Product Differentiation Costs and Global Competition

The growing competitive intensity on the markets determines the emergence of competition costs that are expressed at a corporate level and have implicit repercussions for the supply system. This type of costs makes it possible to identify a close link between competition costs and supply differentiation costs. Classification by competitive intensity presupposes that the analysis performed identifies the classification of company costs as the discriminating element, in terms of the competitive pressure of the context in which the firm operates. The emergence of competition costs is linked to an attempt to squeeze them as an aspect of vertical, or more specifically, horizontal cooperation strategies.Product Differentiation; Differentiation Costs; Over-Supply; Global Competition; Marketing; Market-Driven Management; Global Corporations; Global Markets DOI:http://dx.doi.org/10.4468/2005.1.06garbelli

Ultra-high-field targeted imaging of focal cortical dysplasia: The intracortical black line sign in type IIB

BACKGROUND AND PURPOSE: Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight correlations between neuropathology and ultra-high-field imaging. MATERIALS AND METHODS: Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality. RESULTS: We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (n = 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (n = 1/4) and in all those with focal cortical dysplasia IIb (n = 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (n = 4/5), while its incomplete removal yielded unsatisfactory results (n = 1/5). CONCLUSIONS: The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures

Molecular chaperones and mirnas in epilepsy: Pathogenic implications and therapeutic prospects

Epilepsy is a pathologic condition with high prevalence and devastating consequences for the patient and its entourage. Means for accurate diagnosis of type, patient monitoring for predicting seizures and follow up, and efficacious treatment are desperately needed. To improve this adverse outcome, miRNAs and the chaperone system (CS) are promising targets to understand pathogenic mechanisms and for developing theranostics applications. miRNAs implicated in conditions known or suspected to favor seizures such as neuroinflammation, to promote epileptic tolerance and neuronal survival, to regulate seizures, and others showing variations in expression levels related to seizures are promising candidates as useful biomarkers for diagnosis and patient monitoring, and as targets for developing novel therapies. Components of the CS are also promising as biomarkers and as therapeutic targets, since they participate in epileptogenic pathways and in cytoprotective mechanisms in various epileptogenic brain areas, even if what they do and how is not yet clear. The data in this review should help in the identification of molecular targets among the discussed miRNAs and CS components for research aiming at understanding epileptogenic mechanisms and, subsequently, develop means for predicting/preventing seizures and treating the disease

The application of cortical layer markers in the evaluation of cortical dysplasias in epilepsy

The diagnostic criteria for focal cortical dysplasia type I (FCD I) remain to be well and consistently defined. Cortical layer-specific markers (CLM) provide a potential tool for the objective assessment of any dyslamination. We studied expression patterns of recognised CLM using immunohistochemistry for N200, ER81, Otx1, Map1b (subsets of V/VI projection neurones), Pax6, Tbr1, Tbr2 (differentially expressed in cortical neurones from intermediate progenitor cells), Cux 1 (outer cortical layers) and MASH1 (ventricular zone progenitors). Dysplasia subtypes included FCD I and II, dysplasias adjacent to hippocampal sclerosis (HS) or dysembryoplastic neuroepithelial tumours (DNTs); all were compared to neonatal and adult controls. Laminar expression patterns in normal cortex were observed with Tbr1, Map1b, N200 and Otx1. FCDI cases in younger patients were characterised by abnormal expression in layer II for Tbr1 and Otx1. FCDII showed distinct labelling of balloon cells (Pax6, ER81 and Otx1) and dysmorphic neurones (Tbr 1, N200 and Map1b) supporting origins from radial glia and intermediate progenitor cells, respectively. In temporal lobe sclerosis cases with dysplasia adjacent to HS, Tbr1 and Map1b highlighted abnormal orientation of neurones in layer II. Dyslamination was not confirmed in the perilesional cortex of DNT with CLM. Finally, immature cell types (Otx1, Pax6 and Tbr2) were noted in varied pathologies. One possibility is activation of progenitor cell populations which could contribute to the pathophysiology of these lesions

Medulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutations

Medulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2–5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma

New Procedures to Make Active, Fractal-Like Surfaces on Thin pd Wires

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Micromorphology and differential preservation of Upper Permian brachiopod low-Mg calcite

Calcareous shells of Rhynchonelliform brachiopods fromthe Nesen Formation (Late Permian) of Iran were studied by scanning electron microscope, cathodoluminescence and trace element chemistry to define their microstructure and state of preservation. In the Strophomenata shell succession, the secondary layer consists of cross-bladed, laminar calcite, and in a few species there is a tertiary layer of prisms. In the Rhynchonellata shell succession, the secondary layer consists of elongated fibers and the tertiary layer of prisms. All specimens were classified into six micromorphological types based on the fabric of the layer and the morphology of their microstructural units (laminae, fibres and prisms). Shell micromorphology and enclosing whole rock were further analyzed by cathodoluminescence and trace chemistry to assess preservation of brachiopod low-Mg calcite and specifically of their layers and microstructural units. Relative color frequencies were determined for each morphological type and degree of luminescence based on the lithology of the host rocks to evaluate the main factors that affect shell preservation. Results suggest that diagenetic alteration may depend on shell fabric and taxonomy as well as lithology of the host rock, but it appears that the first and the second features are the most important factors in determining the degree of brachiopod low-Mg calcite preservation. In general, the fibrous secondary layer is likely more often and better preserved than its laminar counterpart irrespective of host rock lithology. Furthermore, tertiary layers tend to be better preserved than secondary ones in Rhynchonellata low-Mg calcite shells, whereas no preferential preservation of either layer over the other was observed in the shells of Strophomenata. This information is important when selecting fossil brachiopod low-Mg calcite shells as geochemical proxies for paleoclimatic, paleoecologic, paleoenvironmental and other studies