ONLINE MONITORING OF HOT DIE FORGING PROCESSES USING ACOUSTIC EMISSION (PART-II)

Abstract In part-I, the feasibility of using AE as an online monitoring technique for industrial forging processes has been investigated. The investigation considered monitoring the upsetting process of axis-symmetric specimens using a self-built data acquisition and analysis system up to 500 kHz. Two magnesium alloys and an aluminium alloy with three different geometries were used during these investigations. The experiments were performed under different thermomechanical loading conditions (temperatures, strains and strain rates). In addition, influences from machine noise, sensor positioning was also investigated and the achieved results were analysed. In this second part, the investigation was performed in the range 400-1600 kHz using the highend professional acoustic emission system AMSY-5 (Vallen Systeme, Germany). In this second series of experiments, specimens of the same geometries but of larger size have been used in order to allow more flexibility in the loading scheme, assure minimum temperature drop during the test, facilitate both macro and microstructure analysis and most important to deliver more AE energy to improve the signal to noise ratio. The first part of this paper is devoted to describe the methodology used to reduce the hydraulic machine noise and discusses the different aspects considered during the choice of the front filters, adjusting the acquisition parameters and setting up signal-selection / rejection criteria. This will be followed by the main results achieved during the upsetting of the Al and Mg alloys specimens. Further, the methodology applied to correlate the obtained AE patterns to the test parameters is introduced

Identification of osteopontin as a novel marker for early hepatocellular carcinoma

The aim of this study was to identify a biomarker that could improve alpha‐fetoprotein (AFP) performance in hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis. We performed proteomic profiling of plasma from patients with cirrhosis or HCC and validated selected candidate HCC biomarkers in two geographically distinct cohorts to include HCC of different etiologies. Mass spectrometry profiling of highly fractionated plasma from 18 cirrhosis and 17 HCC patients identified osteopontin (OPN) as significantly up‐regulated in HCC cases, compared to cirrhosis controls. OPN levels were subsequently measured in 312 plasma samples collected from 131 HCC patients, 76 cirrhosis patients, 52 chronic hepatitis C (CHC) and B (CHB) patients, and 53 healthy controls in two independent cohorts. OPN plasma levels were significantly elevated in HCC patients, compared to cirrhosis, CHC, CHB, or healthy controls, in both cohorts. OPN alone or in combination with AFP had significantly better area under the receiver operating characteristic curve, compared to AFP, in comparing cirrhosis and HCC in both cohorts. OPN overall performance remained higher than AFP in comparing cirrhosis and the following HCC groups: HCV‐related HCC, HBV‐associated HCC, and early HCC. OPN also had a good sensitivity in AFP‐negative HCC. In a pilot prospective study including 22 patients who developed HCC during follow‐up, OPN was already elevated 1 year before diagnosis. Conclusion : OPN was more sensitive than AFP for the diagnosis of HCC in all studied HCC groups. In addition, OPN performance remained intact in samples collected 1 year before diagnosis. (H EPATOLOGY 2012)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90204/1/24703_ftp.pd

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion. We developed a multiparametric in situ immunofluorescence staining to identify and quantify at the cellular level the co-expression of these inhibitory receptors. On a retrospective series of frozen tissue of renal cell carcinomas (RCC), using a fluorescence multispectral imaging technology coupled with an image analysis software, it was found that co-expression of PD-1 and Tim-3 on tumor infiltrating CD8 T cells is correlated with a poor prognosis in RCC. To our knowledge, this represents the first study demonstrating that this automated multiplex in situ technology may have some clinical relevance

Tropical-cyclone-driven erosion of the terrestrial biosphere from mountains

The transfer of organic carbon from the terrestrial biosphere to the oceans via erosion and riverine transport constitutes an important component of the global carbon cycle. More than one third of this organic carbon flux comes from sediment-laden rivers that drain the mountains in the western Pacific region. This region is prone to tropical cyclones, but their role in sourcing and transferring vegetation and soil is not well constrained. Here we measure particulate organic carbon load and composition in the LiWu River, Taiwan, during cyclone-triggered floods. We correct for fossil particulate organic carbon using radiocarbon, and find that the concentration of particulate organic carbon from vegetation and soils is positively correlated with water discharge. Floods have been shown to carry large amounts of clastic sediment. Non-fossil particulate organic carbon transported at the same time may be buried offshore under high rates of sediment accumulation. We estimate that on decadal timescales, 77–92% of non-fossil particulate organic carbon eroded from the LiWu catchment is transported during large, cyclone-induced floods. We suggest that tropical cyclones, which affect many forested mountains within the Intertropical Convergence Zone, may provide optimum conditions for the delivery and burial of non-fossil particulate organic carbon in the ocean. This carbon transfer is moderated by the frequency, intensity and duration of tropical cyclones

Extended analysis of the Z2-FET: Operation as capacitor-less eDRAM

This article has been accepted for publication by IEEE "Navarro Moral, C.; et al. Extended analysis of the Z2-FET: Operation as capacitor-less eDRAM. IEEE Transactions on Electron Devices, 64(11): 4486-4491 (2017). DOI: 10.1109/TED.2017.2751141(c) 2017 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works."The Z2-FET operation as capacitorless DRAM is analyzed using advanced 2-D TCAD simulations for IoT applications. The simulated architecture is built based on actual 28-nm fully depleted silicon-on-insulator devices. It is found that the triggering mechanism is dominated by the front-gate bias and the carrier’s diffusion length. As in other FB-DRAMs, the memory window is defined by the ON voltage shift with the stored body charge. However, the Z2-FET’s memory state is not exclusively defined by the inner charge but also by the reading conditions

Short-lived Nuclei in the Early Solar System: Possible AGB Sources

(Abridged) We review abundances of short-lived nuclides in the early solar system (ESS) and the methods used to determine them. We compare them to the inventory for a uniform galactic production model. Within a factor of two, observed abundances of several isotopes are compatible with this model. I-129 is an exception, with an ESS inventory much lower than expected. The isotopes Pd-107, Fe-60, Ca-41, Cl-36, Al-26, and Be-10 require late addition to the solar nebula. Be-10 is the product of particle irradiation of the solar system as probably is Cl-36. Late injection by a supernova (SN) cannot be responsible for most short-lived nuclei without excessively producing Mn-53; it can be the source of Mn-53 and maybe Fe-60. If a late SN is responsible for these two nuclei, it still cannot make Pd-107 and other isotopes. We emphasize an AGB star as a source of nuclei, including Fe-60 and explore this possibility with new stellar models. A dilution factor of about 4e-3 gives reasonable amounts of many nuclei. We discuss the role of irradiation for Al-26, Cl-36 and Ca-41. Conflict between scenarios is emphasized as well as the absence of a global interpretation for the existing data. Abundances of actinides indicate a quiescent interval of about 1e8 years for actinide group production in order to explain the data on Pu-244 and new bounds on Cm-247. This interval is not compatible with Hf-182 data, so a separate type of r-process is needed for at least the actinides, distinct from the two types previously identified. The apparent coincidence of the I-129 and trans-actinide time scales suggests that the last actinide contribution was from an r-process that produced actinides without fission recycling so that the yields at Ba and below were governed by fission.Comment: 92 pages, 14 figure files, in press at Nuclear Physics

Analysis of Gga Null Mice Demonstrates a Non-Redundant Role for Mammalian GGA2 during Development

Numerous studies using cultured mammalian cells have shown that the three GGAs (Golgi-localized, gamma-ear containing, ADP-ribosylation factor- binding proteins) function in the transport of cargo proteins between the trans- Golgi network and endosomes. However, the in vivo role(s) of these adaptor proteins and their possible functional redundancy has not been analyzed. In this study, the genes encoding GGAs1-3 were disrupted in mice by insertional mutagenesis. Loss of GGA1 or GGA3 alone was well tolerated whereas the absence of GGA2 resulted in embryonic or neonatal lethality, depending on the genetic background of the mice. Thus, GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3. The combined loss of GGA1 and GGA3 also resulted in a high incidence of neonatal mortality but in this case the expression level of GGA2 may be inadequate to compensate for the loss of the other two GGAs. We conclude that the three mammalian GGAs are essential proteins that are not fully redundant

Effect of density and unit cell size grading on the stiffness and energy absorption of short fibre-reinforced functionally graded lattice structures

Architectured structures, particularly functionally graded lattices, are receiving much attention in both industry and academia as they facilitate the customization of the structural response and harness the potential for multi-functional applications. This work experimentally investigates how the severity of density and unit cell size grading as well as the building direction affects the stiffness, energy absorption and structural response of additively manufactured (AM) short fibre-reinforced lattices with same relative density. Specimens composed of tessellated body-centred cubic (BCC), Schwarz-P (SP) and Gyroid (GY) unit cells were tested under compression. Compared to the uniform lattices of equal density, it was found, that modest density grading has a positive and no effect on the total compressive stiffness of SP and BCC lattices, respectively. More severe grading gradually reduces the total stiffness, with the modulus of the SP lattices never dropping below that of the uniform counterparts. Unit cell size grading had no significant influence on the stiffness and revealed an elastomer-like performance as opposed to the density graded lattices of the same relative density, suggesting a foam-like behaviour. Density grading of bending-dominated unit cell lattices showcased better energy absorption capability for small displacements, whereas grading of the stretching-dominated counterparts is advantageous for large displacements when compared to the ungraded lattice. The severity of unit cell size graded lattices does not affect the energy absorption capability. Finally, a power-law approach was used to semi-empirically derive a formula that predicts the cumulative energy absorption as a function of the density gradient and relative density. Overall, these findings will provide engineers with valuable knowledge that will ease the design choices for lightweight multi-functional AM-parts

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field