bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐Penetrating Peptides as Carriers for Oral Delivery of Biopharmaceuticals
Authors: Kristensen Mie , Nielsen Hanne Mørck 
Published: November 2015

AbstractOral delivery of biopharmaceuticals, for example peptides and proteins, constitutes a great challenge in drug delivery due to their low chemical stability and poor permeation across the intestinal mucosa, to a large extent limiting the mode of administration to injections, which is not favouring patient compliance. Nevertheless, cell‐penetrating peptides (CPPs) have shown promising potential as carriers to overcome the epithelium, and this minireview highlights recent knowledge gained within the field of CPP‐mediated transepithelial delivery of therapeutic peptides and proteins from the intestine. Two approaches may be pursued: co‐administration of the carrier and therapeutic peptide in the form of complexes obtained by simple bulk mixing, or administration of covalent conjugates demanding more advanced production methodologies. These formulation approaches have their pros and cons, and which is to be preferred depends on the physicochemical properties of both the specific CPP and the specific cargo. In addition to the physical epithelial barrier, a metabolic barrier must be overcome in order to obtain CPP‐mediated delivery of a cargo drug from the intestine, and a number of strategies have been employed to delay enzymatic degradation of the CPP. The mechanisms by which CPPs translocate across membranes are not fully understood, but possibly involve endocytosis as well as direct translocation, and the CPP‐mediated transepithelial delivery of cargo drugs thus likely involves similar mechanisms for the initial membrane interaction and translocation. However, the mechanisms responsible for transcytosis of the cargo drug, if taken up by an endocytic mechanism, or direct translocation across the epithelium are so far not known.
mTORC2 and Metabolic Reprogramming in GBM: at the Interface of Genetics and Environment
Authors: Masui Kenta , Cavenee Webster K. , Mischel Paul S. 
Published: November 2015

AbstractMetabolic reprogramming is a central hallmark of cancer, enabling tumor cells to obtain the macromolecular precursors and energy needed for rapid tumor growth. Understanding how oncogenes coordinate altered signaling with metabolic reprogramming and how cancer cells harness cellular metabolism and its metabolites for their survival may yield new insights into tumor pathogenesis. Here, we review the recently identified central regulatory role for mTORC2, a downstream effector of many cancer‐causing mutations, in metabolic reprogramming and cancer drug resistance in glioblastoma. We further consider the emerging concept that mTORC2 may connect genetics with environmental alterations in brain cancer.
Constraining provenance, thickness and erosion of nappes using low‐temperature thermochronology: the Northland Allochthon, New Zealand
Authors: Jiao Ruohong , Seward Diane , Little Timothy A. , Herman Frédéric , Kohn Barry P. 
Published: November 2015

AbstractThe Northland Allochthon, an assemblage of Cretaceous–Oligocene sedimentary rocks, was emplaced during the Late Oligocene–earliest Miocene, onto the in situ Mesozoic and early Cenozoic rocks (predominantly Late Eocene–earliest Miocene) in northwestern New Zealand. Using low‐temperature thermochronology, we investigate the sedimentary provenance, burial and erosion histories of the rocks from both the hanging and footwalls of the allochthon. In central Northland (Parua Bay), both the overlying allochthon and underlying Early Miocene autochthon yield detrital zircon and partially reset apatite fission‐track ages that were sourced from the local Jurassic terrane and perhaps Late Cretaceous volcanics; the autochthon contains, additionally, material sourced from Oligocene volcanics. Thermal history modelling indicates that the lower part of the allochthon together with the autochthon was heated to ca. 55–100°C during the Late Oligocene and Early Miocene, most likely due to the burial beneath the overlying nappe sequences. From the Mesozoic basement exposed in eastern Northland, we obtained zircon fission‐track ages tightly bracketed between 153 and 149 Ma; the apatite fission‐track ages on the other hand, generally young towards the northwest, from 129 to 20.9 Ma. Basement thermochronological ages are inverted to simulate the emplacement and later erosion of the Northland Allochthon, using a thermo‐kinematic model coupled with an inversion algorithm. The results suggest that during the Late Oligocene, the nappes in eastern Northland ranged from ca. 4–6‐km thick in the north to zero in the Auckland region (over a distance >200 km). Following the allochthon emplacement, eastern Northland was uplifted and unroofed during the Early Miocene for a period of ca. 1–6 Myr at the rate of 0.1–0.8 km/Myr, leading to rapid erosion of the nappes. Since Middle Miocene, the basement uplift ceased and the erosion of the nappes and the region as a whole slowed down (ca. 0–0.2 km/Myr), implying a decay in the tectonic activity in this region.
Children Seek Historical Traces of Owned Objects
Authors: Gelman Susan A. , Manczak Erika M. , Was Alexandra M. , Noles Nicholaus S. 
Published: November 2015

An object's mental representation includes not just visible attributes but also its nonvisible history. The present studies tested whether preschoolers seek subtle indicators of an object's history, such as a mark acquired during its handling. Five studies with 169 children 3–5 years of age and 97 college students found that children (like adults) searched for concealed traces of object history, invisible traces of object history, and the absence of traces of object history, to successfully identify an owned object. Controls demonstrated that children (like adults) appropriately limit their search for hidden indicators when an owned object is visibly distinct. Altogether, these results demonstrate that concealed and invisible indicators of history are an important component of preschool children's object concepts.
Maternal Sensitivity and Child Secure Base Use in Early Childhood: Studies in Different Cultural Contexts
Authors: Posada German , Trumbell Jill , Noblega Magaly , Plata Sandra , Peña Paola , Carbonell Olga A. , Lu Ting 
Published: November 2015

This study tested whether maternal sensitivity and child security are related during early childhood and whether such an association is found in different cultural and social contexts. Mother–child dyads (N = 237) from four different countries (Colombia, Mexico, Peru, and the United States) were observed in naturalistic settings when children were between 36 and 72 months of age. Maternal and child behavior during interactions at home and in the playground were described using Q methodology. Findings reveal that across cultures, concurrent maternal sensitivity and more specific behavioral domains of maternal care (e.g., contributions to harmonious interactions and secure base support) are important for children's attachment security during early childhood. Implications for the study of attachment relationships beyond infancy and in diverse contexts are highlighted.
How to select networks of marine protected areas for multiple species with different dispersal strategies
Authors: Jonsson Per R. , Nilsson Jacobi Martin , Moksnes Per‐Olav 
Published: November 2015

AbstractAimTo develop and test theory based on connectivity to identify optimal networks of marine protected areas (MPAs) that protect multiple species with a range of dispersal strategies.LocationThe eastern North Sea in the Atlantic Ocean.MethodsTheory of finding optimal MPA network is based on eigenvalue perturbation theory applied to population connectivity. Previous theory is here extended to the persistence of multiple species by solving a maximization problem with constraints, which identifies an optimal consensus network of MPAs. The theory is applied to two test cases within a 120,000 km2 area in the North Sea where connectivity was estimated with a biophysical model. In a realistic case, the theory is applied to the protection of rocky‐reef habitats, where the biophysical model is parameterized with realistic dispersal traits for key species. Theoretical predictions of optimal networks were validated with a simple metapopulation model. Persistence of optimal consensus MPA networks is compared to randomly selected networks as well as to the existing MPA network.ResultsDespite few overlapping MPA sites for the optimal networks based on single dispersal strategies, the consensus network for multiple dispersal strategies performed well for 3 of 4 contrasting strategies even without user‐defined constraints. In the test with five realistic dispersal strategies, representing a community on threatened rocky reefs, the consensus network performed equally well compared to solutions for single species. Different dispersal strategies were also protected jointly across the MPA network (93% of sites), in contrast to simulations of the existing MPA network (2% of sites). Consensus networks based on connectivity were significantly more efficient compared to existing MPAs.Main conclusionsOur findings suggest that the new theoretic framework can identify a consensus MPA network that protects a whole community containing species with multiple dispersal strategies.
Role of incretin‐based therapies and sodium‐glucose co‐transporter‐2 inhibitors as adjuncts to insulin therapy in Type 2 diabetes, with special reference to IDegLira
Authors: Wilding J. P. H. , Bain S. C. 
Published: November 2015

AbstractThe progressive nature of Type 2 diabetes necessitates treatment intensification over time in order to maintain glycaemic control, with many patients ultimately requiring insulin therapy. While insulin has unlimited potential efficacy, its initiation is often delayed and improvements in glycaemic control are typically accompanied by weight gain and an increased risk of hypoglycaemia, particularly as HbA1c approaches and falls below target levels. This may account for the sub‐optimal control often achieved after insulin initiation. Combining insulin with antihyperglycaemic therapies that have a low risk of hypoglycaemia and are weight‐neutral or result in weight loss is a therapeutic strategy with the potential to improve Type 2 diabetes management. Although the effects differ with each individual class of therapy, clinical trials have shown that adding a glucagon‐like peptide‐1 receptor agonist, dipeptidyl peptidase‐4 inhibitor or sodium‐glucose co‐transporter‐2 inhibitor to insulin regimens can offer a significant reduction in HbA1c without substantially increasing hypoglycaemia risk, or weight. The evidence and merit of each approach are reviewed in this paper. Once‐daily co‐formulations of a basal insulin and a glucagon‐like peptide‐1 receptor agonist have been developed (insulin degludec/liraglutide) or are under development (lixisenatide/insulin glargine). Insulin degludec/liraglutide phase III trials and a lixisenatide/insulin glargine phase II trial have shown robust HbA1c reductions, with weight loss and a low risk of hypoglycaemia. With insulin degludec/liraglutide now approved in Europe, an important consideration will be the types of patients who may benefit most from a fixed‐ratio combination; this is discussed in the present review, and we also take a look toward future developments in the field.
Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study
Authors: Aguilar Frank G. , Selvaraj Senthil , Martinez Eva E. , Katz Daniel H. , Beussink Lauren , Kim Kwang‐Youn A. , Ping Jie , Rasmussen‐Torvik Laura , Goyal Amita , Sha Jin , Irvin Marguerite R. , Arnett Donna K. , Shah Sanjiv J. 
Published: November 2015

BackgroundSeveral large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results.MethodsIn the NHLBI HyperGEN study (N = 2234), archived analog echocardiograms were digitized and subsequently analyzed using STE to obtain tissue velocities/strain. Echocardiograms were assigned quality scores and inter‐/intra‐observer agreement was calculated. Accuracy was evaluated in: (1) a separate second study (N = 50) comparing prospective digital strain versus post hoc analog‐to‐digital strain, and (2) in a third study (N = 95) comparing prospectively obtained TDI e’ velocities with post hoc STE e’ velocities. Finally, we replicated previously known associations between tissue velocities/strain, conventional echocardiographic measurements, and clinical data.ResultsOf the 2234 HyperGEN echocardiograms, 2150 (96.2%) underwent successful digitization and STE analysis. Inter/intra‐observer agreement was high for all STE parameters, especially longitudinal strain (LS). In accuracy studies, LS performed best when comparing post hoc STE to prospective digital STE for strain analysis. STE‐derived e’ velocities correlated with, but systematically underestimated, TDI e’ velocity. Several known associations between clinical variables and cardiac mechanics were replicated in HyperGEN. We also found a novel independent inverse association between fasting glucose and LS (adjusted β = −2.4 [95% CI −3.6, −1.2]% per 1‐SD increase in fasting glucose; P < 0.001).ConclusionsArcheological echocardiography, the digitization and speckle tracking analysis of archival echocardiograms, is feasible and generates indices of cardiac mechanics similar to contemporary studies.
Various aspects of barefoot methodology relevant to farriery in equine veterinary practice
Authors: O'Grady S. E. 
Published: November 2015

SummaryThe structures of the equine foot have the unique ability to adapt, change shape and restore. There are multiple benefits in shod vs. barefoot or in allowing the horse to be without shoes for a given time period to improve the palmar section of the foot. However, it requires a transition period, a change in the manner in which the foot is trimmed, a commitment from the owner/trainer and, in the case of leaving the horse without shoes permanently, it depends whether the horse can perform the desired function without shoes.
Severe eosinophilic cholangiohepatitis due to fluke infestation in a pony in Scotland
Authors: Raftery A. G. , Berman K. G. , Sutton D. G. M. 
Published: November 2015

SummaryFasciola hepatica infestation is reported as a cause of severe eosinophilic cholangiohepatitis in a 28‐year‐old Warmblood cross pony gelding. The gelding presented initially for investigation of acute laminitis found to be secondary to pars pituitary intermedia dysfunction (PPID). Six weeks of treatment including administration of pergolide achieved good control of the laminitis but there was a marked general clinical deterioration over this period with notable weight loss, tachycardia, anorexia and ventral oedema. Hepatobiliary enzymes were increased significantly and there was mild elevation of plasma bile acid concentration. An eosinophilia in both blood and peritoneal fluid specimens and histopathological confirmation of an eosinophilic cholangiohepatitis on examination of liver biopsies supported a primary parasitic aetiology. The pony was treated for Fasciola hepatica with triclabendazole 12 mg/kg bwt but clinical signs continued to progress. Due to poor clinical response the pony was subjected to euthanasia and post mortem examination revealed an overwhelming infestation of the biliary tracts with Fasciola hepatica and a secondary chronic and severe cholangiohepatitis with marked fibrosis. To the authors' knowledge this is the first equine report demonstrating the relationship between the clinical disease syndrome, eosinophilic cholangiohepatitis and hepatic fluke infestation. Depending on geographical location, fasciolosis should be considered as a differential diagnosis for equine hepatopathies and can result in severe disease.
Agronomic improvements can make future cereal systems in South Asia far more productive and result in a lower environmental footprint
Authors: Ladha Jagdish Kumar , Rao Adusumilli Narayana , Raman Anitha K. , Padre Agnes Tirol , Dobermann Achim , Gathala Mahesh , Kumar Virender , Saharawat Yashpal , Sharma Sheetal , Piepho Hans Peter , Alam Md Mursedul , Liak Ranjan , Rajendran Ramasamy , Reddy Chinnagangannagari Kesava , Parsad Rajender , Sharma Parbodh C. , Singh Sati shankar , Saha Abhijit , Noor Shamsoon 
Published: November 2015

AbstractSouth Asian countries will have to double their food production by 2050 while using resources more efficiently and minimizing environmental problems. Transformative management approaches and technology solutions will be required in the major grain‐producing areas that provide the basis for future food and nutrition security. This study was conducted in four locations representing major food production systems of densely populated regions of South Asia. Novel production‐scale research platforms were established to assess and optimize three futuristic cropping systems and management scenarios (S2, S3, S4) in comparison with current management (S1). With best agronomic management practices (BMPs), including conservation agriculture (CA) and cropping system diversification, the productivity of rice‐ and wheat‐based cropping systems of South Asia increased substantially, whereas the global warming potential intensity (GWPi) decreased. Positive economic returns and less use of water, labor, nitrogen, and fossil fuel energy per unit food produced were achieved. In comparison with S1, S4, in which BMPs, CA and crop diversification were implemented in the most integrated manner, achieved 54% higher grain energy yield with a 104% increase in economic returns, 35% lower total water input, and a 43% lower GWPi. Conservation agriculture practices were most suitable for intensifying as well as diversifying wheat–rice rotations, but less so for rice–rice systems. This finding also highlights the need for characterizing areas suitable for CA and subsequent technology targeting. A comprehensive baseline dataset generated in this study will allow the prediction of extending benefits to a larger scale.
Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double‐strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines
Authors: Hoa Nguyen Ngoc , Akagawa Remi , Yamasaki Tomomi , Hirota Kouji , Sasa Kentaro , Natsume Toyoaki , Kobayashi Junya , Sakuma Tetsushi , Yamamoto Takashi , Komatsu Kenshi , Kanemaki Masato T. , Pommier Yves , Takeda Shunichi , Sasanuma Hiroyuki 
Published: November 2015

Homologous recombination (HR) is initiated by double‐strand break (DSB) resection, during which DSBs are processed by nucleases to generate 3′ single‐strand DNA. DSB resection is initiated by CtIP and Mre11 followed by long‐range resection by Dna2 and Exo1 in Saccharomyces cerevisiae. To analyze the relative contribution of four nucleases, CtIP, Mre11, Dna2 and Exo1, to DSB resection, we disrupted genes encoding these nucleases in chicken DT40 cells. CtIP and Dna2 are required for DSB resection, whereas Exo1 is dispensable even in the absence of Dna2, which observation agrees with no developmental defect in Exo1‐deficient mice. Despite the critical role of Mre11 in DSB resection in S. cerevisiae, loss of Mre11 only modestly impairs DSB resection in DT40 cells. To further test the role of CtIP and Mre11 in other species, we conditionally disrupted CtIP and MRE11 genes in the human TK6 B cell line. As with DT40 cells, CtIP contributes to DSB resection considerably more significantly than Mre11 in TK6 cells. Considering the critical role of Mre11 in HR, this study suggests that Mre11 is involved in a mechanism other than DSB resection. In summary, CtIP and Dna2 are sufficient for DSB resection to ensure efficient DSB repair by HR.
A feasibility study of Lactobacillus plantarum in fruit powders after processing and storage
Authors: Borges Sandra , Barbosa Joana , Silva Joana , Gomes Ana M. , Pintado Manuela , Silva Cristina L. M. , Morais Alcina M. M. B. , Teixeira Paula 
Published: November 2015

SummaryThe aim of this study was to develop fruit powders (apple, banana and strawberry) enriched with a probiotic strain (Lactobacillus plantarum 299v). Two methodologies were proposed: (i) drying of the fruit with probiotic culture incorporated (by convection) or (ii) drying of fruit (by convection) and addition of spray‐dried probiotic culture. In the first methodology, processing caused a notable reduction in probiotic viable counts in apple, but this reduction was lower during drying of banana and strawberry. A large reduction in viable cells was also recorded during storage. In the second methodology, the survival of L. plantarum 299v was considerably higher during spray‐drying, and fruit powders with a microbial content suitable for a probiotic food (108–109 cfu g−1) were obtained. The fruit powders incorporating L. plantarum 299v can be stored at 4 °C or at room temperature, for at least 3 months. This preliminary study demonstrated that fruit powders are good carriers of probiotic cultures, but the techniques used to produce them should be carefully considered.
EU, US and ASEAN Actorness in G20 Financial Policy‐Making: Bridging the EU Studies–New Regionalism Divide
Authors: Murau Steffen , Spandler Kilian 
Published: November 2015

AbstractThis article compares the European Union's (EU) actorness in foreign financial policy to that of the US and ASEAN. It thus contributes to the dialogue between EU studies and the New Regionalism by putting it into practice through comparative research. It argues that a process‐oriented interpretation of the actorness concept can be used to compare the EU to both nation‐states and international organizations at the same time. This makes it possible to examine the ‘nature of the beast’ in specific foreign policy contexts on empirical grounds. The case study analyses EU, US and ASEAN actorness in the IMF reform negotiations within the G20 framework. The findings suggest that a ‘two‐way comparison’ of the EU is not only possible but also provides valuable empirical insights into the role of informal politics in the EU and other regions.