bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Pharmacokinetics and Pharmacodynamics of Bococizumab Following a Single Subcutaneous Injection Using Drug Substance Manufactured at Two Sites or Administration via Two Different Devices
Authors: Wang Ellen Q. , Plotka Anna , Salageanu Joanne , Baltrukonis Daniel , Mridha Khurshid , Frederich Robert , Sullivan Beth E. 
Published: April 2018

AbstractThe pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, were compared following a single 150‐mg subcutaneous dose administered to healthy subjects (n = 156–158/arm) via: (1) a prefilled syringe (PFS) using drug substance (DS) manufactured by Pfizer, (2) a PFS using DS manufactured by Boehringer Ingelheim Pharma, (3) a prefilled pen using DS manufactured by Pfizer (NCT02458209). Blood samples were collected for 12 weeks postdose. Safety was monitored throughout. Mean maximum plasma concentration (Cmax) ranged between 11.0 and 11.3 μg/mL, and area under the plasma concentration‐time curve (AUCinf) ranged between 177.6 and 185.0 μg·day/mL across treatments. The 90% confidence intervals for the ratios of adjusted geometric means for Cmax and AUCinf fell within the 80%–125% range for both DS and delivery device comparisons. Comparable low‐density lipoprotein cholesterol profiles were observed, with nadir values of 54.3–56.1 mg/dL across treatments. Similar PCSK9 responses were also observed. Safety profiles were similar across treatments, and the majority of adverse events (AEs) were mild. Three subjects reported serious AEs. The most frequently reported AEs were headache, injection‐site reaction, and upper respiratory tract infection, with no clear differences across treatments. Comparable PK, PD, and safety were observed following a single bococizumab 150‐mg subcutaneous injection regardless of site of DS manufacture or delivery device used.
Efficient design and hardware implementation of a secure communication scheme for smart grid
Authors: Abbasinezhad‐Mood Dariush , Nikooghadam Morteza 
Published: April 2018

SummaryIn smart grid, bidirectional communications between the smart meters and control center are subject to several security challenges. Since the smart meters have limited storage space and processing capability, the suggested communication scheme not only must consider the security requirements but also should put the least possible burden on the smart meters' resources. In 2014, an interesting communication scheme has been proposed for the secure consumption reports transmission of the smart meters to the neighbor gateways. In this paper, we first show that this scheme is vulnerable to the smart meter's memory modification, pollution, and denial of service attacks; then, we propose an authenticated communication scheme, which not only is secure against the aforementioned attacks, but also is much more efficient in terms of storage space, communication overhead, and computational complexity. Moreover, our scheme also presents the details of control messages transmission from the neighborhood gateways to the smart meters. Our comparative analysis with several recently published schemes indicates that the proposed scheme is more suitable than the previous ones. More significantly, our realistic implementation on ATmega2560, as a suitable candidate to be used for the smart meters, confirms our claim.
Effects of winter food provisioning on the phenotypes of breeding blue tits
Authors: Plummer Kate E. , Bearhop Stuart , Leech David I. , Chamberlain Dan E. , Blount Jonathan D. 
Published: April 2018

AbstractThroughout the Western World, huge numbers of people regularly supply food for wild birds. However, evidence of negative impacts of winter feeding on future reproduction has highlighted a need to improve understanding of the underlying mechanisms shaping avian responses to supplementary food. Here, we test the possibility that carry‐over effects are mediated via their impact on the phenotypes of breeding birds, either by influencing the phenotypic structure of populations through changes in winter survival and/or by more direct effects on the condition of breeding birds. Using a landscape‐scale 3‐year study of blue tits (Cyanistes caeruleus), we demonstrate the importance of nutritional composition of supplementary food in determining carry‐over effect outcomes. We show that breeding populations which had access to vitamin E‐rich foods during the previous winter were comprised of individuals with reduced feather carotenoid concentrations, indicative of lower pre‐feeding phenotypic condition, compared to fat‐fed and unfed populations. This suggests that supplementary feeding in winter can result in altered population phenotypic structure at the time of breeding, perhaps by enhancing survival and recruitment of lower quality individuals. However, supplementation of a fat‐rich diet during winter was detrimental to the oxidative state of breeding birds, with these phenotypic differences ultimately found to impact upon reproductive success. Our findings demonstrate the complex nature by which supplementary feeding can influence wild bird populations.
Age × stage‐classified demographic analysis: a comprehensive approach
Authors: Caswell Hal , de Vries Charlotte , Hartemink Nienke , Roth Gregory , van Daalen Silke F. 
Published: April 2018

AbstractThis paper presents a comprehensive theory for the demographic analysis of populations in which individuals are classified by both age and stage. The earliest demographic models were age classified. Ecologists adopted methods developed by human demographers and used life tables to quantify survivorship and fertility of cohorts and the growth rates and structures of populations. Later, motivated by studies of plants and insects, matrix population models structured by size or stage were developed. The theory of these models has been extended to cover all the aspects of age‐classified demography and more. It is a natural development to consider populations classified by both age and stage. A steady trickle of results has appeared since the 1960s, analyzing one or another aspect of age × stage‐classified populations, in both ecology and human demography. Here, we use the vec‐permutation formulation of multistate matrix population models to incorporate age‐ and stage‐specific vital rates into demographic analysis. We present cohort results for the life table functions (survivorship, mortality, and fertility), the dynamics of intra‐cohort selection, the statistics of longevity, the joint distribution of age and stage at death, and the statistics of life disparity. Combining transitions and fertility yields a complete set of population dynamic results, including population growth rates and structures, net reproductive rate, the statistics of lifetime reproduction, and measures of generation time. We present a complete analysis of a hypothetical model species, inspired by poecilogonous marine invertebrates that produce two kinds of larval offspring. Given the joint effects of age and stage, many familiar demographic results become multidimensional, so calculations of marginal and mixture distributions are an important tool. From an age‐classified point of view, stage structure is a form of unobserved heterogeneity. From a stage‐classified point of view, age structure is unobserved heterogeneity. In an age × stage‐classified model, variance in demographic outcomes can be partitioned into contributions from both sources. Because these models are formulated as matrices, they are amenable to a complete sensitivity analysis. As more detailed and longer longitudinal studies are developed, age × stage‐classified demography will become more common and more important.
Numerical and experimental investigations on inelastic cyclic performance of mid‐span gusset plate connections
Authors: Kumar P. C. Ashwin , Sahoo Dipti Ranjan 
Published: April 2018

SummaryThe design and detailing of gusset plate connections greatly influence the seismic performance of a special concentrically braced frame (SCBF). Recently, a balanced design approach has been proposed in order to develop significant inelastic deformation from multiple yield mechanisms and to delay the failure of connections of SCBF system. Although extensive studies have been conducted on the corner gusset plate connections of SCBFs, research on the detailing of mid‐span beam gusset plates is rather limited. This study aims at investigating the required free length for the detailing of the mid‐span gusset plates with different brace slenderness ratios. A nonlinear finite element analysis has been conducted for a braced frame with 4 different values of linear clearance in the mid‐span gusset plates and 2 values of brace slenderness ratios. In all simulation models, the corner gusset plates have been designed using balanced design approach and detailed using an elliptical clearance of 8 times the gusset plate thickness. An experimental study has also been conducted on 2 gusset plate sub‐assemblages having similar brace slenderness ratio but with 2 different values of linear clearance in the middle gusset plates. The lateral drift capacity corresponding to the brace fracture and the level of damage are found to be dependent on the detailing of the gusset plates. Based on the results of numerical and experimental studies, the required free length has been recommended for the detailing of middle gusset plates of SCBFs of different brace slenderness ratios.
Nobiletin protects human retinal pigment epithelial cells from hydrogen peroxide–induced oxidative damage
Authors: Liu Libin , Wu Xing wei 
Published: April 2018

AbstractNobiletin (3′,4′,5,6,7,8‐hexamethoxyflavone), a dietary polymethoxylated flavonoid found in Citrus fruits, has been reported to have antioxidant effect. However, the effect of nobiletin on human retinal pigment epithelium (RPE) cells induced by hydrogen peroxide (H2O2) is still unclear. Therefore, we investigated the protective effect of nobiletin against H2O2‐induced cell death in RPE cells. Our results demonstrated that nobiletin significantly increased cell viability from oxidative stress. Nobiletin inhibited H2O2‐induced ROS production and caspase‐3/7 activity in ARPE‐19 cells. Furthermore, nobiletin significantly increased Akt phosphorylation in ARPE‐19 cells exposed to H2O2. Meanwhile, LY294002, an inhibitor of PI3K/Akt, abolished the protective effect of nobiletin against H2O2‐induced decreased cell viability and increased caspase‐3/7 activity in ARPE‐19 cells. In summary, these data show that nobiletin protects RPE cells against oxidative stress through activation of the Akt‐signaling pathway. Thus, nobiletin should be an oxidant that attenuates the development of age‐related macular degeneration.
Signal pathways, diseases, and functions associated with the miR‐19a/92a cluster and the use of berberine to modulate the expression of this cluster in multiple myeloma cells
Authors: Yin Zhao , Yang Juhua , Ning Rong , Liu Yanjun , Feng Maoxiao , Gu Chunmin , Fei Jia , Li Yumin 
Published: April 2018

AbstractBackgroundBerberine downregulated miR‐19a/92a cluster expression in multiple myeloma (MM) cells.MethodsThe cell viability of MM cells after berberine treatment was measured by CCK8 assay. qRT‐PCR assay validated miR‐19a/92a expression in multiple myeloma cells. TAM database analyzed miR‐19a/92a‐associated disease. miREnvironment database revealed that effects of environmental factors on the miR‐19a/92a cluster. By targeting the seed region in the miRNA, the role of t‐anti‐miR‐19a/92a cluster was evaluated by cell proliferation, migration, and colony formation.ResultsBerberine inhibited the cell viability of MM cells and downregulated the expression of miR‐19a/92a. Seven kinds of hematological malignancies are closely associated with miR‐19a/92a expression. By targeting the seed region of the miRNA, t‐anti‐miR‐19a/92a significantly inhibits multiple myeloma cell proliferation, migration, and colony formation.ConclusionOur findings may exhibit that miR‐19a/92a cluster is a therapeutic target for MM and provide new mechanistic insight into the anti‐MM effects of certain compounds in traditional Chinese herbal medicines.
Efficacy and safety of granulocyte adsorption apheresis in elderly patients with ulcerative colitis
Authors: Ito Ayumi , Omori Teppei , Hanafusa Norio , Tsuchiya Ken , Nakamura Shinichi , Tokushige Katsutoshi 
Published: April 2018

AbstractBackgroundElderly ulcerative colitis (UC) is increasing. Elderly UC differ from younger UC with respect to the course of their disease. Granulocyte adsorption apheresis (CAP) is often used to treat elderly UC. We retrospectively analyzed the cases of elderly UC who underwent CAP for remission induction therapy in a comparison with younger UC.Methods96 patients with UC underwent CAP. Patients who concurrently received tacrolimus, biological agents, or high‐dose steroid therapy were excluded. The remaining 80 patients were evaluated. We divided them into an elderly group (aged ≥65 years) and a younger group, and then we compared the groups' (1) clinical characteristics, (2) the efficacy and adverse effects of CAP, and (3) the complications of PSL.ResultsThe remission rate was 70.8% in the elderly group and 87.5% in the younger group. There were significant differences between the two groups with respect to the age at the onset of UC, the estimated glomerular filtration rate on admission, underlying diseases, and complications of PSL therapy. Adverse effects of CAP included headache, complications of blood reinfusion, heparin allergy, hypotension, and failure of blood removal. There were significant differences between the two groups with respect to the complications of PSL therapy (all P < .05).ConclusionsAlthough the elderly group had longer durations of UC, a higher prevalence of underlying diseases, and a higher frequency of adverse events due to PSL therapy. No serious adverse effects of CAP occurred in either group. Thus, CAP was safe and effective in both younger and elderly UC.
Myotendinous junction plasticity in aged ovariectomized rats submitted to aquatic training
Authors: Rissatto Sierra Luan , Fávaro Gabriel , Cerri Bruno Rubin , Rocha Lara Caetano , de Yokomizo de Almeida Sonia Regina , Watanabe Ii‐Sei , Ciena Adriano Polican 
Published: April 2018

AbstractThe study aims to describe the tissue plasticity of MTJ through the morphological analysis of MTJ soleus in ovariectomized aged female Wistar rats submitted to aquatic training. Forty aged Wistar rats, 1 year and 2 months of age, were divided into four groups: sedentary (S), trained (T), ovariectomized (O), and trained/ovariectomized (OT). Employing the transmission electron microscopy, the ultrastructural and morphometric elements were revealed. In the S group, changes in morphological characteristics as a consequence of the aging process were seen, demonstrated by the conical shape of the muscle cell extremity, a large area with collagen deposit, and misalignment of sarcomeres in series. The T group presented ample adjustments when revealed the organization of MTJ, through the increase of the contact area and greater lengths of sarcoplasmatic invaginations and evaginations. The O group revealed extensive tissue disorganization with muscle atrophy, reduction of MTJ contact area, and consequently, changes in sarcoplasmatic invaginations and evaginations. The OT group demonstrated extensive remodeling with restructuring MTJ through the increase of tissue contact area, extensive organization, parallel arrangement, and increased length of sarcoplasmatic invaginations and evaginations. The distal sarcomeres presented higher lengths compared to the proximal sarcomeres in both the groups. We conclude that aquatic training was effective in the organization and structural remodeling of the myotendinous interface of ovariectomized aged rats. There was a greater area of contact, and consequently, greater resistance in the myotendinous interface promoting a lower predisposition to injuries.
Limitations of skipping echoes for exponential T2 fitting
Authors: McPhee Kelly C. , Wilman Alan H. 
Published: April 2018

BackgroundExponential fitting of multiecho spin echo sequences with skipped echoes is still commonly used for quantification of transverse relaxation (T2).PurposeTo examine the efficacy of skipped echo methods for T2 quantification against computational modeling of the exact signal decay.Study TypeProspective comparison of methods.Subjects/PhantomEight volunteers were imaged at 4.7T, six volunteers at 1.5T, and phantoms ([MnCl2] = 68–270 mM).Field Strength/Sequence1.5T and 4.7T; multiple‐echo spin echo.AssessmentExponential fitting for T2 using all echoes, skipping the first echo or skipping all odd echoes, compared with Bloch simulations. Resulting T2 values were examined over a range of T2 (10–150 msec), refocusing flip angles (90–270°), and echo train lengths (ETL = 6–32).Statistical TestsShapiro–Wilk tests and Q‐Q plots were used to check for normality of data. Paired sample t‐tests and Wilcoxon rank tests were used to compare fitting models using α = 0.05. Multiple comparisons were accounted for with Bonferroni correction.ResultsIn examined regions of interest, typical incorrect estimation of T2 ranged from 23–39% for exponential fitting of all echoes, or 15–32% for skipped echo methods. In vivo, T2 estimation error was reduced to as little as 10% with skipped echo methods using 180° refocusing and ETL = 8, although error varied due to refocusing angle, T2, and ETL. In vivo, skipped echo T2 values were significantly different than all echo exponential fitting (P < 0.004), but also were significantly different from reference values (P < 0.002, except frontal white matter). Simulations showed skipping the first echo was the most effective form of exponential fitting, in particular for T2 <50 msec and ETL = 8, with potential to reduce T2 errors to 10%, depending on refocusing angle and T2.Data ConclusionSkipping echoes is insufficient for avoiding stimulated echo contamination. Resulting T2 errors depend on a complicated interplay of T2, refocusing angle, and ETL. Modeling of the multiecho sequence is recommended.Level of Evidence: 2Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2018;47:1432–1440.
Changes in oxidative stability and protein profile of flaxseeds resulting from thermal pre‐treatment
Authors: Waszkowiak Katarzyna , Mikołajczak Beata , Kmiecik Dominik 
Published: April 2018

AbstractBACKGROUNDThe oxidative stability of oilseeds is crucial for their technological/nutritional quality and shelf life. This research aimed to evaluate the effect of thermal pre‐treatment (steaming and roasting under various time/temperature conditions) on flaxseed oil and protein stability. The monitoring of changes in oil oxidation in situ and protein profiles (SDS‐PAGE) and analysis of the antiradical activity of ethanolic and aqueous fractions were included in the study.RESULTSFlaxseed stability during storage was considerably affected by thermal pre‐treatment conditions. Dynamics of oil oxidation was accelerated at 160 °C and 180 °C but slowed at 200 °C. Influence of pre‐treatment conditions on the antiradical activity of the aqueous fraction was clearly observed and no effect concerning the ethanolic fraction was found. The most significant changes in protein profile of 200 °C‐roasted flaxseed were found with the observed disappearance of 19 kDa protein. A treatment‐dependent decrease in the 13 kDa protein was also detected. Based on the aqueous extract protein profiles, roasting conditions were found to be crucial for protein extractability.CONCLUSIONSThe study has broadened knowledge of the consequences of flaxseed thermal treatment. The deterioration of flaxseed oil oxidative stability is shown. The changes of 19 and 13 kDa proteins suggest their sensitivity to thermally induced aggregation and/or cross‐link. © 2018 Society of Chemical Industry
Preparation and physicochemistry properties of smart edible films based on gelatin–starch nanoparticles
Authors: Tao Furong , Shi Chengmei , Cui Yuezhi 
Published: April 2018

AbstractBACKGROUNDAmong the natural polymers able to form edible films, starch and gelatin (Gel) are potential sources. Corn starch is a polysaccharide widely produced around the world, and gelatin differs from other hydrocolloids as a fully digestible protein, containing nearly all the essential amino acids, except tryptophan. Based on this, with advantages such as abundance, relatively low cost, biodegradability, and edibility, studies considering alternative systems for food protection that utilize biopolymers have increased significantly in recent years.RESULTSA novel macromolecular crosslinker starch–BTCAD–NHS (starch–butanetetracarboxylic acid dianhydride–N‐hydroxysuccinimide, SBN) was successfully prepared to modify gelatin film. Compared with the blank gelatin films, the resulting SBN–Gel films exhibited improved surface hydrophobicity, higher tense strength and elongation‐at‐break, lower Young's modulus values, greater opacity, poorer water vapour uptake properties and better anti‐degradation capacity.CONCLUSIONThe modified gelatin film material with advanced properties obtained in this work was safe, stable eco‐friendly and biorefractory, and was an ideal choice to form packaging in the food industry. Also, the crosslinking SBN–Gel coating was effective in reducing corruption and extending the shelf life of peeled apple substantially. © 2018 Society of Chemical Industry
Physicochemical evaluation of low‐fat yoghurt produced with microbial transglutaminase
Authors: García‐Gómez Belén , Romero‐Rodríguez Ángeles , Vázquez‐Odériz Lourdes , Muñoz‐Ferreiro Nieves , Vázquez Manuel 
Published: April 2018

AbstractBACKGROUNDCurrently consumers demand low‐fat or non‐fat yoghurt but their physical properties are less attractive than those of full‐fat yoghurt. It was reported that microbial transglutaminase (TG) can be used in the production of low‐fat yoghurt. The aim of this work was to evaluate the effect of TG on low‐fat yoghurt to improve their physicochemical and textural properties to approach to those of full‐fat yoghurt. Two TG application methods (addition before fermentation or simultaneous addition with the starter), three dose levels and TG origin were evaluated. Results were compared with commercial low‐fat and full‐fat yoghurts.RESULTSNo significant differences between application methods were observed. Simultaneous addition of TG was preferred because additional time‐consuming steps are not required. The best dose was 1 U TG g−1 of protein that allowed a firmness higher (4.25 N) than that of commercial low‐fat (3.05 N) and full‐fat (4.43 N) yoghurts to be achieved. This implies that intermediate values of TG will permit the same firmness as commercial yoghurts to be obtained. It was observed some differences by the TG origin may be due to excipients.CONCLUSIONTG may be used to replace stabilizers in the production of low‐fat yoghurt as it improves texture and avoids initial syneresis. © 2018 Society of Chemical Industry