'I would rather die': reasons given by 16-year-olds for not continuing their study of mathematics

Improving participation rates in specialist mathematics after the subject ceases to be compulsory at age 16 is part of government policy in England. This article provides independent and recent support for earlier findings concerning reasons for non- participation, based on free response and closed items in a questionnaire with a sample of over 1500 students in 17 schools, close to the moment of choice. The analysis supports findings that perceived difficulty and lack of confidence are important reasons for students not continuing with mathematics, and that perceived dislike and boredom, and lack of relevance, are also factors. There is a close relationship between reasons for non-participation and predicted grade, and a weaker relation to gender. An analysis of the effects of schools, demonstrates that enjoyment is the main factor differentiating schools with high and low participation indices. Building on discussion of these findings, ways of improving participation are briefly suggested

Cardiac protein kinases: the cardiomyocyte kinome and differential kinase expression in human failing hearts

Aims. Protein kinases are potential therapeutic targets for heart failure, but most studies of cardiac protein kinases derive from other systems, an approach that fails to account for specific kinases expressed in the heart and the contractile cardiomyocytes. We aimed to define the cardiomyocyte kinome (i.e. the protein kinases expressed in cardiomyocytes) and identify kinases with altered expression in human failing hearts. Methods and Results. Expression profiling (Affymetrix microarrays) detected >400 protein kinase mRNAs in rat neonatal ventricular myocytes (NVMs) and/or adult ventricular myocytes (AVMs), 32 and 93 of which were significantly upregulated or downregulated (>2-fold), respectively, in AVMs. Data for AGC family members were validated by qPCR. Proteomics analysis identified >180 cardiomyocyte protein kinases, with high relative expression of mitogen-activated protein kinase cascades and other known cardiomyocyte kinases (e.g. CAMKs, cAMP-dependent protein kinase). Other kinases are poorly-investigated (e.g. Slk, Stk24, Oxsr1). Expression of Akt1/2/3, BRaf, ERK1/2, Map2k1, Map3k8, Map4k4, MST1/3, p38-MAPK, PKCδ, Pkn2, Ripk1/2, Tnni3k and Zak was confirmed by immunoblotting. Relative to total protein, Map3k8 and Tnni3k were upregulated in AVMs vs NVMs. Microarray data for human hearts demonstrated variation in kinome expression that may influence responses to kinase inhibitor therapies. Furthermore, some kinases were upregulated (e.g. NRK, JAK2, STK38L) or downregulated (e.g. MAP2K1, IRAK1, STK40) in human failing hearts. Conclusions. This characterization of the spectrum of kinases expressed in cardiomyocytes and the heart (cardiomyocyte and cardiac kinomes) identified novel kinases, some of which are differentially expressed in failing human hearts and could serve as potential therapeutic targets

A dynamical model reveals gene co-localizations in nucleus

Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency-or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

Computer simulations of domain growth and phase separation in two-dimensional binary immiscible fluids using dissipative particle dynamics

We investigate the dynamical behavior of binary fluid systems in two dimensions using dissipative particle dynamics. We find that following a symmetric quench the domain size R(t) grows with time t according to two distinct algebraic laws R(t) = t^n: at early times n = 1/2, while for later times n = 2/3. Following an asymmetric quench we observe only n = 1/2, and if momentum conservation is violated we see n = 1/3 at early times. Bubble simulations confirm the existence of a finite surface tension and the validity of Laplace's law. Our results are compared with similar simulations which have been performed previously using molecular dynamics, lattice-gas and lattice-Boltzmann automata, and Langevin dynamics. We conclude that dissipative particle dynamics is a promising method for simulating fluid properties in such systems.Comment: RevTeX; 22 pages, 5 low-resolution figures. For full-resolution figures, connect to http://www.tcm.phy.cam.ac.uk/~ken21/tension/tension.htm

HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group

Lattice-gas simulations of Domain Growth, Saturation and Self-Assembly in Immiscible Fluids and Microemulsions

We investigate the dynamical behavior of both binary fluid and ternary microemulsion systems in two dimensions using a recently introduced hydrodynamic lattice-gas model of microemulsions. We find that the presence of amphiphile in our simulations reduces the usual oil-water interfacial tension in accord with experiment and consequently affects the non-equilibrium growth of oil and water domains. As the density of surfactant is increased we observe a crossover from the usual two-dimensional binary fluid scaling laws to a growth that is {\it slow}, and we find that this slow growth can be characterized by a logarithmic time scale. With sufficient surfactant in the system we observe that the domains cease to grow beyond a certain point and we find that this final characteristic domain size is inversely proportional to the interfacial surfactant concentration in the system.Comment: 28 pages, latex, embedded .eps figures, one figure is in colour, all in one uuencoded gzip compressed tar file, submitted to Physical Review

Processing and Transmission of Information

Contains reports on seven research projects

Designing lattice structures with maximal nearest-neighbor entanglement

In this work, we study the numerical optimization of nearest-neighbor concurrence of bipartite one and two dimensional lattices, as well as non bipartite two dimensional lattices. These systems are described in the framework of a tight-binding Hamiltonian while the optimization of concurrence was performed using genetic algorithms. Our results show that the concurrence of the optimized lattice structures is considerably higher than that of non optimized systems. In the case of one dimensional chains the concurrence is maximized when the system begins to dimerize, i.e. it undergoes a structural phase transition (Peierls distortion). This result is consistent with the idea that entanglement is maximal or shows a singularity near quantum phase transitions and that quantum entanglement cannot be freely shared between many objects (monogamy property). Moreover, the optimization of concurrence in two-dimensional bipartite and non bipartite lattices is achieved when the structures break into smaller subsystems, which are arranged in geometrically distinguishable configurations. This behavior is again related to the monogamy property.Comment: 18 pages, 10 figure