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We propose a surrogate model for predicting in-plane nonlinear structural deformations of a compliant mechanism. Our model utilizing a 2-dimensional co-rotational beam element extracts the essential deformation degrees-of-freedoms (DOFs) of bending flexible beams. The total number of DOFs of nodes at both ends of a 2-dimensional beam is six, while the number of deformation DOFs is three, i.e., axial extension, symmetric bending, and anti-symmetric bending. Therefore, it enables us to reduce the computational cost, from six to three, associated with the models by using the essential deformation DOFs of the co-rotational beam element. Moreover, it is difficult to predict the nonlinear responses of forces derived from displacements of a compliant mechanism due to bifurcation of the deformation-path. To overcome the problem, we generate the datasets by applying external forces and use the inverse response for constructing the surrogate models. In the numerical example, large-deformation behaviors of several types of compliant mechanisms are predicted by our surrogate models constructed by three typical learning algorithms: polynomial approximation, radial basis function, and neural network. The prediction performances and computational costs are investigated for verifying that they can be beneficial tools for designing a compliant mechanism with nonlinear elastic deformation behaviors.

The main purpose of this Guiding Framework document is to present the key elements of a Nutrition Public Expenditure Review (NPER) and offer guidance, practical steps, and examples on carrying out an NPER. It targets a wide-ranging audience, including country nutrition policy makers, development partners (DPs), government technical staff, and advocates and practitioners who are tasked with carrying out NPERs (who are also the main target audience). The Guiding Framework draws upon good practices from the growing body of NPERs as well as common practices and expertise from Public Expenditure Reviews (PERs). However, given the limited number of existing NPERs, this document should be considered as a starting point, or a ‘living document,’ and is not meant to provide a comprehensive coverage of a standard methodology for NPERs, as this would require further work and analysis. Specifically, this Guiding Framework aims to be a useful tool for practitioners involved in developing an NPER. It does this by: (i) situating NPERs within the context of other similar efforts such as a nutrition budget analysis or sector-specific PERs; (ii) presenting the literature of existing NPERs and related literature to serve as reference; (iii) providing guidance on preparatory work before beginning an NPER (i.e., defining the scope, setting up an NPER team, and identifying data sources); (iv) providing guidance on conducting the core analysis (i.e.,framing the analysis, analyzing the institutional framework, and linking the analysis to the policy dialogue); and (v) clearly identifying knowledge gaps and necessary additional work to enhance the robustness of future NPER analysis.

Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear protein that is activated by binding to DNA lesions and catalyzes poly(ADP-ribosyl)ation of nuclear acceptor proteins, including PARP1 itself, to recruit DNA repair machinery to DNA lesions. When excessive DNA damage occurs, poly(ADP-ribose) (PAR) produced by PARP1 is translocated to the cytoplasm, changing the activity and localization of cytoplasmic proteins, e.g., apoptosis-inducing factor (AIF), hexokinase, and resulting in cell death. This cascade, termed parthanatos, is a caspase-independent programmed cell death distinct from necrosis and apoptosis. In contrast, PARP1 is a substrate of activated caspases 3 and 7 in caspase-dependent apoptosis. Once cleaved, PARP1 loses its activity, thereby suppressing DNA repair. Caspase cleavage of PARP1 occurs within a nuclear localization signal near the DNA-binding domain, resulting in the formation of 24-kDa and 89-kDa fragments. In the present study, we found that caspase activation by staurosporine- and actinomycin D-induced PARP1 autopoly(ADP-ribosyl)ation and fragmentation, generating poly(ADP-ribosyl)ated 89-kDa and 24-kDa PARP1 fragments. The 89-kDa PARP1 fragments with covalently attached PAR polymers were translocated to the cytoplasm, whereas 24-kDa fragments remained associated with DNA lesions. In the cytoplasm, AIF binding to PAR attached to the 89-kDa PARP1 fragment facilitated its translocation to the nucleus. Thus, the 89-kDa PARP1 fragment is a PAR carrier to the cytoplasm, inducing AIF release from mitochondria. Elucidation of the caspase-mediated interaction between apoptosis and parthanatos pathways extend the current knowledge on mechanisms underlying programmed cell death and may lead to new therapeutic targets.

Architecture selection for systems undergoing rapid technological and market change is challenging. It is desirable to select architectures that can provide cost-effective possibilities for future changes and avoid architecture lock-in. However, optimal architectures for prevailing conditions may not be changeable for future adaptation. This tension between objectives for system (product) development for both short-term and long-term competitiveness has been an enduring challenge for system architects. Here, we use time-expanded decision networks (TDNs) with time-varying costs and demands to systematically explore future architecture transition pathways and strategically identify useful designs. We demonstrate a new application for autonomous driving (AD) systems, a nascent technology, where the design and capabilities of constituent components (such as sensors, processors, and data communication links) are still evolving and significant market and regulatory uncertainties persist. In this case, we model technology costs with time-based factors to explicitly include future trends. The results show that as cost differences between architectures increase and demand for new functionality changes with time, the approach is able to identify potential transition points between architecture choices that optimize the net present value (NPV) of the system. For some of the specific scenarios analyzed in this study, the NPV with optimal architecture transitions is at least 10–20% larger as compared with fixed cases. Overall, this work presents a case for planning and partly constructing architecture transition roadmaps for new systems wherein dominant architectures have not emerged.

Shaping the Food System to Deliver Jobs is the fourth paper in a series on The Future of Food. This paper focuses on how the food system can deliver jobs. It provides a framework for understanding the factors determining the number and quality of jobs in the food system, including inclusion of women and youth. It highlights a set of actions that countries can adopt, adapt, and apply to their own circumstances to enhance the food system’s contribution to jobs. The food system extends beyond farm production to include food storage, processing, distribution, transport, retailing, restaurants and other services. The paper finds that the food system employs the most people in many developing countries in both self and wage employment, and will continue to do so for the foreseeable future. In many countries the off-farm aspect of the food system accounts for a large share of the economy’s manufacturing and services sectors. While the employment share in farming tends to decline as per capita incomes rise, the share in food manufacturing and services tends to increase. Urbanization and per capita income growth offers significant new opportunities in non-cereal products and in new jobs in the food system beyond the farm.

Despite significant progress the world continues to bear a triple burden of malnutrition. These three burdens are related, but distinctly different, problems: energy deficiencies (hunger), micronutrient deficiencies (hidden hunger), 3 and excessive net energy intake and unhealthy diets overweight/obesity). Despite significant progress, 795 million people still are not getting the minimum dietary energy needs. The majority of these people are in Sub-Saharan Africa, in which 1 in 4 people are hungry; and in South Asia, in which 1 in 6 people are hungry. More than 2 billion people are deficient in key vitamins and minerals7 that are necessary for growth, development, and disease prevention. Globally, over 2 billion people are overweight or obese, two-thirds of whom live in developing countries. This issue clearly is not just a developed country problem. Energy and micronutrient deficiency are contributors to the 165 million children under 5 who are stunted and cannot grow to achieve their full potential. Globally, this number is equivalent to approximately 1 in 4 children under 5 years, with an even more concentrated situation in Sub-Saharan Africa and South Asia (1 in 3 children). Arguably child stunting is one of the biggest development challenges. If not addressed it will profoundly undermine our ability to end poverty and promote shared prosperity.

Despite significant progress the world continues to bear a triple burden of malnutrition. These three burdens are related, but distinctly different, problems: energy deficiencies (hunger), micronutrient deficiencies (hidden hunger), 3 and excessive net energy intake and unhealthy diets overweight/obesity). Despite significant progress, 795 million people still are not getting the minimum dietary energy needs. The majority of these people are in Sub-Saharan Africa, in which 1 in 4 people are hungry; and in South Asia, in which 1 in 6 people are hungry. More than 2 billion people are deficient in key vitamins and minerals7 that are necessary for growth, development, and disease prevention. Globally, over 2 billion people are overweight or obese, two-thirds of whom live in developing countries. This issue clearly is not just a developed country problem. Energy and micronutrient deficiency are contributors to the 165 million children under 5 who are stunted and cannot grow to achieve their full potential. Globally, this number is equivalent to approximately 1 in 4 children under 5 years, with an even more concentrated situation in Sub-Saharan Africa and South Asia (1 in 3 children). Arguably child stunting is one of the biggest development challenges. If not addressed it will profoundly undermine our ability to end poverty and promote shared prosperity.

Although Moraxella catarrhalis is known to be susceptible to macrolides, highly macrolide-resistant M. catarrhalis isolates have recently been reported in Japan and China. In this study, we investigated the prevalence of macrolide-resistant M. catarrhalis isolates in Tokyo and Chiba, Japan, and studied the mechanisms underlying their resistance. Specifically, we determined the susceptibility of 593 clinical isolates (collected between December 2011 and May 2014) to erythromycin, using the disk diffusion method. For isolates with erythromycin resistance, we identified the MICs of seven antimicrobial agents, including macrolides, and used PFGE to analyse the clonal spread. We also performed sequencing analysis to investigate macrolide-resistance targets. Thirteen isolates (2.2 %) were found to be resistant to erythromycin, showing a high MIC90 to erythromycin, clarithromycin, clindamycin and azithromycin. However, those isolates, in addition to 156 randomly selected erythromycin-susceptible strains, were susceptible to amoxicillin–clavulanate, cefixime and levofloxacin. The 13 highly macrolide-resistant isolates were classified into 10 clades and harboured three or four A2058T-mutated 23S rRNA alleles. Three highly macrolide-resistant isolates also exhibited mutations in ribosomal proteins L4 (V27A and R161C) and L22 (K68T). To the best of our knowledge, we have demonstrated for the first time that, whilst the prevalence of macrolide-resistant M. catarrhalis isolates is low in clinical settings in Japan, genetically diverse isolates with high-level macrolide resistance due to the acquisition of an A2058T mutation in the 23S rRNA have already spread. Our study therefore lays the basis for epidemiological studies of macrolide-resistant M. catarrhalis clinical isolates.

We assessed the usefulness of reporting direct blood Gram stain results compared with the results of positive blood cultures in 482 episodes and monitored impact on selection of antimicrobial treatment. We found that the reporting groups “Staphylococcus spp,” “Pseudomonas spp and related organisms,” and “yeasts” identified in this way matched perfectly with later culture identification. When the report indicated Staphylococcus spp or Pseudomonas spp and related organisms, physicians started or changed antimicrobials suitable for these bacteria more frequently than when “other streptococci” and “family Enterobacteriaceae” were reported (P < .05). Incorrect recognition of Acinetobacter spp as Enterobacteriaceae family is still the most challenging problem in this context. Gram stain results that definitively identify Staphylococcus spp, Pseudomonas spp and related organisms, and yeasts reliably can be rapidly provided by clinical laboratories; this information has a significant impact on early selection of effective antimicrobials. Further investigation is needed to assess the clinical impact of reporting Gram stain results in bacteremia.