Analysis of economics of a TV broadcasting satellite for additional nationwide TV programs

The influence of a TV broadcasting satellite, transmitting four additional TV networks was analyzed. It is assumed that the cost of the satellite systems will be financed by the cable TV system operators. The additional TV programs increase income by attracting additional subscribers. Two economic models were established: (1) each local network is regarded as an independent economic unit with individual fees (cost price model) and (2) all networks are part of one public cable TV company with uniform fees (uniform price model). Assumptions are made for penetration as a function of subscription rates. Main results of the study are: the installation of a TV broadcasting satellite improves the economics of CTV-networks in both models; the overall coverage achievable by the uniform price model is significantly higher than that achievable by the cost price model

The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders

Rare disruptions of FOXP2 have been strongly implicated in deficits in language development. Research over the past decade has suggested a role in the formation of underlying neural circuits required for speech. Until recently no evidence existed to suggest that the closely related FOXP1 gene played a role in neurodevelopmental processes. However, in the last few years, novel rare disruptions in FOXP1 have been reported in multiple cases of cognitive dysfunction, including intellectual disability and autism spectrum disorder, together with language impairment. As FOXP1 and FOXP2 form heterodimers for transcriptional regulation, one may assume that they co-operate in common neurodevelopmental pathways through the co-regulation of common targets. Here we compare the phenotypic consequences of FOXP1 and FOXP2 impairment, drawing on well-known studies from the past as well as recent exciting findings and consider what these tell us regarding the functions of these two genes in neural development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-012-1193-z) contains supplementary material, which is available to authorized users

Setting safety stocks for stable rotation cycle schedules

The article of record as published may be found at http://dx.doi.org/10.1016/j.ijpe.2014.05.020In the process industries, specialized equipment and production processes often necessitate the manufacture of products in a pre-determined sequence to minimize change over time and to simplify scheduling complexity; these types of schedules are referred to as pure rotation schedules, or product wheels, where the circumference of the wheel is the production cycle length. In these industries change over times between the production of individual products can consume considerable time as well as raw materials and it is therefore often desirable to stabilize the production cycles in order to minimize unplanned change overs as well as quote accurate lead times to customers. Materials requirements planning (MRP) systems are often used to plan and coordinate production and supply resources with demand in these environments. Central to the effectiveness of the MRP system is the dependability of the lead time parameters. In this paper, we introduce an optimization model to determine safety stock levels that minimize long run expected costs where as table, cyclic schedule is used. Our model may be used strategically to assess inventory investment requirements as a function of capacity investment, product mix, production technology, demand volatility, and customer service levels. It may be used tactically to optimize item-level planning parameters such as lot size, safety stock and lead time in an MRP system and to support sales and operations planning(S&OP) processes where knowing the future costs associated with current decisions is highly desirable

Complex Evolution of a Y-Chromosomal Double Homeobox 4 (DUX4)-Related Gene Family in Hominoids

The human Y chromosome carries four human Y-chromosomal euchromatin/heterochromatin transition regions, all of which are characterized by the presence of interchromosomal segmental duplications. The Yq11.1/Yq11.21 transition region harbours a peculiar segment composed of an imperfectly organized tandem-repeat structure encoding four members of the double homeobox (DUX) gene family. By comparative fluorescence in situ hybridization (FISH) analysis we have documented the primary appearance of Y-chromosomal DUX genes (DUXY) on the gibbon Y chromosome. The major amplification and dispersal of DUXY paralogs occurred after the gibbon and hominid lineages had diverged. Orthologous DUXY loci of human and chimpanzee show a highly similar structural organization. Sequence alignment survey, phylogenetic reconstruction and recombination detection analyses of human and chimpanzee DUXY genes revealed the existence of all copies in a common ancestor. Comparative analysis of the circumjacent beta-satellites indicated that DUXY genes and beta-satellites evolved in concert. However, evolutionary forces acting on DUXY genes may have induced amino acid sequence differences in the orthologous chimpanzee and human DUXY open reading frames (ORFs). The acquisition of complete ORFs in human copies might relate to evolutionary advantageous functions indicating neo-functionalization. We propose an evolutionary scenario in which an ancestral tandem array DUX gene cassette transposed to the hominoid Y chromosome followed by lineage-specific chromosomal rearrangements paved the way for a species-specific evolution of the Y-chromosomal members of a large highly diverged homeobox gene family

Optimizing Inventory in a Multi-Echelon Multi-Item Supply Chain with Time-Based Customer Service Level Agreements

Optimizing Inventory in a Multi-Echelon Multi-Item Supply Chain with Time-Based Customer Service Level Agreement

Molecular Characterization of Embryonic Stem Cell-Derived Cardiac Neural Crest-Like Cells Revealed a Spatiotemporal Expression of an Mlc-3 Isoform

Background and Objectives: Pluripotent embryonic stem (ES) cells represent a perfect model system for the investigation of early developmental processes. Besides their differentiation into derivatives of the three primary germ layers, they can also be differentiated into derivatives of the ‘fourth’ germ layer, the neural crest (NC). Due to its multipotency, extensive migration and outstanding capacity to generate a remarkable number of different cell types, the NC plays a key role in early developmental processes. Cardiac neural crest (CNC) cells are a subpopulation of the NC, which are of crucial importance for precise cardiovascular and pharyngeal glands’ development. CNC-associated malformations are rare, but always severe and life-threatening. Appropriate cell models could help to unravel underlying pathomechanisms and to develop new therapeutic options for relevant heart malformations. Methods: Murine ES cells were differentiated according to a mesodermal-lineage promoting protocol. Expression profiles of ES cell-derived progeny at various differentiation stages were investigated on transcript and protein level. Results: Comparative expression profiling of murine ES cell multilineage progeny versus undifferentiated ES cells confirmed differentiation into known cell derivatives of the three primary germ layers and provided evidence that ES cells have the capacity to differentiate into NC/CNC-like cells. Applying the NC/CNC cell-specific marker, 4E9R, an unambiguous identification of ES cell-derived NC/CNC-like cells was achieved. Conclusions: Our findings will facilitate the establishment of an ES cell-derived CNC cell model for the investigation of molecular pathways during cardiac development in health and disease

Sex chromosome positions in human interphase nuclei as studied by in situ hybridization with chromosome specific DNA probes

Two cloned repetitive DNA probes, pXBR and CY1, which bind preferentially to specific regions of the human X and Y chromosome, respectively, were used to study the distribution of the sex chromosomes in human lymphocyte nuclei by in situ hybridization experiments. Our data indicate a large variability of the distances between the sex chromosomes in male and female interphase nuclei. However, the mean distance observed between the X and Y chromosome was significantly smaller than the mean distance observed between the two X-chromosomes. The distribution of distances determined experimentally is compared with three model distributions of distances, and the question of a non-random distribution of sex chromosomes is discussed. Mathematical details of these model distributions are provided in an Appendix to this paper. In the case of a human translocation chromosome (XqterXp22.2::Yq11Y qter) contained in the Chinese hamster x human hybrid cell line 445 x 393, the binding sites of pXBR and CY1 were found close to each other in most interphase nuclei. These data demonstrate the potential use of chromosome-specific repetitive DNA probes to study the problem of interphase chromosome topography

A direct regulatory link between microRNA-137 and SHANK2: implications for neuropsychiatric disorders

Background: Mutations in the SHANK genes, which encode postsynaptic scaffolding proteins, have been linked to a spectrum of neurodevelopmental disorders. The SHANK genes and the schizophrenia-associated microRNA-137 show convergence on several levels, as they are both expressed at the synapse, influence neuronal development, and have a strong link to neurodevelopmental and neuropsychiatric disorders like intellectual disability, autism, and schizophrenia. This compiled evidence raised the question if the SHANKs might be targets of miR-137. Methods: In silico analysis revealed a putative binding site for microRNA-137 (miR-137) in the SHANK2 3′UTR, while this was not the case for SHANK1 and SHANK3. Luciferase reporter assays were performed by overexpressing wild type and mutated SHANK2-3′UTR and miR-137 in human neuroblastoma cells and mouse primary hippocampal neurons. miR-137 was also overexpressed or inhibited in hippocampal neurons, and Shank2 expression was analyzed by quantitative real-time PCR and Western blot. Additionally, expression levels of experimentally validated miR-137 target genes were analyzed in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control individuals using the RNA-Seq data from the CommonMind Consortium. Results: miR-137 directly targets the 3′UTR of SHANK2 in a site-specific manner. Overexpression of miR-137 in mouse primary hippocampal neurons significantly lowered endogenous Shank2 protein levels without detectable influence on mRNA levels. Conversely, miR-137 inhibition increased Shank2 protein expression, indicating that miR-137 regulates SHANK2 expression by repressing protein translation rather than inducing mRNA degradation. To find out if the miR-137 signaling network is altered in schizophrenia, we compared miR-137 precursor and miR-137 target gene expression in the DLPFC of schizophrenia and control individuals using the CommonMind Consortium RNA sequencing data. Differential expression of 23% (16/69) of known miR-137 target genes was detected in the DLPFC of schizophrenia individuals compared with controls. We propose that in further targets (e.g., SHANK2, as described in this paper) which are not regulated on RNA level, effects may only be detectable on protein level. Conclusion: Our study provides evidence that a direct regulatory link exists between miR-137 and SHANK2 and supports the finding that miR-137 signaling might be altered in schizophrenia

Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed

Comparative expression analysis of Shox2 -deficient embryonic stem cell-derived sinoatrial node-like cells

The homeodomain transcription factor Shox2 controls the development and function of the native cardiac pacemaker, the sinoatrial node (SAN).Moreover, SHOX2 mutations have been associatedwith cardiac arrhythmias in humans. For detailed examination of Shox2-dependent developmentalmechanisms in SAN cells, we established a murine embryonic stem cell (ESC)-based model using Shox2 as a molecular tool. Shox2+/+ and Shox2−/− ESC clones were isolated and differentiated according to five different protocols in order to evaluate the most efficient enrichment of SAN-like cells. Expression analysis of cell subtype-specific marker genes revealed most efficient enrichment after CD166-based cell sorting. Comparative cardiac expression profiles of Shox2+/+ and Shox2−/− ESCs were examined by nCounter technology. Among other genes, we identified Nppb as a novel putative Shox2 target during differentiation in ESCs. Differential expression of Nppb could be confirmed in heart tissue of Shox2−/− embryos. Taken together, we established an ESC-based cardiac differentiation model and successfully purified Shox2+/+ and Shox2−/− SAN-like cells. This now provides an excellent basis for the investigation of molecular mechanisms under physiological and pathophysiological conditions for evaluating novel therapeutic approaches