TGF beta type II receptor signaling controls Schwann cell death and proliferation in developing nerves

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death

Evidence for prelocalization of cytoplasmic factors affecting gene activation in early embryogenesis

Differentiation begins early in embryogenesis as different genes become active in different cells. Within the closed system of the early embryo, equal genomes thus direct the creation of diverse cell types. Though the nuclei of these cells contain complete copies of the same genome,(1,2) the nucleoplasmic and cytoplasmic environments of these genomes are not the same, as a result of the distribution of cleavage nuclei into diverse areas of egg cytoplasm early in the cleavage process. In some cases the fate of these nuclei, i.e., the type of differentiated cell to which they or their descendants give rise, has been seen to depend on the area of cytoplasm in which they come to lie

Transforming growth factor beta (TGF beta) mediates schwann cell death in vitro and in vivo: Examination of c-jun activation, interactions with survival signals, and the relationship of TGF beta-mediated death to schwann cell differentiation

In some situations, cell death in the nervous system is controlled by an interplay between survival factors and negative survival signals that actively induce apoptosis. The present work indicates that the survival of Schwann cells is regulated by such a dual mechanism involving the negative survival signal transforming growth factor beta (TGF beta), a family of growth factors that is present in the Schwann cells themselves. We analyze the interactions between this putative autocrine death signal and previously defined paracrine and autocrine survival signals and show that expression of a dominant negative c-Jun inhibits TGF beta -induced apoptosis. This and other findings pinpoint activation of c-Jun as a key downstream event in TGF beta -induced Schwann cell death. The ability of TGF beta to kill Schwann cells, like normal Schwann cell death in vivo, is under a strong developmental regulation, and we show that the decreasing ability of TGF beta to kill older cells is attributable to a decreasing ability of TGF beta to phosphorylate c-Jun in more differentiated cells

Detection of elliptical shapes via cross-entropy clustering

The problem of finding elliptical shapes in an image will be considered. We discuss the solution which uses cross-entropy clustering. The proposed method allows the search for ellipses with predefined sizes and position in the space. Moreover, it works well for search of ellipsoids in higher dimensions

Gaussian quantum marginal problem

The quantum marginal problem asks what local spectra are consistent with a given spectrum of a joint state of a composite quantum system. This setting, also referred to as the question of the compatibility of local spectra, has several applications in quantum information theory. Here, we introduce the analogue of this statement for Gaussian states for any number of modes, and solve it in generality, for pure and mixed states, both concerning necessary and sufficient conditions. Formally, our result can be viewed as an analogue of the Sing-Thompson Theorem (respectively Horn's Lemma), characterizing the relationship between main diagonal elements and singular values of a complex matrix: We find necessary and sufficient conditions for vectors (d1, ..., dn) and (c1, ..., cn) to be the symplectic eigenvalues and symplectic main diagonal elements of a strictly positive real matrix, respectively. More physically speaking, this result determines what local temperatures or entropies are consistent with a pure or mixed Gaussian state of several modes. We find that this result implies a solution to the problem of sharing of entanglement in pure Gaussian states and allows for estimating the global entropy of non-Gaussian states based on local measurements. Implications to the actual preparation of multi-mode continuous-variable entangled states are discussed. We compare the findings with the marginal problem for qubits, the solution of which for pure states has a strikingly similar and in fact simple form.Comment: 18 pages, 1 figure, material added, references updated, except from figure identical with version to appear in Commun. Math. Phy

‘They’re more like ordinary stroppy British women’: Attitudes and expectations of maternity care professionals to UK-born ethnic minority women

Objective To explore the attitudes and expectations of maternity care professionals to UK-born ethnic minority mothers. Methods Qualitative in-depth interviews with 30 professionals from eight NHS maternity units in England that provide services for large proportions of women of black Caribbean, black African, Indian, Pakistani and Irish descent. Results All the professionals reported providing care to both UK-born and migrant mothers from ethnic minorities. Most of them felt that they could differentiate between UK-born and migrant mothers based mainly on language fluency and accent. ‘Westernized dress’ and ‘freedom’ were also cited as indicators. Overall, professionals found it easier to provide services to UK-born mothers and felt that their needs were more like those of white English mothers than those of migrant mothers. UK-born mothers were generally thought to be assertive and expressive, and in control of care-related decision-making whereas some South Asian Muslim women were thought to be constrained by family influences. Preconceived ideas about ethnic minority mothers' tolerance of pain in labour, use of pharmacological pain relief measures and mode of delivery were recurring themes. Women's education and social class were felt to be major influences on the uptake of maternity care, regardless of ethnicity. Conclusions Professionals appeared to equate the needs of UK-born ethnic minority women with those of white English women. Overall, this has positive implications for care provision. Despite this, specific behavioural expectations and unconscious stereotypical views were evident and have the potential to affect clinical practice

Guidelines for the verification and validation of expert system software and conventional software: Validation scenarios. Volume 6

This report is the sixth volume in a series of reports describing the results of the Expert System Verification and Validation (V&V) project which is jointly funded by the US Nuclear Regulatory Commission and the Electric Power Research Institute. The ultimate objective is the formulation of guidelines for the V&V of expert systems for use in nuclear power applications. This activity was concerned with the development of a methodology for selecting validation scenarios and subsequently applying it to two expert systems used for nuclear utility applications. Validation scenarios were defined and classified into five categories: PLANT, TEST, BASICS, CODE, and LICENSING. A sixth type, REGRESSION, is a composite of the others and refers to the practice of using trusted scenarios to ensure that modifications to software did not change unmodified functions. Rationale was developed for preferring scenarios selected from the categories in the order listed and for determining under what conditions to select scenarios from other types. A procedure incorporating all of the recommendations was developed as a generalized method for generating validation scenarios. The procedure was subsequently applied to two expert systems used in the nuclear industry and was found to be effective, given that an experienced nuclear engineer made the final scenario selections. A method for generating scenarios directly from the knowledge base component was suggested

Guidelines for the verification and validation of expert system software and conventional software: Rationale and description of V&V guideline packages and procedures. Volume 5

This report is the fifth volume in a series of reports describing the results of the Expert System Verification C, and Validation (V&V) project which is jointly funded by the U.S. Nuclear Regulatory Commission and the Electric Power Research Institute toward the objective of formulating Guidelines for the V&V of expert systems for use in nuclear power applications. This report provides the rationale for and description of those guidelines. The actual guidelines themselves are presented in Volume 7, {open_quotes}User`s Manual.{close_quotes} Three factors determine what V&V is needed: (1) the stage of the development life cycle (requirements, design, or implementation); (2) whether the overall system or a specialized component needs to be tested (knowledge base component, inference engine or other highly reusable element, or a component involving conventional software); and (3) the stringency of V&V that is needed (as judged from an assessment of the system`s complexity and the requirement for its integrity to form three Classes). A V&V Guideline package is provided for each of the combinations of these three variables. The package specifies the V&V methods recommended and the order in which they should be administered, the assurances each method provides, the qualifications needed by the V&V team to employ each particular method, the degree to which the methods should be applied, the performance measures that should be taken, and the decision criteria for accepting, conditionally accepting, or rejecting an evaluated system. In addition to the Guideline packages, highly detailed step-by-step procedures are provided for 11 of the more important methods, to ensure that they can be implemented correctly. The Guidelines can apply to conventional procedural software systems as well as all kinds of Al systems