The structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog

We show that desert hedgehog ( dhh), a signaling molecule expressed by Schwann cells, is essential for the structural and functional integrity of the peripheral nerve. Dhh-null nerves display multiple abnormalities that affect myelinating and nonmyelinating Schwann cells, axons, and vasculature and immune cells. Myelinated fibers of these mice have a significantly increased ( more than two times) number of Schmidt-Lanterman incisures ( SLIs), and connexin 29, a molecular component of SLIs, is strongly upregulated. Crossing dhh-null mice with myelin basic protein ( MBP)-deficient shiverer mice, which also have increased SLI numbers, results in further increased SLIs, suggesting that Dhh and MBP control SLIs by different mechanisms. Unmyelinated fibers are also affected, containing many fewer axons per Schwann cell in transverse profiles, whereas the total number of unmyelinated axons is reduced by approximately one-third. In dhh-null mice, the blood-nerve barrier is permeable and neutrophils and macrophage numbers are elevated, even in uninjured nerves. Dhh-null nerves also lack the largest-diameter myelinated fibers, have elevated numbers of degenerating myelinated axons, and contain regenerating fibers. Transected dhh nerves degenerate faster than wild-type controls. This demonstrates that a single identified glial signal, Dhh, plays a critical role in controlling the integrity of peripheral nervous tissue, in line with its critical role in nerve sheath development ( Parmantier et al., 1999). The complexity of the defects raises a number of important questions about the Dhh-dependent cell-cell signaling network in peripheral nerves

c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.

The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue

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: Evaluation of knowledge base certification methods. Volume 4

This report presents the results of the Knowledge Base Certification activity of the expert systems verification and validation (V&V) guideline development 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 is concerned with the development and testing of various methods for assuring the quality of knowledge bases. The testing procedure used was that of behavioral experiment, the first known such evaluation of any type of V&V activity. The value of such experimentation is its capability to provide empirical evidence for -- or against -- the effectiveness of plausible methods in helping people find problems in knowledge bases. The three-day experiment included 20 participants from three nuclear utilities, the Nuclear Regulatory Commission`s Technical training Center, the University of Maryland, EG&G Idaho, and SAIC. The study used two real nuclear expert systems: a boiling water reactor emergency operating procedures tracking system and a pressurized water reactor safety assessment systems. Ten participants were assigned to each of the expert systems. All participants were trained in and then used a sequence of four different V&V methods selected as being the best and most appropriate for study on the basis of prior evaluation activities. These methods either involved the analysis and tracing of requirements to elements in the knowledge base (requirements grouping and requirements tracing) or else involved direct inspection of the knowledge base for various kinds of errors. Half of the subjects within each system group used the best manual variant of the V&V methods (the control group), while the other half were supported by the results of applying real or simulated automated tools to the knowledge bases (the experimental group)

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

Guidelines for the verification and validation of expert system software and conventional software: User`s manual. Volume 7

This report provides a step-by-step guide, or user manual, for personnel responsible for the planning and execution of the verification and validation (V&V), and developmental testing, of expert systems, conventional software systems, and various other types of artificial intelligence systems. While the guide was developed primarily for applications in the utility industry, it applies well to all industries. The user manual has three sections. In Section 1 the user assesses the stringency of V&V needed for the system under consideration, identifies the development stage the system is in, and identifies the component(s) of the system to be tested next. These three pieces of information determine which Guideline Package of V&V methods is most appropriate for those conditions. The V&V Guideline Packages are provided in Section 2. Each package consists of an ordered set of V&V techniques to be applied to the system, guides on choosing the review/evaluation team, measurement criteria, and references to a book or report which describes the application of the method. Section 3 presents details of 11 of the most important (or least well-explained in the literature) methods to assist the user in applying these techniques accurately

Guidelines for the verification and validation of expert system software and conventional software: Bibliography. Volume 8

This volume contains all of the technical references found in Volumes 1-7 concerning the development of guidelines for the verification and validation of expert systems, knowledge-based systems, other AI systems, object-oriented systems, and conventional systems

Gender violence in schools: taking the ‘girls-as-victims’ discourse forward

This paper draws attention to the gendered nature of violence in schools. Recent recognition that schools can be violent places has tended to ignore the fact that many such acts originate in unequal and antagonistic gender relations, which are tolerated and ‘normalised’ by everyday school structures and processes. After examining some key concepts and definitions, we provide a brief overview of the scope and various manifestations of gender violence in schools, noting that most research to date has focused on girls as victims of gender violence within a heterosexual context and ignores other forms such as homophobic and girl violence. We then move on to look at a few interventions designed to address gender violence in schools in the developing world and end by highlighting the need for more research and improved understanding of the problem and how it can be addressed

‘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

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