Light depolarization effects in tip enhanced Raman spectroscopy of silicon (001) and gallium arsenide (001)

We report on the effects of light depolarization induced by sharp metallic tips in Tip-Enhanced Raman Spectroscopy (TERS). Experiments on Si(001) and GaAs(001) crystals show that the excitation field depolarization induces a selective enhancement of specific Raman modes, depending on their Raman tensor symmetry. A complete polarization analysis of the light backscattered from the tip confirms the TERS findings. The spatial confinement of the depolarization field is studied and its dependence on the excitation wavelength and power are explored

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites

Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. We performed systematic database search and identified highly specific MED12 mutations in CLL patients. To study this further, we collected three independent sample series comprising over 700 CLL samples and screened MED12 exons 1 and 2 by direct sequencing. Mutations were identified at significant frequency in all three series with a combined mutation frequency of 5.2% (37/709). Positive mutation status was found to be associated with unmutated IGHV and ZAP70 expression, which are well-known poor prognosis markers in CLL. Our results recognize CLL as the first extrauterine cancer type where 5'terminus of MED12 is mutated at significant frequency. Functional analyses have shown that these mutations lead to dissociation of Cyclin C-CDK8/19 from the core Mediator and to the loss of Mediator-associated CDK kinase activity. Additional studies on the role of MED12 mutation status as a putative prognostic factor as well as mutations' exact tumorigenic mechanism in CLL are warranted.Peer reviewe

A graphical method for performance mapping of machines and milling tools

Optimal design of the machining setup in terms of installed machines, cutting tools and process parameters is of paramount importance for every manufacturing company. In most of the metal cutting companies, all choices related to machine eligibility and cutting parameters selection typically come from heuristic approaches and follow supplier indications or base on the skill of experienced machine operators. More advanced solutions, such as model-based and virtual approaches, are adopted less frequently mainly due to the lack of these techniques in grasping the underlying knowledge successfully. Aim of this work is to introduce a synthetic graphical representation of machining centers and cutting tools capabilities, to provide an accessible way to evaluate the feasibility and close-to-limit conditions of the cutting process. Taking inspiration from previous scientific works from the measurement engineering field, a set of 2D and 3D graphs are presented to map machine, tools and process capabilities, as well as their obtainable manufacturing performances and expectable tool life. This approach synthesizes the nominal data coming from different sources (catalogues, database, tool model geometries etc.) and the real cutting tools parameters used during the production phase. Some examples are provided to show the potential of this graphical evaluation in supporting process planning and decision-making and in formalizing the machining setup knowledge. Further developments are devoted to extend the method to other manufacturing processes, including hybrid processes. At the same time, an in-process data gathering software will be integrated for building a solid database that can be used by an autonomous multi-technological process selector, as well as by a pre-process condition advisor in an Industry 4.0 oriented way

CHEK2 1100delC in patients with metachronous cancers of the breast and the colorectum

BACKGROUND: Development of multiple primary tumors is a hallmark of hereditary cancer. At least 1/10 of breast cancers and colorectal cancers occur because of heredity and recently the cell cycle kinase 2, CHEK2 1100delC allele has been identified at a particularly high frequency in families with hereditary breast and colorectal cancer. METHODS: We utilized the Southern Sweden population-based cancer registry to identify women with double primary breast and colorectal cancer and sequenced tumor material in order to assess the contribution of the CHEK2 1100delC to the development of such metachronous tumors. RESULTS: Among the 75 patients successfully analyzed, 2 (2.5%) carried the CHEK2 1100delC allele. which was not significantly different (p = 0.26) from the 1% (3/300) carriers identified in the control group. CONCLUSION: In summary, our data suggest that the CHEK2 1100delC is not a major cause of double primary breast and colorectal cancer in Sweden, which suggests that this patient group should not routinely be screened for the CHEK2 1100delC variant

Raman characterization of singlewalled carbon nanotubes and PMMA-nanotubes composites

The Raman spectroscopy have allowed us to perform studies on singlewalled nanotubes (SWNT's) produced by following methods: electric arc, laser ablation and solar energy. As this characterization method provides a great deal of informations, we will present a comparison between the nanotubes produced by all these processes and the influence of some synthesis parameters. By using spin casting, we have produced thin films of PMMA-SWNT's for different concentrations. Then, we have characterized these new materials by Raman spectroscopy. The aim of these investigations is to get information on the possible interactions between these two materials. In particular, we have studied the evolution of the composites films spectra as a function of the nanotubes concentration in the polymer.This work has been fully supported by the European Community through its Training and Mobility of Researcher program under network contract : NAMITECH, ERBFMRX- CT96-0067 @GlZ-MIHT) and by the tiench CNRS program : ULTIMATECH.Peer reviewe

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for lynch syndrome

We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister’s colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified