An Updating Method for Finite Element Models of Flexible-Link Mechanisms Based on an Equivalent Rigid-Link System

This paper proposes a comprehensive methodology to update dynamic models of flexible-link mechanisms (FLMs) modeled through ordinary differential equations. The aim is to correct mass, stiffness, and damping matrices of dynamic models, usually based on nominal and uncertain parameters, to accurately represent the main vibrational modes within the bandwidth of interest. Indeed, the availability of accurate models is a fundamental step for the synthesis of effective controllers, state observers, and optimized motion profiles, as those employed in modern control schemes. The method takes advantage of the system dynamic model formulated through finite elements and through the representation of the total motion as the sum of a large rigid-body motion and the elastic deformation. Model updating is not straightforward since the resulting model is nonlinear and its coordinates cannot be directly measured. Hence, the nonlinear model is linearized about an equilibrium point to compute the eigenstructure and to compare it with the results of experimental modal analysis. Once consistency between the model coordinates and the experimental data is obtained through a suitable transformation, model updating has been performed solving a constrained convex optimization problem. Constraints also include results from static tests. Some tools to improve the problem conditioning are also proposed in the formulation adopted, to handle large dimensional models and achieve reliable results. The method has been experimentally applied to a challenging system: a planar six-bar linkage manipulator. The results prove their capability to improve the model accuracy in terms of eigenfrequencies and mode shapes

Differential Hox expression in murine embryonic stem cell models of normal and malignant hematopoiesis

The Hox family are master transcriptional regulators of developmental processes, including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4), and Meis1, along with several individual Hox proteins, are implicated in stem cell expansion during embryonic development, with gene dosage playing a significant role in the overall function of the integrated Hox network. To investigate the role of this network in normal and aberrant, early hematopoiesis, we employed an in vitro embryonic stem cell differentiation system, which recapitulates mouse developmental hematopoiesis. Expression profiles of Hox, Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic differentiation process and compared with the effects of expressing the leukemic oncogene Tel/PDGFR;2. During normal differentiation the Hoxa cluster, Pbx1 and Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39) and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa cluster genes (a9, a10, a11, and a13) maintained or increased expression at the hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7 and a9, were differentially expressed after short-term oncogenic (Tel/PDGFR;2) induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1, and Pbx have previously been implicated in regulating target genes involved in hematopoietic stem cell (HSC) expansion and leukemic progression. These results provide direct evidence that transcriptional flux through the Hox network occurs at very early stages during hematopoietic differentiation and validates embryonic stem cell models for gaining insights into the genetic regulation of normal and malignant hematopoiesis

Atmospheric monitoring for the Pembina Cardium CO2 Monitoring Project using open path laser technology

AbstractThis study aimed to assess remote sensing methods using open path laser technology as a tool for atmospheric monitoring of CO2 storage sites. CH4 and CO2 open path detection systems were tested at the Penn West Pembina Cardium CO2 enhanced oil recovery monitoring pilot. The tested CH4 detection system was found to be very sensitive and small increases in the gas concentration due to controlled releases were easily distinguishable. The detection capability of the CO2 detection system was impacted by the larger natural background concentration of CO2. Where possible, CH4 should be used as an indicator due to the better detection capabilities and smaller background concentration variations compared to CO2

Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs

Effects of spatial confinement on migratory properties of Dictyostelium discoideum cells.

Migratory environments of various eukaryotic cells, such as amoeba, leukocytes and cancer cells, typically involve spatial confinement. Numerous studies have recently emerged, aimed to develop experimental platforms that better recapitulate the characteristics of the cellular microenvironment. Using microfluidic technologies, we show that increasing confinement of Dictyostelium discoideum cells into narrower micro-channels resulted in a significant change in the mode of migration and associated arrangement of the actomyosin cytoskeleton. We observed that cells tended to migrate at constant speed, the magnitude of which was dependent on the size of the channels, as was the locomotory strategy adopted by each cell. Two different migration modes were observed, pseudopod-based and bleb-based migration, with bleb based migration being more frequent with increasing confinement and leading to slower migration. Beside the migration mode, we found that the major determinants of cell speed are its protrusion rate, the amount of F-actin at its leading edge and the number of actin foci. Our results highlighted the impact of the microenvironments on cell behavior. Furthermore, we developed a novel quantitative movement analysis platform for mono-dimensional cell migration that allows for standardization and simplification of the experimental conditions and aids investigation of the complex and dynamic processes occurring at the single-cell level

Multi-domain optimization of the eigenstructure of controlled underactuated vibrating systems

The paper proposes a multi-domain approach to the optimization of the dynamic response of an underactuated vibrating linear system through eigenstructure assignment, by exploiting the concurrent design of the mechanical properties, the regulator and state observers. The approach relies on handling simultaneously mechanical design and controller synthesis in order to enlarge the set of the achievable performances. The underlying novel idea is that structural properties of controlled mechanical systems should be designed considering the presence of the controller through a concurrent approach: this can considerably improve the optimization possibilities. The method is, first, developed theoretically. Starting from the definition of the set of feasible system responses, defined through the feasible mode shapes, an original formulation of the optimality criterion is proposed to properly shape the allowable subspace through the optimal modification of the design variables. A proper choice of the modifications of the elastic and inertial parameters, indeed, changes the space of the allowable eigenvectors that can be achieved through active control and allows obtaining the desired performances. The problem is then solved through a rank-minimization with constraints on the design variables: a convex optimization problem is formulated through the \u201csemidefinite embedding lemma\u201d and the \u201ctrace heuristics\u201d. Finally, experimental validation is provided through the assignment of a mode shape and of the related eigenfrequency to a cantilever beam controlled by a piezoelectric actuator, in order to obtain a region of the beam with negligible oscillations and the other one with large oscillations. The results prove the effectiveness of the proposed approach that outperforms active control and mechanical design when used alone

Pole assignment for active vibration control of linear vibrating systems through Linear Matrix Inequalities

This paper proposes a novel method for pole placement in linear vibrating systems through state feedback and rank-one control. Rather than assigning all the poles to the desired locations of the complex plane, the proposed method exactly assigns just the dominant poles, while the remaining ones are free to assume arbitrary positions within a pre-specified region in the complex plane. Therefore, the method can be referred to as "regional pole placement". A two-stage approach is proposed to accomplish both the tasks. In the first stage, the subset of dominant poles is assigned to exact locations by exploiting the receptance method, formulated for either symmetric or asymmetric systems. Then, in the second stage, a first-order model formulated with a reduced state, together with the theory of Linear Matrix Inequalities, are exploited to cluster the subset of the unassigned poles into some stable regions of the complex plane while keeping unchanged the poles assigned in the first stage. The additional degrees of freedom in the choice of the gains, i.e., the non-uniqueness of the solution, is exploited through a semidefinite programming problem to reduce the control gains. The method is validated by means of four meaningful and challenging test-cases, also borrowed from the literature. The results are also compared with those of classic partial pole placement, to show the benefits and the effectiveness of the proposed approach

Branch-and-lift algorithm for deterministic global optimization in nonlinear optimal control

This paper presents a branch-and-lift algorithm for solving optimal control problems with smooth nonlinear dynamics and potentially nonconvex objective and constraint functionals to guaranteed global optimality. This algorithm features a direct sequential method and builds upon a generic, spatial branch-and-bound algorithm. A new operation, called lifting, is introduced, which refines the control parameterization via a Gram-Schmidt orthogonalization process, while simultaneously eliminating control subregions that are either infeasible or that provably cannot contain any global optima. Conditions are given under which the image of the control parameterization error in the state space contracts exponentially as the parameterization order is increased, thereby making the lifting operation efficient. A computational technique based on ellipsoidal calculus is also developed that satisfies these conditions. The practical applicability of branch-and-lift is illustrated in a numerical example. © 2013 Springer Science+Business Media New York

Anti-angiogenic therapies for the treatment of angiosarcoma: a clinical update

Summary: Angiosarcomas are rare aggressive endothelial tumours, and are associated with a poor prognosis. Due to their vascular nature, there is great interest in their response to anti-angiogenic agents. A number of small prospective studies have reported angiosarcoma response to vascular-targeted agents, including agents that target vascular endothelial growth factor. To date, the response to these agents has been disappointing, and similar to the response observed in other soft tissue sarcoma subtypes. This short review will summarise the recent data in this field

Validation of MIPAS-ENVISAT NO2 operational data

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument was launched aboard the environmental satellite ENVISAT into its sun-synchronous orbit on 1 March 2002. The short-lived species NO₂ is one of the key target products of MIPAS that are operationally retrieved from limb emission spectra measured in the stratosphere and mesosphere. Within the MIPAS validation activities, a large number of independent observations from balloons, satellites and ground-based stations have been compared to European Space Agency (ESA) version 4.61 operational NO₂ data comprising the time period from July 2002 until March 2004 where MIPAS measured with full spectral resolution. Comparisons between MIPAS and balloon-borne observations carried out in 2002 and 2003 in the Arctic, at mid-latitudes, and in the tropics show a very good agreement below 40 km altitude with a mean deviation of roughly 3%, virtually without any significant bias. The comparison to ACE satellite observations exhibits only a small negative bias of MIPAS which appears not to be significant. The independent satellite instruments HALOE, SAGE II, and POAM III confirm in common for the spring-summer time period a negative bias of MIPAS in the Arctic and a positive bias in the Antarctic middle and upper stratosphere exceeding frequently the combined systematic error limits. In contrast to the ESA operational processor, the IMK/IAA retrieval code allows accurate inference of NO₂ volume mixing ratios under consideration of all important non-LTE processes. Large differences between both retrieval results appear especially at higher altitudes, above about 50 to 55 km. These differences might be explained at least partly by non-LTE under polar winter conditions but not at mid-latitudes. Below this altitude region mean differences between both processors remain within 5% (during night) and up to 10% (during day) under undisturbed (September 2002) conditions and up to 40% under perturbed polar night conditions (February and March 2004). The intercomparison of ground-based NDACC observations shows no significant bias between the FTIR measurements in Kiruna (68° N) and MIPAS in summer 2003 but larger deviations in autumn and winter. The mean deviation over the whole comparison period remains within 10%. A mean negative bias of 15% for MIPAS daytime and 8% for nighttime observations has been determined for UV-vis comparisons over Harestua (60° N). Results of a pole-to-pole comparison of ground-based DOAS/UV-visible sunrise and MIPAS mid-morning column data has shown that the mean agreement in 2003 falls within the accuracy limit of the comparison method. Altogether, it can be indicated that MIPAS NO₂ profiles yield valuable information on the vertical distribution of NO₂ in the lower and middle stratosphere (below about 45 km) during day and night with an overall accuracy of about 10–20% and a precision of typically 5–15% such that the data are useful for scientific studies. In cases where extremely high NO₂ occurs in the mesosphere (polar winter) retrieval results in the lower and middle stratosphere are less accurate than under undisturbed atmospheric conditions