We study the linear space of Cs-smooth isogeometric functions defined on a multi-patch domain Ω⊂R2. We show that the construction of these functions is closely related to the concept of geometric ...continuity of surfaces, which has originated in geometric design. More precisely, the Cs-smoothness of isogeometric functions is found to be equivalent to geometric smoothness of the same order (Gs-smoothness) of their graph surfaces. This motivates us to call them Cs-smooth geometrically continuous isogeometric functions. We present a general framework to construct a basis and explore potential applications in isogeometric analysis. The space of C1-smooth geometrically continuous isogeometric functions on bilinearly parameterized two-patch domains is analyzed in more detail. Numerical experiments with bicubic and biquartic functions for performing L2 approximation and for solving Poisson’s equation and the biharmonic equation on two-patch geometries are presented and indicate optimal rates of convergence.
•Investigation of the C1-smooth space of trilinearly parameterized volumetric two-patch domains.•Computation of dimension of the space.•Construction of explicitly given and locally supported basis ...functions of the space.•A first possible extension of the approach to more general two-patch domains than trilinear ones.
We study the C1-smooth isogeometric spline space over a specific class of unstructured hexahedral meshes, namely over the class of trilinearly parameterized volumetric two-patch domains. Recently, the structure of this space was experimentally analyzed in Birner et al. (2018) by numerically computing a basis and the dimension of this space. In this work, we develop the theoretical framework to explore the C1-smooth isogeometric space. Amongst others, we use the framework to prove the numerically obtained dimension from Birner et al. (2018) and to describe a simple explicit basis construction which consists of locally supported functions.
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We analyze the spaces of trivariate C1–smooth isogeometric functions on two-patch domains. Our aim is to generalize the corresponding results from the bivariate (Kapl et al. (2015) ...25) to the trivariate case. In the first part of the paper, we introduce the notion of gluing data and use it to define glued spline functions on two-patch domains. Applying the fundamental observation that “matched Gk–constructions always yield Ck–continuous isogeometric elements”, see Groisser and Peters (2015) 14, to graph hypersurfaces in four-dimensional space, allows us to characterize C1–smooth geometrically continuous isogeometric functions as the push-forwards of these functions for suitable gluing data. The second part of the paper is devoted to various special classes of gluing data. We analyze how the generic dimensions depend on the number of knot spans (elements) and on the spline degree. Finally we show how to construct locally supported basis functions in specific situations.
We analyze the spaces of trivariate C 1-smooth isogeometric functions on two-patch domains. Our aim is to generalize the corresponding results from the bivariate 25 to the trivariate case. In the ...first part of the paper, we introduce the notion of gluing data and use it to define glued spline functions on two-patch domains. Applying the fundamental observation that "matched G k-constructions always yield C k-continuous isogeometric elements", see 14, to graph hypersurfaces in four-dimensional space, allows us to characterize C 1-smooth geometrically continuous isogeometric functions as the push-forwards of these functions for suitable gluing data. The second part of the paper is devoted to various special classes of gluing data. We analyze how the generic dimensions depend on the number of knot spans (elements) and on the spline degree. Finally we show how to construct locally supported basis functions in specific situations.
Large-scale social safety net programs such as India's National Rural Employment Guarantee Act (NREGA) are difficult to implement due to governance challenges related to elite capture, leakages, and ...corruption. The ability to identify how the governance challenges of program implementation can be met requires detailed insights into the actual process of program implementation, with clear views on the source of leakage and mismanagement, the sensitivity of program implementation to the influence of different actors, local power structures and informal bureaucratic processes. This paper uses a new participatory research method, referred to as Process-Influence Mapping, to shed light on these issues and related governance challenges, using the implementation of NREGA as an example. The Process-Influence Mapping tool helps identify the specific features of the NREGA implementation process that limit the program's effectiveness (for example, elite capture in the definition of work and capacity limitations due to staff shortages and lack of training) and create scope for the misappropriation of funds. The insights gained can be used to identify policy options for reforming the administrative process of NREGA implementation so as to create an effective social safety net.
"In 1993, India introduced quota-based political reservations for women in rural areas with the objective to promote gender equality in human development by making rural service provision and local ...governance inclusive and responsive to the needs of women. Recent evidence shows that reservation policies for women (1) stimulate the political participation of women in rural areas, (2) shift rural service provision to public goods that reflect gender preferences, and (3) improve the access to and the quality of public services. Despite the suggested positive effects of women’s reservation policies on service provision and local governance, the gender bias in human development is still pronounced. This casts doubt on the effectiveness of reservation policies as an instrument for making rural service provision and local governance more gender equitable and raises questions about the nature and direction of the major constraints. This paper aims to qualify and quantify the role of political reservation policies for women as a determinant of rural service provision and local governance and seeks to identify the social, economic, and institutional factors that constrain effective local governance and rural service provision beyond the women’s reservation effect. Our empirical sample consists of 80 Gram Panchayats (GP) and 966 households in 12 districts in Karnataka in 2006. In contrast to the main existing literature, the empirical evidence from (non-)linear probability models lends weak support to the existence of gender effects of reservation policies on local governance and rural service provision. The local governance and service delivery outcomes are predominantly determined by social, economic, and institutional factors that are unrelated to women’s reservation requirements. For example, (1) individual characteristics such as literacy, household institutional and political linkages, or the household location in the GP and (2) GP-specific factors such as the degree of community involvement in service provision and the fiscal devolution of activities are more likely to have a significant effect on service provision and governance than reservation policies for women. These results suggest that women’s reservation policies per se are insufficient means for making rural service provision and local governance more inclusive and gender equitable. In addition, it appears that gender-integrated policy approaches that are targeted at both women and men are needed." --from authors' abstract
Strategies to reform rural service provision in India have focused on improving people‘s capacity to demand better services from government agencies. However, efforts to reform the public-sector ...agencies that provide essential rural services have been limited. Moreover, major knowledge gaps exist on how incentive problems and governance challenges vary across the agencies that provide the services and how they can be addressed. This paper aims to contribute to this knowledge gap. The empirical analysis is based on a survey of 206 field-level staff members of five government departments that provide rural services: Agriculture, Animal Husbandry, Food and Civil Supplies, Women and Child Development, and Rural Development and Panchayati Raj (local government). The paper also draws on a survey of 966 rural households that receive services from these departments. The analysis indicates that there are significant differences across departments regarding the incentives and constraints faced by their frontline service providers. Lack of staff was found to be a major constraint for agricultural and veterinary services, whereas frontline staff in charge of food distribution and civil works experienced political interference as a particularly serious constraint. Contrary to widely held assumptions, availability of funding and administrative procedures was not considered by frontline staff as a major constraint. The findings from the household survey indicate that access and satisfaction with services differ significantly according to caste and gender, even though these effects are not uniform across services. The paper compares the findings of the study with the recommendations of the country‘s Second Administrative Reform Commission and concludes that some constraints, such as political interference, require more attention to make service delivery responsive to the needs of the poor.
Lysosomal acid lipase (LAL) is the sole lysosomal enzyme responsible for the degradation of cholesteryl esters and triacylglycerols at acidic pH. Impaired LAL activity leads to LAL deficiency ...(LAL-D), a severe and fatal disease characterized by ectopic lysosomal lipid accumulation. Reduced LAL activity also contributes to the development and progression of non-alcoholic fatty liver disease (NAFLD). To advance our understanding of LAL-related liver pathologies, we performed comprehensive proteomic profiling of livers from mice with systemic genetic loss of LAL (Lal−/−) and from mice with hepatocyte-specific LAL-D (hepLal−/−). Lal−/− mice exhibited drastic proteome alterations, including dysregulation of multiple proteins related to metabolism, inflammation, liver fibrosis, and cancer. Global loss of LAL activity impaired both acidic and neutral lipase activities and resulted in hepatic lipid accumulation, indicating a complete metabolic shift in Lal−/− livers. Hepatic inflammation and immune cell infiltration were evident, with numerous upregulated inflammation-related gene ontology biological process terms. In contrast, both young and mature hepLal−/− mice displayed only minor changes in the liver proteome, suggesting that loss of LAL solely in hepatocytes does not phenocopy metabolic alterations observed in mice globally lacking LAL. These findings provide valuable insights into the mechanisms underlying liver dysfunction in LAL-D and may help in understanding why decreased LAL activity contributes to NAFLD. Our study highlights the importance of LAL in maintaining liver homeostasis and demonstrates the drastic consequences of its global deficiency on the liver proteome and liver function.
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The function of many protein kinases is controlled by the phosphorylation of a critical tyrosine residue in the activation loop. Dual specificity tyrosine‐phosphorylation‐regulated kinases (DYRKs) ...autophosphorylate on this tyrosine residue but phosphorylate substrates on aliphatic amino acids. This study addresses the mechanism of dual specificity kinase activity in DYRK1A and related kinases. Tyrosine autophosphorylation of DYRK1A occurred rapidly during in vitro translation and did not depend on the non‐catalytic domains or other proteins. Expression in bacteria as well as in mammalian cells revealed that tyrosine kinase activity of DYRK1A is not restricted to the co‐translational autophosphorylation in the activation loop. Moreover, mature DYRK1A was still capable of tyrosine autophosphorylation. Point mutants of DYRK1A and DYRK2 lacking the activation loop tyrosine showed enhanced tyrosine kinase activity. A series of structurally diverse DYRK1A inhibitors was used to pharmacologically distinguish different conformational states of the catalytic domain that are hypothesized to account for the dual specificity kinase activity. All tested compounds inhibited substrate phosphorylation with higher potency than autophosphorylation but none of the tested inhibitors differentially inhibited threonine and tyrosine kinase activity. Finally, the related cyclin‐dependent kinase‐like kinases (CLKs), which lack the activation loop tyrosine, autophosphorylated on tyrosine both in vitro and in living cells. We propose a model of DYRK autoactivation in which tyrosine autophosphorylation in the activation loop stabilizes a conformation of the catalytic domain with enhanced serine/threonine kinase activity without disabling tyrosine phosphorylation. The mechanism of dual specificity kinase activity probably applies to related serine/threonine kinases that depend on tyrosine autophosphorylation for maturation.
Structured digital
CLK1 and CLK1 phosphorylate by protein kinase assay (View interaction)
HIPK2 and HIPK2 phosphorylate by protein kinase assay (View interaction)
DYRK1A phosphorylates SF3B1 by protein kinase assay (View interaction)
DYRK1A and DYRK1A phosphorylate by protein kinase assay (View interaction)
This study addresses the mechanism of dual specificity kinase activity in DYRK1A and related kinases. Here, present results that support a model of DYRK autoactivation in which the one‐time tyrosine autophosphorylation in the activation loop stabilizes a conformation of the catalytic domain with enhanced serine/threonine kinase activity without disabling tyrosine phosphorylation by the mature kinase.
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