897 research outputs found
Popularity versus Similarity in Growing Networks
Popularity is attractive -- this is the formula underlying preferential
attachment, a popular explanation for the emergence of scaling in growing
networks. If new connections are made preferentially to more popular nodes,
then the resulting distribution of the number of connections that nodes have
follows power laws observed in many real networks. Preferential attachment has
been directly validated for some real networks, including the Internet.
Preferential attachment can also be a consequence of different underlying
processes based on node fitness, ranking, optimization, random walks, or
duplication. Here we show that popularity is just one dimension of
attractiveness. Another dimension is similarity. We develop a framework where
new connections, instead of preferring popular nodes, optimize certain
trade-offs between popularity and similarity. The framework admits a geometric
interpretation, in which popularity preference emerges from local optimization.
As opposed to preferential attachment, the optimization framework accurately
describes large-scale evolution of technological (Internet), social (web of
trust), and biological (E.coli metabolic) networks, predicting the probability
of new links in them with a remarkable precision. The developed framework can
thus be used for predicting new links in evolving networks, and provides a
different perspective on preferential attachment as an emergent phenomenon
Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects
Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved
Rare Z-decay into light CP-odd Higgs bosons: a comparative study in different new physics models
Various new physics models predict a light CP-odd Higgs boson (labeled as
) and open up new decay modes for Z-boson, such as ,
and , which could be explored at the GigaZ option of
the ILC. In this work we investigate these rare decays in several new physics
models, namely the type-II two Higgs doublet model (type-II 2HDM), the
lepton-specific two Higgs doublet model (L2HDM), the nearly minimal
supersymetric standard model (nMSSM) and the next-to-minimal supersymmetric
standard model (NMSSM). We find that in the parameter space allowed by current
experiments, the branching ratios can reach for
(), for and for , which
implies that the decays and may be accessible
at the GigaZ option. Moreover, since different models predict different
patterns of the branching ratios, the measurement of these rare decays at the
GigaZ may be utilized to distinguish the models.Comment: Version in JHEP (discussions added, errors corrected
Clinical-pathological study on ÎČ-APP, IL-1ÎČ, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis
Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for ÎČAPP, GFAP, IL-1ÎČ, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of ÎČ-APP, IL-1ÎČ, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury
Qualitative study of the impact of an authentic electronic portfolio in undergraduate medical education
Background
Portfolios are increasingly used in undergraduate and postgraduate medical education. Four medical schools have collaborated with an established NHS electronic portfolio provider to develop and implement an authentic professional electronic portfolio for undergraduate students. We hypothesized that using an authentic portfolio would have significant advantages for students, particularly in familiarizing them with the tool many will continue to use for years after graduation. This paper describes the early evaluation of this undergraduate portfolio at two participating medical schools.
Methods
To gather data, a questionnaire survey with extensive free text comments was used at School 1, and three focus groups were held at School 2. This paper reports thematic analysis of studentsâ opinions expressed in the free text comments and focus groups.
Results
Five main themes, common across both schools were identified. These concerned the purpose, use and acceptability of the portfolio, advantages of and barriers to the use of the portfolio, and the impacts on both learning and professional identity.
Conclusions
An authentic portfolio mitigated some of the negative aspects of using a portfolio, and had a positive effect on studentsâ perception of themselves as becoming past of the profession. However, significant barriers to portfolio use remained, including a lack of understanding of the purpose of a portfolio and a perceived damaging effect on feedback
All Our Babies Cohort Study: recruitment of a cohort to predict women at risk of preterm birth through the examination of gene expression profiles and the environment
<p>Abstract</p> <p>Background</p> <p>Preterm birth is the leading cause of perinatal morbidity and mortality. Risk factors for preterm birth include a personal or familial history of preterm delivery, ethnicity and low socioeconomic status yet the ability to predict preterm delivery before the onset of preterm labour evades clinical practice. Evidence suggests that genetics may play a role in the multi-factorial pathophysiology of preterm birth. The All Our Babies Study is an on-going community based longitudinal cohort study that was designed to establish a cohort of women to investigate how a women's genetics and environment contribute to the pathophysiology of preterm birth. Specifically this study will examine the predictive potential of maternal leukocytes for predicting preterm birth in non-labouring women through the examination of gene expression profiles and gene-environment interactions.</p> <p>Methods/Design</p> <p>Collaborations have been established between clinical lab services, the provincial health service provider and researchers to create an interdisciplinary study design for the All Our Babies Study. A birth cohort of 2000 women has been established to address this research question. Women provide informed consent for blood sample collection, linkage to medical records and complete questionnaires related to prenatal health, service utilization, social support, emotional and physical health, demographics, and breast and infant feeding. Maternal blood samples are collected in PAXgeneâą RNA tubes between 18-22 and 28-32 weeks gestation for transcriptomic analyses.</p> <p>Discussion</p> <p>The All Our Babies Study is an example of how investment in clinical-academic-community partnerships can improve research efficiency and accelerate the recruitment and data collection phases of a study. Establishing these partnerships during the study design phase and maintaining these relationships through the duration of the study provides the unique opportunity to investigate the multi-causal factors of preterm birth. The overall All Our Babies Study results can potentially lead to healthier pregnancies, mothers, infants and children.</p
How the oxygen tolerance of a [NiFe]-hydrogenase depends on quaternary structure
âOxygen-tolerantâ [NiFe]-hydrogenases can catalyze H(2) oxidation under aerobic conditions, avoiding oxygenation and destruction of the active site. In one mechanism accounting for this special property, membrane-bound [NiFe]-hydrogenases accommodate a pool of electrons that allows an O(2) molecule attacking the active site to be converted rapidly to harmless water. An important advantage may stem from having a dimeric or higher-order quaternary structure in which the electron-transfer relay chain of one partner is electronically coupled to that in the other. Hydrogenase-1 from E. coli has a dimeric structure in which the distal [4Fe-4S] clusters in each monomer are located approximately 12Â Ă
apart, a distance conducive to fast electron tunneling. Such an arrangement can ensure that electrons from H(2) oxidation released at the active site of one partner are immediately transferred to its counterpart when an O(2) molecule attacks. This paper addresses the role of long-range, inter-domain electron transfer in the mechanism of O(2)-tolerance by comparing the properties of monomeric and dimeric forms of Hydrogenase-1. The results reveal a further interesting advantage that quaternary structure affords to proteins
Measurement of the Relative Branching Fraction of to Charged and Neutral B-Meson Pairs
We analyze 9.7 x 10^6 B\bar{B}$ pairs recorded with the CLEO detector to
determine the production ratio of charged to neutral B-meson pairs produced at
the Y(4S) resonance. We measure the rates for B^0 -> J/psi K^{(*)0} and B^+ ->
J/psi K^{(*)+} decays and use the world-average B-meson lifetime ratio to
extract the relative widths f+-/f00 = Gamma(Y(4S) -> B+B-)/Gamma(Y(4S) ->
B0\bar{B0}) = = 1.04 +/- 0.07(stat) +/- 0.04(syst). With the assumption that
f+- + f00 = 1, we obtain f00 = 0.49 +/- 0.02(stat) +/- 0.01(syst) and f+- =
0.51 +/- 0.02(stat) +/- 0.01(syst). This production ratio and its uncertainty
apply to all exclusive B-meson branching fractions measured at the Y(4S)
resonance.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
Study of the Decays B0 --> D(*)+D(*)-
The decays B0 --> D*+D*-, B0 --> D*+D- and B0 --> D+D- are studied in 9.7
million Y(4S) --> BBbar decays accumulated with the CLEO detector. We determine
Br(B0 --> D*+D*-) = (9.9+4.2-3.3+-1.2)e-4 and limit Br(B0 --> D*+D-) < 6.3e-4
and Br(B0 --> D+D-) < 9.4e-4 at 90% confidence level (CL). We also perform the
first angular analysis of the B0 --> D*+D*- decay and determine that the
CP-even fraction of the final state is greater than 0.11 at 90% CL. Future
measurements of the time dependence of these decays may be useful for the
investigation of CP violation in neutral B meson decays.Comment: 21 pages, 5 figures, submitted to Phys. Rev.
Improved Measurement of the Pseudoscalar Decay Constant
We present a new determination of the Ds decay constant, f_{Ds} using 5
million continuum charm events obtained with the CLEO II detector. Our value is
derived from our new measured ratio of widths for Ds -> mu nu/Ds -> phi pi of
0.173+/- 0.021 +/- 0.031. Taking the branching ratio for Ds -> phi pi as (3.6
+/- 0.9)% from the PDG, we extract f_{Ds} = (280 +/- 17 +/- 25 +/- 34){MeV}. We
compare this result with various model calculations.Comment: 23 page postscript file, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
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