A renormalization group model for the stick-slip behavior of faults

A fault which is treated as an array of asperities with a prescribed statistical distribution of strengths is described. For a linear array the stress is transferred to a single adjacent asperity and for a two dimensional array to three ajacent asperities. It is shown that the solutions bifurcate at a critical applied stress. At stresses less than the critical stress virtually no asperities fail on a large scale and the fault is locked. At the critical stress the solution bifurcates and asperity failure cascades away from the nucleus of failure. It is found that the stick slip behavior of most faults can be attributed to the distribution of asperities on the fault. The observation of stick slip behavior on faults rather than stable sliding, why the observed level of seismicity on a locked fault is very small, and why the stress on a fault is less than that predicted by a standard value of the coefficient of friction are outlined

Self-affine Asperity Model for earthquakes

A model for fault dynamics consisting of two rough and rigid brownian profiles that slide one over the other is introduced. An earthquake occurs when there is an intersection between the two profiles. The energy release is proportional to the overlap interval. Our model exhibits some specific features which follow from the fractal geometry of the fault: (1) non-universality of the exponent of the Gutenberg-Richter law for the magnitude distribution; (2) presence of local stress accumulation before a large seismic event; (3) non-trivial space-time clustering of the epicenters. These properties are in good agreement with various observations and lead to specific predictions that can be experimentally tested.Comment: TeX file, 14 pages, 3 figures available from [email protected]

Earthquake statistics and fractal faults

We introduce a Self-affine Asperity Model (SAM) for the seismicity that mimics the fault friction by means of two fractional Brownian profiles (fBm) that slide one over the other. An earthquake occurs when there is an overlap of the two profiles representing the two fault faces and its energy is assumed proportional to the overlap surface. The SAM exhibits the Gutenberg-Richter law with an exponent $\beta$ related to the roughness index of the profiles. Apart from being analytically treatable, the model exhibits a non-trivial clustering in the spatio-temporal distribution of epicenters that strongly resembles the experimentally observed one. A generalized and more realistic version of the model exhibits the Omori scaling for the distribution of the aftershocks. The SAM lies in a different perspective with respect to usual models for seismicity. In this case, in fact, the critical behaviour is not Self-Organized but stems from the fractal geometry of the faults, which, on its turn, is supposed to arise as a consequence of geological processes on very long time scales with respect to the seismic dynamics. The explicit introduction of the fault geometry, as an active element of this complex phenomenology, represents the real novelty of our approach.Comment: 40 pages (Tex file plus 8 postscript figures), LaTeX, submitted to Phys. Rev.

Scalar models for the generalized Chaplygin gas and the structure formation constraints

The generalized Chaplygin gas model represents an attempt to unify dark matter and dark energy. It is characterized by a fluid with an equation of state $p = - A/\rho^\alpha$. It can be obtained from a generalization of the DBI action for a scalar, tachyonic field. At background level, this model gives very good results, but it suffers from many drawbacks at perturbative level. We show that, while for background analysis it is possible to consider any value for $\alpha$, the perturbative analysis must be restricted to positive values of $\alpha$. This restriction can be circumvented if the origin of the generalized Chaplygin gas is traced back to a self-interacting scalar field, instead of the DBI action. But, in doing so, the predictions coming from formation of large scale structures reduce the generalized Chaplygin gas model to a kind of quintessence model, and the unification scenario is lost, if the scalar field is the canonical one. However, if the unification condition is imposed from the beginning as a prior, the model may remain competitive. More interesting results, concerning the unification program, are obtained if a non-canonical self-interacting scalar field, inspired by Rastall's theory of gravity, is imposed. In this case, an agreement with the background tests is possible.Comment: Latex file, 25 pages, 33 figures in eps format. New section on scalar models. Accepted for publication in Gravitation&Cosmolog

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma

Cyclooxygenase 2 (Cox-2) is upregulated in colorectal adenomas and carcinomas. Polymorphisms in the Cox-2 gene may influence its function and/or its expression and may modify the protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thereby impacting individuals' risk of developing colorectal cancer and response to prevention/intervention strategies. In a nested case–control study, four polymorphisms in the Cox-2 gene (two in the promoter, −663 insertion/deletion, GT/(GT) and −798 A/G; one in intron 5-5229, T/G; one in 3′untranslated region (UTR)-8494, T/C) were genotyped in 726 cases of colorectal adenomas and 729 age- and gender-matched controls in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. There was no significant association between the Cox-2 polymorphisms and adenoma development in the overall population. However, in males, the relatively rare heterozygous genotype GT/(GT) at −663 in the promoter and the variant homozygous genotype G/G at intron 5-5229 appeared to have inverse associations (odds ratio (OR)=0.59, confidence interval (CI): 0.34–1.02 and OR=0.48, CI: 0.24–0.99, respectively), whereas the heterozygous genotype T/C at 3′UTR-8494 had a positive association (OR=1.31, CI: 1.01–1.71) with adenoma development. Furthermore, the haplotype carrying the risk-conferring 3′UTR-8494 variant was associated with a 35% increase in the odds for adenoma incidence in males (OR=1.35, CI: 1.07–1.70), but the one with a risk allele at 3′UTR-8494 and a protective allele at intron 5-5229 had no effect on adenoma development (OR=0.85, CI: 0.66–1.09). Gender-related differences in adenoma risk were also noted with tobacco usage and protective effects of NSAIDs. Our analysis underscores the significance of the overall allelic architecture of Cox-2 as an important determinant for risk assessment

Modulation of Brain β-Endorphin Concentration by the Specific Part of the Y Chromosome in Mice

International audienceBackground: Several studies in animal models suggest a possible effect of the specific part of the Y-chromosome (Y NPAR) on brain opioid, and more specifically on brain b-endorphin (BE). In humans, male prevalence is found in autistic disorder in which observation of abnormal peripheral or central BE levels are also reported. This suggests gender differences in BE associated with genetic factors and more precisely with Y NPAR. Methodology/Principal Findings: Brain BE levels and plasma testosterone concentrations were measured in two highly inbred strains of mice, NZB/BlNJ (N) and CBA/HGnc (H), and their consomic strains for the Y NPAR. An indirect effect of the Y NPAR on brain BE level via plasma testosterone was also tested by studying the correlation between brain BE concentration and plasma testosterone concentration in eleven highly inbred strains. There was a significant and major effect (P,0.0001) of the Y NPAR in interaction with the genetic background on brain BE levels. Effect size calculated using Cohen's procedure was large (56% of the total variance). The variations of BE levels were not correlated with plasma testosterone which was also dependent of the Y NPAR. Conclusions/Significance: The contribution of Y NPAR on brain BE concentration in interaction with the genetic background is the first demonstration of Y-chromosome mediated control of brain opioid. Given that none of the genes encompassed by the Y NPAR encodes for BE or its precursor, our results suggest a contribution of the sex-determining region (Sry, carried by Y NPAR) to brain BE concentration. Indeed, the transcription of the Melanocortin 2 receptor gene (Mc2R gene, identified as the proopiomelanocortin receptor gene) depends on the presence of Sry and BE is derived directly from proopiomelanocortin. The results shed light on the sex dependent differences in brain functioning and the role of Sry in the BE system might be related to the higher frequency of autistic disorder in males

Aspirin induces cell death and caspase-dependent phosphatidylserine externalization in HT-29 human colon adenocarcinoma cells

The induction of cell death by aspirin was analysed in HT-29 colon carcinoma cells. Aspirin induced two hallmarks of apoptosis: nuclear chromatin condensation and increase in phosphatidylserine externalization. However, aspirin did not induce either oligonucleosomal fragmentation of DNA, decrease in DNA content or nuclear fragmentation. The effect of aspirin on Annexin V binding was inhibited by the caspase inhibitor Z-VAD.fmk, indicating the involvement of caspases in the apoptotic action of aspirin. However, aspirin did not induce proteolysis of PARP, suggesting that aspirin does not increase nuclear caspase 3-like activity in HT-29 cells. This finding may be related with the ‘atypical’ features of aspirin-induced apoptosis in HT-29 cells. © 1999 Cancer Research Campaig

Mirror, mirror on the wall: which microbiomes will help heal them all?

BACKGROUND: Clinicians have known for centuries that there is substantial variability between patients in their response to medications—some individuals exhibit a miraculous recovery while others fail to respond at all. Still others experience dangerous side effects. The hunt for the factors responsible for this variation has been aided by the ability to sequence the human genome, but this just provides part of the picture. Here, we discuss the emerging field of study focused on the human microbiome and how it may help to better predict drug response and improve the treatment of human disease. DISCUSSION: Various clinical disciplines characterize drug response using either continuous or categorical descriptors that are then correlated to environmental and genetic risk factors. However, these approaches typically ignore the microbiome, which can directly metabolize drugs into downstream metabolites with altered activity, clearance, and/or toxicity. Variations in the ability of each individual’s microbiome to metabolize drugs may be an underappreciated source of differences in clinical response. Complementary studies in humans and animal models are necessary to elucidate the mechanisms responsible and to test the feasibility of identifying microbiome-based biomarkers of treatment outcomes. SUMMARY: We propose that the predictive power of genetic testing could be improved by taking a more comprehensive view of human genetics that encompasses our human and microbial genomes. Furthermore, unlike the human genome, the microbiome is rapidly altered by diet, pharmaceuticals, and other interventions, providing the potential to improve patient care by re-shaping our associated microbial communities

Hydrologically-driven crustal stresses and seismicity in the New Madrid Seismic Zone

The degree to which short-term non-tectonic processes, either natural and anthropogenic, influence the occurrence of earthquakes in active tectonic settings or ‘stable’ plate interiors, remains a subject of debate. Recent work in plate-boundary regions demonstrates the capacity for long-wavelength changes in continental water storage to produce observable surface deformation, induce crustal stresses and modulate seismicity rates. Here we show that a significant variation in the rate of microearthquakes in the intraplate New Madrid Seismic Zone at annual and multi-annual timescales coincides with hydrological loading in the upper Mississippi embayment. We demonstrate that this loading, which results in geodetically observed surface deformation, induces stresses within the lithosphere that, although of small amplitude, modulate the ongoing seismicity of the New Madrid region. Correspondence between surface deformation, hydrological loading and seismicity rates at both annual and multi-annual timescales indicates that seismicity variations are the direct result of elastic stresses induced by the water load