Wheel-flat diagnostic tool via wavelet transform

The detection and acknowledgement of signatures, for condition monitoring and fault diagnostics by wavelet transform, deserves increased attention, due to its property of variable time–frequency resolution, which overcomes limitations of classical time–frequency approaches.In the paper, a diagnostic tool is presented, based on the wavelet transform, able to detect and to quantify the wheel-flat defect of a test train at different speeds and to measure the train speed with proper accuracy. The designed diagnostic tool minimises the hardware requirements, since only one accelerometer is needed, and provides results in real time.The results, achieved by an exhaustive experimental campaign, permit to validate the effectiveness of the diagnostic tool and to demonstrate the advantages of wavelet-based detection of signatures.     

Etiological Contributions to Heavy Drinking From Late Adolescence to Young Adulthood.

The authors examined genetic and environmental contributions to stability and change in heavy drinking from late adolescence to young adulthood in a sample of 1,152 twin pairs. In men, heavy drinking was similarly heritable at ages 17 (h2 = .57) and 20 (h2 = .39), and its stability owed primarily to common genetic factors. In women, heavy drinking was less heritable than in men at ages 17 (h2 = .18) and 20 (h2 = .30) and its stability was primarily due to enduring shared environmental influences. P3 amplitude, an event-related brain potential marker of alcoholism risk, was less predictive of heavy drinking in women than in men, providing further support for the proposition that biological factors have less impact on heavy drinking in young adult women than in young adult men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fabrication of Copper Nanowire Films and their Incorporation into Polymer Matrices for Antibacterial and Marine Antifouling Applications

With the ban of tributyltin, copper‐based biocides are now widely used in antifouling coatings as the major active ingredients. Given the past experience of heavy‐metal accumulation in harbors with limited water exchange, there is a significant interest in developing copper materials that greatly reduce the amount of copper ions released into marine surroundings. In this paper, copper nanowires (NWs) encapsulated in polymer matrices are investigated as the means to control the release of copper ions and to achieve a long‐lasting antifouling effect. Very long CuNWs with high aspect ratio in organic solution are drop‐coated onto substrates to fabricate uniform thin films. They are then incorporated into an elastomeric polydimethylsiloxane (PDMS) matrix. A small amount of CuNWs in PDMS can inhibit barnacle cyprid settlement, while it exhibits low mortality to cyprids and nauplii present in the surrounding seawater environment. The low levels of copper released after 50 days suggest that the intersecting and interconnected CuNWs embedded in PDMS could potentially release copper ions continuously over a few years in seawater. This approach provides a novel platform to use hybrid materials as effective marine antifouling coatings, and may be applied to fouling release materials to enhance their antifouling properties.     

Electrospray deposition of nanohydroxyapatite coatings: A strategy to mimic bone apatite mineral

The biological performance of orthopaedic and oral metallic implants can be enhanced significantly by the application of bioactive coatings. In this work, a cost-efficient alternative to the traditional technique to produce a hydroxyapatite (HA) coating with a nanostructured feature onto a metallic implant surface at room temperature via electrospray deposition, is presented. To evaluate the bioactive capacity of these nanoHA (nHA) coatings in vitro, an acellular simulated body fluid soaking experiment and a human osteoblast (HOB) cell culture work were conducted. Under these physiological conditions, the accelerated apatite precipitation process occurred on the nHA-coated titanium surfaces as compared to the uncoated titanium surfaces. HOB cells developed mature cytoskeletons with distinct evidence of actin stress fibres and vinculin adhesion plaques, on these nHA coatings. Hence, this deposition technique holds great potential in producing high quality nHA coatings for biomedical applications.     

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CALR) via dissociation of the PP1/GADD34 complex. In this regard, we computationally predicted the ability of SIX2G to induce CALR exposure by interacting with the PP1 RVxF domain. We then assessed both the potential cytotoxic and immunogenic activity of SIX2G on in vitro models of multiple myeloma (MM), which is an incurable hematological malignancy characterized by an immunosuppressive milieu. We found that the treatment with SIX2G inhibited cell viability by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, we observed the increase of hallmarks of ICD such as CALR exposure, ATP release and phospho-eIF2α protein level. Through co-culture experiments with immune cells, we demonstrated the increase of (i) CD86 maturation marker on dendritic cells, (ii) CD69 activation marker on cytotoxic T cells, and (iii) phagocytosis of tumor cells following treatment with SIX2G, confirming the onset of an immunogenic cascade. In conclusion, our findings provide a framework for further development of SIX2G as a new potential anti-MM agent.     

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways’ genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells’ differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells’ phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future.     

Parametric-gain approach to the analysis of single-channel DPSK/DQPSK systems with nonlinear phase noise

This paper presents a novel method based on a parametric gain (PG) approach to study the impact of nonlinear phase noise in single-channel dispersion-managed differentially phase-modulated systems. This paper first shows through Monte Carlo simulations that the received amplified spontaneous emission (ASE) noise statistics, before photodetection, can be reasonably assumed to be Gaussian, provided a sufficiently large chromatic dispersion is present in the transmission fiber. This paper then evaluates in a closed form the ASE power spectral density by linearizing the interaction between a signal and a noise in the limit of a distributed system. Even if the received ASE is nonstationary in time due to pulse shape and modulation, this paper shows that it can be approximated by an equivalent stationary process, as if the signal were continuous wave (CW). This paper then applies the CW-equivalent ASE model to bit-error-rate evaluation by using an extension of a known Karhunen-Loe/spl acute/ve method for quadratic detectors in colored Gaussian noise. Such a method avoids calculation of the nonlinear phase statistics and accounts for intersymbol interference due to a nonlinear waveform distortion and optical and electrical postdetection filtering. This paper compares binary and quaternary schemes with both nonreturn- and return-to-zero (RZ) pulses for various values of nonlinear phases and bit rates. The results confirm that PG deeply affects the system performance, especially with RZ pulses and with quaternary schemes. This paper also compares ON-OFF keying (OOK) differential phase-shifted keying (DPSK) systems, showing that the initial 3-dB advantage of DPSK is lost for increasing nonlinear phases because DPSK is less robust to PG than OOK.     

Association of HLA profiles with early plasma viral load, CD4+ cell count and rate of progression to AIDS following acute HIV-1 infection. Multicenter AIDS Cohort Study

The products of a growing number of genes have been shown to display seemingly contradictory functions; namely, the induction of tumorigenesis and the induction of apoptosis. Heregulin's involvement in oncogenesis occurs through its interactions with members of the EGF receptor tyrosine kinase family. Recently one isoform of heregulin, beta2b, was isolated in an in vitro screen for dominant, apoptosis-inducing genes in kidney epithelial cells. Here we show that heregulin is also capable of mediating apoptosis in human and murine mammary tumor cell lines and murine tumors. Furthermore, through transfection of the human breast cancer cell line MCF-7 with the truncated transmembrane/cytoplasmic segment of the heregulin gene, we show that the intracellular region of the heregulin precursor is sufficient for induction of apoptosis. Through the use of DNA fragmentation assays we also show that apoptosis occurs in cell lines established from heregulin-induced mammary gland tumors. TdT addition of digoxigenin labeled nucleotides to 3' OH ends of DNA breaks recapitulated these results in the actual tumors. Finally, over-expression of heregulin is shown to lead to the down-regulation of Bcl-2, an inhibitor of apoptosis. Conversely, the transfection of Bcl-2 into MCF-7 cells inhibits heregulin-mediated programmed cell death.