Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Beams with a Varying Cross Section in the Generalized Strain Formulation for Flexure Modeling

Flexure joints are rapidly gaining ground in precision engineering because of their predictable behavior. However, their range of motion is limited due to a stress limitation and a loss of support stiffness in deformed configurations. The support stiffness can be significantly increased by using leafsprings of which the width and thickness vary over the length of the leafspring. This paper presents formulations for two beam elements with a varying cross section that can be used for the efficient modeling of these types of leafsprings. One of these beam-formulations includes the modeling of the warping due to torsion, which is shown to be essential for accurate modeling. The 90% accuracy in stiffness results and 80% accuracy in stress results, in comparison with results of finite element analyses, are sufficient for the evaluation of concept-designs. Optimizations show that the support stiffness of two typical flexure joints can be increased by a factor of up to 4.0 keeping the same range of motion, by allowing the cross section to vary over the length of the leafspring. In these two flexure joints, 98% of this improvement can already be obtained by only varying the thickness, and keeping a constant width

Derivation of a superelement with deformable interfaces – applied to model flexure joint

Design and optimization, as well as real time control, of flexure mechanisms require efficient but accurate models. The flexures can be modelled using beam elements and the frame parts can be modelled using superelements. Such a superelement efficiently models arbitrarily shaped bodies by few coordinates, using models obtained by model order reduction. The interfaces between the frame parts and the flexures often experience considerable deformation which affects the stiffness. To define the interface deformation in a reduced order model, this paper derives a multipoint constraint formulation, which relates the nodes on the deformable interface surface of a finite element model to a few coordinates. The multipoint constraints are imposed using a combination of the Lagrange multiplier method and master–slave elimination for efficient model order reduction. The resulting reduced order models are used in the generalized-strain multi-node superelement (GMS) that was defined in (Dwarshuis et al. in Multibody Syst. Dyn. 56(4):367–399, 2022). The interface deformations can be coupled to the cross-sectional deformation of higher order beam elements (i.e. beam elements of which the deformation of the cross-sections is explicitly taken into account). This paper applies this technique to model flexure joints, where the flexures are modelled with beam elements, and the frame components and critical connections using the GMS. This approach gives generally over 94% accurate stiffness, compared to nonlinear finite element models. The errors were often more than 50% lower than errors of models which only contain beam elements

A multinode superelement in the generalized strain formulation

Design and optimization of flexure mechanisms and real time high bandwidth control of flexure based mechanisms require efficient but accurate models. The flexures can be modeled using sophisticated beam elements that are implemented in the generalized strain formulation. However, complex shaped frame parts of the flexure mechanisms could not be modeled in this formulation. The generalized strain formulation for flexible multibody analysis defines the configuration of elements using a combination of absolute nodal coordinates and deformation modes. This paper defines a multinode superelement in this formulation, i.e., an element having its properties derived from a reduced linear finite element model. This is accomplished by defining a local element frame with the coordinates depending on the absolute nodal coordinates. The linear elastic deformation is defined with respect to this frame, where rotational displacements are defined using the off-diagonal terms of local rotation matrices. The element frame can be defined in multiple ways; the most accurate results are obtained if the resulting elastic rotations are as small as possible. The inertia is defined in two different ways: the so-called "full approach" gives more accurate results than the so-called "corotational approach" but requires a special term that is not available from standard finite element models. Simulations show that (flexure based) mechanisms can be modeled accurately using smart combinations of superelements and beam elements

Kinematically started efficient position analysis of deformed compliant mechanisms utilizing data of standard joints

Topology optimization of a flexure-based mechanism requires the properties of the mechanism in several deformed configurations. This paper presents a fast and accurate method to compute these configurations. It is generally applicable on mechanisms with complex standard flexure joints. First kinematic equations of the mechanism are derived by allowing the mechanism to move only in the directions for which it is designed. Secondly the configurations of the joints are approximated based on the rotations of the elements by which the joints are modeled. These orientations are obtained by a parameterization based on a priori knowledge of standard flexure joints. Finally, the resulting approximation is used as initial guess to obtain the configuration accurately, after which relevant properties like stiffness can be derived. For a manipulator with three complex joints the computation time was reduced up to a factor of 65 compared to a conventional method. When for optimization purposes an approximation is acceptable, the computation time can be reduced by a factor of 600, using a linear description of the deformation that remains in the first part of the method

Efficient Computation of Large Deformation of Spatial Flexure-Based Mechanisms in Design Optimizations

Design optimizations of flexure-based mechanisms take a lot of computation time, in particular when large deformations are involved. In an optimization procedure, statically deformed configurations of many designs have to be obtained, while finding the statically deformed configuration itself requires tens to hundreds of load step iterations. The kinematically started deformation method (KSD-method) (Dwarshuis, K.S., Aarts, R.G.K.M., Ellenbroek, M.H.M., and Brouwer, D.M., 2020, "Kinematically Started Efficient Position Analysis of Deformed Compliant Mechanisms Utilizing Data of Standard Joints," Mech. Mach. Theory, 152, p. 103911) computes deformed configurations fast by starting the computation from an approximation. This approximation is obtained by allowing the mechanism only to move in the compliant motion-direction, based on kinematic equations, using data of the flexure joints in the mechanism. This is possible as flexure-based mechanisms are typically designed to be kinematically determined in the motion directions. In this paper, the KSD-method is extended such that it can also be applied without joint-data, such that it is not necessary to maintain a database with joint-data. This paper also shows that the method can be used for mechanisms containing joints that allow full spatial motion. Several variants of the KSD-method are presented and evaluated for accuracy and required computation time. One variant, which uses joint-data, is 21 times faster and shows errors in stress and stiffness below 1% compared to a conventional multibody analysis on the same model. Another variant, which does not use joint-data, reduces the computation time by a factor of 14, keeping errors below 1%. The KSD-method is shown to be helpful in design optimizations of complex flexure mechanisms for large range of motion

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening