Design and Fabrication of Components with Optimized Lattice Microstructures

The design and fabrication of components with optimized lattice microstructures is a new approach to creating lightweight high-performance objects. This paper introduces a unique and complete integration of design and fabrication leading to the creation of structural components with complex composite microstructures. Rather than a solid cast component with optimized outer shape this new approach leads to a component with an inner skeleton or microstructure maximizing one or more properties such as the stiffness-to-weight ratio. Three dimensional gradient materials are a natural outcome of this approach. An introduction to the design optimization and hybrid fabrication approach will be provided in addition to research progress and challenges through Spring 2004.Mechanical Engineerin

Elastic-Net Regularization in Learning Theory

Within the framework of statistical learning theory we analyze in detail the so-called elastic-net regularization scheme proposed by Zou and Hastie for the selection of groups of correlated variables. To investigate on the statistical properties of this scheme and in particular on its consistency properties, we set up a suitable mathematical framework. Our setting is random-design regression where we allow the response variable to be vector-valued and we consider prediction functions which are linear combination of elements ({\em features}) in an infinite-dimensional dictionary. Under the assumption that the regression function admits a sparse representation on the dictionary, we prove that there exists a particular ``{\em elastic-net representation}'' of the regression function such that, if the number of data increases, the elastic-net estimator is consistent not only for prediction but also for variable/feature selection. Our results include finite-sample bounds and an adaptive scheme to select the regularization parameter. Moreover, using convex analysis tools, we derive an iterative thresholding algorithm for computing the elastic-net solution which is different from the optimization procedure originally proposed by Zou and HastieComment: 32 pages, 3 figure

Microstructure and chemical composition of Roman orichalcum coins emitted after the monetary reform of Augustus (23 B.C.)

A collection of ancient Roman orichalcum coins, i.e., a copper-zinc alloy, minted under the reigns from Caesar to Domitianus, have been characterised using scanning electron microscopy (SEM-EDS) and electron microprobe analysis (EMPA). We studied, for the first time, coins emitted by Romans after the reforms of Augustus (23 B.C.) and Nero (63-64 A.D). These coins, consisting of asses, sestertii, dupondii and semisses, were analysed using non- and invasive analyses, aiming to explore microstructure, corrosive process and to acquire quantitative chemical analysis. The results revealed that the coins are characterized by porous external layers, which are affected by dezincification and decuprification processes. As pictured by the X-ray maps, the elemental distribution of Cu and Zn shows patterns of depletion that in some cases penetrate in deep up to 1 mm. The composition of the un-corroded nucleus is a Cu-Zn alloy containing up to 30% of Zn, typical of coins produced via cementation process

Ultrasound shear wave elastography for liver disease. A critical appraisal of the many actors on the stage

In the last 12\u200a-\u200a18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(\uae) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(\uae), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4\u200acm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8\u200acm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(\uae) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(\uae) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2\u200a-\u200a3\u200acm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1\u200a-\u200a2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(\uae), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(\uae) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i.\u200ae., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5\u200aHz and in larger regions; thus this technique is also termed real-time 2\u200aD SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(\uae) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. \ub7 The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e.\u200ag. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2\u200a-\u200a3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. \ub7 Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. \ub7 Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan\uae, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. \ub7 Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED

The X-ray emission of z>2.5 active galactic nuclei can be obscured by their host galaxies

We present a multi-wavelength study of seven AGN at spectroscopic redshift >2.5 in the 7 Ms Chandra Deep Field South, selected to have good FIR/sub-mm detections. Our aim is to investigate the possibility that the obscuration observed in the X-rays can be produced by the interstellar medium (ISM) of the host galaxy. Based on the 7 Ms Chandra spectra, we measured obscuring column densities N$_{H, X}$ in excess of 7x10$^{22}$ cm$^{-2}$ and intrinsic X-ray luminosities L$_{X}$>10$^{44}$ erg s$^{-1}$ for our targets, as well as equivalent widths for the Fe K$\alpha$ emission line EW>0.5-1 keV. We built the UV-to-FIR spectral energy distributions by using broad-band photometry from CANDELS and Herschel catalogs. By means of an SED decomposition technique, we derived stellar masses (M$_{*}$~10$^{11}$ Msun), IR luminosities (L$_{IR}$>10$^{12}$ Lsun), star formation rates (SFR~190-1680 Msun yr$^{-1}$) and AGN bolometric luminosities (L$_{bol}$~10$^{46}$ erg s$^{-1}$) for our sample. We used an empirically-calibrated relation between gas masses and FIR/sub-mm luminosities and derived M$_{gas}$~0.8-5.4x10$^{10}$ Msun. High-resolution (0.3-0.7'') ALMA data (when available, CANDELS data otherwise) were used to estimate the galaxy size and hence the volume enclosing most of the ISM under simple geometrical assumptions. These measurements were then combined to derive the column density associated with the ISM of the host, on the order of N$_{H, ISM}$~10$^{23-24}$ cm$^{-2}$. The comparison between the ISM column densities and those measured from the X-ray spectral analysis shows that they are similar. This suggests that, at least at high redshift, significant absorption on kpc scales by the dense ISM in the host likely adds to or substitutes that produced by circumnuclear gas on pc scales (i.e., the torus of unified models). The lack of unobscured AGN among our ISM-rich targets supports this scenario.Comment: 15 pages, 3 figures. Accepted for publication in A&

Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.

Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles) involved in AR expression and their possible role as therapeutic targets

State Biotechnology Oversight: The Juncture of Technology, Law, and Public Policy

In a 1980 landmark decision, the Supreme Court of the United States ruled that genetically engineered lifeforms such as bacteria were patentable. The significance of this decision to the emerging biotechnology industry—an industry predicated on intellectual property rights—was incalculable. The characteristically research-intensive, capital-intensive biotechnology industry now had the economic incentive to push the technology of genetic engineering to previously unimagined extremes. The genetic engineering and recombinant DNA applications pursued by the biotechnology industry over the past ten years have engendered a spectrum of perplexing inquiries concerning ethical and moral values; agricultural, ecological and environmental matters; global competitiveness and economic priorities; and regulatory and public policy issues. This Comment will focus upon the regulatory and public policy issues associated with the biotechnology industry. Although the specific issue to be discussed is the introduction of genetically engineered organisms into the environment, it will become evident that virtually all the other above-mentioned issues are intrinsically and inevitably linked to regulatory philosophy and public policy values

Effect of Scatterering on Coherent Anti-Stokes Raman Scattering (CARS) signals

We develop a computational framework to examine the factors responsible for scattering-induced distortions of coherent anti-Stokes Raman scattering (CARS) signals in turbid samples. We apply the Huygens-Fresnel Wave-based Electric Field Superposition (HF-WEFS) method combined with the radiating dipole approximation to compute the effects of scattering-induced distortions of focal excitation fields on the far-field CARS signal. We analyze the effect of spherical scatterers, placed in the vicinity of the focal volume, on the CARS signal emitted by different objects (2{\mu}m diameter solid sphere, 2{\mu}m diameter myelin cylinder and 2{\mu}m diameter myelin tube). We find that distortions in the CARS signals arise not only from attenuation of the focal field but also from scattering-induced changes in the spatial phase that modifies the angular distribution of the CARS emission. Our simulations further show that CARS signal attenuation can be minimized by using a high numerical aperture condenser. Moreover, unlike the CARS intensity image, CARS images formed by taking the ratio of CARS signals obtained using x- and y-polarized input fields is relatively insensitive to the effects of spherical scatterers. Our computational framework provide a mechanistic approach to characterizing scattering-induced distortions in coherent imaging of turbid media and may inspire bottom-up approaches for adaptive optical methods for image correction.Comment: 15 pages, 7 figure

Evaluation of the utility of sediment data in NASQAN (National Stream Quality Accounting Network)

Monthly suspended sediment discharge measurements, made by the USGS as part of the National Stream Quality Accounting Network (NASQAN), are analysed to assess the adequacy in terms of spatial coverage, temporal sampling frequency, accuracy of measurements, as well as in determining the sediment yield in the nation's rivers. It is concluded that the spatial distribution of NASQAN stations is reasonable but necessarily judgemental. The temporal variations of sediment data contain much higher frequencies than monthly. Sampling error is found to be minor when compared with other causes of data scatter which can be substantial. The usefulness of the monthly measurements of sediment transport is enhanced when combined with the daily measurements of water discharge. Increasing the sampling frequency moderately would not materially improve the accuracy of sediment yield determinations