Finite Sized Atomistic Simulations of Screw Dislocations

The interaction of screw dislocations with an applied stress is studied using atomistic simulations in conjunction with a continuum treatment of the role played by the far field boundary condition. A finite cell of atoms is used to consider the response of dislocations to an applied stress and this introduces an additional force on the dislocation due to the presence of the boundary. Continuum mechanics is used to calculate the boundary force which is subsequently accounted for in the equilibrium condition for the dislocation. Using this formulation, the lattice resistance curve and the associated Peierls stress are calculated for screw dislocations in several close packed metals. As a concrete example of the boundary force method, we compute the bow out of a pinned screw dislocation; the line-tension of the dislocation is calculated from the results of the atomistic simulations using a variational principle that explicitly accounts for the boundary force.Comment: LaTex, 20 pages, 11 figure

Putting health status guided COPD management to the test:protocol of the MARCH study

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible and usually progressive. Current guidelines, among which the Dutch, have so far based their management strategy mainly on lung function impairment as measured by FEV(1), while it is well known that FEV(1) has a poor correlation with almost all features of COPD that matter to patients. Based on this discrepancy the GOLD 2011 update included symptoms and impact in their treatment algorithm proposal. Health status measures capture both symptoms and impact and could therefore be used as a standardized way to capture the information a doctor could otherwise only collect by careful history taking and recording. We hypothesize that a treatment algorithm that is based on a simple validated 10 item health status questionnaire, the Clinical COPD Questionnaire (CCQ), improves health status (as measured by SGRQ) and classical COPD outcomes like exacerbation frequency, patient satisfaction and health care utilization compared to usual care based on guidelines. METHODS/DESIGN: This hypothesis will be tested in a randomized controlled trial (RCT) following 330 patients for two years. During this period general practitioners will receive treatment advices every four months that are based on the patient’s health status (in half of the patients, intervention group) or on lung function (the remaining half of the patients, usual care group). DISCUSSION: During the design process, the selection of outcomes and the development of the treatment algorithm were challenging. This is discussed in detail in the manuscript to facilitate researchers in designing future studies in this changing field of implementation research. TRIAL REGISTRATION: Netherlands Trial Register, NTR264

Bauschinger effect in thin metal films: Discrete dislocation dynamics study

The effects of dislocation climb on plastic deformation during loading and unloading are studied using a two-dimensional discrete dislocation dynamics model. Simulations are performed for polycrystalline thin films passivated on both surfaces. Dislocation climb lowers the overall level of the stress inside thin films and reduces the work hardening rate. Climb decreases the density of dislocations in pile-ups and reduces back stresses. These factors result in a smaller Bauschinger effect on unloading compared to simulations without climb. As dislocations continue to climb at the onset of unloading and the dislocation density continues to increase, the initial unloading slope increases with decreasing unloading rate. Because climb disperses dislocations, fewer dislocations are annihilated during unloading, leading to a higher dislocation density at the end of the unloading step.Engineering and Applied Science

Tracing tumorigenesis in a solid tumor model at single-cell resolution

Characterizing the complex composition of solid tumors is fundamental for understanding tumor initiation, progression and metastasis. While patient-derived samples provide valuable insight, they are heterogeneous on multiple molecular levels, and often originate from advanced tumor stages. Here, we use single-cell transcriptome and epitope profiling together with pathway and lineage analyses to study tumorigenesis from a developmental perspective in a mouse model of salivary gland squamous cell carcinoma. We provide a comprehensive cell atlas and characterize tumor-specific cells. We find that these cells are connected along a reproducible developmental trajectory: initiated in basal cells exhibiting an epithelial-to-mesenchymal transition signature, tumorigenesis proceeds through Wnt-differential cancer stem cell-like subpopulations before differentiating into luminal-like cells. Our work provides unbiased insights into tumor-specific cellular identities in a whole tissue environment, and emphasizes the power of using defined genetic model systems

Contrasting magma emplacement mechanisms within the Rogart igneous complex, NW Scotland, record the switch from regional contraction to strike-slip during the Caledonian orogeny

The Rogart igneous complex is unique within the northern Scottish Caledonides because it comprises an apparent continuum of magma types that records a progressive change in emplacement mechanisms related to large-scale tectonic controls. Syn-D2 leucogranites and late-D2 quartz monzodiorites were emplaced during crustal thickening and focused within the broad zone of ductile deformation associated with the Naver Thrust. In contrast, emplacement of the post-D2 composite central pluton was controlled by development of a steeply dipping dextral shear zone along the Loch Shin Line, interpreted as an anti-Riedel shear within the Great Glen Fault system. The mantle-derived nature of the late-to-post-D2 melts implies that the Naver Thrust and the Loch Shin Line were both crustal-scale structures along which magmas were channelled during deformation. A U–Pb zircon age of 425±1.5 Ma for the outer component of the central pluton provides an upper limit on regional deformation and metamorphism within host Moine rocks. These findings are consistent with the view that a fundamental change in tectonic regime occurred in the Scottish Caledonides at c. 425 Ma, corresponding to the switch from regional thrusting that resulted from the collision of Baltica and Laurentia, to the development of the orogen-parallel Great Glen Fault system

The use of a direct bronchial challenge test in primary care to diagnose asthma

Many asthmatics in primary care have mild symptoms and lack airflow obstruction. If variable expiratory airflow limitation cannot be determined by spirometry or peak expiratory flow, despite a history of respiratory symptoms, a positive bronchial challenge test (BCT) can confirm the diagnosis of asthma. However, BCT is traditionally performed in secondary care. In this observational real-life study, we retrospectively analyze 5-year data of a primary care diagnostic center carrying out BCT by histamine provocation. In total, 998 primary care patients aged ≥16 years underwent BCT, without any adverse events reported. To explore diagnostic accuracy, we examine 584 patients with a high pretest probability of asthma. Fifty-seven percent of these patients have a positive BCT result and can be accurately diagnosed with asthma. Our real-life data show BCT is safe and feasible in a suitably equipped primary care diagnostic center. Furthermore, it could potentially reduce diagnostic referrals to secondary care

Curved Tails in Polymerization-Based Bacterial Motility

The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2

Pinning of a solid--liquid--vapour interface by stripes of obstacles

We use a macroscopic Hamiltonian approach to study the pinning of a solid--liquid--vapour contact line on an array of equidistant stripes of obstacles perpendicular to the liquid. We propose an estimate of the density of pinning stripes for which collective pinning of the contact line happens. This estimate is shown to be in good agreement with Langevin equation simulation of the macroscopic Hamiltonian. Finally we introduce a 2--dimensional mean field theory which for small strength of the pinning stripes and for small capillary length gives an excellent description of the averaged height of the contact line.Comment: Plain tex, 12 pages, 3 figures available upon reques