Effects of Sex and Gender on Adaptation to Space: Musculoskeletal Health

There is considerable variability among individuals in musculoskeletal response to long-duration spaceflight. The specific origin of the individual variability is unknown but is almost certainly influenced by the details of other mission conditions such as individual differences in exercise countermeasures, particularly intensity of exercise, dietary intake, medication use, stress, sleep, psychological profiles, and actual mission task demands. In addition to variations in mission conditions, genetic differences may account for some aspect of individual variability. Generally, this individual variability exceeds the variability between sexes that adds to the complexity of understanding sex differences alone. Research specifically related to sex differences of the musculoskeletal system during unloading is presented and discussed

The effects of cash transfers and vouchers on the use and quality of maternity care services: a systematic review

Background Cash transfers and vouchers are forms of 'demand-side financing' that have been widely used to promote maternal and newborn health in low- and middle-income countries during the last 15 years. Methods This systematic review consolidates evidence from seven published systematic reviews on the effects of different types of cash transfers and vouchers on the use and quality of maternity care services, and updates the systematic searches to June 2015 using the Joanna Briggs Institute approach for systematic reviewing. The review protocol for this update was registered with PROSPERO (CRD42015020637). Results Data from 51 studies (15 more than previous reviews) and 22 cash transfer and voucher programmes suggest that approaches tied to service use (either via payment conditionalities or vouchers for selected services) can increase use of antenatal care, use of a skilled attendant at birth and in the case of vouchers, postnatal care too. The strongest evidence of positive effect was for conditional cash transfers and uptake of antenatal care, and for vouchers for maternity care services and birth with a skilled birth attendant. However, effects appear to be shaped by a complex set of social and healthcare system barriers and facilitators. Studies have typically focused on an initial programme period, usually two or three years after initiation, and many lack a counterfactual comparison with supply-side investment. There are few studies to indicate that programmes have led to improvements in quality of maternity care or maternal and newborn health outcomes. Conclusion Future research should use multiple intervention arms to compare cost-effectiveness with similar investment in public services, and should look beyond short- to medium-term service utilisation by examining programme costs, longer-term effects on service utilisation and health outcomes, and the equity of those effects

Pengurangan Waste Pada Proses Produksi Botol X Menggunakan Metode Lean Sigma

Waste merupakan semua aktivitas kerja yang tidak memberikan nilai tambah dalam proses pembuatan produk sehingga harus segera direduksi atau dihilangkan dari proses produksi. Penelitian ini bertujuan untuk mengidentifikasi jenis-jenis waste yang terjadi dalam proses produksi, menganalisis faktor-faktor penyebab waste, serta memberikan usulan rekomendasi perbaikan untuk meminimasi waste. Metode yang digunakan dalam penelitian ini adalah lean Sigma, yaitu perpaduan antara metode lean manufacturing dan six Sigma yang bertujuan untuk mengidentifikasi dan meminimasi waste, memperbaiki proses, serta meningkatkan kualitas dari proses produksi. Penelitian ini dilakukan sebagai upaya continuous improvement untuk perbaikan proses dalam langkah kerja six Sigma (DMAIC). Dari tujuh kategori waste, teridentifikasi empat jenis waste dalam proses produksi botol X, yaitu defect, overproduction, waiting, dan inventories. Rekomendasi perbaikan yang diusulkan dalam penelitian ini ini didasarkan dari hasil identifikasi CTQ waste yang telah dianalisis menggunakan fishbone diagram dan pemilihan prioritas rekomendasi menggunakan FMEA. Hasil rekomendasi dari penelitian ini adalah mengenai peningkatan kedisiplinan operator maupun pihak manajemen

Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation

<p>Abstract</p> <p>Background</p> <p>Mammary glands harbor a profound burden of apoptotic cells (ACs) during post-lactational involution, but little is known regarding mechanisms by which ACs are cleared from the mammary gland, or consequences if this process is interrupted. We investigated AC clearance, also termed efferocytosis, during post-lactational remodeling, using mice deficient for MerTK, Axl, and Tyro3, three related receptor tyrosine kinases (RTKs) regulating macrophage-mediated efferocytosis in monocytes. MerTK expression, apoptosis and the accumulation of apoptotic debris were examined in histological sections of MerTK-deficient, Axl/Tyro3-deficient, and wild-type mammary glands harvested at specific time points during lactation and synchronized involution. The ability of primary mammary epithelial cells (MECs) to engulf ACs was assessed in culture. Transplant of MerTK-deficient mammary epithelium into cleared WT mammary fat pads was used to assess the contribution of WT mammary macrophages to post-lactational efferocytosis.</p> <p>Results</p> <p>ACs induced MerTK expression in MECs, resulting in elevated MerTK levels at the earliest stages of involution. Loss of MerTK resulted in AC accumulation in post-lactational MerTK-deficient mammary glands, but not in Axl and Tyro3-deficient mammary glands. Increased vascularization, fibrosis, and epithelial hyperproliferation were observed in MerTK-deficient mammary glands through at least 60 days post-weaning, due to failed efferocytosis after lactation, but did not manifest in nulliparous mice. WT host-derived macrophages failed to rescue efferocytosis in transplanted MerTK-deficient mammary epithelium.</p> <p>Conclusion</p> <p>Efferocytosis by MECs through MerTK is crucial for mammary gland homeostasis and function during the post-lactational period. Efferocytosis by MECs thus limits pathologic consequences associated with the apoptotic load following lactation.</p

Evaluating the catalytic efficiency of paired, single-atom catalysts for the oxygen reduction reaction

Paired, single-atom catalysts have been shown to demonstrate synergistic effects computationally and experimentally which enable them to outperform the benchmark catalyst, Pt/C, for electrochemical reactions. We explore the limit of these catalysts by screening different transition metal atoms (M = Co, Pt, Fe, Ni) in nitrogen-doped graphene for their ability to catalyze the oxygen reduction reaction (ORR). We employ density functional theory methods to explore the electronic factors affecting catalytic activity in an effort to rationalize trends in the performance of materials which are promising candidates for the next generation of electrocatalysts. It is found that CoPt@N8V4, composed of paired Co and Pt in a nitrogen-doped four-atom vacancy in graphene (N8V4), performs ideally for the ORR with an overpotential (η) of 0.30 V, followed closely by Co and Ni (η = 0.35 V) and paired Co (η = 0.37 V). The origin of activity is suggested to be the changing reduction potential of the active Co atom via the local distortion of the pore by the spectating metal partner. We utilize the ORR scaling relations and plot catalytic activity on a volcano plot, which we correlate with the degree of antibonding interactions with the O atom in the OH intermediate of the ORR. We establish that the local tuning of paired catalysts allows for the reactivity of metal atoms to be specifically modified for desirable reactivity

Citrullinated and Malondialdehyde-Acetaldehyde Modified Fibrinogen Activates Macrophages and Promotes an Aggressive Synovial Fibroblast Phenotype in Patients with Rheumatoid Arthritis

Objective: Post-translational protein modifications with malondialdehyde-acetaldehyde (MAA) and citrulline (CIT) are implicated in the pathogenesis of rheumatoidarthritis (RA). Although precise mechanisms have not been elucidated, macrophage-fibroblast interactions have been proposed to play a central role in the development and progression of RA. The purpose of our study was to evaluate the downstream effects of macrophage released soluble mediators, following stimulation with fibrinogen (FIB) modified antigens, on human fibroblast-like synoviocytes (HFLS). Methods: PMA-treated U-937 monocytes (Mϕ) and macrophage-differentiated peripheral blood mononuclear cells (MP) were stimulated with FIB, FIB-MAA, FIB-CIT, or FIB-MAA-CIT. HFLS-RA cells were stimulated directly with FIB antigens or with supernatants (SN) from macrophages (Mϕ-SN or MP-SN) stimulated with FIB antigens. Genes associated with an aggressive HFLS phenotype, extracellular matrix proteins, and activated signaling pathways were evaluated. Results: HFLS-RA cells treated with Mϕ-SNFIB-CIT and Mϕ-SNFIB-MAA-CIT demonstrated significant increases in mRNA expression of genes associated with an aggressive phenotype at 24-h as compared to direct stimulation with the same antigens. Similar results were obtained using MP-SN. Cellular morphology was altered and protein expression of vimentin (p\u3c0.0001 vs. Mϕ-SNFIB) and type II collagen (p\u3c0.0001) were significantly increased in HFLS-RA cells treated with any of the Mϕ-SN generated following stimulation with modified antigens. Phosphorylation of JNK, Erk1/2, and Akt were increased most substantially in HFLS-RA treated with Mϕ-SNFIB-MAA-CIT (p\u3c0.05 vs Mϕ-SNFIB). These and other data suggested the presence of PDGF-BB in Mϕ-SN. Mϕ-SNFIB-MAA-CIT contained the highest concentration of PDGF-BB (p\u3c0.0001 vs. Mϕ-SNFIB) followed by Mϕ-SNFIB-CIT then Mϕ-SNFIB-MAA. HFLS-RA cells treated with PDGF-BB showed similar cellular morphology to the Mϕ-SN generated following stimulation with modified FIB, as well as the increased expression of vimentin, type II collagen, and the phosphorylation of JNK, Erk1/2 and Akt signaling molecules. Conclusion: Together, these findings support the hypothesis that in response to MAA-modified and/or citrullinated fibrinogen,macrophages release soluble factors including PDGF-BB that induce fibroblast activation and promote an aggressive fibroblast phenotype. These cellular responses were most robust following macrophage activation with dually modified fibrinogen, compared to single modification alone, providing novel insights into the combined role of multiple post-translational protein modifications in the development of RA

An Open System for Social Computation

Part of the power of social computation comes from using the collective intelligence of humans to tame the aggregate uncertainty of (otherwise) low veracity data obtained from human and automated sources. We have witnessed a surge in development of social computing systems but, ironically, there have been few attempts to generalise across this activity so that creation of the underlying mechanisms themselves can be made more social. We describe a method for achieving this by standardising patterns of social computation via lightweight formal specifications (we call these social artifacts) that can be connected to existing internet architectures via a single model of computation. Upon this framework we build a mechanism for extracting provenance meta-data across social computations

Citrullinated and malondialdehyde-acetaldehyde modified fibrinogen activates macrophages and promotes an aggressive synovial fibroblast phenotype in patients with rheumatoid arthritis

ObjectivePost-translational protein modifications with malondialdehyde-acetaldehyde (MAA) and citrulline (CIT) are implicated in the pathogenesis of rheumatoid arthritis (RA). Although precise mechanisms have not been elucidated, macrophage-fibroblast interactions have been proposed to play a central role in the development and progression of RA. The purpose of our study was to evaluate the downstream effects of macrophage released soluble mediators, following stimulation with fibrinogen (FIB) modified antigens, on human fibroblast-like synoviocytes (HFLS).MethodsPMA-treated U-937 monocytes (Mϕ) and macrophage-differentiated peripheral blood mononuclear cells (MP) were stimulated with FIB, FIB-MAA, FIB-CIT, or FIB-MAA-CIT. HFLS-RA cells were stimulated directly with FIB antigens or with supernatants (SN) from macrophages (Mϕ-SN or MP-SN) stimulated with FIB antigens. Genes associated with an aggressive HFLS phenotype, extracellular matrix proteins, and activated signaling pathways were evaluated.ResultsHFLS-RA cells treated with Mϕ-SNFIB-CIT and Mϕ-SNFIB-MAA-CIT demonstrated significant increases in mRNA expression of genes associated with an aggressive phenotype at 24-h as compared to direct stimulation with the same antigens. Similar results were obtained using MP-SN. Cellular morphology was altered and protein expression of vimentin (p&lt;0.0001 vs. Mϕ-SNFIB) and type II collagen (p&lt;0.0001) were significantly increased in HFLS-RA cells treated with any of the Mϕ-SN generated following stimulation with modified antigens. Phosphorylation of JNK, Erk1/2, and Akt were increased most substantially in HFLS-RA treated with Mϕ-SNFIB-MAA-CIT (p&lt;0.05 vs Mϕ-SNFIB). These and other data suggested the presence of PDGF-BB in Mϕ-SN. Mϕ-SNFIB-MAA-CIT contained the highest concentration of PDGF-BB (p&lt;0.0001 vs. Mϕ-SNFIB) followed by Mϕ-SNFIB-CIT then Mϕ-SNFIB-MAA. HFLS-RA cells treated with PDGF-BB showed similar cellular morphology to the Mϕ-SN generated following stimulation with modified FIB, as well as the increased expression of vimentin, type II collagen, and the phosphorylation of JNK, Erk1/2 and Akt signaling molecules.ConclusionTogether, these findings support the hypothesis that in response to MAA-modified and/or citrullinated fibrinogen, macrophages release soluble factors including PDGF-BB that induce fibroblast activation and promote an aggressive fibroblast phenotype. These cellular responses were most robust following macrophage activation with dually modified fibrinogen, compared to single modification alone, providing novel insights into the combined role of multiple post-translational protein modifications in the development of RA

Improving protein function prediction methods with integrated literature data

<p>Abstract</p> <p>Background</p> <p>Determining the function of uncharacterized proteins is a major challenge in the post-genomic era due to the problem's complexity and scale. Identifying a protein's function contributes to an understanding of its role in the involved pathways, its suitability as a drug target, and its potential for protein modifications. Several graph-theoretic approaches predict unidentified functions of proteins by using the functional annotations of better-characterized proteins in protein-protein interaction networks. We systematically consider the use of literature co-occurrence data, introduce a new method for quantifying the reliability of co-occurrence and test how performance differs across species. We also quantify changes in performance as the prediction algorithms annotate with increased specificity.</p> <p>Results</p> <p>We find that including information on the co-occurrence of proteins within an abstract greatly boosts performance in the Functional Flow graph-theoretic function prediction algorithm in yeast, fly and worm. This increase in performance is not simply due to the presence of additional edges since supplementing protein-protein interactions with co-occurrence data outperforms supplementing with a comparably-sized genetic interaction dataset. Through the combination of protein-protein interactions and co-occurrence data, the neighborhood around unknown proteins is quickly connected to well-characterized nodes which global prediction algorithms can exploit. Our method for quantifying co-occurrence reliability shows superior performance to the other methods, particularly at threshold values around 10% which yield the best trade off between coverage and accuracy. In contrast, the traditional way of asserting co-occurrence when at least one abstract mentions both proteins proves to be the worst method for generating co-occurrence data, introducing too many false positives. Annotating the functions with greater specificity is harder, but co-occurrence data still proves beneficial.</p> <p>Conclusion</p> <p>Co-occurrence data is a valuable supplemental source for graph-theoretic function prediction algorithms. A rapidly growing literature corpus ensures that co-occurrence data is a readily-available resource for nearly every studied organism, particularly those with small protein interaction databases. Though arguably biased toward known genes, co-occurrence data provides critical additional links to well-studied regions in the interaction network that graph-theoretic function prediction algorithms can exploit.</p