BACKGROUND: Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this ...increased risk. METHODS: Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes. RESULTS AND CONCLUSIONS: We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (≥100 repeats).
The TEDMOS computer aided design (CAD) system is described and it comprises a suitable system for application specific integrated circuit (ASIC) design on IBM PC like computers. The paper discusses ...the main assets and shortcomings of TEDMOS, when compared with other CAD systems, and presents its architecture. Emphasis is placed on both a software overview and on the algorithms. Particular attention is paid to hierarchical design, fast circuit simulation, and the hardware limitations imposed by IBM PC like machines.< >
Dynamic cell identities underlie flexible developmental programs. The stomatal lineage in the Arabidopsis leaf epidermis features asynchronous and indeterminate divisions that can be modulated by ...environmental cues. The products of the lineage, stomatal guard cells and pavement cells, regulate plant-atmosphere exchanges, and the epidermis as a whole influences overall leaf growth. How flexibility is encoded in development of the stomatal lineage and how cell fates are coordinated in the leaf are open questions. Here, by leveraging single-cell transcriptomics and molecular genetics, we uncovered models of cell differentiation within Arabidopsis leaf tissue. Profiles across leaf tissues identified points of regulatory congruence. In the stomatal lineage, single-cell resolution resolved underlying cell heterogeneity within early stages and provided a fine-grained profile of guard cell differentiation. Through integration of genome-scale datasets and spatiotemporally precise functional manipulations, we also identified an extended role for the transcriptional regulator SPEECHLESS in reinforcing cell fate commitment.
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•Distinct models of cell differentiation and lineage trajectories define leaf tissue•Cell-cycle regulators exhibit distinct, yet overlapping, expression profiles•Flexible stomatal lineage cell states exist along a continuum•Single-cell resolution refines cell fate commitment decisions that yield stomata
How do cells build developmentally flexible organs? Lopez-Anido et al. employed single-cell transcriptomics to uncover distinct models of cell differentiation within Arabidopsis leaf tissue. Along with revealing dynamics of cellular programs, they identified underlying cell heterogeneity within the epidermal lineage and interrogated new roles for a core transcriptional regulator.
Interactive Ray Tracing on Reconfigurable SIMD MorphoSys Du, H.; Sanchez-Elez, M.; Tabrizi, N. ...
Proceedings of the conference on Design, Automation and Test in Europe: Designers' Forum - Volume 2,
03/2003
Conference Proceeding
MorphoSys is a reconfigurable SIMD architecture. In this paper, a BSP-based ray tracing is gracefully mapped onto MorphoSys. The mapping highly exploits ray-tracing parallelism. A straightforward ...mechanism is used to handle irregularity among parallel rays in BSP. To support this mechanism, a special data structure is established, in which no intermediate data has to be saved. Moreover, optimizations such as object reordering and merging are facilitated. Data starvation is avoided by overlapping data transfer with intensive computation so that applications with different complexity can be managed efficiently. Since MorphoSys is small in size and power efficient, we demonstrate that MorphoSys is an economic platform for 3D animation applications on portable devices.
The aim of this paper is to discuss the needs for investment in electricity interconnectors in Europe by 2025. We evaluate the impact of cross-border transmission capacity on dispatch costs, ...curtailment needs for renewable energy sources (RES), on CO2 emissions, on hydro storage utilisation and on security of supply (in terms of energy not served). The analysis is performed with EUPowerDispatch, a minimum-cost dispatch model. For the evolution of the electricity generation portfolio and electricity consumption we use the latest Scenario Outlook and Adequacy Forecast of the European Network of Transmission System Operators for Electricity (ENTSO-E). The model results show that the planned additional cross-border transmission capacity between 2010 and 2025 will reduce annual dispatch costs, will have limited impact on the security of supply and will not be a significant cause of variable RES curtailment. However, in case of more RES, it will reduce dispatch costs to a larger extent and will considerably reduce RES curtailment needs, and, if demand grows at the historical rate of 2%, it will be needed to maintain the current level of security of supply. Moreover, our study shows that hydro pumping and storage and cross-border transmission are partly complementary technologies.
•A model for assessing the benefits of cross-border transmission capacity in Europe.•Current cross-border transmission: not an important constraint for RES by 2025.•CO2 emissions from electricity generation decrease by 17% (2010–2025).•Transmission investment necessary if demand is slightly higher than projected.•Storage and transmission are at least partly complementary technologies.
Myelination is essential for nervous system function. Schwann cells interact with neurons and the basal lamina to myelinate axons using known receptors, signals and transcription factors. In ...contrast, the transcriptional control of axonal sorting and the role of mechanotransduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. We describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice, we show that Taz is required in Schwann cells for radial sorting and myelination and that Yap is redundant with Taz. Yap and Taz are activated in Schwann cells by mechanical stimuli and regulate Schwann cell proliferation and transcription of basal lamina receptor genes, both necessary for radial sorting of axons and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.
Background Women with HER2–overexpressing breast cancers have poor prognosis, and many are resistant to the HER2 monoclonal antibody trastuzumab. A subgroup of HER2–overexpressing tumors also express ...p95HER2, an amino terminally truncated receptor that has kinase activity. Because p95HER2 cannot bind to trastuzumab but should be responsive to the HER2 tyrosine kinase inhibitor lapatinib, we compared the sensitivity of tumors expressing p95HER2 and tumors expressing the full-length HER2 receptor to these agents. Methods MCF-7 and T47D breast cancer cells were stably transfected with either full-length HER2 or p95HER2. We studied the effects of trastuzumab and lapatinib on receptor signaling, cell proliferation, and the growth of xenograft tumors. A paraffin-based immunofluorescence assay was developed to study the association between p95HER2 expression and sensitivity to trastuzumab in patients with advanced breast cancer. All statistical tests were two-sided. Results Treatment of p95HER2–expressing cells with lapatinib inhibited p95HER2 phosphorylation, reduced downstream phosphorylation of Akt and mitogen-activated protein kinases, inhibited cell growth (MCF-7p95HER2 clones, lapatinib versus control, mean growth inhibition = 57.6% versus 22.6%, difference = 35%, 95% confidence interval CI = 22.5% to 47.3%; P<.001; T47Dp95HER2 clones, lapatinib versus control, mean growth inhibition = 36.8% versus 20%, difference = 16.8%, 95% CI = 11.3% to 22.3%, P<.001), and inhibited growth of MCF-7p95HER2 xenograft tumors (lapatinib versus control, mean = 288.8 versus 435 mm3, difference = 146.2 mm3, CI = 73.8 to 218.5 mm3, P = .002). By contrast, treatment with trastuzumab had no effect on any of these parameters. Of 46 patients with metastatic breast cancer who were treated with trastuzumab, only one of nine patients (11.1%) expressing p95HER2 responded to trastuzumab (with a partial response), whereas 19 of the 37 patients (51.4%) with tumors expressing full-length HER2 achieved either a complete (five patients) or a partial (14 patients) response (P = .029). Conclusions Breast tumors that express p95HER2 are resistant to trastuzumab and may require alternative or additional anti-HER2–targeting strategies.
To determine whether smart conversational agents can be used for detection of neuropsychiatric disorders. Therefore, we reviewed the technologies used, targeted mental disorders and validation ...procedures of relevant proposals in this field.
We searched Scopus, PubMed, Pro-Quest, IEEE Xplore, Web of Science, CINAHL and the Cochrane Library using a predefined search strategy. Studies were included if they focused on neuropsychiatric disorders and involved conversational data for detection and diagnosis. They were assessed for eligibility by independent reviewers and ultimately included if a consensus was reached about their relevance.
2356 references were initially retrieved. Eventually, 17 articles – referring 9 smart conversational agents – met the inclusion criteria. Out of the selected studies, 7 are targeted at neurocognitive disorders, 7 at depression and 3 at other conditions. They apply diverse technological solutions and analysis techniques (82.4% use Artificial Intelligence), and they usually rely on gold standard tests for criterion validity assessment. Acceptability, reliability and other aspects of validity were rarely addressed.
The use of smart conversational agents for the detection of neuropsychiatric disorders is an emerging and promising field of research, with a broad coverage of mental disorders and extended use of AI. However, the few published studies did not undergo robust psychometric validation processes. Future research in this field would benefit from more rigorous validation mechanisms and standardized software and hardware platforms.
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•Smart conversational agents can potentially detect neuropsychiatric diseases.•The scientific literature was reviewed using the PRISMA methodology.•The coverage of mental disorders is broad, and the use of AI is widespread.•Emerging and promising field, with lack of robust psychometric validation.
Developing a distributed architecture for design rule checking Pais, A.P.V.; Anido, M.L.; Oliveira, C.E.T.
Proceedings of the 44th IEEE 2001 Midwest Symposium on Circuits and Systems. MWSCAS 2001 (Cat. No.01CH37257),
2001, Letnik:
2
Conference Proceeding
Odprti dostop
This paper describes the design and implementation of a distributed object-oriented design rule checker (DRC). The main focus is on the methodology employed to implement this distributed application. ...Code reusability is achieved using an OO approach, making objects available for other tools, such as circuit extractor. The paper also addresses the application of design patterns, which produce loosely coupled elements, facilitating the integration of system modules.
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