Three-dimensional particle tracking with subnanometer resolution using off-focus images

A three-dimensional (3D) particle tracking algorithm based on microscope off-focus images is presented in this paper. Subnanometer resolution in all three axes at 400 Hz sampling rate is achieved using a complementary metal-oxide-semiconductor (CMOS) camera. At each sampling, the lateral position of the spherical particle is first estimated by the centroid method. The axial position is then estimated by comparing the radius vector, which is converted from the off-focus two-dimensional image of the particle with no information loss, with an object-specific model, calibrated automatically prior to each experiment. Estimation bias and variance of the 3D tracking algorithm are characterized through analytical analysis. It leads to an analytical model, enabling prediction of the measurement performance based on calibration data. Finally, experimental results are presented to illustrate the performance of the measurement method in terms of precision and range. The validity of the theoretical analysis is also experimentally confirmed.     

Uncertainty analysis and variation reduction of three dimensional coordinate metrology. Part 1: geometric error decomposition

In this paper our study focuses on the uncertainty analysis and variation reduction of coordinate system estimation using discrete measurement data and is associated with the applications that deal with parts produced by end-milling processes and having complex geometry. This paper consists of three parts. Since the uncertainty of the estimated coordinate transformation arises from the geometric errors on a part surface, Part 1 is devoted to the study of surface geometric errors. In this study, according to the characteristics of end-milling processes the sampled geometric error is divided into two components, and a decomposition procedure is developed for geometric error decomposition. The results of surface geometric error decomposition will be used in Part 2 for uncertainty analysis and in Part 3 for variation reduction.     

Translational Study of Copy Number Variations in Schizophrenia

Rare copy number variations (CNVs) are part of the genetics of schizophrenia; they are highly heterogeneous and personalized. The CNV Analysis Group of the Psychiatric Genomic Consortium (PGC) conducted a large-scale analysis and discovered that recurrent CNVs at eight genetic loci were pathogenic to schizophrenia, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.23, 15q13.3, distal 16p11.2, proximal 16p11.2, and 22q11.2. We adopted a two-stage strategy to translate this knowledge into clinical psychiatric practice. As a screening test, we first developed a real-time quantitative PCR (RT-qPCR) panel that simultaneously detected these pathogenic CNVs. Then, we tested the utility of this screening panel by investigating a sample of 557 patients with schizophrenia. Chromosomal microarray analysis (CMA) was used to confirm positive cases from the screening test. We detected and confirmed thirteen patients who carried CNVs at these hot loci, including two patients at 1q21.1, one patient at 7q11.2, three patients at 15q13.3, two patients at 16p11.2, and five patients at 22q11.2. The detection rate in this sample was 2.3%, and the concordance rate between the RT-qPCR test panel and CMA was 100%. Our results suggest that a two-stage approach is cost-effective and reliable in achieving etiological diagnosis for some patients with schizophrenia and improving the understanding of schizophrenia genetics.     

The prediction of cutting forces in the ball-end milling process—II. Cut geometry analysis and model verification

This paper presents a model for the prediction of cutting forces in the ball-end milling process. The steps used in developing the force model are based on the mechanistic principles of metal cutting. The cutting forces are calculated on the basis of the engaged cut geometry, the underformed chip thickness distribution along the cutting edges, and the empirical relationships that relate the cutting forces to the undeformed chip geometry. A simplified cutter runout model, which characterizes the effect of cutter axis offset and tilt on the undeformed chip geometry, has been formulated. A model building procedure based on experimentally measured average forces and the associated runout data is developed to identify the numerical values of the empirical model parameters for the particular workpiece/cutter combination.     

Control of tip-to-sample distance in atomic force microscopy: a dual-actuator tip-motion control scheme

The control of tip-to-sample distance in atomic force microscopy (AFM) is achieved through controlling the vertical tip position of the AFM cantilever. In the vertical tip-position control, the required z motion is commanded by laser reading of the vertical tip position in real time and might contain high frequency components depending on the lateral scanning rate and topographical variations of the sample. This paper presents a dual-actuator tip-motion control scheme that enables the AFM tip to track abrupt topographical variations. In the dual-actuator scheme, an additional magnetic mode actuator is employed to achieve high bandwidth tip-motion control while the regular z scanner provides the necessary motion range. This added actuator serves to make the entire cantilever bandwidth available for tip positioning, and thus controls the tip-to-sample distance. A fast programmable electronics board was employed to realize the proposed dual-actuator control scheme, in which model cancellation algorithms were implemented to enlarge the bandwidth of the magnetic actuation and to compensate the lightly damped dynamics of the cantilever. Experiments were conducted to illustrate the capabilities of the proposed dual-actuator tip-motion control in terms of response speed and travel range. It was shown that while the bandwidth of the regular z scanner was merely a small fraction of the cantilever's bandwidth, the dual-actuator control scheme led to a tip-motion control system, the bandwidth of which was comparable to that of the cantilever, where the dynamics overdamped, and the motion range comparable to that of the z scanner.     

Lutein Inhibits the Migration of Retinal Pigment Epithelial Cells via Cytosolic and Mitochondrial Akt Pathways (Lutein Inhibits RPE Cells Migration)

During the course of proliferative vitreoretinopathy (PVR), the retinal pigment epithelium (RPE) cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF) can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation.     

Involvement of Rare Mutations of SCN9A,DPP4, ABCA13, and SYT14 in Schizophrenia and Bipolar Disorder

Rare mutations associated with schizophrenia (SZ) and bipolar disorder (BD) usually have high clinical penetrance; however, they are highly heterogeneous and personalized. Identifying rare mutations is instrumental in making the molecular diagnosis, understanding the pathogenesis, and providing genetic counseling for the affected individuals and families. We conducted whole-genome sequencing analysis in two multiplex families with the dominant inheritance of SZ and BD. We detected a G327E mutation of SCN9A and an A654V mutation of DPP4 cosegregating with SZ and BD in one three-generation multiplex family. We also identified three mutations cosegregating with SZ and BD in another two-generation multiplex family, including L711S of SCN9A, M4554I of ABCA13, and P159L of SYT14. These five missense mutations were rare and deleterious. Mutations of SCN9A have initially been reported to cause congenital insensitivity to pain and neuropathic pain syndromes. Further studies showed that rare mutations of SCN9A were associated with seizure and autism spectrum disorders. Our findings suggest that SZ and BD might also be part of the clinical phenotype spectra of SCN9A mutations. Our study also indicates the oligogenic involvement in SZ and BD and supports the multiple-hit model of SZ and BD.     

Uncertainty analysis and variation reduction of three dimensional coordinate metrology. Part 3: variation reduction

In this part of the paper, the uncertainty analysis of coordinate estimation for the case in which the sampled geometric errors are dominated by the random component is investigated. In practice, the uncertainty analysis of coordinate estimation using high-precision datum surfaces often falls into this type. In this paper, a sensitivity matrix, which serves as the theoretical basis of the uncertainty analysis, is presented to establish a linearized relationship between the variations of the coordinate estimation and the geometric errors of the part surface at the measurement points. Based on the sensitivity matrix, quantitative measures are derived for the prediction of coordinate variation. Computer simulation and experiments are conducted to verify the theoretical predictions when the surface geometric errors are small and dominated by the random component.     

Integrated planning for precision machining of complex surfaces—III. Compensation of dimensionai errors

This paper presents an approach that compensates machining errors in ball-end milling processes using the control-surface strategy. In the proposed approach, machining errors induced by cutter deflections are predicted from a surface generation model so that actual machining experiments and dimensional inspections are not required. Therefore, the proposed approach can be integrated into an integrated framework for machining planning in which prediction and compensation of dimensional errors take place in the process development phase rather than in the manufacturing phase of the production cycle. Based on the predictive capability of the surface generation model, a sensitivity function is defined so as to characterize the variations of the machining errors when perturbing the control surface. Using the defined sensitivity function, a compensated control surface can be constructed, based on which new cutting paths can be planned and “near-zero” surface dimensional errors can be accomplished. In order to verify the proposed strategy, actual production of a turbine blade die using a CNC machining center was conducted. By using the control-surface strategy with the sensitivity function approach, the maximum surface dimensional error is reduced from ± 340 to ± 10 μm.     

Integrated planning for precision machining of complex surfaces. Part 2: Application to the machining of a turbine blade die

The applications of the proposed cutting-path-adaptive-feedrate strategy, described in part 1 of this paper, to real three-dimensional complex surfaces are examined. Its applications to the aerospace, automobile, and die-mold industries are of particular interest. As an example, the proposed strategy is used in planning the machining of a turbine blade die. This process consists of rough milling (using the stock material), and the subsequent semi-finish and finish milling operations. Computer simulations along with experimental verifications are presented in this paper.