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The stability of a thin wall workpiece milling process is investigated through a single degree of freedom system that mimics the milling machine operation. The stability lobes were computed by using the Enhanced Multistage Homotopy Perturbation Method (EMHPM), the Chebyshev Collocation, the Semi-Discretization and Full-Discretization methods. A comparison of these methods with respect to experimental data and computational time was made to identify the method with the best performance in terms of accuracy and computational time in order to optimize the material removal rate by using the Simulated Annealing algorithm (SA). Then, we have used the EMHPM with the SA algorithm to establish the optimal cutting conditions. Based on numerical simulation computed by combining the SA algorithm with the EMHPM and experimental data, we have determined the optimum cutting condition in less than 400 ms which is 100 times faster than the off-line methods used to find the stability lobes.

Indeterminate pulmonary nodules are a common radiographic finding and require further evaluation because of the concern for lung cancer.We developed an algorithm to assign patients to a low- or high-risk category for lung cancer, based on a combination of serum biomarker levels and nodule size.For the serum biomarker assay, we determined levels of carcinoembryonic antigen, α1-antitrypsin, and squamous cell carcinoma antigen. Serum data and nodule size from a training set of 509 patients with (n = 298) and without (n = 211) lung cancer were subjected to classification and regression tree and logistic regression analyses. Multiple models were developed and tested in an independent, masked validation set for their ability to categorize patients with (n = 203) or without (n = 196) lung cancer as being low- or high-risk for lung cancer.In all models, a large percentage of individuals in the validation study with small nodules (1 cm) were assigned to the low-risk group, and a large percentage of individuals with large nodules (≥3 cm) were assigned to the high-risk group. In the validation study, the classification and regression tree algorithm had overall sensitivity, specificity, and positive and negative predictive values for determining lung cancer of 88%, 82%, 84%, and 87%, respectively. The logistic regression model had overall sensitivity, specificity, and positive and negative predictive values of 80%, 89%, 89%, and 81%, respectively.Integration of biomarkers with lung nodule size has the potential to help guide the management of patients with indeterminate pulmonary nodules.

Conference Paper presented at The Joint International Conference of the XII International Conference on Mechanisms and Mechanical Transmissions (MTM) and the XXIII International Conference on Robotics (Robotics ’16) In the field of parallel kinematics few designs use highly deformable elements to obtain the end effector movement. Most compliant mechanisms rely on notches or shape changes to simulate a standard kinematic joint. In this work a kinematic model of a simple parallel continuum mechanism that combines a deformable element and cable is presented. The kinematic model is used to study the workspace of the manipulator and is validated by experimental measurements of a prototype. The authors wish to acknowledge the financial support received from the Spanish Government through the Ministerio de Economía y Competitividad (Project DPI2015-64450-R) and the Regional Government of the Basque Country through the Departamento de Educación, Universidades e Investigación (Project IT445-10) and UPV/EHU under program UFI 11/29.

High performance position control in machine tools can only be achieved modelling the dynamic behavior of the mechatronic system composed by the motor, transmission and control during the design stage. In this work, a complex analytical model of a ball screw drive is presented and integrated in a mechatronic model of the actuator to predict the dynamic behaviour and analyze the impact of each component of the transmission. First, a simple 2 degrees of freedom model is presented, and is analysis sets the basis for the development of a more complex model of several degrees of freedom, whose resulting fundamental transfer functions are represented using natural and modal coordinates. The modeling in modal coordinates carries a reduction of the transfer function that reduces computational work. The two models are compared and experimentally validated in time and frequency domain by means of experimental tests carried out on a specifically developed ball screw drive test bench Ministerio de Economía y Competitividad: Project DPI2015-64450-R (MINECO/FEDER, UE) University of the Basque Country (UPV/EHU) under the program UFI 11/29 Departamento de Educación, Política Lingüística y Cultura” of the regional government of the Basque Country (IT949-16)

In this work, a methodology for the assessment of the geometrical accuracy of a multiaxis machine, the type usually called multitasking machine, was fully developed. For this purpose, the well-known formulation by Denavit and Hartenberg was applied. Multitasking machines are derived from lathes in which turrets are substituted by milling spindles, or they are also derived from milling centres including a turning headstock on the machine bed. In both cases, they are kinematically much more complex than lathes or milling centres, where it is not easy to previously calculate the consequence of parallelism and squareness errors between elements and joints. In this paper, a radical new ‘multitasking’ machine model was studied. Literature shows a complete lack of values for this kind of machine. In the methodology presented here, errors were introduced as additional geometric parameters in each elemental transformation matrices, resulting in the real transformation matrix for a multitasking machine. Elemental errors and the way to introduce them into the Denavit and Hartenberg matrices are fully described. Some simulations are tested, giving a useful outcome regarding the sensitivity of the machine with respect to the feasible assembly errors or errors produced by light misalignments caused by the machine tool continuous use.

Aeronautics is a business in a continuous growing sector and aircraft manufacturing is without any doubt a high-priced process. Each part of the aircraft and particularly engine parts represent the most expensive elements due to the difficulty of manufacturing their complex geometry. In this case, the test piece to carry out the study has been the Blisk. The predicted lead time for one of these components is so long that any progress related to the manufacturing process implies a considerable amount of saving. Due to the critical nature of the parts common defects such as chatter marks, smearings or pickups originated during the manufacturing process that will reduce the part life are not allowed. In this article, considering the existing demand of better manufacturing technologies a study case based on an Inconel 718 Blisk finishing operations study is developed. A static model for machining forces prediction is developed to finally validate it with the real machining forces measured during the machining process.

Introduction Most pulmonary nodules found on imaging studies are indeterminate, but because of the concern for lung cancer, all patients require further evaluation with resultant radiation risk, significant cost, and delays in diagnosis. We hypothesized that a diagnostic blood test based on detection of autoantibodies against cancer antigens would be able to distinguish a benign nodule from lung cancer. Methods We identified a panel of 25 serum autoantibodies associated with NSCLC and constructed a protein microarray containing the autoantigens. We tested the microarray with human sera (from 125 patients with NSCLC and 125 matched controls with a benign nodule) and attempted to develop a classification algorithm that would separate the two groups. Results In the training data set the logistic regression c-index statistic was 0.691; in the validation data set, the model predicting the score generated from the training set model had a c-index of 0.490. The relationship between the score and outcome (final diagnosis) was not statistically significant ( p = 0.460). Conclusions When the current panel of antigens and assay format was used, classification algorithms based on levels of autoantibodies to cancer antigens did not prove to have statistically significant value for predicting the presence of cancer. We suggest that there are inherent biological limitations to this approach.

The objective of this work is to develop a manipulator of 5 degrees of freedom for micromilling. It consists of a XY stage under a 3PRS compliant parallel mechanism, obtaining the advantages of the compliant joints as are higher repetitiveness, smoother motion and a higher bandwidth, due to the high precision demanded from the process, under 0.1 μm. In this work, the dynamics of the compliant stage will be developed. The modelling approach is based on the use of the Principle of Energy Equivalence combined with the Boltzmann-Hamel equations to analyze the rotational dynamics of the platform. A pseudo-rigid model has been assumed for the compliant joints, calculating the flexural and torsional stiffness by FEA. Finally, a prototype has been built and some preliminary results are shown comparing the simulation and the measurements. The authors of this paper wish to acknowledge the financial support received from the Spanish Government via the Ministerio de Economía y Competitividad (Project DPI2015-64450-R), the ERDF of the European Union, the Government of the Basque Country (Project GIC07/78, IT445-10 and SAIOTEK 2013 SAI13/245, SPC13UN011), and the University of the Basque Country (Zabalduz-2012)

This paper deals with the static characterisation of a parallel manipulator for routing processes. Since accuracy and surface finishing are critical in all machining processes, the performance of a parallel machine is analysed in this paper in terms of these parameters. Using a previously developed static analysis methodology, the stiffness of the machine structure is obtained and used as an input for a process model. This approach allows the static behaviour of the machine to be evaluated in terms of the surface location error for a given routing operation in the manipulator workspace. The study focusses on certain discrete points in the operational workspace for each direction of the tool feed. Then, the global behaviour of the machine is presented using surface location maps. Furthermore, some static constraints are imposed to obtain the static workspace of the manipulator for the routing process.

This work deals with the characterization of a three stage multivariable tool used for high-performance milling and the modelling of its dynamic behaviour to predict the stability against chatter. The influence of the variable pitch, variable helix and variable rake angle on each cutting edge of the tool is modeled to calculate the stability lobes diagrams. The proposed approach includes a mechanistic milling forces model and a cutting coefficients characterization procedure along with a modification of the Enhanced Multistage Homotopy Perturbation Method (EMHPM) to capture the multivariable phenomena of the tool in stability prediction, resulting in an accurate method to reproduce the regenerative vibration problem in end milling. Experimental data is provided to validate the followed approach for this new tool concept.

Boring operations of deep holes with a slender boring bar are often hindered by the precision because of their low static stiffness and high deformations. Because of that, it is not possible to remove much larger depths of cuts than the nose radius of the tool, unlike the case of turning and face milling operations, and consequently, the relationship between the cutting force distribution, tool geometry, feed rate and depth of cut becomes non-linear and complex. This problem gets worse when working with a rotating boring head where apart from the cutting forces and the variation of the inclination angle because of shape boring, the bar and head are affected by de centrifugal forces. The centrifugal forces, and therefore the centrifugal deflection, will vary as a function of the rotating speed, boring bar mass distribution and variable radial position of the bar in shape boring. Taking in to account all this effects, a load and deformation model was created. This model has been experimentally validated to use as a corrector factor of the radial position of the U axis in the boring head.

Chatter vibrations produced during turning of slender parts or boring with flexible tools lead to a wavy work surface, and reduce the spindle headstock life span as well. This study deals with the problem of chatter prediction in straight turning of non-rigid parts, making use of round inserts. A stability model for straight turning has been developed using the Chebyshev collocation method for the first. This algorithm allows the introduction of an accurate round insert edge geometry, discretising the lead position angle and the variable cutting coefficients of the forces model along the edge. The method is applied to a SDOF system by means of a specially designed testpart and demonstrates its usefulness to determine chatter-free conditions.

Modern industry requires high-precision machines and processes. This requirement implies the determination and reduction of all possible sources of error. For turning, a main error is related to machine–tool–workpiece deformation caused by cutting force. On the other hand, current turning centers are structurally more complicated than conventional lathes. However, stiffness values for this kind of machine are not described yet in literature. Thus, the aim of this work is to provide stiffness values for this type of machines clamping a common workpiece. To obtain this information an experimental methodology to measure static stiffness along kinematic chain of the turning center is proposed. The method may be useful for both users and machine manufacturers in order to consider this factor in the general error budget of the turning process. At the same time, stiffness values for lathes with a Y-axis incorporated in a three-axis turret and equipped with living tools are registered.

Ever increasingly, universities have to face the demands of their students regarding tools and methods to complete their education in preparation for the industrial environment. On the other hand, the university has to meet a Research and Development function oriented to the improvement of the competitiveness of that environment. These are two different functions that the university must unite to offer an optimum service. Hence, the university needs tools that can meet this dual function: teaching and researching. This paper proposes the concept of a “Glass Machine” as a dual purpose approach based on the adaptation of machine tools to satisfy that dual function. This concept has been applied to a machine tool by means of two machines: a turn-milling centre and a feed-drive test bench, which have been used for practices in the subjects of 4th and 5th year of Industrial Engineering, allowing at the same time the usual research activity of the High Performance Machining Team. In short, this work is about the optimization of the available resources of the university, thus satisfying the needs of the students and the industrial environment.

This paper provides an integrated approach for designing large milling machines, taking both mass reduction of mobile structural components and the maximum material removal rate into account. This approach considers a representative milling operation and a productivity target as a starting point, and then deals with the design of the machine to achieve the targeted productivity with structural components of minimum mass. The procedure is based on modeling the interactions between process and machine by means of a stability model of the milling process in modal coordinates. The model allows the identification of the mechanical design parameters that limit the productivity as well as the threshold values that must be met to ensure the targeted productivity. Those values are reached in an iterative procedure that minimizes the mass of the critical structural components of the machine. This approach has been applied to the re-design of an actual milling machine, on which, once built and adjusted, the machining tests conducted have shown increases above 100% in productivity, consuming at the same time 13% less energy due to mass reduction above 20% in mobile structural components. In this way, an eco-efficient milling machine that performs highly productive machining processes has been designed and built.

BACKGROUND: Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized. METHODS: Serum samples from patients enrolled in the Cancer and Leukemia Group B 80303 phase 3 trial, “Randomized Study of Gemcitabine With Versus Without Bevacizumab in Patients With Locally Advanced or Metastatic Adenocarcinoma of the Pancreas” were used to discover novel biomarkers. For the discovery phase, 40 sera were selected based on length of survival and type of therapy, and subjected to liquid chromatography coupled to tandem mass spectrometry analysis (LC-MS-MS). The top features (proteins) were then further selected for validation by enzyme-linked immunosorbent assay (ELISA). RESULTS: Quantification by nano–LC-MS-MS resulted in 1452 peptides mapping to 156 proteins across all 40 samples, 92 of which had 2 or more peptides. After curation of the data, the authors selected 1 putative prognostic protein, alpha 1-antichymotrypsin (AACT), and 2 putative predictive proteins, histidine-rich glycoprotein (HRG) and complement factor H (CFH), for validation by ELISA. AACT was found to be negatively correlated with overall survival (τ = −0.30 [−0.38, −0.22]; P < .00001). There was no evidence for interaction with bevacizumab and HRG, but there was some evidence for a weak positive correlation of HRG with overall survival (τ = 0.11 [0.03, 0.19]; P < .01). CFH was found to be neither a predictive nor a prognostic factor for overall survival. CONCLUSIONS: AACT may be a useful prognostic marker in patients with advanced stage pancreatic carcinoma, although additional validation studies are needed. Cancer 2011;. © 2011 American Cancer Society.

High-speed machining has improved performance in manufacturing sectors such as the aeronautical, automotive, and mould and die industries. However, one problem of reaching such high speeds is the self-excitation of the spindle-tool system during the machining process. This so-called chatter vibration produces several negative effects: a reduction in surface quality and accuracy, and in tool and spindle life. Nowadays, it is still the most common limitation to increased productivity and quality of metal-removal operations. Although theoretically calculated stability-lobe diagrams can be used to calculate stable cutting conditions, some uncertainties affect the accuracy of this solution. This paper presents a method based on experimental tests where an inclined plane in the workpiece is machined at several spindle speeds. The gradual increase of the axial depth of cut allows the milling to be interrupted when chatter is detected. The final result is that the stability lobes are machined in the workpiece. This method can be used for process optimization and avoiding trial and error tests to determine optimal depths of cut and spindle speeds. The creation of a database with the optimal cutting conditions for a given spindle-tool holder-tool system can help the computer aided manufacturing (CAM) programmer select the cutting conditions that maximize the material removal rate and avoid vibration problems. The method presented is especially suitable for small- and medium-sized workshops where operators are unfamiliar with analytical methods or modelling techniques. It is an interesting way of saving money that does not require complex knowledge, and can easily be applied without additional costs owing to its simplicity.

New iron-zinc chlorine single crystals of Fe1.5Zn1.5B7O13Cl boracite were grown by chemical transport reactions in closed quartz ampoules, at a temperature of 1173 K. The crystal structure was characterized by X-ray powder diffraction (XRD) using the Rietveld refinement method and belongs to the trigonal/rombohedral system with space group R3c (No. 161). The cell parameters were a = 8.5726(1) angstroms, c = 21.0116(4) angstroms, V = 1337.26(3) angstroms3 and Z = 6. The refinement successfully proceeded and ended with sound merit figure values chi2 = 2.25, R(B) = 6.12%. Chemical analysis was performed with X-ray energy dispersive spectroscopy (EDS) and X-ray fluorescence (XRF). Ferroelectric nano and micro reoriented domains were found in this material using polarizing optical microscopy (PLM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The examination by TEM showed that in the trigonal/rombohedral system of Fe1.5Zn1.5B7O13Cl nanodomain structures exist. Thin (50-100 nm) mostly planar domains parallel to (100) were frequently observed in Fe1.5Zn1.5B7O13Cl boracite.

Chatter is the most classical problem in machining. It is prone to occur in low rigidity structures generating poor surface quality and harmful vibrations which could damage any part of the machine-tool system. In finishing operations, the effect of the tool nose radius should be taken into account in order to obtain safe and reliable cutting conditions. The present paper uses a simple SDOF model to study the stability during finishing operations.

This article deals with the new development of a family of router milling tools for the high-performance milling of carbon fiber reinforced plastics. The new milling tools are shaped by multiple left-hand and right-hand helical edges, which form small pyramidal edges along the cutting length. Several substrates and coatings have been tested including AlTiN and the new naCO with nanocrystalline structure. After the analysis of tests and modifications on the tool prototypes, the final result is a series of routing endmills optimized for carbon fiber composites defining the influence of each of milling tool features on tool performance, which was not clearly established till date. The specific cutting forces, tool wear, and others aspects are discussed in detail.

A protease digestion strategy was incorporated into single-point stability of unpurified proteins from rates of H/D exchange (SUPREX), which is a hydrogen/deuterium (H/D) exchange- and mass spectrometry-based assay for the detection of protein-ligand binding. Single-point SUPREX is an abbreviated form of SUPREX in which protein-ligand binding interactions are detected by measuring the increase in a protein's thermodynamic stability upon ligand binding. The new protease digestion protocol provides a noteworthy increase in the efficiency of single-point SUPREX because peptide masses can be determined with greater precision than intact protein masses in the matrix-assisted laser desorption ionization (MALDI) readout of single-point SUPREX. The protocol was evaluated in test screens on two model protein systems, including cyclophilin A (CypA) and the minor allele variant of human alanine:glyoxylate aminotransferase (AGTmi). The test screening results obtained on both proteins revealed that the peptide readout of the single-point SUPREX-protease digestion protocol was more efficient than the intact protein readout of the original single-point SUPREX protocol at discriminating hits and nonhits. In addition to this improvement in screening efficiency, the protease digestion strategy described here is expected to significantly increase the generality of the single-point SUPREX assay.

γ-Al 2 O 3 modified supports with bimodal pore-size distributions were prepared by the addition of different types of natural sepiolites (α or β) into alumina. The supports were characterized by nitrogen physisorption, mercury porosimetry, X-ray diffraction, HRTEM and DTA techniques. A wide range of S BET (94–238 m 2 g − 1 ), pore volumes (0.3–0.82 cm 3 g − 1 ), and pore sizes were obtained in the supports depending on the type of sepiolite and its concentration added into alumina. The pore sizes were distributed as follows: mesopores around 1.8 nm in radius, mesopores in the radius range 3.0–25 nm and macropores between 25 and 300 nm in radius. The shape of the pore-size distributions depended on the type of sepiolite: the modal peak for pores larger than 3.0 nm was broad with β-type sepiolites and narrow with α-type sepiolites. The mesopore and macropore sizes can be controlled by the type of sepiolite as well as its concentration added to alumina.

This paper presents a model for the prediction of surface topography in peripheral milling operations taking into account that the tool vibrates during the cutting process. The model includes the effect of tool vibrations in the equations of the cutting edge paths, which are transformed into equivalent polynomial equations and solved for discrete positions along the feed direction by applying a standard root finder. Through this procedure, surface topography generation is simplified with respect to other models in literature. The model allows the topography, the roughness values and the form errors of the milled surface to be predicted. Cutting test results show good agreement with model predictions.

This paper presents a model for the topography prediction of ball-end milled surfaces, considering the tool parallel axis offset. First, the equations of cutting edge trajectories and the envelope equation of the material swept by the tool are derived. Later, the trajectories are cut by planes perpendicular to the feed direction obtaining a set of transcendental equations that are solved by transforming them to polynomial equations through Chebyshev expansions. This procedure presents the advantage on previous models in literature of not requiring any starting point to achieve the solution. Finally, experimental results are presented and compared to the model predictions.

In this paper, a procedure for the kinematic design of a 3-PRS compliant parallel manipulator of 3 degrees of freedom is proposed. First, under the assumption of small displacements, the solid body kinematics of the 3-PRS has been studied, performing a comprehensive analysis of the inverse and forward kinematic problem, and calculating the rotations that the revolute and spherical flexure joints must perform. Then, after defining some design requirements and therefore the necessary displacements to fulfill, a design process based on the finite element calculations has been stablished, giving the necessary guidelines to reach the optimal solution on a 3-PRS compliant mechanism. Also, a prototype has been tested, using a coordinate measuring machine to verify its dimensions and the resulting displacements in the end effector and the actuated joints. Finally, those measurements have been compared with the FEM and the rigid body kinematics predictions, contrasting the validity of those two modelling approaches for the kinematic design of compliant mechanisms. The authors of this paper wish to acknowledge the financial support received from the Spanish Government via the Ministerio de Educación y Ciencia (Project DPI2011-22955) and Ministerio de Economía y Competitividad (Project DPI2015-64450-R), the ERDF of the European Union, the Government of the Basque Country (Project GIC07/78, IT445-10 and SAIOTEK 2013 SAI13/245, SPC13UN011), and the University of the Basque Country (Project EHUA13/30 and Zabalduz-2012). Thanks are also addressed to Dr. Jorge Presa and Alfonso Urzainki from Egile Corporation XXI for their valuable contributions.

In this paper, a three-dimensional dynamic model for the calculation of the stability lobes of low rigidity parts is applied for the prediction of chatter vibrations during the finish milling of aeronautical parts that include thin walls and thin floors. Hence, an accurate selection of both axial depth of cut and spindle speed can be done. The following methodology is applied: first, a modal analysis of the test device is performed; second, stability lobes are calculated; finally milling tests validate the approach. In the example included in this work, the lobes diagrams obtained for the thin floors are accurate, defining an approximate borderline of stability.

The structural properties of La 2 O 3 and Al 2 O 3 –La 2 O 3 binary oxides prepared by sol–gel were studied by XRD, HRTEM and UV–vis. The binary oxides with high lanthana contents show an amorphous structure after calcination at 650 °C. At calcination temperatures higher than 1000 °C there is a phase transformation from the amorphous state to the crystalline LaAlO 3 with a perovskite structure. The structure of La 2 O 3 is consistent with the hexagonal system; however, some crystalline microdomains with a monoclinic structure were detected by HRTEM. Islands of La 2 O 3 and LaAl 11 O 18 phases were detected at high lanthana concentration in the binary oxide. The modification in the coordination shell of the Al 3+ cations due to the interaction with La 3+ cations confirms the formation of phases with a perovskite structure and the presence of islands of the LaAl 11 O 18 phase.

The use of MALDI-TOF mass spectrometry as a means of analyzing the proteome has been evaluated extensively in recent years. One of the limitations of this technique that has impeded the development of robust data analysis algorithms is the variability in the location of protein ion signals along the x-axis. We studied technical variations of MALDI-TOF measurements in the context of proteomics profiling. By acquiring a benchmark data set with five replicates, we estimated 76% to 85% of the total variance is due to phase variation. We devised a lobster plot, so named because of the resemblance to a lobster claw, to help detect the phase variation in replicates. We also investigated a peak alignment algorithm to remove the phase variation. This operation is analogous to the normalization step in microarray data analysis. Only after this critical step can features of biological interest be clearly revealed. With the help of principal component analysis, we demonstrated that after peak alignment, the differences among replicates are reduced. We compared this approach to peak alignment with a model-based calibration approach in which there was known information about peaks in common among all spectra. Finally, we examined the potential value at each point in an analysis pipeline of having a set of methods available that includes parametric, semiparametric and nonparametric methods; among such methods are those that benefit from the use of prior information.

Knowledge of the scatter in the mass-observable relation is a key ingredient for a cosmological analysis based on galaxy clusters in a photometric survey. In this paper we aim to quantify the capability of the correlation function of galaxy cluster to constrain the intrinsic scatter $\sigma_{\ln M}$. We demonstrate how the linear bias measured in the correlation function of clusters can be used to determine the value of this parameter. The new method is tested in simulations of a $5, 000 deg^2$ optical survey up to $z \sim 1$, similar to the ongoing Dark Energy Survey (DES). Our results show that our method works better at lower scatter values. We can measured the intrinsic scatter $\sigma_{ln M} = 0.1$ with a standard deviation of $\sigma(\sigma_{ln M}) \sim 0.03$ using this technique. However, the expected intrinsic scatter of the DES RedMaPPer cluster catalog $\sigma_{ln M} \sim 0.2$ cannot be recovered with this method at suitable accuracy and precision because the area coverage is insufficient. For future photometric surveys with a larger area such as LSST and Euclid, the statistical errors will be reduced. Therefore, we forecast higher precision to measure the intrinsic scatter including the value mention before. We conclude that this method can be used as an internal consistency check method on their simplifying assumptions and complementary to cross-calibration techniques in multi-wavelength cluster observations, Comment: Accepted for publication on ApJ

The Dark Energy Camera is a new imager with a 2.2-degree diameter field of view mounted at the prime focus of the Victor M. Blanco 4-meter telescope on Cerro Tololo near La Serena, Chile. The camera was designed and constructed by the Dark Energy Survey Collaboration, and meets or exceeds the stringent requirements designed for the wide-field and supernova surveys for which the collaboration uses it. The camera consists of a five element optical corrector, seven filters, a shutter with a 60 cm aperture, and a CCD focal plane of 250 micron thick fully-depleted CCDs cooled inside a vacuum Dewar. The 570 Mpixel focal plane comprises 62 2kx4k CCDs for imaging and 12 2kx2k CCDs for guiding and focus. The CCDs have 15 microns x15 microns pixels with a plate scale of 0.263 arc sec per pixel. A hexapod system provides state-of-the-art focus and alignment capability. The camera is read out in 20 seconds with 6-9 electrons readout noise. This paper provides a technical description of the camera's engineering, construction, installation, and current status., Comment: submitted to AJ Corresponding Authors H. T. Diehl (diehl@fnal.gov)

Intratumoral B lymphocytes are an integral part of the lung tumor microenvironment. Interrogation of the antibodies they express may improve our understanding of the host response to cancer and could be useful in elucidating novel molecular targets. We used two strategies to explore the repertoire of intratumoral B cell antibodies. First, we cloned VH and VL genes from single intratumoral B lymphocytes isolated from one lung tumor, expressed the genes as recombinant mAbs, and used the mAbs to identify the cognate tumor antigens. The Igs derived from intratumoral B cells demonstrated class switching, with a mean VH mutation frequency of 4%. Although there was no evidence for clonal expansion, these data are consistent with antigen-driven somatic hypermutation. Individual recombinant antibodies were polyreactive, although one clone demonstrated preferential immunoreactivity with tropomyosin 4 (TPM4). We found that higher levels of TPM4 antibodies were more common in cancer patients, but measurement of TPM4 antibody levels was not a sensitive test for detecting cancer. Second, in an effort to focus our recombinant antibody expression efforts on those B cells that displayed evidence of clonal expansion driven by antigen stimulation, we performed deep sequencing of the Ig genes of B cells collected from seven different tumors. Deep sequencing demonstrated somatic hypermutation but no dominant clones. These strategies may be useful for the study of B cell antibody expression, although identification of a dominant clone and unique therapeutic targets may require extensive investigation.

In this paper, a 3D dynamic model for the prediction of the stability lobes of high speed milling is presented, considering the combined flexibility of both tool and workpiece. The main aim is to avoid chatter vibrations on the finish milling of aeronautical parts, which include thin walls and thin floors. In this way the use of complex fixtures is eliminated. Hence, an accurate selection of both axial depth of cut and spindle speed can be accomplished. The model has been validated by means of a test device that simulates the behaviour of a thin floor.

A new zinc brome boracite Zn3B7O13Br has been grown by a chemical transport reaction in closed quartz ampoules at 920 K. The crystal structure was characterized by Rietveld refinement. Ferroelectric nano and micro reorientable domains were found in this material using polarizing optical microscopy (PLM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Chemical analysis was performed with x-ray energy dispersive spectroscopy (EDX). In the crystal, a new structure transition at 586 K from orthorhombic (Pca 21) to cubic cell () has been found. This transition was corroborated by differential scanning calorimetry (DSC).

BACKGROUND. Early stage lung cancer has a variable prognosis, and there are currently no markers that predict which patients will recur. This study examined the relation between tumor-regulatory T (Treg) cells and total tumor-infiltrating T-cell lymphocytes (TIL) to determine whether they correlated with recurrence. METHODS. The authors reviewed all patients in our tissue databank from 1996 to 2001 and identified 64 consecutive pathologic stage I non-small cell lung cancer (NSCLC) patients who had surgical resection and at least a 2.5 years disease-free follow-up or documented recurrence within 2 years. Immunohistochemical analyses were performed on paraffin-embedded lung cancer tissue and the relation between Treg cells, TIL, and disease-specific survival was determined. A risk index was devised deductively for various possible combinations of Treg cells and TIL. RESULTS. Treg cells and TIL were detected in 33 of 64 (51%) and 53 of 64 (83%) patients, respectively. When data were analyzed by using a Treg/TIL Combination Risk Index, patients with high-risk and intermediate-risk indices had hazard ratios of 8.2 (P = .007) and 3.3 (P = .109), respectively. CONCLUSIONS. Patients with stage I NSCLC who have a higher proportion of tumor Treg cells relative to TIL had a significantly higher risk of recurrence. These data may be useful, particularly if combined with a panel of tumor markers, to suggest at the time of diagnosis which patients with seemingly early-stage NSCLC will relapse. Cancer 2006. © 2006 American Cancer Society.

High speed machining of low rigidity structures is a widely used process in the aeronautical industry. Along the machining of this type of structures, the so-called monolithic components, large quantities of material are removed using high removal rate conditions, with the risk of the instability of the process. Very thin walls will also be milled, with the possibility of lateral vibration of them in some cutting conditions and at some stages of machining. Chatter is an undesirable phenomenon in all machining processes, causing a reduction in productivity, low quality of the finished workpieces, and a reduction of the machine-spindle's working life. In this study, a method for obtaining the instability or stability lobes, applicable when both the machine structure and the machined workpiece have similar dynamic behaviours, is presented. Thus, a 3-dimensional lobe diagram has been developed based on the relative movement of both systems, to cover all the intermediate stages of the machining of the walls. This diagram is different and more exact than the one that arises out of the mere superposition of the machine and the workpiece lobe diagrams. A previous step of rejecting resonance modes that are not involved in the milling at the bottom zones of the thin walls must be previously performed. Finally, the proposed method has been validated, by machining a series of thin walls, applying cutting conditions contrasted with the limits previously obtained in the three-dimensional lobe diagram.

At present, airframes are mainly composed of monolithic components, instead of small parts joined using welding or riveting. Ribs, stringers, spars, and bulkheads can be included in this category. After milling, they are assembled and joined to the aircraft skins, which have also been milled. The aim of these parts is to obtain a good strength-weight ratio, owing to their homogeneity. The milling of a monolithic structural part implies removing up to 95 per cent of the weight from the raw block material. Therefore, the main objective is to achieve the highest removal rate possible. However, conditions required to achieve this (high feed, large depth of cut) in milling imply high cutting forces, which in turn induce part deflection or vibrations in those zones (thin walls and floors) where stiffness is not sufficiently high. These static and dynamic problems often lead to inaccuracy of geometry, roughness, and possible damage to the machine spindle. This paper proposes a working methodology for efficient process planning, based on previous analysis of the static and dynamic phenomena that can occur during high-speed cutting. This methodology provides several steps that can be taken in order to minimize the bending and vibration effects; suggests optimal monitoring methods to detect process instability; and describes the best way to tune the cutting conditions and chip load, by means of simulation at different machining stages. In this way, the reliability of aeronautical production significantly increases. The global approach presented in this paper has been applied to two test pieces and two real parts, which were milled without suffering either static or dynamic problems.

Cyclophilin A (CypA) was recently reported to be overexpressed in non–small-cell lung cancer, and represents a potentially novel therapeutic target. To determine the role of CypA in oncogenesis, stable RNA interference (RNAi)–mediated knockdown of CypA was established in two non–small-cell lung cancer cell lines (ADLC-5M2 and LC-103H), and these cells were grown as xenografts in severe combined immunodeficient mice. Tumor cell proliferation, apoptosis, and angiogenesis were measured by Ki67, terminal deoxyribonucleotidyl transferase–mediated dUTP nick-end labeling, and CD31 immunohistochemistry, respectively. Tumor glucose metabolism was assessed by fluorodeoxyglucose positron emission tomography imaging. Knockdown of CypA correlated in vivo with slower growth, less fluorodeoxyglucose uptake, decreased proliferation, and a greater degree of apoptosis in the tumors. These results establish the relevance of CypA to tumor growth in vivo, specifically to proliferation and apoptosis. Elucidation of the precise role of CypA in these pathways may lead to new targeted therapies for lung cancer.

The use of MALDI-TOF mass spectrometry as a means of analyzing the proteome has been evaluated extensively in recent years. One of the limitations of this technique that has impeded the development of robust data analysis algorithms is the variability in the location of protein ion signals along the x-axis. We studied technical variations of MALDI-TOF measurements in the context of proteomics profiling. By acquiring a benchmark data set with five replicates, we estimated 76% to 85% of the total variance is due to phase variation. We devised a lobster plot, so named because of the resemblance to a lobster claw, to help detect the phase variation in replicates. We also investigated a peak alignment algorithm to remove the phase variation. This operation is analogous to the normalization step in microarray data analysis. Only after this critical step can features of biological interest be clearly revealed. With the help of principal component analysis, we demonstrated that after peak alignment, the differences among replicates are reduced. We compared this approach to peak alignment with a model-based calibration approach in which there was known information about peaks in common among all spectra. Finally, we examined the potential value at each point in an analysis pipeline of having a set of methods available that includes parametric, semiparametric and nonparametric methods; among such methods are those that benefit from the use of prior information.

Direct matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of human serum yielded ion signals from only a fraction of the total number of peptides and proteins expected to be in the sample. We increased the number of peptide and protein ion signals observed in the MALDI-TOF mass spectra analysis of human serum by using a prefractionation protocol based on liquid phase isoelectric focusing electrophoresis. This pre-fractionation technique facilitated the MALDI-TOF MS detection of as many as 262 different peptide and protein ion signals from human serum. The results obtained from three replicate fractionation experiments on the same serum sample indicated that 148 different peptide and protein ion signals were reproducibly detected using our isoelectric focusing and MALDI-TOF MS protocol.

Explicit Dynamic equations are needed for simulation and control in the field of Mechatronics. Several classical methods are available to get Dynamic equations. Regarding those methods that aim exclusively at the equations relating applied torques and motion generated, i.e. avoiding any calculus of joint wrenches, Analytical mechanics offers several approaches. For serial mechanisms, Lagrange equations are very convenient and systematic. However, finding such mathematical expressions can be cumbersome when facing closed-loop mechanisms even with the help of Lagrange multipliers. Moreover, this is quite complex if spatial rotations are considered, and hence, generalized coordinates are very much coupled in the expressions of Lagrange functions to be differentiated. Boltzmann-Hamel equations come to help in this regard. In this paper, authors show the finding of the dynamic equations of the \(3\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{P} RS\) lower-mobility parallel manipulator using the Boltzmann-Hamel equations and exploring the effect of coupled freedoms in the rotation of the end-effector.

Flexure stages are widely used in the field of micro and nanopositioning because of their repeatability and precision, which is due to the lack of joints that induces uncertainty. In the present Twork, a XY flexure stage has been analyzed and redesigned to reduce the axis cross-coupling, which is due to a parasitic motion in the amplification stage of the mechanism. The performed modifications result in a high reduction of the undesired motion, while maintaining a similar amplification and natural frequencies. The main advantage of the redesign is that the cross-coupling reduction is achieved mechanically, instead of using the position control loops.

The domain structures of Zn(3)B(7)O(13)Cl, Zn(3)B(7)O(13)Br and Zn(3)B(7)O(13)I boracite single crystals were studied by means of polarized light in conjunction with electron microscopy. Single crystals of the three compositions were grown by chemical transport reactions in closed quartz ampoules, at a temperature of 900 degreesC and were examined by polarizing optical microscopy (PLM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For both PLM and SEM, the same as-grown samples were used without having to resort to metallization of the crystal faces. For TEM the single crystals were crushed and mounted on holey carbon films. Comparative electron microscope images were useful for revealing the domain structure of these ferroelectric/ferroelastic materials previously observed between the crossed polars of an optical microscope. X-ray diffraction analysis of the pulverized crystals was performed for this triad of halogen boracites containing zinc as a common metal.

The VISible imager instrument (VIS) on board the Euclid mission will deliver high resolution shape measurements of galaxies down to very faint limits (R ~ 25 at 10σ) in a large part of the sky, in order to infer the distribution of dark matter in the Universe. To help mitigate radiation damage effects that will accumulate in the detectors over the mission lifetime, the properties of the radiation induced traps needs to be known with as high precision as possible. For this purpose the trap pumping method will be employed as part of the in-orbit calibration routines. Using trap pumping it is possible to identify and characterise single traps in a Charge-Coupled Device (CCD), thus providing information such as the density, emission time constants and sub-pixel positions of the traps in the detectors. This paper presents the trap pumping algorithms used for the radiation testing campaign of the CCD273 detectors, performed by the Centre for Electronic Imaging (CEI) at the Open University, that will be used for the VIS instrument. The CCD273 is a four-phase device with uneven phase widths, which complicates the trap pumping analysis. However, we find that by optimising the trap pumping algorithms and analysis routines, it is possible to obtain sub-pixel and even sub-phase positional information about the traps. Further, by comparing trap pumping data with simulations, it is possible to gain more information about the effective electrode widths of the device.

Since the early demonstration of the ferroelectric effect in boracites, the physical properties of several of these materials have extensively been studied. The purpose of this contribution is to summarize recent results on structural and thermal properties in some members of this large family of ferroics.

In this paper, a mechatronic model of a planar parallel manipulator is developed and experimentally validated. The model considers the dynamics of the actuators, as well as the PID control algorithm with position, velocity and current cascaded loops and their timing. As our main contributions, the dynamics of the manipulator have been solved using the principle of equivalent energy to split up the closed-loop mechanism, and the torque calculated is regarded as a disturbance on the actuators, avoiding solving the forward dynamic problem. Also, the dynamics of the actuators take into account the inertia and the friction parameters, which have been experimentally identified by means of a grey-box identification method. Several experiments have been carried out on a prototype, varying the motion profile, the velocity and acceleration, and the position control gain. The results show a reasonable correlation and provide the basis for further discussion.

(+)-4-[(αR)-α-[(2S, 5R)-4-(iodopropen-2-yl)-2,5-dimethyl-1-piperazinyl]]-3-hydroxybenzyl]-N, N-diethylbenzamide (1), a novel radioiodinated derivative of the selective δ-opioid antagonist (+)-BW373U86, was synthesized and evaluated in vitro for binding to opioid receptor subtypes. This new compound was found to have high affinity (Ki = 0.57 ± 0.10 nM) and good selectivity for delta (δ) opioid receptors over mu (μ) (Ki μ/δ = 13.6) and kappa (K) (Ki K/6 = 175) receptors. The corresponding 123 I and 125 I derivatives were prepared by oxidative radioiododestannylation from a trans-vinyltributyltin precursor. The radiochemical yield was 72-78% EOS (74.3 ± 2.6%, n = 3) for 125 I-1 and 40-62% EOS (53.9 ± 9.8%, n = 3) for 123 I-1. The specific activities were 200-300 mCi/μmol and >5,000 mCi/μmol for the 125 I and 123 I-labeled tracers, respectively.

The aim of the present work is to present a fast identification method to estimate the inertial and friction parameters of a rigid body dynamic model of an electromechanical actuator. These are the dominant effects that determine the dynamics of machines and although the inertia is easily predictable, the friction can only be accurately known performing experimental measurements. The work provides the mathematical aspects of the identification method as well as several practical aspects for its implementation. The procedure is applied to an actuator based on a motor and a gearbox, and a comparison of the torque estimated and the real one are provided.

Crystals of halogen manganese boracite, the mineral Mg3B7O13Cl, which is currently found in bedded sedimentary deposits of anhydrite, gypsum and halite, have been grown by chemical transport reactions and were examined by polarizing light microscopy and scanning electron microscopy. For both methods the same as-grown samples were used without having to metallize the crystal faces. Comparative electron microscope images were useful not only for observing the charging mechanism of an insulating sample bombarded by an electron beam but also for revealing the domain structure of these ferroelectric/ferroelastic materials previously observed between the crossed polars of a light microscope. EDS qualitative analysis of the crystal faces was performed for the three compositions under study, i.e. Mn3B7O13Cl, Mn3B7O13Br and Mn3B7O13I.

The static ferroelectric/ferroelastic domain structure in uncoated samples of Ni3B7O13Cl single crystals has been observed in the orthorhombic phase of this ferroic boracite by means of scanning electron microscopy and polarised light microscopy. Analytical and optical measurements on the crystal faces are also reported.

The aim of this work is to approach the difficulties students usually encounter when facing up to kinematic analysis of mechanisms. A deep understanding of the kinematic analysis is necessary to go a step further into design and synthesis of mechanisms. We can conclude from experience that supporting and complementing the theoretical lectures with specific software is really helpful. In this sense, software is used during the practical exercises, serving as an educational complementary tool reinforcing the knowledge acquired by the students. Several questions are outlined to the students, so that they are encouraged to justify the validity of their results. GIM software performs kinematic analysis and motion simulation of planar mechanisms. The main capacities of the software are: solving the position problem, computing velocities and accelerations, singular analysis, and visualization of instantaneous center of rotation, acceleration pole, curvature center and circle, fixed and moving centrodes and main circles. The graphical representation of all results favors the learning of the theoretical concepts explained in the subject and also, stimulates the critical reasoning the students must acquire.