The phase plane of moving discrete breathers

We study anharmonic localization in a periodic five atom chain with quadratic-quartic spring potential. We use discrete symmetries to eliminate the degeneracies of the harmonic chain and easily find periodic orbits. We apply linear stability analysis to measure the frequency of phonon-like disturbances in the presence of breathers and to analyze the instabilities of breathers. We visualize the phase plane of breather motion directly and develop a technique for exciting pinned and moving breathers. We observe long-lived breathers that move chaotically and a global transition to chaos that prevents forming moving breathers at high energies.Comment: 8 pages text, 4 figures, submitted to Physical Review Letters. See http://www.msc.cornell.edu/~houle/localization

Energy thresholds for discrete breathers in one-, two- and three-dimensional lattices

Discrete breathers are time-periodic, spatially localized solutions of equations of motion for classical degrees of freedom interacting on a lattice. They come in one-parameter families. We report on studies of energy properties of breather families in one-, two- and three-dimensional lattices. We show that breather energies have a positive lower bound if the lattice dimension of a given nonlinear lattice is greater than or equal to a certain critical value. These findings could be important for the experimental detection of discrete breathers.Comment: 10 pages, LaTeX, 4 figures (ps), Physical Review Letters, in prin

Discrete breathers in classical spin lattices

Discrete breathers (nonlinear localised modes) have been shown to exist in various nonlinear Hamiltonian lattice systems. In the present paper we study the dynamics of classical spins interacting via Heisenberg exchange on spatial $d$-dimensional lattices (with and without the presence of single-ion anisotropy). We show that discrete breathers exist for cases when the continuum theory does not allow for their presence (easy-axis ferromagnets with anisotropic exchange and easy-plane ferromagnets). We prove the existence of localised excitations using the implicit function theorem and obtain necessary conditions for their existence. The most interesting case is the easy-plane one which yields excitations with locally tilted magnetisation. There is no continuum analogue for such a solution and there exists an energy threshold for it, which we have estimated analytically. We support our analytical results with numerical high-precision computations, including also a stability analysis for the excitations.Comment: 15 pages, 12 figure

Optical creation of vibrational intrinsic localized modes in anharmonic lattices with realistic interatomic potentials

Using an efficient optimal control scheme to determine the exciting fields, we theoretically demonstrate the optical creation of vibrational intrinsic localized modes (ILMs) in anharmonic perfect lattices with realistic interatomic potentials. For systems with finite size, we show that ILMs can be excited directly by applying a sequence of femtosecond visible laser pulses at THz repetition rates. For periodic lattices, ILMs can be created indirectly via decay of an unstable extended lattice mode which is excited optically either by a sequence of pulses as described above or by a single picosecond far-infrared laser pulse with linearly chirped frequency. In light of recent advances in experimental laser pulse shaping capabilities, the approach is experimentally promising.Comment: 20 pages, 7 eps figures. Accepted, Phys. Rev.

Discrete breathers in dissipative lattices

We study the properties of discrete breathers, also known as intrinsic localized modes, in the one-dimensional Frenkel-Kontorova lattice of oscillators subject to damping and external force. The system is studied in the whole range of values of the coupling parameter, from C=0 (uncoupled limit) up to values close to the continuum limit (forced and damped sine-Gordon model). As this parameter is varied, the existence of different bifurcations is investigated numerically. Using Floquet spectral analysis, we give a complete characterization of the most relevant bifurcations, and we find (spatial) symmetry-breaking bifurcations which are linked to breather mobility, just as it was found in Hamiltonian systems by other authors. In this way moving breathers are shown to exist even at remarkably high levels of discreteness. We study mobile breathers and characterize them in terms of the phonon radiation they emit, which explains successfully the way in which they interact. For instance, it is possible to form ``bound states'' of moving breathers, through the interaction of their phonon tails. Over all, both stationary and moving breathers are found to be generic localized states over large values of $C$, and they are shown to be robust against low temperature fluctuations.Comment: To be published in Physical Review

Discovery of os cordis in the cardiac skeleton of chimpanzees (Pan troglodytes)

Cardiovascular diseases, especially idiopathic myocardial fibrosis, is one of the most significant causes of morbidity and mortality in captive great apes. This study compared the structure and morphology of 16 hearts from chimpanzees (Pan troglodytes) which were either healthy or affected by myocardial fibrosis using X-ray microtomography. In four hearts, a single, hyperdense structure was detected within the right fibrous trigone of the cardiac skeleton. High resolution scans and histopathology revealed trabecular bones in two cases, hyaline cartilage in another case and a focus of mineralised fibro-cartilaginous metaplasia with endochondral ossification in the last case. Four other animals presented with multiple foci of ectopic calcification within the walls of the great vessels. All hearts affected by marked myocardial fibrosis presented with bone or cartilage formation, and increased collagen levels in tissues adjacent to the bone/cartilage, while unaffected hearts did not present with os cordis or cartilago cordis. The presence of an os cordis has been described in some ruminants, camelids, and otters, but never in great apes. This novel research indicates that an os cordis and cartilago cordis is present in some chimpanzees, particularly those affected by myocardial fibrosis, and could influence the risk of cardiac arrhythmias and sudden death

Systematic Reviews of Animal Experiments Demonstrate Poor Human Clinical and Toxicological Utility

The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive Scopus biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. In 20 reviews in which clinical utility was examined, the authors concluded that animal models were either significantly useful in contributing to the development of clinical interventions, or were substantially consistent with clinical outcomes, in only two cases, one of which was contentious. These included reviews of the clinical utility of experiments expected by ethics committees to lead to medical advances, of highly-cited experiments published in major journals, and of chimpanzee experiments — those involving the species considered most likely to be predictive of human outcomes. Seven additional reviews failed to clearly demonstrate utility in predicting human toxicological outcomes, such as carcinogenicity and teratogenicity. Consequently, animal data may not generally be assumed to be substantially useful for these purposes. Possible causes include interspecies differences, the distortion of outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments, which was evident in at least 11 reviews. No reviews existed in which the majority of animal experiments were of good methodological quality. Whilst the effects of some of these problems might be minimised with concerted effort (given their widespread prevalence), the limitations resulting from interspecies differences are likely to be technically and theoretically impossible to overcome. Non-animal models are generally required to pass formal scientific validation prior to their regulatory acceptance. In contrast, animal models are simply assumed to be predictive of human outcomes. These results demonstrate the invalidity of such assumptions. The consistent application of formal validation studies to all test models is clearly warranted, regardless of their animal, non-animal, historical, contemporary or possible future status. Likely benefits would include, the greater selection of models truly predictive of human outcomes, increased safety of people exposed to chemicals that have passed toxicity tests, increased efficiency during the development of human pharmaceuticals and other therapeutic interventions, and decreased wastage of animal, personnel and financial resources. The poor human clinical and toxicological utility of most animal models for which data exists, in conjunction with their generally substantial animal welfare and economic costs, justify a ban on animal models lacking scientific data clearly establishing their human predictivity or utility

Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study

Objectives; Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods; Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results; The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (S.D.) HAQ-DI 1.1 (0.83)], with ‘grip’ and ‘activity’ being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = −0.53, P < 0.0001). Conclusion; The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope