bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial nitric oxide synthase inhibition triggers inflammatory responses in the brain of male rats exposed to ischemia‐reperfusion injury
Authors: Greco Rosaria , Demartini Chiara , Zanaboni Anna Maria , Blandini Fabio , Amantea Diana , Tassorelli Cristina
Published: June 2017

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) plays a role in preserving and maintaining the brain's microcirculation, inhibiting platelet aggregation, leukocyte adhesion, and migration. Inhibition of eNOS activity results in exacerbation of neuronal injury after ischemia by triggering diverse cellular mechanisms, including inflammatory responses.

To examine the relative contribution of eNOS in stroke‐induced neuroinflammation, we analyzed the effects of systemic treatment with l‐N‐(1‐iminoethyl)ornithine (L‐NIO), a relatively selective eNOS inhibitor, on the expression of MiR‐155‐5p, a key mediator of innate immunity regulation and endothelial dysfunction, in the cortex of male rats subjected to transient middle cerebral artery occlusion (tMCAo) followed by 24 hr of reperfusion. Inducible NO synthase (iNOS) and interleukin‐10 (IL‐10) mRNA expression were evaluated by real‐time polymerase chain reaction in cortical homogenates and in resident and infiltrating immune cells isolated from ischemic cortex. These latter cells were also analyzed for their expression of CD40, a marker of M1 polarization of microglia/macrophages.tMCAo produced a significant elevation of miR155‐5p and iNOS expression in the ischemic cortex as compared with sham surgery. eNOS inhibition by L‐NIO treatment further elevated the cortical expression of these inflammatory mediators, while not affecting IL‐10 mRNA levels. Interestingly, modulation of iNOS occurred in resident and infiltrating immune cells of the ischemic hemisphere. Accordingly, L‐NIO induced a significant increase in the percentage of CD40+ events in CD68+ microglia/macrophages of the ischemic cortex as compared with vehicle‐injected animals.

These findings demonstrate that inflammatory responses may underlie the detrimental effects due to pharmacological inhibition of eNOS in cerebral ischemia.
Analysis of variability and trends of precipitation extremes in Singapore during 1980–2013
Authors: Li Xin , Wang Xuan , Babovic Vladan
Published: June 2017

Changes in precipitation extremes in the tropical urban context is complex, where the precipitation activities are influenced by the combined effects of El Niño–Southern Oscillation (ENSO), global warming and local effects. This study presents a comprehensive framework to investigate the variability and trends in precipitation extremes in a tropical urban city‐state, Singapore, based on a set of extreme indices recommended by the Expert Team on Climate Change Detection and Indices (ETCCDI). The long‐term trends in the precipitation extremes over the period from 1980 until 2013 are examined using an iterative‐based Mann–Kendall trend test. Besides, the relative importance of precipitation frequency and intensity in inter‐annual variability of wet‐day precipitation totals is investigated. Finally, the correlations between precipitation extremes and three potential large‐scale and local factors, i.e.ENSO, global mean temperature and local temperature are analysed based on linear regression method. Results reveal that annual wet‐day precipitation totals, as well as average wet‐day precipitation intensity, have increased significantly, accompanied by a significant increase in the frequency and intensity of precipitation extremes in Singapore. The inter‐annual variability of wet‐day precipitation totals is mainly dominated by precipitation intensity. Significant correlations are found between precipitation extremes and all the three factors, and the signature of local effects is more evident than global warming. These findings have implications for adaption planning and disaster risk reduction in Singapore in the context of global warming.
Control of abusive water addition to Octopus vulgaris with non‐destructive methods
Authors: Mendes Rogério , Schimmer Ove , Vieira Helena , Pereira João , Teixeira Bárbara
Published: June 2017

BACKGROUND

Abusive water addition to octopus has evidenced the need for quick non‐destructive methods for product qualification in the industry and control of fresh commercial products in markets. Electric conductivity (EC)/pH and dielectric property measurements were selected to detect water uptake in octopus.

RESULTS

A significant EC decrease was determined after soaking octopus in freshwater for 4 h. EC reflected the water uptake of octopus and the correspondent concentration decrease of available ions in the interstitial fluid. Significant correlations were determined between octopus water uptake, EC (R = −0.940) and moisture/protein (M/P) ratio (R = 0.923) changes. Seasonal and spatial variation in proximate composition did not introduce any uncertainty in EC discrimination of freshwater tampering. Immersion in 5 g L−1 sodium tripolyphosphate (STPP) increased EC to a value similar to control octopus. EC false negatives resulting from the use of additives (STPP and citric acid) were eliminated with the additional determination of pH. Octopus soaked in freshwater, STPP and citric acid can also be clearly discriminated from untreated samples (control) and also from frozen (thawed) ones using the dielectric properties. No significant differences in the dielectric property scores were found between octopus sizes or geographical locations.

CONCLUSION

Simultaneous EC/pH or dielectric property measurements can be used in a handheld device for non‐destructive water addition detection in octopus. M/P ratio can be used as a reference destructive method. © 2017 Society of Chemical Industry
Progress and challenges associated with halal authentication of consumer packaged goods
Authors: Premanandh Jagadeesan , Bin Salem Samara
Published: June 2017

Abusive business practices are increasingly evident in consumer packaged goods. Although consumers have the right to protect themselves against such practices, rapid urbanization and industrialization result in greater distances between producers and consumers, raising serious concerns on the supply chain. The operational complexities surrounding halal authentication pose serious challenges on the integrity of consumer packaged goods. This article attempts to address the progress and challenges associated with halal authentication. Advancement and concerns on the application of new, rapid analytical methods for halal authentication are discussed. The significance of zero tolerance policy in consumer packaged foods and its impact on analytical testing are presented. The role of halal assurance systems and their challenges are also considered. In conclusion, consensus on the establishment of one standard approach coupled with a sound traceability system and constant monitoring would certainly improve and ensure halalness of consumer packaged goods. © 2017 Society of Chemical Industry
Hydroxyapatite cement resurfacing the dehiscent jugular bulb: Novel treatment for pulsatile tinnitus
Authors: DeHart Austin N. , Shaia Wayne T. , Coelho Daniel H.
Published: June 2017

Objectives/Hypothesis

The objectives were to discuss the presentation and symptomatology of patients with jugular bulb abnormalities, summarize the literature describing jugular bulb abnormalities, compare methods of treating symptomatic dehiscent jugular bulb, describe a novel surgical technique and pitfalls to repair dehiscent bulbs with hydroxyapatite cement, and present a case series to demonstrate outcomes with this technique

Study Design

Case series presentation, PubMed literature review, and description of operative technique.

Methods

A series of patients presenting with pulsatile tinnitus due to dehiscent jugular bulbs who underwent operative repair with hydroxyapatite cement resurfacing is described. Literature review was conducted via a PubMed database search. Abstracts and references were reviewed to identify relevant sources. Surgical technique of repair and outcomes are reported.

Results

Three patients who presented with unilateral, bothersome, pulsatile tinnitus with history and imaging consistent with a diagnosis of high riding, dehiscent jugular bulbs underwent jugular bulb resurfacing with hydroxyapatite cement. Two patients associated the onset of their symptoms with trauma. All patients reported complete resolution of their tinnitus at an average follow‐up of 15 months. No hearing, vestibular, or intracranial complications were encountered.

Conclusions

Compressive, obliterative, and endovascular interventions have been attempted to treat pulsatile tinnitus due to high‐riding dehiscent jugular bulbs. Reconstruction of the middle ear floor with autologous tissue grafts has also been described. These techniques have been associated with variable results and with the risk of increased intracranial pressure. Hydroxyapatite cement resurfacing may be considered as an alternative for the treatment of this pathology.

Level of Evidence

4. Laryngoscope, 128:1186–1190, 2018
Fiber Laser Welding Cuts Costs and Improves Results
Authors: Rath Wolfram
Published: June 2017

Lasers have been employed in a variety of welding applications for many years. And, as laser technology further develops and diversifies, its uses in welding continue to expand. This article provides an overview of high power lasers in keyhole welding. It then examines the characteristics and advantages of fiber laser sources for welding from Coherent‐Rofin, in particular, and reviews a specific application that has benefitted from these lasers.
Copper Welding with High‐Brightness Fiber Lasers
Authors: Grupp Michael , Reinermann Nils
Published: June 2017

The consumer electronics and automotive industry are the driving forces for an increased use of copper in industrial processes and products. With the development of new battery technologies and higher battery capacities, the demands to the joining technologies are increasing. While soldering is still the state of the art for low power applications in consumer electronics, it is necessary to apply welding technology whenever high currents have to be transmitted, or high and dynamic loads stress the joints. The e‐mobility sector is especially driving this trend and the automotive industry and its suppliers are looking for robust and efficient processes for high volume production in electrical power storage and transmission line applications.
The Challenge in Realizing Truly Agile Fiber Lasers
Authors: Berendt Martin Ole , Barbosa Hugo , Melo Miguel
Published: June 2017

The master oscillator power amplifier (MOPA) fiber laser has been around for several years but the bulk of applications use Q‐switched fiber lasers. Now, with the processing capabilities of the Q‐switched fiber laser fully explored, the MOPA fiber laser is getting revived attention. Laser‐diode seeded MOPAs hold promise of arbitrarily modulated high‐power laser output. Pulse‐pumping the amplifiers to handle ON/OFF gating and low repetition rate pulse trains without overshoot or undershoot is of special interest.
Soil Colloidal P Release Potentials under Various Polyacrylamide Addition Levels
Authors: Liang Xin‐Qiang , Liu Zi‐Wen , Liu Jin , Chen Ling‐Ling , Tian Guang‐Ming
Published: June 2017

Anionic polyacrylamide (PAM) can prevent soil erosion, but its effect on fine particulate phosphorus (P), such as colloidal P, has not been thoroughly examined. The effects of PAM on the release potentials of water‐dispersible colloids (WDC) and total P, molybdenum‐reactive P (MRP), and molybdenum‐unreactive P (MUP) in the colloidal and truly dissolved phases (i.e., TPcoll, MRPcoll, MUPcoll, TPtruly, MRPtruly, and MUPtruly) from six soils across South China were tested in this study. The results showed that the release potentials of TPcoll in the control treatments were 6·9–46·1 mg kg−1 and generally highest in sandy loam soil. Following low (12·5 kg ha−1), middle (25 kg ha−1), and high (50 kg ha−1) levels of PAM application, the release potential of TPcoll decreased by 41·7, 63·2, and 77·4% compared to the control group, respectively. Additionally, PAM may trigger MRPcoll and TPtruly releases in sandy loam and/or silt soils, and for most soils, MRPtruly and MUPtruly showed the highest release potentials at middle or high PAM levels. A significant PAM application level by soil site interaction for the release potentials of WDC and colloidal P was observed. Multiple linear regression showed that the PAM rate combined with soil sand content can successfully predict the release potentials of WDC (R2 = 0·552, p < 0·001) and TPcoll (R2 = 0·738, p < 0·001). Our results suggest that PAM can effectively reduce the loss of soil colloids and colloidal P, while its effects are related to both application level and soil texture. Copyright © 2017 John Wiley & Sons, Ltd.
Differential effects of nitrate, ammonium, and urea as N sources for microbial communities in the North Pacific Ocean
Authors: Shilova I. N. , Mills M. M. , Robidart J. C. , Turk‐Kubo K. A. , Björkman K. M. , Kolber Z. , Rapp I. , van Dijken G. L. , Church M. J. , Arrigo K. R. , Achterberg E. P. , Zehr J. P.
Published: June 2017

Nitrogen (N) is the major limiting nutrient for phytoplankton growth and productivity in large parts of the world's oceans. Differential preferences for specific N substrates may be important in controlling phytoplankton community composition. To date, there is limited information on how specific N substrates influence the composition of naturally occurring microbial communities. We investigated the effect of nitrate (
), ammonium (
), and urea on microbial and phytoplankton community composition (cell abundances and 16S rRNA gene profiling) and functioning (photosynthetic activity, carbon fixation rates) in the oligotrophic waters of the North Pacific Ocean. All N substrates tested significantly stimulated phytoplankton growth and productivity. Urea resulted in the greatest (>300%) increases in chlorophyll a (<0.06 μg L−1 and ∼0.19 μg L−1 in the control and urea addition, respectively) and productivity (<0.4 μmol C L−1 d−1 and ∼1.4 μmol C L−1 d−1 in the control and urea addition, respectively) at two experimental stations, largely due to increased abundances of Prochlorococcus (Cyanobacteria). Two abundant clades of Prochlorococcus, High Light I and II, demonstrated similar responses to urea, suggesting this substrate is likely an important N source for natural Prochlorococcus populations. In contrast, the heterotrophic community composition changed most in response to
. Finally, the time and magnitude of response to N amendments varied with geographic location, likely due to differences in microbial community composition and their nutrient status. Our results provide support for the hypothesis that changes in N supply would likely favor specific populations of phytoplankton in different oceanic regions and thus, affect both biogeochemical cycles and ecological processes.
Multigroup deterministic and stochastic SEIRI epidemic models with nonlinear incidence rates and distributed delays: A stability analysis
Authors: Zhang Hong , Xia Juan , Georgescu Paul
Published: June 2017

In this paper, we investigate the dynamics of a multigroup disease propagation model with distributed delays and nonlinear incidence rates, which accounts for the relapse of recovered individuals. The main concern is the stability of the equilibria, sufficient conditions for global stability being obtained by applying Lyapunov‐LaSalle invariance principle and using Lyapunov functionals, which are constructed using their single‐group counterparts. The situation in which the deterministic model is subject to perturbations of white noise type is also investigated from a stability viewpoint.
Evolutionary generation of high‐order, explicit, two‐step methods for second‐order linear IVPs
Authors: Simos T. E. , Tsitouras Ch.
Published: June 2017

In this paper, we consider the integration of systems of second‐order linear inhomogeneous initial value problems with constant coefficients. Hybrid Numerov methods are used that are constructed in the sense of Runge‐Kutta ones. Thus, the Taylor expansions at the internal points are matched properly in the final expression. We present the order conditions taking advantage of the special structure of the problem at hand. These equations are solved using differential evolution technique, and we present a method with algebraic order eighth at a cost of only 5 function evaluations per step. Numerical results over some linear problems, especially arising from the semidiscretization of the wave equation indicate the superiority of the new method.
Guar gum fiber increases suppressor of cytokine signaling‐1 expression via toll‐like receptor 2 and dectin‐1 pathways, regulating inflammatory response in small intestinal epithelial cells
Authors: Van Hung Tran , Suzuki Takuya
Published: June 2017

Scope

Direct regulation of intestinal inflammation by intact dietary fibers is still unclear. Here, the anti‐inflammatory regulation by intact guar gum (GG) was investigated using mice and human intestinal Caco‐2 cells.

Methods and results

Administration of dextran sodium sulfate (DSS) increased myeloperoxidase activity and CXC motif chemokine ligand2 (an IL‐8 homolog) expression in the small intestines of mice, while supplemental GG reduced these increases. Stimulation of Caco‐2 cells with tumor necrosis factor (TNF)‐α induced IL‐8 expression through nuclear factor kappa B p65, spleen tyrosine kinase, and mitogen‐activated protein kinases pathways. Pre‐treatment of cells with GG reduced the TNF‐α‐induced IL‐8 expression and cellular signaling. GG increased the suppressor of cytokine signaling (SOCS)‐1 expression in Caco‐2 cells, suggesting that this is one of the probable mechanisms involved in GG‐mediated anti‐inflammatory regulation. The anti‐inflammatory regulation and SOCS‐1 expression induced by GG were sensitive to neutralization of toll‐like receptor (TLR)2 and dectin‐1, and to inhibition of Janus kinase (JAK) and tyrosine kinase cSrc pathways. Finally, supplemental GG increased SOCS‐1 expression in the small intestines of both DSS‐administered and normal mice.

Conclusion

Intact GG activates TLR2 and dectin‐1, and increases SOCS‐1 expression via JAK and cSrc pathways, resulting in anti‐inflammatory regulation in intestinal epithelium.
Artificial insemination with frozen‐thawed boar sperm
Authors: Yeste Marc , Rodríguez‐Gil Joan E. , Bonet Sergi
Published: June 2017

Artificial insemination with frozen‐thawed semen in pigs is not a routine technique; its use is restricted to specific cases, such as preservation of valuable genetic material (germplasm banks), safety strategies in case of natural disasters, long‐distance transport of sperm, and in combination with sex‐sorting. Cryoinjuries resulting from freeze‐thawing protocols are a major concern with regard to the fertilization capacity of the treated sperm, which is lower than that of liquid‐stored semen. Here, we provide an overview of artificial insemination using cryopreserved sperm, and summarize the factors that influence cryopreservation success before, during, and after freeze‐thaw (i.e., sperm selection before starting the cryopreservation process, holding time, use of cryoprotectants, and rates of freezing and thawing) and that are driving the identification of biomarkers to predict sensitivity to cryodamage. Three different artificial insemination techniques (conventional or intracervical; intrauterine; and deep intrauterine) are also discussed with regards to their relevance when using frozen‐thawed semen. Finally, we review the use of additives to freezing and thawing media, given reports that they may maintain and improve the quality and fertilizing capacity of frozen‐thawed sperm. In sum, artificial insemination with frozen‐thawed boar sperm can provide reasonable fertility outcomes, if freezable ejaculates, specific additives, and appropriate insemination techniques are used.
Interleaved EPI diffusion imaging using SPIRiT‐based reconstruction with virtual coil compression
Authors: Dong Zijing , Wang Fuyixue , Ma Xiaodong , Zhang Zhe , Dai Erpeng , Yuan Chun , Guo Hua
Published: June 2017

Purpose

To develop a novel diffusion imaging reconstruction framework based on iterative self‐consistent parallel imaging reconstruction (SPIRiT) for multishot interleaved echo planar imaging (iEPI), with computation acceleration by virtual coil compression.

Methods

As a general approach for autocalibrating parallel imaging, SPIRiT improves the performance of traditional generalized autocalibrating partially parallel acquisitions (GRAPPA) methods in that the formulation with self‐consistency is better conditioned, suggesting SPIRiT to be a better candidate in k‐space–based reconstruction. In this study, a general SPIRiT framework is adopted to incorporate both coil sensitivity and phase variation information as virtual coils and then is applied to 2D navigated iEPI diffusion imaging. To reduce the reconstruction time when using a large number of coils and shots, a novel shot‐coil compression method is proposed for computation acceleration in Cartesian sampling. Simulations and in vivo experiments were conducted to evaluate the performance of the proposed method.

Results

Compared with the conventional coil compression, the shot‐coil compression achieved higher compression rates with reduced errors. The simulation and in vivo experiments demonstrate that the SPIRiT‐based reconstruction outperformed the existing method, realigned GRAPPA, and provided superior images with reduced artifacts.

Conclusion

The SPIRiT‐based reconstruction with virtual coil compression is a reliable method for high‐resolution iEPI diffusion imaging. Magn Reson Med 79:1525–1531, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Urodynamic effects of intravenous and intrathecal administration of E‐series prostaglandin 1 receptor antagonist on detrusor overactivity in rats with spinal cord injury
Authors: Wada Naoki , Kadekawa Katsumi , Majima Tsuyoshi , Shimizu Takahiro , Tyagi Pradeep , Kakizaki Hidehiro , Yoshimura Naoki
Published: June 2017

Aims

We examined the effect of an E‐series prostaglandin 1 (EP1) receptor antagonist on bladder activity using a rat model of spinal cord injury (SCI).

Methods

Female Sprague‐Dawley rats were used. Six weeks after spinal cord transection, conscious‐filling cystometry was performed. We evaluated the urodynamic parameters before and after intravenous (0.1 and 1.0 mg/kg) or intrathecal (0.1 and 1.0 µg) administration of SC51089, an EP1 antagonist. Spinal prostaglandin E2 (PGE2) concentration and EP1 receptor transcripts in the spinal cord and dorsal root ganglia (DRG) were measured by enzyme‐linked immunosorbent assay and RT‐PCR, respectively.

Results

The time to the first non‐voiding contraction (NVC) was significantly prolonged after both 0.1 and 1.0 mg/kg of intravenous administration of SC51089 (75% prolongation at 1.0 mg/kg) whereas other parameters were not significantly changed compared to vehicle treatment. In addition, the time to the first NVC was also significantly prolonged after 1.0 µg of intrathecal administration of SC51089 (18% prolongation at 1.0 µg) whereas other parameters were not significantly changed. The spinal PGE2 concentration in SCI rats was significantly higher than that in spinal intact rats. The mRNA expressions of EP1 receptors in the both spinal cord and DRG from SCI rats were significantly higher than those from spinal intact rats.

Conclusions

The PGE2‐induced activation of EP1 receptors in the spinal cord contributes to the initiation of detrusor overactivity in SCI. Thus, the EP1 receptor could be a therapeutic target for the treatment of neurogenic detrusor overactivity due to SCI.
SMARCA4 inactivating mutations cause concomitant Coffin–Siris syndrome, microphthalmia and small‐cell carcinoma of the ovary hypercalcaemic type
Authors: Errichiello Edoardo , Mustafa Noor , Vetro Annalisa , Notarangelo Lucia Dora , de Jonge Hugo , Rinaldi Berardo , Vergani Debora , Giglio Sabrina Rita , Morbini Patrizia , Zuffardi Orsetta
Published: June 2017

SMARCA4 chromatin remodelling factor is mutated in 11% of Coffin–Siris syndrome (CSS) patients and in almost all small‐cell carcinoma of the ovary hypercalcaemic type (SCCOHT) tumours. Missense mutations with gain‐of‐function or dominant‐negative effects are associated with CSS, whereas inactivating mutations, leading to loss of SMARCA4 expression, have been exclusively found in SCCOHT. We applied whole‐exome sequencing to study a 15‐year‐old patient with mild CSS who concomitantly developed SCCOHT at age 13 years. Interestingly, our patient also showed congenital microphthalmia, which has never previously been reported in CSS patients. We detected a de novo germline heterozygous nonsense mutation in exon 19 of SMARCA4 (c.2935C > T;p.Arg979*), and a somatic frameshift mutation in exon 6 (c.1236_1236delC;p.Gln413Argfs*88), causing complete loss of SMARCA4 immunostaining in the tumour. The immunohistochemical findings are supported by the observation that the c.2935C > T mutant transcript was detected by reverse transcription polymerase chain reaction at a much lower level than the wild‐type allele in whole blood and the lymphoblastoid cell line of the proband, confirming nonsense‐mediated mRNA decay. Accordingly, immunoblotting demonstrated that there was approximately half the amount of SMARCA4 protein in the proband's cells as in controls. This study suggests that SMARCA4 constitutional mutations associated with CSS are not necessarily non‐truncating, and that haploinsufficiency may explain milder CSS phenotypes, as previously reported for haploinsufficient ARID1B. In addition, our case supports the dual role of chromatin remodellers in developmental disorders and cancer, as well as the involvement of SMARCA4 in microphthalmia, confirming previous findings in mouse models and the DECIPHER database. Finally, we speculate that mild CSS might be under‐recognized in a proportion of SCCOHT patients harbouring SMARCA4 mutations. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Bayesian Forecasting Tool to Predict the Need for Antidote in Acute Acetaminophen Overdose
Authors: Desrochers Julie , Wojciechowski Jessica , Klein‐Schwartz Wendy , Gobburu Jogarao V.S. , Gopalakrishnan Mathangi
Published: June 2017

Study Objective

Acetaminophen (APAP) overdose is the leading cause of acute liver injury in the United States. Patients with elevated plasma acetaminophen concentrations (PACs) require hepatoprotective treatment with N‐acetylcysteine (NAC). These patients have been primarily risk‐stratified using the Rumack–Matthew nomogram. Previous studies of acute APAP overdoses found that the nomogram failed to accurately predict the need for the antidote. The objectives of this study were to develop a population pharmacokinetic (PK) model for APAP following acute overdose and evaluate the utility of population PK model–based Bayesian forecasting in NAC administration decisions.

Design, Patients and Measurements

Limited APAP concentrations from a retrospective cohort of acute overdosed subjects from the Maryland Poison Center were used to develop the population PK model and to investigate the effect of type of APAP products and other prognostic factors. The externally validated population PK model was used a prior for Bayesian forecasting to predict the individual PK profile when one or two observed PACs were available. The utility of Bayesian forecasted APAP concentration–time profiles inferred from one (first) or two (first and second) PAC observations were also tested in their ability to predict the observed NAC decisions.

Main Results

A one‐compartment model with first‐order absorption and elimination adequately described the data with single activated charcoal and APAP products as significant covariates on absorption and bioavailability. The Bayesian forecasted individual concentration–time profiles had acceptable bias (6.2% and 9.8%) and accuracy (40.5% and 41.9%) when either one or two PACs were considered, respectively. The sensitivity and negative predictive value of the Bayesian forecasted NAC decisions using one PAC were 84% and 92.6%, respectively.

Conclusion

The population PK analysis provided a platform for acceptably predicting an individual's concentration–time profile following acute APAP overdose with at least one PAC, and the individual's covariate profile, and can potentially be used for making early NAC administration decisions.
Crystal Structure, Thermal Behavior and Detonation Characterization of Bis(3,3‐dinitroazetidin‐1‐yl)methane
Authors: Yan Biao , Li Hongya , Guan Yulei , Ma Haixia , Song Jirong , Zhao Fengqi
Published: June 2017

Bis(3,3‐dinitroazetidin‐1‐yl)methane (BDNAZM) was synthesized and the crystal structure was determined by a X‐ray diffraction. It belongs to monoclinic system with space group P21/n. Its thermal behavior and non‐isothermal decomposition kinetics were studied with DSC and TG/DTG methods. The self‐accelerating decomposition temperature (TSADT), thermal ignition temperature (TTIT), and critical temperature of thermal explosion (Tb) are 141.06 °C, 154.15 °C and 160.62 °C, respectively. BDNAZM has a low melting point (86.82 °C), and it has higher detonation velocity (7217 ms−1) and detonation pressure (22.0 GPa) than these of TNT.
Crystal structural characterization reveals novel oligomeric interactions of human voltage‐dependent anion channel 1
Authors: Hosaka Toshiaki , Okazaki Masateru , Kimura‐Someya Tomomi , Ishizuka‐Katsura Yoshiko , Ito Kaori , Yokoyama Shigeyuki , Dodo Kosuke , Sodeoka Mikiko , Shirouzu Mikako
Published: June 2017

Voltage‐dependent anion channel 1 (VDAC1), which is located in the outer mitochondrial membrane, plays important roles in various cellular processes. For example, oligomerization of VDAC1 is involved in the release of cytochrome c to the cytoplasm, leading to apoptosis. However, it is unknown how VDAC1 oligomerization occurs in the membrane. In the present study, we determined high‐resolution crystal structures of oligomeric human VDAC1 (hVDAC1) prepared by using an Escherichia coli cell‐free protein synthesis system, which avoided the need for denaturation and refolding of the protein. Broad‐range screening using a bicelle crystallization method produced crystals in space groups C222 and P22121, which diffracted to a resolution of 3.10 and 3.15 Å, respectively. Each crystal contained two hVDAC1 protomers in the asymmetric unit. Dimer within the asymmetrical unit of the crystal in space group C222 were oriented parallel, whereas those of the crystal in space group P22121 were oriented anti‐parallel. From a model of the crystal in space group C222, which we constructed by using crystal symmetry operators, a heptameric structure with eight patterns of interaction between protomers, including hydrophobic interactions with β‐strands, hydrophilic interactions with loop regions, and protein–lipid interactions, was observed. It is possible that by having multiple patterns of interaction, VDAC1 can form homo‐ or hetero‐oligomers not only with other VDAC1 protomers but also with other proteins such as VDAC2, VDAC3 and apoptosis‐regulating proteins in the Bcl‐2 family.
The chloroplast‐localized small heat shock protein Hsp21 associates with the thylakoid membranes in heat‐stressed plants
Authors: Bernfur Katja , Rutsdottir Gudrun , Emanuelsson Cecilia
Published: June 2017

The small heat shock protein (sHsp) chaperones are crucial for cell survival and can prevent aggregation of client proteins that partially unfold under destabilizing conditions. Most investigations on the chaperone activity of sHsps are based on a limited set of thermosensitive model substrate client proteins since the endogenous targets are often not known. There is a high diversity among sHsps with a single conserved β‐sandwich fold domain defining the family, the α‐crystallin domain, whereas the N‐terminal and C‐terminal regions are highly variable in length and sequence among various sHsps and conserved only within orthologues. The endogenous targets are probably also varying among various sHsps, cellular compartments, cell type and organism. Here we have investigated Hsp21, a non‐metazoan sHsp expressed in the chloroplasts in green plants which experience huge environmental fluctuations not least in temperature. We describe how Hsp21 can also interact with the chloroplast thylakoid membranes, both when isolated thylakoid membranes are incubated with Hsp21 protein and when plants are heat‐stressed. The amount of Hsp21 associated with the thylakoid membranes was precisely determined by quantitative mass spectrometry after metabolic 15N‐isotope labeling of either recombinantly expressed and purified Hsp21 protein or intact Arabidopsis thaliana plants. We found that Hsp21 is among few proteins that become associated with the thylakoid membranes in heat‐stressed plants, and that approximately two thirds of the pool of chloroplast Hsp21 is affected. We conclude that for a complete picture of the role of sHsps in plant stress resistance also their association with the membranes should be considered.
An EWMA chart for monitoring the covariance matrix of a multivariate process based on dissimilarity index
Authors: Huwang Longcheen , Lin Po‐Chun , Chang Chih‐Hsiang , Lin Li‐Wei , Tee Yeu‐Shiang
Published: June 2017

In this article, we propose an exponentially weighted moving average (EWMA) control chart for monitoring the covariance matrix of a multivariate process based on the dissimilarity index of 2 matrices. The proposed control chart essentially monitors the covariance matrix by comparing the individual eigenvalues of the estimated EWMA covariance matrix with those of the estimated covariance matrix from the in‐control (IC) phase I data. It is different from the conventional EWMA charts for monitoring the covariance matrix, which are either based on comparing the sum or product or both of the eigenvalues of the estimated EWMA covariance matrix with those of the IC covariance matrix. We compare the performance of the proposed chart with that of the best existing chart under the multivariate normal process. Furthermore, to prevent the control limit of the proposed EWMA chart developed using the limited IC phase I data from having extensively excessive false alarms, we use a bootstrap resampling method to adjust the control limit to guarantee that the proposed chart has the actual IC ARL(average run length) not less than the nominal level with a certain probability. Finally, we use an example to demonstrate the applicability and implementation of the proposed EWMA chart.
Using reliability analysis to support decision making in phased mission systems
Authors: Zhang Yang , Prescott Darren
Published: June 2017

Because of the environments in which they will operate, future autonomous systems must be capable of reconfiguring quickly and safely following faults or environmental changes. Past research has shown how, by considering autonomous systems to perform phased missions, reliability analysis can support decision making by allowing comparison of the probability of success of different missions following reconfiguration. Binary decision diagrams (BDDs) offer fast, accurate reliability analysis that could contribute to real‐time decision making. However, phased mission analysis using existing BDD models is too slow to contribute to the instant decisions needed in time‐critical situations. This paper investigates 2 aspects of BDD models that affect analysis speed: variable ordering and quantification efficiency. Variable ordering affects BDD size, which directly affects analysis speed. Here, a new ordering scheme is proposed for use in the context of a decision‐making process. Variables are ordered before a mission, and reordering is unnecessary no matter how the mission configuration changes. Three BDD models are proposed to address the efficiency and accuracy of existing models. The advantages of the developed ordering scheme and BDD models are demonstrated in the context of their application within a reliability analysis methodology used to support decision making in an unmanned aerial vehicle.
Nonadditive kinetic potentials from inverted Kohn–Sham problem
Authors: Banafsheh Mojdeh , Adam Wesolowski Tomasz
Published: June 2017

The nonadditive kinetic potential is a key element in density‐dependent embedding methods. The correspondence between the ground‐state density and the total effective Kohn–Sham potential provides the basis for various methods to construct the nonadditive kinetic potential for any pair of electron densities. Several research groups used numerical or analytical inversion procedures to explore this strategy which overcomes the failures of known explicit density functional approximations. The numerical inversions, however, apply additional approximations/simplifications. The relations known for the exact quantities cannot be assumed to hold for quantities obtained in numerical inversions. The exact relations are discussed with special emphasis on such issues as: the admissibility of the densities for which the potential is constructed, the choice of densities to be used as independent variables, self‐consistency between the potentials and observables calculated using the embedded wavefunction, and so forth. The review focuses on how these issues are treated in practice. The review is supplemented with the analysis of the inverted potentials for weakly overlapping pairs of electron densities—the case not studied previously.
Blinded sample size re‐estimation in three‐arm trials with ‘gold standard’ design
Authors: Mütze Tobias , Friede Tim
Published: June 2017

In this article, we study blinded sample size re‐estimation in the ‘gold standard’ design with internal pilot study for normally distributed outcomes. The ‘gold standard’ design is a three‐arm clinical trial design that includes an active and a placebo control in addition to an experimental treatment. We focus on the absolute margin approach to hypothesis testing in three‐arm trials at which the non‐inferiority of the experimental treatment and the assay sensitivity are assessed by pairwise comparisons. We compare several blinded sample size re‐estimation procedures in a simulation study assessing operating characteristics including power and type I error. We find that sample size re‐estimation based on the popular one‐sample variance estimator results in overpowered trials. Moreover, sample size re‐estimation based on unbiased variance estimators such as the Xing–Ganju variance estimator results in underpowered trials, as it is expected because an overestimation of the variance and thus the sample size is in general required for the re‐estimation procedure to eventually meet the target power. To overcome this problem, we propose an inflation factor for the sample size re‐estimation with the Xing–Ganju variance estimator and show that this approach results in adequately powered trials. Because of favorable features of the Xing–Ganju variance estimator such as unbiasedness and a distribution independent of the group means, the inflation factor does not depend on the nuisance parameter and, therefore, can be calculated prior to a trial. Moreover, we prove that the sample size re‐estimation based on the Xing–Ganju variance estimator does not bias the effect estimate. Copyright © 2017 John Wiley & Sons, Ltd.
Using Poisson–gamma model to evaluate the duration of recruitment process when historical trials are available
Authors: Minois Nathan , Lauwers‐Cances Valérie , Savy Stéphanie , Attal Michel , Andrieu Sandrine , Anisimov Vladimir , Savy Nicolas
Published: June 2017

At the design of clinical trial operation, a question of a paramount interest is how long it takes to recruit a given number of patients. Modelling the recruitment dynamics is the necessary step to answer this question. Poisson–gamma model provides very convenient, flexible and realistic approach. This model allows predicting the trial duration using data collected at an interim time with very good accuracy. A natural question arises: how to evaluate the parameters of recruitment model before the trial begins? The question is harder to handle as there are no recruitment data available for this trial. However, if there exist similar completed trials, it is appealing to use data from these trials to investigate feasibility of the recruitment process. In this paper, the authors explore the recruitment data of two similar clinical trials (Intergroupe Francais du Myélome 2005 and 2009). It is shown that the natural idea of plugging the historical rates estimated from the completed trial in the same centres of the new trial for predicting recruitment is not a relevant strategy. In contrast, using the parameters of a gamma distribution of the rates estimated from the completed trial in the recruitment dynamic model of the new trial provides reasonable predictive properties with relevant confidence intervals. Copyright © 2017 John Wiley & Sons, Ltd.
Detecting display energy hotspots in Android apps
Authors: Wan Mian , Jin Yuchen , Li Ding , Gui Jiaping , Mahajan Sonal , Halfond William G. J.
Published: June 2017

The energy consumption of mobile apps has become an important consideration for developers as the underlying mobile devices are constrained by battery capacity. Display represents a significant portion of an app's energy consumption—up to 60% of an app's total energy consumption. However, developers lack techniques to identify the user interfaces in their apps for which energy needs to be improved. This paper presents a technique for detecting display energy hotspots—user interfaces of a mobile app whose energy consumption is greater than optimal. The technique leverages display power modeling and automated display transformation techniques to detect these hotspots and prioritize them for developers. The evaluation of the technique shows that it can predict display energy consumption to within 14% of the ground truth and accurately rank display energy hotspots. Furthermore, the approach found 398 display energy hotspots in a set of 962 popular Android apps, showing the pervasiveness of this problem. For these detected hotspots, the average power savings that could be realized through better user interface design was 30%. Taken together, these results indicate that the approach represents a potentially impactful technique for helping developers to detect energy related problems and reduce the energy consumption of their mobile apps.
Circular advantage anyone? Sustainability‐driven innovation and circularity at Patagonia, Inc.
Authors: Rattalino Francesco
Published: June 2017

For many years, companies have perceived sustainability and corporate social responsibility as annoying trends involving regulations and extra costs. A new concept of industrial organization is required to dissociate growth in resource consumption from increasing prosperity. This concept must move beyond significant efficiency gains in order to successfully deliver change—an idea that is known as a circular economy. The increasing amount of attention paid to environmental issues and pressure from stakeholders have forced businesses to embrace the complexity and interdependencies between shareholder value and sustainable value. Sustainability‐driven innovation that increases the circularity of resources, as in the case of Patagonia, Inc., is the key to generating a sustainable competitive advantage that marries economic and social objectives. This article explores ways in which corporations can pursue economic, social, and environmental objectives while simultaneously embracing circularity.
Chromosomal microarray as primary diagnostic genomic tool for pregnancies at increased risk within a population‐based combined first‐trimester screening program
Authors: Vogel I. , Petersen O. B. , Christensen R. , Hyett J. , Lou S. , Vestergaard E. M.
Published: June 2017

Objective

To evaluate the performance of high‐resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on combined first‐trimester screening (cFTS).

Methods

This was a retrospective study of genomic findings in a cohort of 575 consecutive pregnancies undergoing invasive testing because of a cFTS risk ≥ 1:300 on a publicly funded population‐based screening program in the Central and Northern Regions of Denmark, between September 2015 and September 2016. Women with fetal nuchal translucency thickness ≥ 3.5 mm or opting for non‐invasive prenatal testing (NIPT) were excluded. Comparative genomic hybridization was performed using a 180‐K oligonucleotide array on DNA extracted directly from chorionic villus/amniocentesis samples. Genomic outcomes were reported in relation to cFTS findings.

Results

Of the 575 pregnancies that underwent invasive testing, CMA detected 22 (3.8% (95% CI, 2.5–5.7%)) cases of trisomies 21, 18 and 13, 14 (2.4% (95% CI, 1.4–4.0%)) cases of other types of aneuploidy and 15 (2.6% (95% CI, 1.5–4.3%)) cases with a pathogenic or probably pathogenic copy number variant (CNV). Of the 15 CNVs, three were > 10 Mb and would probably have been detected by chromosomal analysis, but the other 12 would most probably not have been detected using conventional cytogenetic techniques; therefore, the overall detection rate of CMA (8.9% (95% CI, 6.8–11.5%)) was significantly higher than that estimated for conventional cytogenetic analysis (6.8% (95% CI, 5.0–9.1%)) (P = 0.0049). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being missed.

Conclusions

CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk on cFTS. Limiting diagnostic testing to pregnancies with a risk above 1 in 100 or 1 in 50, as proposed in contingent NIPT/invasive testing models, would lead to a significant proportion of pathogenic CNVs being missed at first‐trimester screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Climate change and loss, as if people mattered: values, places, and experiences
Authors: Tschakert Petra , Barnett Jon , Ellis Neville , Lawrence Carmen , Tuana Nancy , New Mark , Elrick‐Barr Carmen , Pandit Ram , Pannell David
Published: June 2017

The United Nations Framework Convention on Climate Change (UNFCCC) is seeking to prepare for losses arising from climate change. This is an emerging issue that challenges climate science and policy to engage more deeply with values, places, and people's experiences. We first provide insight into the UNFCCC framing of loss and damage and current approaches to valuation. We then draw on the growing literature on value‐ and place‐based approaches to adaptation, including limits to adaptation, which examines loss as nuanced and sensitive to the nature of people's lives. Complementary perspectives from human geography, psychology, philosophy, economics, and ecology underscore the importance of understanding what matters to people and what they may likely consider to constitute loss. A significant body of knowledge illustrates that loss is often given meaning through lived, embodied, and place‐based experiences, and so is more felt than tangible. We end with insights into recent scholarship that addresses how people make trade‐offs between different value priorities. This emerging literature offers an opening in the academic debate to further advance a relational framing of loss in which trade‐offs between lived values are seen as dynamic elements in a prospective loss space. WIREs Clim Change 2017, 8:e476. doi: 10.1002/wcc.476

This article is categorized under:

Climate, Nature, and Ethics > Comparative Environmental Values