Coarse-graining of overdamped Langevin dynamics via the Mori-Zwanzig formalism

The Mori–Zwanzig formalism is applied to derive an equation for the evolution of linear observables of the overdamped Langevin equation. To illustrate the resulting equation and its use in deriving approximate models, a particular benchmark example is studied both numerically and via a formal asymptotic expansion. The example considered demonstrates the importance of memory effects in determining the correct temporal behaviour of such systems

Analysis of cell size effects in atomistic crack propagation

We consider crack propagation in a crystalline material in terms of bifurcation analysis. We provide evidence that the stress intensity factor is a natural bifurcation parameter, and that the resulting bifurcation diagram is a periodic "snaking curve". We then prove qualitative properties of the equilibria and convergence rates of finite-cell approximations to the "exact" bifurcation diagram

Talking Drugs: The Burden of Proof in Post-\u3ci\u3eGarcetti\u3c/i\u3e Speech Retaliation Claims

Law Enforcement agencies fire their employees for speaking out in favor of drug legalization, which leads the employees to sue their former employers for violating their First Amendment Free Speech rights. These employee claims fall under the U.S. Supreme Court’s complex speech retaliation test, most recently articulated in Garcetti v. Ceballos. The analysis reveals that circuit courts are inconsistent as to who bears the burden of proving that they prevail under “Pickering balancing,” and how they should construct that burden. This Comment argues that U.S. Supreme Court precedent demands that the employer bears the “Pickering balancing” burden, and that the Court should require employers to meet their burden with clear and convincing evidence. Further, when applying the speech retaliation test to law enforcement employees criticizing the war on drugs, the Court should rule that it constitutes speech as a “citizen on a matter of public concern,” and should abandon the quasimilitary rule when engaging in “Pickering balancing.

Stochastic homogenization for a scalar viscoelastic model exhibiting stress–strain hysteresis

Motivated by rate-independent stress-strain hysteresis observed in filled rubber, this article considers a scalar viscoelastic model in which the constitutive law is random and varies on a lengthscale which is small relative to the overall size of the solid. Using stochastic two-scale convergence as introduced by Bourgeat, Mikelic and Wright, we obtain the homogenized limit of the evolution, and demonstrate that under certain hypotheses, the homogenized model exhibits hysteretic behaviour which persists under asymptotically slow loading. These results are illustrated by means of numerical simulations in a particular one-dimensional instance of the model

The effect of topology on the structure and free energy landscape of DNA kissing complexes

We use a recently developed coarse-grained model for DNA to study kissing complexes formed by hybridization of complementary hairpin loops. The binding of the loops is topologically constrained because their linking number must remain constant. By studying systems with linking numbers -1, 0 or 1 we show that the average number of interstrand base pairs is larger when the topology is more favourable for the right-handed wrapping of strands around each other. The thermodynamic stability of the kissing complex also decreases when the linking number changes from -1 to 0 to 1. The structures of the kissing complexes typically involve two intermolecular helices that coaxially stack with the hairpin stems at a parallel four-way junction

Systematic derivation of hybrid coarse-grained models

Molecular dynamics represents a key enabling technology for applications ranging from biology to the development of new materials. However, many real-world applications remain inaccessible to fully-resolved simulations due their unsustainable computational costs and must therefore rely on semi-empirical coarse-grained models. Significant efforts have been devoted in the last decade towards improving the predictivity of these coarse-grained models and providing a rigorous justification of their use, through a combination of theoretical studies and data-driven approaches. One of the most promising research effort is the (re)discovery of the Mori-Zwanzig projection as a generic, yet systematic, theoretical tool for deriving coarse-grained models. Despite its clean mathematical formulation and generality, there are still many open questions about its applicability and assumptions. In this work, we propose a detailed derivation of a hybrid multi-scale system, generalising and further investigating the approach developed in [Español, P., EPL, 88, 40008 (2009)]. Issues such as the general coexistence of atoms (fully-resolved degrees of freedom) and beads (larger coarse-grained units), the role of the fine-to-coarse mapping chosen, and the approximation of effective potentials are discussed. The theoretical discussion is supported by numerical simulations of a monodimensional nonlinear periodic benchmark system with an open-source parallel Julia code, easily extensible to arbitrary potential models and fine-to-coarse mapping functions. The results presented highlight the importance of introducing, in the macroscopic model, non-constant fluctuating and dissipative terms, given by the Mori-Zwanzig approach, to correctly reproduce the reference fine-grained results, without requiring ad-hoc calibration of interaction potentials and thermostats

Target Markets for Grain and Cotton Marketing Consultants and Market Information Systems

This paper examines the use of market consultants and market information systems by grain and cotton producers. A model of producer demand for marketing information and consultants is proposed that decomposes price received into exogenous and endogenous components. The analysis is based on a survey of over 1,600 producers. The results suggest that expenditures on market information systems and market consultants are not independent and, more specifically, expenditures on marketing consultants substitute for expenditures on market information systems.expected utility, market information, marketing, risk, Tobit, Marketing,

Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells

Impact and experiences of delayed discharge: A mixed-studies systematic review

BACKGROUND: The impact of delayed discharge on patients, health-care staff and hospital costs has been incompletely characterized. AIM: To systematically review experiences of delay from the perspectives of patients, health professionals and hospitals, and its impact on patients' outcomes and costs. METHODS: Four of the main biomedical databases were searched for the period 2000-2016 (February). Quantitative, qualitative and health economic studies conducted in OECD countries were included. RESULTS: Thirty-seven papers reporting data on 35 studies were identified: 10 quantitative, 8 qualitative and 19 exploring costs. Seven of ten quantitative studies were at moderate/low methodological quality; 6 qualitative studies were deemed reliable; and the 19 studies on costs were of moderate quality. Delayed discharge was associated with mortality, infections, depression, reductions in patients' mobility and their daily activities. The qualitative studies highlighted the pressure to reduce discharge delays on staff stress and interprofessional relationships, with implications for patient care and well-being. Extra bed-days could account for up to 30.7% of total costs and cause cancellations of elective operations, treatment delay and repercussions for subsequent services, especially for elderly patients. CONCLUSIONS: The poor quality of the majority of the research means that implications for practice should be cautiously made. However, the results suggest that the adverse effects of delayed discharge are both direct (through increased opportunities for patients to acquire avoidable ill health) and indirect, secondary to the pressures placed on staff. These findings provide impetus to take a more holistic perspective to addressing delayed discharge

An electric analog type response spectrum analyzer for earthquake excitation studies

The design of a response spectrum analyzer for earthquake excitation studies is described. Electric analog techniques are used, with a series inductance, capacitance, and resistance circuit forming a direct analog to the mechanical structure. The circuit arrangement permits a determination of system response for a sequence of periods at constant damping. Provision is made for obtaining zero damping in the circuit. An arbitrary function generator of the variable width film photoelectric cell type is described. The results obtained with the function generator- spectrum analyzer system for a half-sine wave pulse are compared with the mathematically obtained exact answers for the zero damping case, and the accuracy of the system is shown to be satisfactory