present in the literature, but none successfully yielded a quantitative indicator of dispersion quality for the micrographs. In contrast, generating cumulative volume percent curves for each sample appeared to be a preferred method of quantifying and comparing dispersions in TEM micrographs. The volume diameter values obtained by this method can be used for “ranking” and tabulation of dispersion quality and account for both “good” additive dispersions (i.e. those with small domains of a narrow size range around 1 μm or less) and “bad” additive dispersions (i.e. those with non-uniform domains ranging in size by several microns or more). As a result, the numerical values generated by this method can be used to quantitatively determine correlations between the dispersion quality of nanoparticles in polymer-based nanocomposite materials and various macroscale physical and/or performance properties of such materials. This method’s precision was statistically determined to decrease with increasing particle size and be heavily dependent on representative sampling.