Generic Model Refactorings

Many modeling languages share some common concepts and principles. For example, Java, MOF, and UML share some aspects of the concepts\ud of classes, methods, attributes, and inheritance. However, model\ud transformations such as refactorings specified for a given language\ud cannot be readily reused for another language because their related\ud metamodels may be structurally different. Our aim is to enable a\ud flexible reuse of model transformations across various metamodels.\ud Thus, in this paper, we present an approach allowing the specification\ud of generic model transformations, in particular refactorings, so\ud that they can be applied to different metamodels. Our approach relies\ud on two mechanisms: (1) an adaptation based mainly on the weaving\ud of aspects; (2) the notion of model typing, an extension of object\ud typing in the model-oriented context. We validated our approach by\ud performing some experiments that consisted of specifying three well\ud known refactorings (Encapsulate Field, Move Method, and Pull Up Method)\ud and applying each of them onto three different metamodels (Java,\ud MOF, and UML)

α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo

Effects of resuscitation with crystalloid fluids on cardiac function in patients with severe sepsis

<p>Abstract</p> <p>Background</p> <p>The use of hypertonic crystalloid solutions, including sodium chloride and bicarbonate, for treating severe sepsis has been much debated in previous investigations. We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension.</p> <p>Methods</p> <p>Ninety-four severe sepsis patients with hypotension were randomly assigned to three groups. The patients received the following injections within 15 min at initial treatment: Ns group (n = 32), 5 ml/kg normal saline; Hs group (n = 30), with 5 ml/kg 3.5% sodium chloride; and Sb group (n = 32), 5 ml/kg 5% sodium bicarbonate. Cardiac output (CO), systolic blood pressure, mean arterial pressure (MAP), body temperature, heart rate, respiratory rate and blood gases were measured.</p> <p>Results</p> <p>There were no differences among the three groups in CO, MAP, heart rate or respiratory rate during the 120 min trial or the 8 hour follow-up, and no significant differences in observed mortality rate after 28 days. However, improvement of MAP and CO started earlier in the Sb group than in the Ns and Hs groups. Sodium bicarbonate increased the base excess but did not alter blood pH, lactic acid or [HCO₃]^-values; and neither 3.5% hypertonic saline nor 5% sodium bicarbonate altered the Na⁺, K⁺, Ca²⁺or Cl^-levels.</p> <p>Conclusion</p> <p>All three crystalloid solutions may be used for initial volume loading in severe sepsis, and sodium bicarbonate confers a limited benefit on humans with severe sepsis.</p> <p>Trial registration</p> <p>ISRCTN36748319.</p

Minimum Strictly Convex Quadrangulations of Convex Polygons

We present a linear-time algorithm that decomposes a convex polygon conformally into a minimum number of strictly convex quadrilaterals. Moreover, we characterize the polygons that can be decomposed without additional vertices inside the polygon, and we present a linear-time algorithm for such decompositions, too. As an application, we consider the problem of constructing a minimum conformal refinement of a mesh in the three-dimensional space, which approximates the surface of a workpiece. It turns out that this problem is NP-hard, and we present a linear-time algorithm with a constant approximation ratio of 4