Bakhtin’s Problems of Dostoevsky’s Poetics and the Ideological Problem of The Brothers Karamazov

Dostoevsky’s final novel, The Brothers Karamazov, strives to resolve the question of God’s existence. But many critics have acknowledged that Dostoevsky seems to present Ivan’s skeptical voice with equal, if not greater, force than Alyosha’s affirmative voice—a feature of the novel that is difficult to explain in the context of Dostoevsky’s avowed Christianity. There is an overwhelming consensus among critics that The Brothers is a thesis-novel. But in order to establish the novel as a defense of faith, the critic must ultimately dismiss the strength of Ivan’s voice; and in attempting to demonstrate that the voice of doubt prevails, the critic must similarly dismiss the value of Alyosha’s faith. By utilizing Bakhtin’s theory of polyphony, I propose an interpretation of The Brothers that does not attempt to resolve this opposition. Because Bakhtin’s theory is often seen to sanction all interpretations as equally valid, it has been used to endorse each of these mutually incompatible positions on the novel. But I hope to show that the theory of polyphony is, in its essence, diametrically opposed to the interpretation of Dostoevsky’s work as either a defense of faith or a concession to doubt. Further, I propose—contra Bakhtin—that the polyphonic novel can be thesis-driven, if its very thesis resides in its formal polyphony. The thesis of The Brothers, I argue, does not resolve the question of God’s existence, but posits instead that the inability to resolve this question is fundamental to human nature

Exact Thermodynamics of the Double sinh-Gordon Theory in 1+1-Dimensions

We study the classical thermodynamics of a 1+1-dimensional double-well sinh-Gordon theory. Remarkably, the Schrodinger-like equation resulting from the transfer integral method is quasi-exactly solvable at several temperatures. This allows exact calculation of the partition function and some correlation functions above and below the short-range order (``kink'') transition, in striking agreement with high resolution Langevin simulations. Interesting connections with the Landau-Ginzburg and double sine-Gordon models are also established.Comment: 4 pages, 3 figures (embedded using epsf), uses RevTeX plus macro (included). Minor revision to match journal version, Phys. Rev. Lett. (in press

A systematic review of naturalistic interventions in refugee populations

Naturalistic interventions with refugee populations examine outcomes following mental health interventions in existing refugee service organisations. The current review aimed to examine outcomes of naturalistic interventions and quality of the naturalistic intervention literature in refugee populations with the view to highlight the strengths and limitations of naturalistic intervention studies. Database search was conducted using the search terms ‘refugee’, ‘asylum seeker’, ‘treatment’, ‘therapy’ and ‘intervention. No date limitations were applied, but searches were limited to articles written in English. Seven studies were identified that assessed the outcome of naturalistic interventions on adult refugees or asylum seekers in a country of resettlement using quantitative outcome measures. Results showed significant variation in the outcomes of naturalistic intervention studies, with a trend towards showing decreased symptomatology at post-intervention. However, conclusions are limited by methodological problems of the studies reviewed, particularly poor documentation of intervention methods and lack of control in the design of naturalistic intervention studies. Further examination of outcomes following naturalistic interventions is needed with studies which focus on increasing the rigour of the outcome assessment process

Noise-Induced Phase Space Transport in Two-Dimensional Hamiltonian Systems

First passage time experiments were used to explore the effects of low amplitude noise as a source of accelerated phase space diffusion in two-dimensional Hamiltonian systems, and these effects were then compared with the effects of periodic driving. The objective was to quantify and understand the manner in which ``sticky'' chaotic orbits that, in the absence of perturbations, are confined near regular islands for very long times, can become ``unstuck'' much more quickly when subjected to even very weak perturbations. For both noise and periodic driving, the typical escape time scales logarithmically with the amplitude of the perturbation. For white noise, the details seem unimportant: Additive and multiplicative noise typically have very similar effects, and the presence or absence of a friction related to the noise by a Fluctuation-Dissipation Theorem is also largely irrelevant. Allowing for colored noise can significantly decrease the efficacy of the perturbation, but only when the autocorrelation time becomes so large that there is little power at frequencies comparable to the natural frequencies of the unperturbed orbit. Similarly, periodic driving is relatively inefficient when the driving frequency is not comparable to these natural frequencies. This suggests strongly that noise-induced extrinsic diffusion, like modulational diffusion associated with periodic driving, is a resonance phenomenon. The logarithmic dependence of the escape time on amplitude reflects the fact that the time required for perturbed and unperturbed orbits to diverge a given distance scales logarithmically in the amplitude of the perturbation.Comment: 15 pages, including 13 Figures and 1 Table, uses Phys. Rev. macro

Protein kinase Cδ expression in breast cancer as measured by real-time PCR, western blotting and ELISA

The protein kinase C (PKC) family of genes encode serine/threonine kinases that regulate proliferation, apoptosis, cell survival and migration. Multiple isoforms of PKC have been described, one of which is PKCδ. Currently, it is unclear whether PKCδ is involved in promoting or inhibiting cancer formation/progression. The aim of this study was therefore to investigate the expression of PKCδ in human breast cancer and relate its levels to multiple parameters of tumour progression. Protein kinase Cδ expression at the mRNA level was measured using real-time PCR (n=208) and at protein level by both immunoblotting (n=94) and ELISA (n=98). Following immunoblotting, two proteins were identified, migrating with molecular masses of 78 and 160 kDa. The 78 kDa protein is likely to be the mature form of PKCδ but the identity of the 160 kDa form is unknown. Levels of both these proteins correlated weakly but significantly with PKCδ concentrations determined by ELISA (for the 78 kDa form, r=0.444, P<0.005, n=91 and for the 160 kDa form, r=0.237, P=0.023, n=91) and with PKCδ mRNA levels (for the 78 kDa form, r=0.351, P=0.001, n=94 and for the 160 kDa form, r=0.216, P=0.037, n=94). Protein kinase Cδ mRNA expression was significantly higher in oestrogen receptor (ER)-positive compared with ER-negative tumours (P=0.007, Mann–Whitney U-test). Increasing concentrations of PKCδ mRNA were associated with reduced overall patient survival (P=0.004). Our results are consistent with a role for PKCδ in breast cancer progression

Chaos and the continuum limit in the gravitational N-body problem II. Nonintegrable potentials

This paper continues a numerical investigation of orbits evolved in `frozen,' time-independent N-body realisations of smooth time-independent density distributions corresponding to both integrable and nonintegrable potentials, allowing for N as large as 300,000. The principal focus is on distinguishing between, and quantifying, the effects of graininess on initial conditions corresponding, in the continuum limit, to regular and chaotic orbits. Ordinary Lyapunov exponents X do not provide a useful diagnostic for distinguishing between regular and chaotic behaviour. Frozen-N orbits corresponding in the continuum limit to both regular and chaotic characteristics have large positive X even though, for large N, the `regular' frozen-N orbits closely resemble regular characteristics in the smooth potential. Viewed macroscopically both `regular' and `chaotic' frozen-N orbits diverge as a power law in time from smooth orbits with the same initial condition. There is, however, an important difference between `regular' and `chaotic' frozen-N orbits: For regular orbits, the time scale associated with this divergence t_G ~ N^{1/2}t_D, with t_D a characteristic dynamical time; for chaotic orbits t_G ~ (ln N) t_D. At least for N>1000 or so, clear distinctions exist between phase mixing of initially localised orbit ensembles which, in the continuum limit, exhibit regular versus chaotic behaviour. For both regular and chaotic ensembles, finite-N effects are well mimicked, both qualitatively and quantitatively, by energy-conserving white noise with amplitude ~ 1/N. This suggests strongly that earlier investigations of the effects of low amplitude noise on phase space transport in smooth potentials are directly relevant to real physical systems.Comment: 20 pages, including 21 FIGURES, uses RevTeX macro

Chaos and Noise in Galactic Potentials

ABBREVIATED ABSTRACT: This paper summarises an investigation of the effects of weak friction and noise in time-independent, nonintegrable potentials which admit both regular and stochastic orbits. The aim is to understand the qualitative effects of internal and external irregularities associated, e.g., with discreteness effects or couplings to an external environment, which stars in any real galaxy must experience. The two principal conclusions are: (1) These irregularities can be important on time scales much shorter than the natural relaxation time scale t_R associated with the friction and noise. For stochastic orbits friction and noise induce an average exponential divergence from the unperturbed Hamiltonian trajectory at a rate set by the value of the local Lyapunov exponent. Even weak noise can make a pointwise interpretation of orbits suspect already on time scales much shorter than t_R. (2) The friction and noise can also have significant effects on the statistical properties of ensembles of stochastic orbits, these also occurring on time scales much shorter than t_R. Potential implications for galactic dynamics are discussed, including the problem of shadowing.Comment: 45 pages, uuencoded PostScript (figures included), LA-UR-94-282

Antiproliferative activity of PEP005, a novel ingenol angelate that modulates PKC functions, alone and in combination with cytotoxic agents in human colon cancer cells

PEP005 is a novel ingenol angelate that modulates protein kinases C (PKC) functions by activating PKCδ and inhibiting PKCα. This study assessed the antiproliferative effects of PEP005 alone and in combination with several other anticancer agents in a panel of 10 human cancer cell lines characterised for expression of several PKC isoforms. PEP005 displayed antiproliferative effects at clinically relevant concentrations with a unique cytotoxicity profile that differs from that of most other investigated cytotoxic agents, including staurosporine. In a subset of colon cancer cells, the IC50 of PEP005 ranged from 0.01–140 μM. The antiproliferative effects of PEP005 were shown to be concentration- and time-dependent. In Colo205 cells, apoptosis induction was observed at concentrations ranging from 0.03 to 3 μM. Exposure to PEP005 also induced accumulation of cells in the G1 phase of the cell cycle. In addition, PEP005 increased the phosphorylation of PKCδ and p38. In Colo205 cells, combinations of PEP005 with several cytotoxic agents including oxaliplatin, SN38, 5FU, gemcitabine, doxorubicin, vinorelbine, and docetaxel yielded sequence-dependent antiproliferative effects. Cell cycle blockage induced by PEP005 in late G1 lasted for up to 24 h and therefore a 24 h lag-time between PEP005 and subsequent exposure to cytotoxics was required to optimise PEP005 combinations with several anticancer agents. These data support further evaluation of PEP005 as an anticancer agent and may help to optimise clinical trials with PEP005-based combinations in patients with solid tumours

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting