On the application of replica molding technology for the indirect measurement of surface and geometry of micromilled components

The evaluation of micromilled parts quality requires detailed assessments of both geometry and surface topography. However, in many cases, the reduced accessibility caused by the complex geometry of the part makes it impossible to perform direct measurements. This problem can be solved by adopting the replica molding technology. The method consists of obtaining a replica of the feature that is inaccessible for standard measurement devices and performing its indirect measurement. This paper examines the performance of a commercial replication media applied to the indirect measurement of micromilled components. Two specifically designed micromilled benchmark samples were used to assess the accuracy in replicating both surface texture and geometry. A 3D confocal microscope and a focus variation instrument were employed and the associated uncertainties were evaluated. The replication method proved to be suitable for characterizing micromilled surface texture even though an average overestimation in the nano-metric level of the Sa parameter was observed. On the other hand, the replicated geometry generally underestimated that of the master, often leading to a different measurement output considering the micrometric uncertainty

Genomic profiling of cortical neurons following exposure to β-amyloid

In vitro and in vivo studies have shown that beta-amyloid peptide induces neuronal cell death. To explore the molecular basis underlying beta-amyloid-induced toxicity, we analyzed gene expression profiles of cultured rat cortical neurons treated for 24 and 48 h with synthetic beta-amyloid peptide. From the 8740 genes interrogated by oligonucleotide microarray analysis, 241 genes were found to be differentially expressed and segregated into distinct clusters. Functional clustering based on gene ontologies showed coordinated expression of genes with common biological functions and metabolic pathways. The comparison with genes differentially expressed in cerebellar granule neurons following serum and potassium deprivation indicates the existence of common regulatory mechanisms underlying neuronal cell death. Our results offer a genomic view of the changes that accompany beta-amyloid-induced neurodegeneration

A Plackett-Burman Design to Optimize Wood Chipper Settings

The wood-chipping process is affected by several factors, notably chipper settings and wood characteristics. It is often difficult to test all of these factors in a full factorial experimental plan, due to the large number of trials required. On the other hand, a screening design of the experiment makes it possible to manage a large number of variables in a small number of trials. Hence, this approach is used to test six factors, in order to optimize the productivity and chip quality of a drum wood-chipper. These factors are: feeding speed, screen size, PTO-speed, wood species, wood moisture content, and wood diameter. Productivity was significantly affected by screen size, while chip quality was related to feeding speed, screen size, PTO-speed, and wood species. The results suggest that the optimal configuration can be achieved by adjusting feeding speed, the PTO-speed, and the wood species, as these settings maximize chip quality. Screen size requires further analysis, as larger sizes increase productivity but reduce quality, while the opposite is true for smaller sizes. Thus, the optimal screen size requires a consideration of costs and benefits that may change according to the retail price of premium and regular wood chips, and production costs

Performance verification of focus variation and confocal microscopes measuring tilted ultra-fine surfaces

The behaviour of two optical instruments, scilicet a laser scanning confocal microscope and a focus-variation microscope, was investigated considering measurements of tilted surfaces. The measured samples were twelve steel artefacts for mould surface finish reference, covering Sa roughness parameter in the range (101-103) nm. The 3D surface texture parameters considered were Sa, Sq and Sdq. The small working distance of the confocal microscope objectives influenced the measurement setup, preventing from selecting a high tilting angle. The investigation was carried out comparing measurements of flat surfaces (0° tilt) with measurements of 12.5° tilted surfaces. The confocal microscope results showed a high sensitivity to tilting due to the laser beam reflection on the metal surfaces. The focus variation microscope results were more robust with respect to the considered angular variation, although they were out of the instrument operating range except for one of the twelve artefacts

Loss of expression of μ-protocadherin and protocadherin-24 in sporadic and hereditary nonpolyposis colorectal cancers

Colorectal cancer (CRC) is a neoplastic disease in which normal mucosa undergoes a process of malignant transformation due to the progressive accumulation of molecular alterations affecting proto-oncogenes and oncosuppressor genes. Some of these modifications exert their carcinogenic potential by promoting a constitutive activation of the β-catenin signaling proliferation pathway, and when present, loss of cadherin expression also significantly contributes to the same effect. Using a combined approach of molecular and immunohistochemical analysis, we have previously demonstrated that most sporadic CRCs exhibit a down-regulated expression of a cadherin, named μ-protocadherin, that is generally observed in association with a higher proliferation rate and a worse prognosis. The aim of this report was to perform a comparative immunohistochemical assessment of μ-protocadherin and a similar cadherin, named protocadherin-24, in sporadic CRC and hereditary nonpolyposis colorectal cancer. The data obtained put in evidence that double-negative CRCs, lacking both the analyzed protocadherins, are more represented among sporadic tumors, whereas double-positive CRCs, maintaining their expression, exhibit an opposite trend. As expected, loss of protocadherin expression was accompanied by nuclear localization of β-catenin and increased positivity of the Ki-67 proliferation marker. This finding is consistent with the different clinical evolution of the 2 considered CRC sets according to which patients with hereditary nonpolyposis colorectal cancer experience a better prognosis as compared with those affected by a sporadic CRC

Efficacy of Systemically Administered Retargeted Oncolytic Herpes Simplex Viruses—Clearance and Biodistribution in Naïve and HSV-Preimmune Mice

We investigated the anticancer efficacy, blood clearance, and tissue biodistribution of systemically administered retargeted oncolytic herpes simplex viruses (ReHVs) in HSV-naive and HSV-preimmunized (HSV-IMM) mice. Efficacy was tested against lung tumors formed upon intravenous administration of cancer cells, a model of metastatic disease, and against subcutaneous distant tumors. In naive mice, HER2- and hPSMA-retargeted viruses, both armed with mIL-12, were highly effective, even when administered to mice with well-developed tumors. Efficacy was higher for combination regimens with immune checkpoint inhibitors. A significant amount of infectious virus persisted in the blood for at least 1 h. Viral genomes, or fragments thereof, persisted in the blood and tissues for days. Remarkably, the only sites of viral replication were the lungs of tumor-positive mice and the subcutaneous tumors. No replication was detected in other tissues, strengthening the evidence of the high cancer specificity of ReHVs, a property that renders ReHVs suitable for systemic administration. In HSV-IMM mice, ReHVs administered at late times failed to exert anticancer efficacy, and the circulating virus was rapidly inactivated. Serum stability and in vivo whole blood stability assays highlighted neutralizing antibodies as the main factor in virus inactivation. Efforts to deplete mice of the neutralizing antibodies are ongoing

STRATEGIES TO PREDICT TREATMENT RESPONSE AND SELECT THERAPIES IN METASTATIC BREAST CANCER PATIENTS USING A NEXT GENERATION SEQUENCING MULTI-GENE PANEL

The standard of care for many patients with advanced breast cancer (BC )is gradually evolving from empirical treatment based on clinicalpathological characteristics to the use of targeted approaches based on the molecular profile of the tumor. In the last decade, an increasing number of molecularly targeted drugs have been developed for the treatment of metastatic BC. These drugs target specific molecular abnormalities that confer to cancer cells a survival advantage. Interestingly, the ability to perform multigene testing for a range of molecular alterations may provide an opportunity to clarify the mechanisms of treatment response, to find the strategies to overcome treatment resistance and thus, to identify patients who are more likely to develop relapse and who may be candidates for matched targeted therapies. The main aim of this study is to find prognostic and predictive molecular biomarkers for the management of metastatic BC patients in clinical practice