Routing for analog chip designs at NXP Semiconductors

During the study week 2011 we worked on the question of how to automate certain aspects of the design of analog chips. Here we focused on the task of connecting different blocks with electrical wiring, which is particularly tedious to do by hand. For digital chips there is a wealth of research available for this, as in this situation the amount of blocks makes it hopeless to do the design by hand. Hence, we set our task to finding solutions that are based on the previous research, as well as being tailored to the specific setting given by NXP. This resulted in an heuristic approach, which we presented at the end of the week in the form of a protoype tool. In this report we give a detailed account of the ideas we used, and describe possibilities to extend the approach

Sex: Not all that it's cracked up to be?

While sexual reproduction is generally thought to be, evolutionarily speaking, a good idea, there are a small number of organisms that are testament to the contrary. The root-knot nematodes Meloidogyne incognita, M. javanica, and M. arenaria reproduce clonally using mitotic parthenogenesis but have a broader host range, a wider geographical distribution, and a greater agricultural impact than their sexual relatives (Fig 1) [1]. Remarkably, some of these species even have the ability to overcome host resistance [2], suggesting a mechanism for adaptation in the absence of sex. The genetic basis of this plasticity, both in terms of host range and adaptability, is not fully understood. Previous genome sequencing of Meloidogyne has shown that the genome of one of these species, M. incognita, is polyploid [3], most likely as a result of hybridisation (allopolyploid), with a further study suggesting that M. incognita may be the result of multiple additive hybridisation events: a hybrid of a hybrid [4]

Exploring Patterns of Activities of Daily Living in the Home Environment

Background: Senior citizens tend to live longer and longer independently. Judging whether a senior person is still capable of living on his own is often based on the occurrence of incidents, with all consequences thereof. In the specific case of early dementia, the symptoms are not immediately apparent and the occurrence and severity of incidents progress gradually over time. In this case, the children or grandchildren are burdened by the question whether or not the elderly adult can still live safely and independently in his or her own home. This decision is only based on input obtained through incidental visits. We believe that the capability of independent living can only be objectively judged, by a health professional, if long term objective information on the elderly person's daily activities of living (ADL) is available

Аксиологоческое пространство культуры

Introduction. This study was performed to assess the applicability of the WHO Maternal Near Miss Tool (MNM Tool) and the organ dysfunction criteria in a high-income country. Material and methods. The MNM tool was applied to 2552 women who died of pregnancy-related causes or sustained severe acute maternal morbidity between August 2004 and August 2006 in one of the 98 hospitals with a maternity unit in the Netherlands. Fourteen (0.6%) cases had insufficient data for application. Each case was assessed according to the three main "MNM categories" specified in the MNM tool and their subcategory criteria: five disease-, four intervention- and seven organ dysfunction-based criteria. Potentially life-threatening conditions (disease-based inclusions) and life-threatening cases (organ dysfunction-based inclusions) were differentiated according to WHO methodology. Outcomes were incidence of all (sub)categories and case-fatality rates. Results. Of the 2538 cases, 2308 (90.9%) women fulfilled disease-based, 2116 (83.4%) intervention-based and 1024 (40.3%) organ dysfunction-based criteria. Maternal death occurred in 48 women, of whom 23 (47.9%) fulfilled disease-based, 33 (68.8%) intervention-based and 31 (64.6%) organ dysfunction-based criteria. Case-fatality rates were 23/2308 (1.0%) for cases fulfilling the disease-based criteria, 33/2116 (1.6%) for intervention-based criteria and 31/1024 (3.0%) for women fulfilling the organ dysfunction-based criteria. Conclusions. In the Netherlands, where advanced laboratory and clinical monitoring are available, organ dysfunction-based criteria of the MNM tool failed to identify nearly two-thirds of sustained severe acute maternal morbidity cases and more than one-third of maternal deaths. Disease-based criteria remain important, and using only organ dysfunction-based criteria would lead to underestimating severe acute maternal morbidity

Characterisation of arabinogalactan endo β 1,4 galactanases from Globodera rostochiensis, Globodera pallida and Rotylenchulus reniformis

KL was funded by a BBSRC EASTBIO DTP studentship provided through the UKRI Biotechnology and Biological Sciences Research Council (BBSRC) grant number BB/T00875X/1 and by the Rural and Environment Science and Analytical Services Division of the Scottish Government at The James Hutton Institute and The University of St Andrews. Work on plant-parasitic nematodes at the University of Cambridge is supported by DEFRA licence 125034/359149/3 and funded by BBSRC grants BB/R011311/1, BB/N021908/1, and BB/S006397/1.Plant parasitic nematodes need to overcome the barrier presented by the plant cell wall in order to invade their host. A variety of plant cell wall degrading enzymes are present in endoparasitic nematodes including enzymes that degrade cellulose (beta 1,4 endoglucanases) and various pectin components. We describe the cloning and functional analysis of genes encoding GH53 arabinogalactan endo-1,4-beta-galactosidases from three related plant parasitic nematodes Globodera rostochiensis, Globodera pallida and Rotylenchulus reniformis. Phylogenetic and structural analyses strongly indicate that these genes have been acquired by horizontal gene transfer from bacteria. We show that the genes are expressed at invasive stages of the parasites in the secretory gland cells. We also demonstrate that the enzymes from these species are biochemically active, showing the expected hydrolytic enzymatic activity when galactan was used as a substrate. This work further demonstrates the importance of cell wall degradation to the success of the parasitic process and the extensive role that horizontal gene transfer has played in the evolution of plant parasitism by nematodes.Publisher PDFPeer reviewe

Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients.

PurposeMany women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing.MethodsWe tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma.ResultsAcross the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene.ConclusionsAmong women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing

Multi-omic analyses in immune cell development with lessons learned from T cell development

Traditionally, flow cytometry has been the preferred method to characterize immune cells at the single-cell level. Flow cytometry is used in immunology mostly to measure the expression of identifying markers on the cell surface, but—with good antibodies—can also be used to assess the expression of intracellular proteins. The advent of single-cell RNA-sequencing has paved the road to study immune development at an unprecedented resolution. Single-cell RNA-sequencing studies have not only allowed us to efficiently chart the make-up of heterogeneous tissues, including their most rare cell populations, it also increasingly contributes to our understanding how different omics modalities interplay at a single cell resolution. Particularly for investigating the immune system, this means that these single-cell techniques can be integrated to combine and correlate RNA and protein data at the single-cell level. While RNA data usually reveals a large heterogeneity of a given population identified solely by a combination of surface protein markers, the integration of different omics modalities at a single cell resolution is expected to greatly contribute to our understanding of the immune system

Identification and characterisation of a hyper-variable apoplastic effector gene family of the potato cyst nematodes.

Sedentary endoparasitic nematodes are obligate biotrophs that modify host root tissues, using a suite of effector proteins to create and maintain a feeding site that is their sole source of nutrition. Using assumptions about the characteristics of genes involved in plant-nematode biotrophic interactions to inform the identification strategy, we provide a description and characterisation of a novel group of hyper-variable extracellular effectors termed HYP, from the potato cyst nematode Globodera pallida. HYP effectors comprise a large gene family, with a modular structure, and have unparalleled diversity between individuals of the same population: no two nematodes tested had the same genetic complement of HYP effectors. Individuals vary in the number, size, and type of effector subfamilies. HYP effectors are expressed throughout the biotrophic stages in large secretory cells associated with the amphids of parasitic stage nematodes as confirmed by in situ hybridisation. The encoded proteins are secreted into the host roots where they are detectable by immunochemistry in the apoplasm, between the anterior end of the nematode and the feeding site. We have identified HYP effectors in three genera of plant parasitic nematodes capable of infecting a broad range of mono- and dicotyledon crop species. In planta RNAi targeted to all members of the effector family causes a reduction in successful parasitism

Ex vivo expansion and differentiation of erythroblasts: From culture dishes to stirred tank reactors for the production of red blood cells

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