bluuebunny/crossref_metadata_2025 huggingface dataset:
Urgent need for warming experiments in tropical forests
Authors: Cavaleri Molly A. , Reed Sasha C. , Smith W. Kolby , Wood Tana E.
Published: January 2015

Although tropical forests account for only a fraction of the planet's terrestrial surface, they exchange more carbon dioxide with the atmosphere than any other biome on Earth, and thus play a disproportionate role in the global climate. In the next 20 years, the tropics will experience unprecedented warming, yet there is exceedingly high uncertainty about their potential responses to this imminent climatic change. Here, we prioritize research approaches given both funding and logistical constraints in order to resolve major uncertainties about how tropical forests function and also to improve predictive capacity of earth system models. We investigate overall model uncertainty of tropical latitudes and explore the scientific benefits and inevitable trade‐offs inherent in large‐scale manipulative field experiments. With a Coupled Model Intercomparison Project Phase 5 analysis, we found that model variability in projected net ecosystem production was nearly 3 times greater in the tropics than for any other latitude. Through a review of the most current literature, we concluded that manipulative warming experiments are vital to accurately predict future tropical forest carbon balance, and we further recommend the establishment of a network of comparable studies spanning gradients of precipitation, edaphic qualities, plant types, and/or land use change. We provide arguments for long‐term, single‐factor warming experiments that incorporate warming of the most biogeochemically active ecosystem components (i.e. leaves, roots, soil microbes). Hypothesis testing of underlying mechanisms should be a priority, along with improving model parameterization and constraints. No single tropical forest is representative of all tropical forests; therefore logistical feasibility should be the most important consideration for locating large‐scale manipulative experiments. Above all, we advocate for multi‐faceted research programs, and we offer arguments for what we consider the most powerful and urgent way forward in order to improve our understanding of tropical forest responses to climate change.
Climate warming and agricultural stressors interact to determine stream macroinvertebrate community dynamics
Authors: Piggott Jeremy J. , Townsend Colin R. , Matthaei Christoph D.
Published: January 2015

Global climate change is likely to modify the ecological consequences of currently acting stressors, but potentially important interactions between climate warming and land‐use related stressors remain largely unknown. Agriculture affects streams and rivers worldwide, including via nutrient enrichment and increased fine sediment input. We manipulated nutrients (simulating agricultural run‐off) and deposited fine sediment (simulating agricultural erosion) (two levels each) and water temperature (eight levels, 0–6°C above ambient) simultaneously in 128 streamside mesocosms to determine the individual and combined effects of the three stressors on macroinvertebrate community dynamics (community composition and body size structure of benthic, drift and insect emergence assemblages). All three stressors had pervasive individual effects, but in combination often produced additive or antagonistic outcomes. Changes in benthic community composition showed a complex interplay among habitat quality (with or without sediment), resource availability (with or without nutrient enrichment) and the behavioural/physiological tendency to drift or emerge as temperature rose. The presence of sediment and raised temperature both resulted in a community of smaller organisms. Deposited fine sediment strongly increased the propensity to drift. Stressor effects were most prominent in the benthic assemblage, frequently reflected by opposite patterns in individuals quitting the benthos (in terms of their propensity to drift or emerge). Of particular importance is that community measures of stream health routinely used around the world (taxon richness, EPT richness and diversity) all showed complex three‐way interactions, with either a consistently stronger temperature response or a reversal of its direction when one or both agricultural stressors were also in operation. The negative effects of added fine sediment, which were often stronger at raised temperatures, suggest that streams already impacted by high sediment loads may be further degraded under a warming climate. However, the degree to which this will occur may also depend on in‐stream nutrient conditions.
Rain events decrease boreal peatland net CO2 uptake through reduced light availability
Authors: Nijp Jelmer J. , Limpens Juul , Metselaar Klaas , Peichl Matthias , Nilsson Mats B. , van der Zee Sjoerd E. A. T. M. , Berendse Frank
Published: January 2015

Boreal peatlands store large amounts of carbon, reflecting their important role in the global carbon cycle. The short‐term exchange and the long‐term storage of atmospheric carbon dioxide (CO2) in these ecosystems are closely associated with the permanently wet surface conditions and are susceptible to drought. Especially, the single most important peat forming plant genus, Sphagnum, depends heavily on surface wetness for its primary production. Changes in rainfall patterns are expected to affect surface wetness, but how this transient rewetting affects net ecosystem exchange of CO2 (NEE) remains unknown. This study explores how the timing and characteristics of rain events during photosynthetic active periods, that is daytime, affect peatland NEE and whether rain event associated changes in environmental conditions modify this response (e.g. water table, radiation, vapour pressure deficit, temperature). We analysed an 11‐year time series of half‐hourly eddy covariance and meteorological measurements from Degerö Stormyr, a boreal peatland in northern Sweden. Our results show that daytime rain events systematically decreased the sink strength of peatlands for atmospheric CO2. The decrease was best explained by rain associated reduction in light, rather than by rain characteristics or drought length. An average daytime growing season rain event reduced net ecosystem CO2 uptake by 0.23–0.54 gC m−2. On an annual basis, this reduction of net CO2 uptake corresponds to 24% of the annual net CO2 uptake (NEE) of the study site, equivalent to a 4.4% reduction of gross primary production (GPP) during the growing season. We conclude that reduced light availability associated with rain events is more important in explaining the NEE response to rain events than rain characteristics and changes in water availability. This suggests that peatland CO2 uptake is highly sensitive to changes in cloud cover formation and to altered rainfall regimes, a process hitherto largely ignored.
Drug‐induced liver injury in a chronic hepatitis C patient treated by peginterferon, ribavirin and simeprevir
Authors: Okajima Akira , Yamaguchi Kanji , Taketani Hiroyoshi , Hara Tasuku , Ishiba Hiroshi , Seko Yuya , Nishimura Takeshi , Nishikawa Taichiro , Fujii Hideki , Moriguchi Michihisa , Mitsuyoshi Hironori , Sumida Yoshio , Yasui Kohichiroh , Minami Masahito , Itoh Yoshito
Published: January 2015

A 56‐year‐old male patient with chronic hepatitis C was treated with pegylated interferon (PEG IFN)‐α‐2b and ribavirin (RBV) for 72 weeks in 2006. The patient achieved an early virological response (EVR); however, hepatitis C relapsed 12 weeks after discontinuation of PEG IFN and RBV. In 2012, the patient was treated with a PEG IFN/RBV/telaprevir combination therapy. After 5 days of treatment, he suffered from a telaprevir‐associated skin rash on his body and four limbs. He chose to be treated with PEG IFN and RBV until 60 weeks. He again achieved EVR but no sustained virological response. In 2014, he was treated with PEG IFN/RBV/simeprevir combination therapy. He achieved rapid virological response, but after 6 weeks of therapy, a striking elevation of serum aminotransferase level was recorded with no accompanying skin rash; he was admitted to our hospital. PEG IFN/RBV/simeprevir was stopped, but sodium valproate (400 mg/day), which had been administrated for more than 10 years to prevent epilepsy was continued. Liver biopsy revealed typical features of drug‐induced liver injury. After stopping PEG IFN/RBV/simeprevir, serum aminotransferase levels soon returned to the normal range. We diagnosed this case to be simeprevir‐induced hepatitis clinically and histologically. Physicians need to stay alert to the possibility of drug‐induced liver injury in using simeprevir.
Combination of heat treatment and chitosan coating to improve postharvest quality of wolfberry (Lycium barbarum)
Authors: Ban Zhaojun , Wei Wenwen , Yang Xiangzheng , Feng Jianhua , Guan Junfeng , Li Li
Published: January 2015

The synergistic application of hot water dip at 42 °C for 30 min and 1% chitosan coating on differentiation in postharvest quality traits, microstructure as well as microbiological evolution of wolfberry fruits was investigated. Fresh wolfberry fruits were stored at 2 ± 0.5 °C and 90% relative humidity (RH) for 28 days. Results indicated the combination of prestorage heat treatment and chitosan coating maintained higher levels of ascorbic acid, total phenolic contents and antioxidant capacity as well as lower decay, compared with untreated wolfberry fruits. The possible mechanism was that the heat treatment almost sealed open stomata to limit the sites of pathogen penetration into fruits independently, followed by the biofilm formed by chitosan which controlled secondary infections as well as slowed changes in fruit respiration and metabolic activity in wolfberries. The synergistically treated fruit also exhibited a higher acceptability obtained by sensory analysis after cold storage. In this sense, the integrated application of heat treatment and chitosan coating could be regarded as an effective strategy to extend storage life and maintain the postharvest quality of wolfberry fruits.
Influence of extraction methods on functional properties of protein concentrates prepared from South African bambara groundnut landraces
Authors: Arise Abimbola K. , Amonsou Eric O. , Ijabadeniyi Oluwatosin A.
Published: January 2015

Functional properties of protein concentrates prepared from three bambara groundnut landraces using acid precipitation and salt solubilisation methods were evaluated. The protein content of bambara grains (26–27%) was similar for the three landraces. The acid precipitation gave a much higher yield of protein concentrates (52%), which were also high in protein (79%) compared to the salt solubilisation method (yield: 25%, protein content: 57%). Functional properties of proteins were more influenced by the methods of preparation rather than the landraces. Protein concentrate prepared by salt solubilisation method showed higher emulsifying (63–66%), foaming (53–57%), water (1.4–2.0 mg mL−1) and oil absorption properties (2.2–2.6 mg mL−1) than the acid‐precipitated concentrates (53–57%, 63–66%, 2.0–2.7 mg mL−1, 1.4–1.7 mg mL−1). The foaming capacity and stability of all the protein concentrates decreased with increasing pH from 3 to 8. Salt solubilisation may be the most appropriate method for the enhanced functionality and utilisation of bambara groundnuts’ protein concentrates.
Elucidation of colour development and microstructural characteristics of Allium sativum fumigated with acetic acid
Authors: Li Li , Wang Dan , Li Xihong , Wang Yu , Ju Xiaofeng
Published: January 2015

It has been well known that the greening of Allium sativum cloves could be formed after immersed in acetic acid solution. Nonetheless, no investigation was reported on colour development of A. sativum in response to acetic acid vapour until now. In this study, the brief exposure of A. sativum to acetic acid vapour (200–400 ppm) was combined with controlled atmosphere (5%, 20% and 80% CO2) packaging storage to break cell membrane and green garlic. The garlic bulbs were fumigated with acetic acid before controlled CO2 atmosphere packaging for 25 days at 4 °C. Fumigation with 200 ppm acetic acid followed by high CO2 atmosphere packaging (80% CO2) facilitated the garlic greening. It was also verified that γ‐glutamyl transpeptidase was involved in garlic greening in present study, and the compromise of glacial acetic acid vapour fumigation and CO2 gas atmosphere in package stored at low temperature could result in garlic greening as well.
Effect of enterohaemorrhagic Escherichia coli O157:H7‐specific enterohaemolysin on interleukin‐1β production differs between human and mouse macrophages due to the different sensitivity of NLRP3 activation
Authors: Cheng Yu‐Li , Song Li‐qiong , Huang Yuan‐Ming , Xiong Yan‐Wen , Zhang Xiao‐Ai , Sun Hui , Zhu Xin‐Ping , Meng Guang‐Xun , Xu Jian‐Guo , Ren Zhi‐Hong
Published: January 2015

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection in humans can cause acute haemorrhagic colitis and severe haemolytic uraemic syndrome. The role of enterohaemolysin (Ehx) in the pathogenesis of O157:H7‐mediated disease in humans remains undefined. Recent studies have revealed the importance of the inflammatory response in O157:H7 pathogenesis in humans. We previously reported that Ehx markedly induced interleukin‐1β (IL‐1β) production in human macrophages. Here, we investigated the disparity in Ehx‐induced IL‐1β production between human and mouse macrophages and explored the underlying mechanism regarding the activation of NOD‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasomes. In contrast to the effects on human differentiated THP‐1 cells and peripheral blood mononuclear cells, Ehx exerted no effect on IL‐1β production in mouse macrophages and splenocytes because of a disparity in pro‐IL‐1β cleavage into mature IL‐1β upon caspase‐1 activation. Additionally, Ehx significantly contributed to O157:H7‐induced ATP release from THP‐1 cells, which was not detected in mouse macrophages. Confocal microscopy demonstrated that Ehx was a key inducer of cathepsin B release in THP‐1 cells but not in mouse IC‐21 cells upon O157:H7 challenge. Inhibitor experiments indicated that O157:H7‐induced IL‐1β production was largely dependent upon caspase‐1 activation and partially dependent upon ATP signalling and cathepsin B release, which were both involved in NLRP3 activation. Moreover, inhibition of K+ efflux drastically diminished O157:H7‐induced IL‐1β production and cytotoxicity. The findings in this study may shed light on whether and how the Ehx contributes to the development of haemolytic uraemic syndrome in human O157:H7 infection.
Which life course model better explains the association between socioeconomic position and periodontal health?
Authors: Shin Bo‐Mi , Ryu Jae‐In , Sheiham Aubrey , Do Loc Giang , Jung Se‐Hwan
Published: January 2015

Aim

To assess whether the relationship between socioeconomic position (SEP) and periodontal health fitted the Critical Period or the Social Mobility life course models.

Methods

A nationally representative sample of 5570 Korean adults from KNHANES IV study. Log‐binomial regression models adjusting for adulthood or childhood socioeconomic (SES) variables was used to assess independent effects of socioeconomic differences for childhood, adulthood and period of transition from child to adult in periodontal health.

Results

In the Critical Period model, poorer periodontal status was associated with SES disadvantage in adulthood and not predicted by SES disadvantage in childhood. For the intergenerational Social Mobility model, prevalence of current periodontal disease was only different for females aged 30–39 and 40–49 years, after adjustment. Prevalence of periodontal disease in females was highest in the downwardly mobile group.

Conclusions

The Critical Period model was better at explaining association between socioeconomic position and periodontal health, such as the adulthood socioeconomic variables (SEP), had a stronger effect than childhood factors on periodontal disease. The Social Mobility model explained more of the variation in the association between SEP and periodontal health among women than among men.
White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in attention‐deficit/hyperactivity disorder
Authors: Francx Winke , Zwiers Marcel P. , Mennes Maarten , Oosterlaan Jaap , Heslenfeld Dirk , Hoekstra Pieter J. , Hartman Catharina A. , Franke Barbara , Faraone Stephen V. , O'Dwyer Laurence , Buitelaar Jan K.
Published: January 2015

Background

A developmental improvement of symptoms in attention‐deficit/hyperactivity disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental improvement of ADHD symptoms.

Methods

A cross‐sectional magnetic resonance imaging (MRI) analysis was embedded in a prospective follow‐up of an adolescent cohort of ADHD and control subjects (NeuroIMAGE). Mean age at baseline was 11.9 years, mean interval of follow‐up was 5.9 years. About 75.3% of the original cohort was retained successfully. Data of 101 participants with ADHD combined type at baseline and 40 healthy controls were analysed. ADHD symptoms were measured with semistructured, investigator‐based interviews and Conners' questionnaires, on the basis of DSM‐IV criteria. Fractional anisotropy (FA) and mean diffusivity (MD) indices of white matter microstructure were measured using whole brain diffusion tensor imaging at follow‐up only. In a dimensional analysis FA and MD were related to change in ADHD symptoms. To link this analysis to DSM‐IV diagnoses, a post hoc categorical group analysis was conducted comparing participants with persistent (n = 59) versus remittent (n = 42) ADHD and controls.

Results

Over time, participants with ADHD showed improvement mainly in hyperactive/impulsive symptoms. This improvement was associated with lower FA and higher MD values in the left corticospinal tract at follow‐up. Findings of the dimensional and the categorical analysis strongly converged. Changes in inattentive symptoms over time were minimal and not related to white matter microstructure.

Conclusions

The corticospinal tract is important in the control of voluntary movements, suggesting the importance of the motor system in the persistence of hyperactive/impulsive symptoms.
Lipid peroxidation is essential for α‐synuclein‐induced cell death
Authors: Angelova Plamena R. , Horrocks Mathew H. , Klenerman David , Gandhi Sonia , Abramov Andrey Y. , Shchepinov Mikhail S.
Published: January 2015

Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated α‐synuclein (α‐Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric α‐Syn on one of the major markers of oxidative stress, lipid peroxidation, in primary co‐cultures of neurons and astrocytes. We found that oligomeric but not monomeric α‐Syn significantly increases the rate of production of reactive oxygen species, subsequently inducing lipid peroxidation in both neurons and astrocytes. Pre‐incubation of cells with isotope‐reinforced polyunsaturated fatty acids (D‐PUFAs) completely prevented the effect of oligomeric α‐Syn on lipid peroxidation. Inhibition of lipid peroxidation with D‐PUFAs further protected cells from cell death induced by oligomeric α‐Syn. Thus, lipid peroxidation induced by misfolding of α‐Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease.

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We have found that aggregated α‐synuclein‐induced production of reactive oxygen species (ROS) that subsequently stimulates lipid peroxidation and cell death in neurons and astrocytes. Specific inhibition of lipid peroxidation by incubation with reinforced polyunsaturated fatty acids (D‐PUFAs) completely prevented the effect of α‐synuclein on lipid peroxidation and cell death.
The cytochrome P450 2D‐mediated formation of serotonin from 5‐methoxytryptamine in the brain in vivo: a microdialysis study
Authors: Haduch Anna , Bromek Ewa , Kot Marta , Kamińska Katarzyna , Gołembiowska Krystyna , Daniel Wladyslawa A.
Published: January 2015

The cytochrome P450 2D (CYP2D) mediates synthesis of serotonin from 5‐methoxytryptamine (5‐MT), shown in vitro for cDNA‐expressed CYP2D‐isoforms and liver and brain microsomes. We aimed to demonstrate this synthesis in the brain in vivo. We measured serotonin tissue content in brain regions after 5‐MT injection into the raphe nuclei (Model‐A), and its extracellular concentration in rat frontal cortex and striatum using an in vivo microdialysis (Model‐B) in male Wistar rats. Naïve rats served as control animals. 5‐MT injection into the raphe nuclei of PCPA‐(tryptophan hydroxylase inhibitor)‐pretreated rats increased the tissue concentration of serotonin (from 40 to 90% of the control value, respectively, in the striatum), while the CYP2D inhibitor quinine diminished serotonin level in some brain structures of those animals (Model‐A). 5‐MT given locally through a microdialysis probe markedly increased extracellular serotonin concentration in the frontal cortex and striatum (to 800 and 1000% of the basal level, respectively) and changed dopamine concentration (Model‐B). Quinine alone had no effect on serotonin concentration; however, given jointly with 5‐MT, it prevented the 5‐MT‐induced increase in cortical serotonin in naïve rats and in striatal serotonin in PCPA‐treated animals. These results indicate that the CYP2D‐catalyzed alternative pathway of serotonin synthesis from 5‐MT is relevant in the brain in vivo, and set a new target for the action of psychotropics.

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The aim of this study was to demonstrate that the cytochrome P450 (CYP2D)‐mediated synthesis of serotonin from 5‐methoxytryptamine (5‐MT) can take place in rat brain in vivo. Intracerebral injection of 5‐MT increased tissue and extracellular serotonin concentration in the brain. Quinine (a CYP2D inhibitor) prevented the 5‐MT‐induced increase in serotonin concentration. The results confirm our hypothesis and indicate that the CYP2D‐catalyzed serotonin synthesis from 5‐MT in the brain can be considered as a new pharmacological target. 5‐HT = 5‐hydroxytryptamine (serotonin); QUIN = quinine. Symbols: *p < 0.01 versus control, ^p < 0.1 versus 5‐MT, !p < 0.01 versus QUIN (repeated measures anova and Tukey's post hoc test).
Dose–responses of zinc–methionine supplements on growth, blood metabolites and gastrointestinal development in sheep
Authors: Jafarpour N. , Khorvash M. , Rahmani H. R. , Pezeshki A. , Hosseini Ghaffari M.
Published: January 2015

The effects of zinc–methionine (Zn‐Met) supplementation on growth, blood metabolites and gastrointestinal development were investigated in two experiments with sheep. The objective of Experiment 1 was to determine the effects of Zn‐Met supplementation on hormones and metabolites involved in growth and energy balance regulation, while Experiment 2 aimed to determine the effects of Zn‐Met on feed intake, body weight, gastrointestinal development and liver glycogen concentration in lamb. The animals were assigned to groups with different concentrations of dietary Zn‐Met (0, 0.4, 0.8 and 1.2 g/day) in both experiments. In Experiment 1, feeding different doses of Zn‐Met increased plasma insulin‐like growth factor 1 (IGF‐1) concentration, but it linearly decreased plasma growth hormone (GH). No differences were observed in blood cortisol, insulin and glucose concentrations among the treatments. In Experiment 2, addition of Zn‐Met to the diets did not lead to changes in the body weights of the lambs. Both average daily gain and dry matter intake (DMI) increased linearly with increasing concentrations of dietary Zn‐Met. Lambs receiving Zn‐Met showed higher liver glycogen concentrations than the control. While significant increases were observed in the villus height and crypt depth in the duodenum and jejunum as a result of Zn‐Met supplementation, no change was detected in blood glucose concentrations (p > 0.05). Our findings suggest that dietary Zn‐Met may improve growth, energy balance and gastrointestinal development in sheep.
Fasting Urinary Calcium‐to‐Creatinine and Oxalate‐to‐Creatinine Ratios in Dogs with Calcium Oxalate Urolithiasis and Breed‐Matched Controls
Authors: Furrow E. , Patterson E.E. , Armstrong P.J. , Osborne C.A. , Lulich J.P.
Published: January 2015

Background

Hypercalciuria and hyperoxaluria are risk factors for calcium oxalate (CaOx) urolithiasis, but breed‐specific reports of urinary metabolites and their relationship with stone status are lacking.

Objective

To compare urinary metabolites (calcium and oxalate) and blood ionized calcium (iCa) concentrations between CaOx stone formers and breed‐matched stone‐free controls for the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds.

Animals

Forty‐seven Miniature Schnauzers (23 cases and 24 controls), 27 Bichons Frise (14 cases and 13 controls), and 15 Shih Tzus (7 cases and 8 controls).

Methods

Prospective study. Fasting spot urinary calcium‐to‐creatinine and oxalate‐to‐creatinine ratios (UCa/Cr and UOx/Cr, respectively) and bloodiCa concentrations were measured and compared between cases and controls within and across breeds. Regression models were used to test the effect of patient and environmental factors on these variables.

Results

UCa/Cr was higher in cases than controls for each of the 3 breeds. In addition to stone status, being on a therapeutic food designed to prevent CaOx stone recurrence was associated with higher UCa/Cr. UOx/Cr did not differ between cases and controls for any of the breeds. BloodiCa was higher in cases than controls in the Miniature Schnauzer and Bichon Frise breeds and had a moderate correlation with UCa/Cr.

Conclusions and Clinical Importance

Hypercalciuria is associated with CaOx stone status in the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds.UOx/Cr did not correlate with stone status in these 3 breeds. These findings may influence breed‐specific stone prevention recommendations.
Elusive Counterfactuals
Authors: Lewis Karen S.
Published: January 2015

I offer a novel solution to the problem of counterfactual skepticism: the worry that all contingent counterfactuals without explicit probabilities in the consequent are false. I argue that a specific kind of contextualist semantics and pragmatics for would‐ and might‐counterfactuals can block both central routes to counterfactual skepticism. One, it can explain the clash between would‐ and might‐counterfactuals as in: (1) If you had dropped that vase, it would have broken. and (2) If you had dropped that vase, it might have safely quantum tunneled to China. Two, it can explain why counterfactuals like (1) can be true despite the fact that quantum tunneling worlds are among the most similar worlds. I further argue that this brand of contextualism accounts for the data better than other existing solutions to the problem.
Optimal design in pediatric pharmacokinetic and pharmacodynamic clinical studies
Authors: Roberts Jessica K. , Stockmann Chris , Balch Alfred , Yu Tian , Ward Robert M. , Spigarelli Michael G. , Sherwin Catherine M. T.
Published: January 2015

It is not trivial to conduct clinical trials with pediatric participants. Ethical, logistical, and financial considerations add to the complexity of pediatric studies. Optimal design theory allows investigators the opportunity to apply mathematical optimization algorithms to define how to structure their data collection to answer focused research questions. These techniques can be used to determine an optimal sample size, optimal sample times, and the number of samples required for pharmacokinetic and pharmacodynamic studies. The aim of this review is to demonstrate how to determine optimal sample size, optimal sample times, and the number of samples required from each patient by presenting specific examples using optimal design tools. Additionally, this review aims to discuss the relative usefulness of sparse vs rich data. This review is intended to educate the clinician, as well as the basic research scientist, whom plan on conducting a pharmacokinetic/pharmacodynamic clinical trial in pediatric patients.
Extended Cognition and Propositional Memory
Authors: Adam Carter J. , Kallestrup Jesper
Published: January 2015

The philosophical case for extended cognition is often made with reference to ‘extended‐memory cases’ (e.g. Clark & Chalmers 1998); though, unfortunately, proponents of the hypothesis of extended cognition (HEC) as well as their adversaries have failed to appreciate the kinds of epistemological problems extended‐memory cases pose for mainstream thinking in the epistemology of memory. It is time to give these problems a closer look. Our plan is as follows: in §1, we argue that an epistemological theory remains compatible with HEC only if its epistemic assessments do not violate what we call ‘the epistemic parity principle’. In §2, we show how the constraint of respecting the epistemic parity principle stands in what appears to be a prima facie intractable tension with mainstream thinking about cases of propositional memory. We then outline and evaluate in §3 several lines of response.
Platelet‐derived microparticles induce polymorphonuclear leukocyte‐mediated damage of human pulmonary microvascular endothelial cells
Authors: Xie Ru Feng , Hu Ping , Wang Zhi Cheng , Yang Jie , Yang Yi Ming , Gao Li , Fan Hua Hua , Zhu Yong Ming
Published: January 2015

Background

Platelets (PLTs) stored at 22°C accumulate microparticles and biologic response modifiers (BRMs) that induce inflammatory reactions in transfusion recipients. However, soluble BRMs are fully diluted in the recipient's blood circulation. The mechanisms by which BRMs exert their effects have not been elucidated. The objectives of this study were to determine the effect of PLT microparticles (PMPs) on polymorphonuclear leukocyte (PMN)‐mediated human pulmonary microvascular endothelial cell (HMVEC) damage and determine the role of soluble CD40 ligand (sCD40L).

Study Design and Methods

PMPs were isolated from apheresis PLT concentrates. We used a two‐insult in vitro model of HMVEC damage to investigate the effects of PMP and sCD40L and role of apocynin, an inhibitor of PMN respiratory burst. Their priming activities were measured using hydrogen peroxide production. The expression of intercellular cell adhesion molecule‐1 (ICAM‐1) and integrin αM (CD11b) were also determined.

Results

Lipopolysaccharide (LPS)‐activated HMVEC damage and PMN respiratory burst depend on the presence of PMP and the concentration of sCD40L. PMP‐induced PMN‐mediated HMVEC damage was significantly reduced by apocynin‐treated PMNs (p < 0.05). The surface expression of ICAM‐1 on HMVEC was increased by LPS stimulation. The expression of CD11b on PMNs was increased by PMP priming. Blocking ICAM‐1 with a monoclonal antibody (MoAb) CD54 significantly reduced HMVEC damage (p < 0.05). The treatment of endothelial cells but not PMN with a MoAb targeting CD40 failed to prevent the HMVEC damage caused by PMPs (p > 0.05).

Conclusion

PMPs carry a concentrated CD40L signal, promote PMN‐mediated HMVEC damage, and may affect the development of transfusion‐related acute lung injury.
Improved Force Transmission of a Flexible Surgical Instrument by Combining Input Motion
Authors: Khatait Jitendra P. , Brouwer Dannis M. , Aarts Ronald G. K. M. , Herder Just L.
Published: January 2015

The force transmission of a flexible instrument through an endoscope is considerably deteriorated due to friction between the contacting surfaces. Friction force along the axial direction can be reduced by combining the translational motion input with rotation. A ratio ζ is defined to measure the reduction in the friction force along the axial direction due to the combined motion input at the proximal end of the instrument. An analytical formula is derived that shows the reduction in the friction force for the combined motion input. A flexible multibody model was setup and various simulations were performed with different motion inputs. The simulation result showed a reduction of 80% in the value of ζ in accordance with the analytical result for the given velocity ratio. Several experiments were performed with constant translational motion input combined with constant and sinusoidal rotational motion input. A maximum reduction of 84% is obtained in the value of ζ against a reduction of 89% calculated analytically. The knowledge of force transmission with a combination of motions can be used to increase the force fidelity of a flexible instrument in applications like robotic surgery with a flexible instrument.
Effect of C-Arm Year Model on Radiation Scatter
Authors: Bakr Omar , Morshed Saam , Marmor Meir
Published: January 2015

Since the 1980’s C-arm fluoroscopy has been an integral part of orthopaedic trauma surgery. The advancement in C-arm technology has resulted in different generations of C-arms co-existing in the operating rooms. The purpose of this study was to compare the radiation scatter patterns of different generation C-arms. Three generation of C-arms were tested: GE OEC 9800 Plus (1999/2000), Siemens Arcadis Orbic 3D (2004), Philips BV Pulsera 2.3 (2008). Radiation scatter was measured using six real-time dosimetry badges set up on either side of the surgical table (Mizuho OSI, flat-top). Distance of C-arm was normalized at 20 in. and 10 in. from Image Intensifier. Each device was set to the automatic brightness control (ABC) setting. A phantom limb was irradiated for 120 s and radiation scatter was summed for both AP and lateral positions. At their typical operating room settings there was a reduction in radiation scatter using the newer generation C-arms. Results for total radiation, normalized to Philips, are as follows: Philips 1 (100%), GE 2.4 (240%), and Siemens 1.4 (140%). Newer generation C-arms can be expected to generate lower radiation scatter. Special care should be taken to attempt a lower dose setting, especially when utilizing older generation C-arms to minimize radiation scatter to practitioner.
Four dimensional magnetic resonance imaging with retrospective k‐space reordering: A feasibility study
Authors: Liu Yilin , Yin Fang‐Fang , Chen Nan‐kuei , Chu Mei‐Lan , Cai Jing
Published: January 2015

Purpose:

Current four dimensional magnetic resonance imaging (4D‐MRI) techniques lack sufficient temporal/spatial resolution and consistent tumor contrast. To overcome these limitations, this study presents the development and initial evaluation of a new strategy for 4D‐MRI which is based on retrospective k‐space reordering.

Methods:

We simulated a k‐space reordered 4D‐MRI on a 4D digital extended cardiac‐torso (XCAT) human phantom. A 2D echo planar imaging MRI sequence [frame rate (F) = 0.448 Hz; image resolution (R) = 256 × 256; number of k‐space segments (NKS) = 4] with sequential image acquisition mode was assumed for the simulation. Image quality of the simulated “4D‐MRI” acquired from the XCAT phantom was qualitatively evaluated, and tumor motion trajectories were compared to input signals. In particular, mean absolute amplitude differences (D) and cross correlation coefficients (CC) were calculated. Furthermore, to evaluate the data sufficient condition for the new 4D‐MRI technique, a comprehensive simulation study was performed using 30 cancer patients’ respiratory profiles to study the relationships between data completeness (Cp) and a number of impacting factors: the number of repeated scans (NR), number of slices (NS), number of respiratory phase bins (NP), NKS, F, R, and initial respiratory phase at image acquisition (P0). As a proof‐of‐concept, we implemented the proposed k‐space reordering 4D‐MRI technique on a T2‐weighted fast spin echo MR sequence and tested it on a healthy volunteer.

Results:

The simulated 4D‐MRI acquired from the XCAT phantom matched closely to the original XCAT images. Tumor motion trajectories measured from the simulated 4D‐MRI matched well with input signals (D = 0.83 and 0.83 mm, and CC = 0.998 and 0.992 in superior–inferior and anterior–posterior directions, respectively). The relationship between Cp and NR was found best represented by an exponential function (, when NS = 30, NP = 6). At a CP value of 95%, the relative error in tumor volume was 0.66%, indicating that NR at a CP value of 95% (NR,95%) is sufficient. It was found that NR,95% is approximately linearly proportional to NP (r = 0.99), and nearly independent of all other factors. The 4D‐MRI images of the healthy volunteer clearly demonstrated respiratory motion in the diaphragm region with minimal motion induced noise or aliasing.

Conclusions:

It is feasible to generate respiratory correlated 4D‐MRI by retrospectively reordering k‐space based on respiratory phase. This new technology may lead to the next generation 4D‐MRI with high spatiotemporal resolution and optimal tumor contrast, holding great promises to improve the motion management in radiotherapy of mobile cancers.
Microbial Engineering for Aldehyde Synthesis
Authors: Kunjapur Aditya M. , Prather Kristala L. J.
Published: January 2015

Aldehydes are a class of chemicals with many industrial uses. Several aldehydes are responsible for flavors and fragrances present in plants, but aldehydes are not known to accumulate in most natural microorganisms. In many cases, microbial production of aldehydes presents an attractive alternative to extraction from plants or chemical synthesis. During the past 2 decades, a variety of aldehyde biosynthetic enzymes have undergone detailed characterization. Although metabolic pathways that result in alcohol synthesis via aldehyde intermediates were long known, only recent investigations in model microbes such as
Escherichia coli
have succeeded in minimizing the rapid endogenous conversion of aldehydes into their corresponding alcohols. Such efforts have provided a foundation for microbial aldehyde synthesis and broader utilization of aldehydes as intermediates for other synthetically challenging biochemical classes. However, aldehyde toxicity imposes a practical limit on achievable aldehyde titers and remains an issue of academic and commercial interest. In this minireview, we summarize published efforts of microbial engineering for aldehyde synthesis, with an emphasis on
de novo
synthesis, engineered aldehyde accumulation in
E. coli
, and the challenge of aldehyde toxicity.
l
-Lactate Production from Biodiesel-Derived Crude Glycerol by Metabolically Engineered Enterococcus faecalis: Cytotoxic Evaluation of Biodiesel Waste and Development of a Glycerol-Inducible Gene Expression System
Authors: Doi Yuki
Published: January 2015

Biodiesel waste is a by-product of the biodiesel production process that contains a large amount of crude glycerol. To reuse the crude glycerol, a novel bioconversion process using
Enterococcus faecalis
was developed through physiological studies. The
E. faecalis
strain W11 could use biodiesel waste as a carbon source, although cell growth was significantly inhibited by the oil component in the biodiesel waste, which decreased the cellular NADH/NAD
+
ratio and then induced oxidative stress to cells. When W11 was cultured with glycerol, the maximum culture density (optical density at 600 nm [OD
600
]) under anaerobic conditions was decreased 8-fold by the oil component compared with that under aerobic conditions. Furthermore, W11 cultured with dihydroxyacetone (DHA) could show slight or no growth in the presence of the oil component with or without oxygen. These results indicated that the DHA kinase reaction in the glycerol metabolic pathway was sensitive to the oil component as an oxidant. The lactate dehydrogenase (Ldh) activity of W11 during anaerobic glycerol metabolism was 4.1-fold lower than that during aerobic glycerol metabolism, which was one of the causes of low
l
-lactate productivity. The
E. faecalis
pflB
gene disruptant (Δ
pfl
mutant) expressing the

ldhL1
LP

gene produced 300 mM
l
-lactate from glycerol/crude glycerol with a yield of >99% within 48 h and reached a maximum productivity of 18 mM h
−1
(1.6 g liter
−1
h
−1
). Thus, our study demonstrates that metabolically engineered
E. faecalis
can convert crude glycerol to
l
-lactate at high conversion efficiency and provides critical information on the recycling process for biodiesel waste.
Efficient Metabolic Exchange and Electron Transfer within a Syntrophic Trichloroethene-Degrading Coculture of Dehalococcoides mccartyi 195 and Syntrophomonas wolfei
Authors: Mao Xinwei , Stenuit Benoit , Polasko Alexandra , Alvarez-Cohen Lisa
Published: January 2015

Dehalococcoides mccartyi
195 (strain 195) and
Syntrophomonas wolfei
were grown in a sustainable syntrophic coculture using butyrate as an electron donor and carbon source and trichloroethene (TCE) as an electron acceptor. The maximum dechlorination rate (9.9 ± 0.1 μmol day
−1
) and cell yield [(1.1 ± 0.3) × 10
8
cells μmol
−1
Cl
−
] of strain 195 maintained in coculture were, respectively, 2.6 and 1.6 times higher than those measured in the pure culture. The strain 195 cell concentration was about 16 times higher than that of
S. wolfei
in the coculture. Aqueous H
2
concentrations ranged from 24 to 180 nM during dechlorination and increased to 350 ± 20 nM when TCE was depleted, resulting in cessation of butyrate fermentation by
S. wolfei
with a theoretical Gibbs free energy of −13.7 ± 0.2 kJ mol
−1
. Carbon monoxide in the coculture was around 0.06 μmol per bottle, which was lower than that observed for strain 195 in isolation. The minimum H
2
threshold value for TCE dechlorination by strain 195 in the coculture was 0.6 ± 0.1 nM. Cell aggregates during syntrophic growth were observed by scanning electron microscopy. The interspecies distances to achieve H
2
fluxes required to support the measured dechlorination rates were predicted using Fick's law and demonstrated the need for aggregation. Filamentous appendages and extracellular polymeric substance (EPS)-like structures were present in the intercellular spaces. The transcriptome of strain 195 during exponential growth in the coculture indicated increased ATP-binding cassette transporter activities compared to the pure culture, while the membrane-bound energy metabolism related genes were expressed at stable levels.
Anoxygenic Photosynthesis Controls Oxygenic Photosynthesis in a Cyanobacterium from a Sulfidic Spring
Authors: Klatt Judith M. , Al-Najjar Mohammad A. A. , Yilmaz Pelin , Lavik Gaute , de Beer Dirk , Polerecky Lubos
Published: January 2015

Before the Earth's complete oxygenation (0.58 to 0.55 billion years [Ga] ago), the photic zone of the Proterozoic oceans was probably redox stratified, with a slightly aerobic, nutrient-limited upper layer above a light-limited layer that tended toward euxinia. In such oceans, cyanobacteria capable of both oxygenic and sulfide-driven anoxygenic photosynthesis played a fundamental role in the global carbon, oxygen, and sulfur cycle. We have isolated a cyanobacterium,
Pseudanabaena
strain FS39, in which this versatility is still conserved, and we show that the transition between the two photosynthetic modes follows a surprisingly simple kinetic regulation controlled by this organism's affinity for H
2
S. Specifically, oxygenic photosynthesis is performed in addition to anoxygenic photosynthesis only when H
2
S becomes limiting and its concentration decreases below a threshold that increases predictably with the available ambient light. The carbon-based growth rates during oxygenic and anoxygenic photosynthesis were similar. However,
Pseudanabaena
FS39 additionally assimilated NO
3
−
during anoxygenic photosynthesis. Thus, the transition between anoxygenic and oxygenic photosynthesis was accompanied by a shift of the C/N ratio of the total bulk biomass. These mechanisms offer new insights into the way in which, despite nutrient limitation in the oxic photic zone in the mid-Proterozoic oceans, versatile cyanobacteria might have promoted oxygenic photosynthesis and total primary productivity, a key step that enabled the complete oxygenation of our planet and the subsequent diversification of life.
Resistant Microbial Cooccurrence Patterns Inferred by Network Topology
Authors: Peura Sari , Bertilsson Stefan , Jones Roger I. , Eiler Alexander
Published: January 2015

Although complex cooccurrence patterns have been described for microbes in natural communities, these patterns have scarcely been interpreted in the context of ecosystem functioning and stability. Here we constructed networks from species cooccurrences between pairs of microorganisms which were extracted from five individual aquatic time series, including a dystrophic and a eutrophic lake as well as an open ocean site. The resulting networks exhibited higher clustering coefficients, shorter path lengths, and higher average node degrees and levels of betweenness than those of random networks. Moreover, simulations demonstrated that taxa with a large number of cooccurrences and placement at convergence positions in the network, so-called “hubs” and “bottlenecks,” confer resistance against random removal of “taxa.” Accordingly, we refer to cooccurrences at convergence positions as system-relevant interdependencies, as they, like hubs and bottlenecks, determine network topology. These topology features of the cooccurrence networks point toward microbial community dynamics being resistant over time and thus could provide indicators for the state of ecosystem stability.
Improvement of LysM-Mediated Surface Display of Designed Ankyrin Repeat Proteins (DARPins) in Recombinant and Nonrecombinant Strains of Lactococcus lactis and Lactobacillus Species
Authors: Zadravec Petra , Štrukelj Borut , Berlec Aleš
Published: January 2015

Safety and probiotic properties make lactic acid bacteria (LAB) attractive hosts for surface display of heterologous proteins. Protein display on nonrecombinant microorganisms is preferred for therapeutic and food applications due to regulatory requirements. We displayed two designed ankyrin repeat proteins (DARPins), each possessing affinity for the Fc region of human IgG, on the surface of
Lactococcus lactis
by fusing them to the Usp45 secretion signal and to the peptidoglycan-binding C terminus of AcmA, containing lysine motif (LysM) repeats. Growth medium containing a secreted fusion protein was used to test its heterologous binding to 10 strains of species of the genus
Lactobacillus
, using flow cytometry, whole-cell enzyme-linked immunosorbent assay (ELISA), and fluorescence microscopy. The fusion proteins bound to the surfaces of all lactobacilli; however, binding to the majority of bacteria was only 2- to 5-fold stronger than that of the control.
Lactobacillus salivarius
ATCC 11741 demonstrated exceptionally strong binding (32- to 55-fold higher than that of the control) and may therefore be an attractive host for nonrecombinant surface display. Genomic comparison of the species indicated the exopolysaccharides of
Lb. salivarius
as a possible reason for the difference. Additionally, a 15-fold concentration-dependent increase in nonrecombinant surface display on
L. lactis
was demonstrated by growing bacteria with sublethal concentrations of the antibiotics chloramphenicol and erythromycin. Nonrecombinant surface display on LAB, based on LysM repeats, was optimized by selecting
Lactobacillus salivarius
ATCC 11741 as the optimal host and by introducing antibiotics as additives for increasing surface display on
L. lactis
. Additionally, effective display of DARPins on the surfaces of nonrecombinant LAB has opened up several new therapeutic possibilities.