bluuebunny/crossref_metadata_2025 huggingface dataset:
Envelope tests for spatial point patterns with and without simulation
Authors: Wiegand Thorsten , Grabarnik Pavel , Stoyan Dietrich
Published: July 2016

Model testing is a central step of spatial point pattern analysis, which allows ecologists to judge if their data agree with ecological hypotheses. We present a simple and elegant solution of a challenging problem: the construction of a goodness‐of‐fit envelope test with prescribed significance levelα. Our new Analytical Global Envelope (AGE) test is not restricted to the narrow frame of complete spatial randomness testing and its envelopes can be determined by mathematical calculations. This allows us to investigate the influence of key settings of theAGEtest on the width of the envelope strip. To circumvent some assumptions of the simulation‐freeAGEtest we present a corresponding Simulation‐Based Global Envelope (SBGE) test. The envelope strip of theAGEand theSBGEtest encircles the range of a summary function such as the pair correlation function under the null model, and it has the desired property that the null hypothesis can be rejected with significance levelαif the empirical summary function wanders outside the envelopes. TheAGEtest can be applied under the mild conditions that the values of the summary functions under the null model are (approximately) normally distributed and are (approximately) independent for different distance binsrj. TheSBGEtest requires only the independence assumption. The width of the strip of theAGEenvelopes scales for a broad range of point processes with 1/n, wherenis the number of points. This casts doubt about attempts of goodness‐of‐fit testing with lown(say <100). TheAGEandSBGEtest operate with wider envelope strips than the classical “pointwise” test. Therefore, the pointwise test has to be considered as too liberal. Furthermore, we show that the width of theAGE/SBGEstrip increases approximately with ln(b), wherebis the number of distance bins. For example, theAGE/SBGEenvelopes are forb = 20 more than 50% wider than the corresponding pointwise envelopes. Our study opens up new avenues to the test problem in point pattern statistics and the newAGEandSBGEtests can be widely applied in ecology to improve the practice in null model testing.
Postdefoliation ecosystem carbon and water flux and canopy growth dynamics in sagebrush steppe bunchgrasses
Authors: Hamerlynck Erik P. , Sheley Roger L. , Davies Kirk W. , Svejcar Tony J.
Published: July 2016

Developing land‐use practices that lead to sustainable net primary productivity in rangelands are important, but understanding their consequences to population and community processes is not often accounted for in basic ecosystem studies. Grazed and ungrazed upland ecosystems generally do not differ in net ecosystemCO2exchange (NEE), but the underlying mechanisms and the concurrent effects of defoliation to vegetative and reproductive biomass allocation are unclear. To address this, we measured evapotranspiration (ET),NEE, and its constituent fluxes of ecosystem respiration (Reco) and gross ecosystem photosynthesis (GEP) with live canopy leaf area index (LAIlive; m2live leaf area/m2ground area) and aboveground leaf, culm, and reproductive biomass in plots of clipped and unclipped squirreltail (Elymus elymoides) and bluebunch wheatgrass (Pseudoroegneria spicata) growing in intact sagebrush steppe. Clipping reducedLAIliveby 75%, but subsequent re‐growth rates in clipped plots was similar toLAIliveaccumulation in unclipped plots. Concurrently,ETandNEEwas similar between clipped and unclipped plots, withNEEprimarily determined byGEP.GEPwas initially lower in clipped plots, but then converged with unclippedGEPeven asLAIlivecontinued to increase in both treatments.GEPconvergence was driven by higher whole‐plant photosynthesis (GEPlive = GEP/LAIlive) in clipped plots. Ecosystem water use efficiency (GEP/ET) was reduced by 16% with clipping, due to lowGEP/ET2 weeks following defoliation, butGEP/ETconverged beforeGEPlevels did. Proportional reproductive biomass was higher inE. elymoides(21.4% total biomass) than inP. spicata(0.5% total biomass) due to lower allocation to specific leaf and culm mass. Clipping reduced reproductive effort inE. elymoides, in terms of total reproductive biomass (−56%), seed mass per unit leaf area (−64%), and seed mass per flowering head (−77%). We concluded defoliation increased canopy‐level light penetration, facilitating rapid recovery of ecosystem fluxes, but that allocation to vegetative regrowth supporting this led to lower reproductive effort in these range grasses. Insights from studies such as this will be useful in formulating systems‐based land management strategies aimed at maintaining annual productivity and long‐term population and community goals in semiarid rangeland ecosystems.
Cs2CO3‐Promoted Direct N‐Alkylation: Highly Chemoselective Synthesis of N‐Alkylated Benzylamines and Anilines
Authors: Castillo Juan‐Carlos , Orrego‐Hernández Jessica , Portilla Jaime
Published: July 2016

Herein is described an efficient and chemoselective method for the synthesis of diversely substituted secondary amines in yields up to 98 %. Direct mono‐N‐alkylation of primary benzylamines and anilines with a wide range of alkyl halides is promoted by a cesium base in the absence of any additive or catalyst. The basicity and solubility of cesium carbonate in anhydrous N,N‐dimethylformamide not only enables mono‐N‐alkylation of primary amines but also suppresses undesired dialkylation of the desired amines.
One‐pot Synthesized Co/Co3O4‐N‐Graphene Composite as Electrocatalyst for Oxygen Reduction Reaction and Oxygen Evolution Reaction
Authors: He Bincai , Chen Xingxing , Lu Jingming , Yao Songdong , Wei Jiong , Zhao Qi , Jing Deshui , Huang Xinning , Wang Tao
Published: July 2016

Efficient bifunctional catalysts for reversible oxygen electrodes, for electrocatalysis of both the oxygen reduction reaction (ORR) and the oxygen evolution reactions (OER) are envisioned to make a significant contribution towards the need for environmentally friendly and renewable energy systems. Despite tremendous efforts, there is still need for further development of bifunctional catalysts to achieve low‐cost catalysts with stable satisfactory long‐term performance, enhanced kinetics of the ORR and OER and high round‐trip electrolytic‐galvanic mode voltage efficiency. Herein, we demonstrate a simple one‐pot procedure for synthesis of a bifunctional catalyst comprised of a composite of cobalt/cobalt oxide and N‐doped graphene (denoted as Co/Co3O4‐N‐graphene), which exhibits very good performance in the electrocatalysis of both ORR and OER in alkaline solution. The prepared composite was characterized by TEM, SEM, Raman, XRD and XPS, to give insight of its structure‐performance correlation. The results reveal that the structure of N‐doped graphene is preserved and that both metallic Co and its oxide form of Co3O4 co‐existed in the prepared composite, with metallic Co being predominant crystalline component. Generally, a high ratio of Co in the prepared composite led to improvement of the onset potential for the OER.
Serial multiple crossed immunoelectrophoresis at a microscale: A stamp‐sized 2D immunoanalysis of protein C3 activation caused by nanoparticles
Authors: Coty Jean‐Baptiste , Varenne Fanny , Vachon Jean‐Jacques , Vauthier Christine
Published: July 2016

Crossed immunoelectrophoresis (C‐IE) is used to detect and quantify specific proteins. An application allowed the evaluation of complement system activation by nanomaterials. The work aimed to improve the C‐IE toward a higher throughput and less tedious method. A new concept was implemented to prepare and run agarose gels. The first and the second dimension of electrophoresis were performed on a single gel plate, prepared before the beginning of the analysis. Several samples were migrated simultaneously on the same migration line. Up to 35 analyses were run at once, providing stamp‐sized electrophoregrams (2.8 × 3 cm2) maintaining the performance of the original method performed on 5 × 7 cm2 gel slabs. Robustness and precision of the method were demonstrated through a validation approach using ANOVA. Handling, experimental duration, amount of reagents, and overall cost of one analysis were considerably reduced compared to the original method. With the same equipment, seven times more analyses can be performed in one run. C‐IE can be used to analyze many types of proteins. The new experimental modalities were suitable for the application developed in the present work that was to evaluate activation of protein C3 of the complement system triggered by nanomaterials.
5G‐XHaul: a converged optical and wireless solution for 5G transport networks
Authors: Gutiérrez Jesús , Maletic Nebojsa , Camps‐Mur Daniel , García Eduard , Berberana Ignacio , Anastasopoulos Markos , Tzanakaki Anna , Kalokidou Vaia , Flegkas Paris , Syrivelis Dimitris , Korakis Thanasis , Legg Peter , Markovic Dusan , Lyberopoulos George , Bartelt Jens , Chaudhary Jay Kant , Grieger Michael , Vucic Nikola , Zou Jim , Grass Eckhard
Published: July 2016

The common European Information and Communications Technology sector vision for 5G is that it should leverage on the strengths of both optical and wireless technologies. In the 5G context, a wide spectra of radio access technologies—such as millimetre wave transmission, massive multiple‐input multiple‐output and new waveforms—demand for high capacity, highly flexible and convergent transport networks. As the requirements imposed on future 5G networks rise, so do the challenges in the transport network. Hence, 5G‐XHaul proposes a converged optical and wireless transport network solution with a unified control plane based on software defined networking. This solution is able to support the flexible backhaul and fronthaul—X‐Haul—options required to tackle the future challenges imposed by 5G radio access technologies. 5G‐XHaul studies the trade‐offs involving fully or partially converged backhaul and fronthaul functions, with the aim of maximising the associated sharing benefits, improving efficiency in resource utilisation and providing measurable benefits in terms of overall cost, scalability and sustainability. Copyright © 2016 John Wiley & Sons, Ltd.
The rehydration behavior of microwave‐dried amaranth (Amaranthus dubius) leaves
Authors: Mujaffar Saheeda , Lee Loy Alex
Published: July 2016

The effect of temperature (35, 50, and 60°C) on the rehydration behavior of microwave‐dried amaranth (Amaranthus dubius) leaves was investigated. Leaves were dried at 700 W power level before rehydrating in water. The higher the rehydration temperature, the higher the equilibrium moisture content of the leaves, although the effect was not statistically significant. The increase in rehydration ratio was significant only as temperature increased from 50 to 60°C. The process was adequately described by the Peleg sorption model, with the Peleg rate constant (K1) and the Peleg capacity constant (K2), both decreasing as rehydration temperature increased. While the color difference (ΔE) between fresh leaves and leaves rehydrated at 35°C was significantly higher than for the leaves rehydrated at 50 and 60°C, this difference was not visible. Cooking of leaves occurred beyond 120 min at the higher rehydration temperatures . Based on the results, rehydration of microwave‐dried leaves was successfully carried out at 35°C, however, rehydrated leaves were darker than the fresh leaves. Increasing the temperature to 50°C improved the rehydration capacity and the color of the leaves, however, cooking of leaves occurred by the second hour of the process.
Geochemical Characterization of Four Quaternary Obsidian Sources and Provenance of Obsidian Artifacts from the Middle Stone Age Site of Gademotta, Main Ethiopian Rift
Authors: Shackley M. Steven , Sahle Yonatan
Published: July 2016

Twenty‐six Middle Stone Age obsidian artifacts from the Gademotta Formation were instrumentally characterized by energy dispersive X‐ray fluorescence. Analysis of artifacts from the type locality enabled sampling of a greater time depth while avoiding the uncertainties in previous results on artifacts sampled from a “disturbed” context at Kulkuletti. Moreover, the analysis here of source samples from Alutu, Worja, and the previously unstudied Bora and Ficke sources in the broader region offers a better understanding of prehistoric lithic raw material procurement. The local Worja source, an aphyric obsidian excellent for tool production, substantially dominates the assemblage. Bora, another aphyric obsidian in the wider region, is also present, but not common. The vitrophyric Ficke and Alutu obsidian sources with abundant sanidine phenocrysts were not present in the archaeological assemblage, and likely did not compete with Worja and Bora for tool production. At least one artifact appears to be from an as yet unknown source, thus confirming results of previous studies. A few artifacts share similar geochemical composition with the Worja and Bora sources, thus highlighting the complexity of obsidian source studies in this part of the rift where multiple geographically close sources may share similar crustal material.
Effectiveness of critical care pathways for head and neck cancer surgery: A systematic review
Authors: Gordon Steven A. , Reiter Evan R.
Published: July 2016

Background

Critical care pathways (CCPs) are implemented within health care systems as a means to systematically decrease resource utilization, whereas maintaining a high level of care for patients with a specific diagnosis. Previous studies have shown equivocal results for CCPs in head and neck cancer surgery.

Methods

We conducted a systematic review evaluating studies of CCPs for head and neck cancer surgery, with individual outcome measures analyzed separately to describe the effect of each implemented pathway.

Results

Ten before and after studies were included for systematic review. Nine reported statistically significant decreases in median/mean length of stay and 5 reported statistically significant decreases in cost of care per case.

Conclusion

Although the results are encouraging and point toward the ability of CCPs to decrease length of stay and cost of care, the evidence cannot be considered exhaustive because of the studies’ inability to account for temporal trends. Further controlled studies are recommended to validate the benefits of CCPs. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1421–1427, 2016
A Plot‐Scale Monitoring Experiment To Assess The Agricultural Non‐Point Source Pollution Reductions Achieved By Silt Fences and Berms
Authors: Jang Min Won , Kim Dong Hyeon , Jang Jeong Ryeol , Kim Sang Min
Published: July 2016

The objective of this study was to assess the non‐point source pollution reductions by a silt fence and berm through field monitoring. Experimental plots were established in two sizes on three slopes (110 m2 on 3 and 9% slopes, and 225 m2 on 6% slope). Flumes were used to monitor plot runoff. Runoff samples were collected during heavy rainfall (12 events from 2011 to 2014) for subsequent analysis. Cultivated crops were radish, Chinese cabbage and soybean. Runoff from the silt fence and berm treatment plots was 23.1 and 25.8% lower, respectively, than that from the control plot. On average the silt fence reduced BOD losses by −10.0% (i.e. 10% increase), COD by 28.7%, T‐N by 42.5%, T–P by 22.7%, and SS by 48.0% compared to losses from the control plot. The berm reduced BOD losses by 34.1%, COD by 30.0%, T‐N by 30.8%, T–P by 68.9%, and SS by 59.9% compared to losses from the control plot. The SS load reductions were statistically significant (5% level). Thus, the silt fence and berm were both effective in reducing pollutant losses in surface runoff. However, long‐term monitoring is required to obtain a more quantitative and reliable description of the reduction effect for diverse crops. Copyright © 2016 John Wiley & Sons, Ltd.
The component leaching from decellularized pericardial bioscaffolds and its implication in the macrophage response
Authors: Mendoza‐Novelo Birzabith , Castellano Laura E. , Padilla‐Miranda Ruth G. , Lona‐Ramos María C. , Cuéllar‐Mata Patricia , Vega‐González Arturo , Murguía‐Pérez Mario , Mata‐Mata José L. , Ávila Eva E.
Published: July 2016

The extracellular matrix molecules remaining in bioscaffolds derived from decellularized xenogeneic tissues appear to be important for inducing cell functions conducting tissue regeneration. Here, we studied whether decellularization methods, that is, detergent Triton X‐100 (TX) alone and TX combined with reversible alkaline swelling (STX), applied to bovine pericardial tissue, could affect the bioscaffold components. Thein vitromacrophage response, subdermal biodegradation, and cell infiltration were also studied. The results indicate a lower leaching of fibronectin, but a higher leaching of laminin and sulfated glycosaminoglycans from tissues decellularized with STX and TX, respectively. Thein vitrosecretion of interleukin‐6 and monocyte chemoattractant protein by RAW264.7 macrophages is promoted by decellularized bioscaffold leachates. A lower polymorphonuclear cell density is observed around decellularized bioscaffolds at 1‐day implantation; concurrently showing a higher cell infiltration in STX‐ than in TX‐implant. Cells infiltrated into TX‐implant show a fibroblastic morphology at 7‐day implantation, concurrently the capillary formation is observed at 14‐day. Pericardial bioscaffolds suffer biodegradation more pronounced in STX‐ than in TX‐implant. Both TX and STX decellularization methods favor a high leaching of basal lamina components, which presumably promotes a faster macrophage stimulation compared to nondecellularized tissue, and appear to be associated with an increased host cell infiltration in a rat subdermal implantation. Meanwhile, the connective tissue components leaching from TX decellularized bioscaffolds, unlike the STX ones, appear to be associated with an enhanced angiogenesis accompanied by an early‐promoted fibroblastic cell transition. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2810–2822, 2016.
Biofilm formation of periodontal pathogens on hydroxyapatite surfaces: Implications for periodontium damage
Authors: Jaffar Norzawani , Miyazaki Toshiki , Maeda Toshinari
Published: July 2016

Biofilm formation of periodontal pathogens on teeth surfaces promotes the progression of periodontal disease. Hence, understanding the mechanisms of bacterial attachment to the dental surfaces may inform strategies for the maintenance of oral health. Although hydroxyapatite (HA) is a major calcium phosphate component of teeth, effect of biofilm formation on HA surfaces remains poorly characterized. In this study, biofilm‐forming abilities by the periodontal pathogens Aggregatibacter actinomycetemcomitans Y4 and Porphyromonas gingivalis 381 were investigated on dense and porous HAs that represent enamel and dentin surfaces, respectively. These experiments showed greater biofilm formation on porous HA, but differing attachment profiles and effects of the two pathogens. Specifically, while the detachment of A. actinomycetemcomitans Y4 biofilm was observed, P. gingivalis 381 biofilm increased with time. Moreover, observations of HA morphology following formation of A. actinomycetemcomitans Y4 biofilm revealed gaps between particles, whereas no significant changes were observed in the presence of P. gingivalis 381. Finally, comparisons of calcium leakage showed only slight differences between bacterial species and HA types and may be masked by bacterial calcium uptake. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2873–2880, 2016.
Low Dentin Matrix Protein 1 Is Associated With Incident Cardiovascular Events in Peritoneal Dialysis Patients
Authors: Yoon Chang-Yun , Park Jimin , Seo Changhwan , Nam Bo Young , Kim Seonghun , Kee Youn Kyung , Lee Misol , Cha Min-Uk , Kim Hyoungnae , Park Seohyun , Yun Hae-Ryong , Jung Su-Young , Jhee Jong Hyun , Kwon Young Eun , Wu Meiyan , Um Jae Eun , Kang Hye-Young , Park Jung Tak , Han Seung Hyeok , Kang Shin-Wook , Kim Hyeon Chang , Park Sungha , Lim Sung-Kil , Yoo Tae-Hyun
Published: July 2016

Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log-transformed plasma DMP1 levels. Lateral lumbar spine radiographs were used for measurement of vascular calcification. Major cardiovascular events were compared between the two groups. A Cox proportional hazards analysis determined DMP1 was independently associated with cardiovascular outcomes. In vitro mouse osteocytes were cultured in media containing indoxyl sulfate (IS), and the expressions of DMP1 were examined. The mean age was 52.1 ± 11.8 years, and 116 (52.0%) patients were male. The median value of log DMP1 was 0.91 (0.32–2.81 ng/mL). The multiple logistic regression analysis indicated that DMP1 levels were independently associated with the presence of vascular calcification after adjustment for multiple confounding factors (odds ratio = 0.719; 95% confidence interval [CI] 0.522–0.989; p = 0.043). During a mean follow-up duration of 34.6 months, incident cardiovascular events were observed in 41 (18.4%) patients. A Kaplan-Meier plot showed that the low DMP1 group had a significantly higher rate of incident cardiovascular events compared with the high DMP1 group (log-rank test, p = 0.026). In addition, multiple Cox analysis showed that low DMP1 was significantly associated with incident cardiovascular events (log 1 increase: hazard ratio = 0.855; 95% CI 0.743–0.984; p = 0.029) after adjustment for multiple confounding factors. In IS-stimulated osteocytes, mRNA and protein expression levels of DMP1 were significantly decreased compared with control osteocytes. We showed that low DMP1 levels were significantly associated with presence of vascular calcification and were independently associated with the incident cardiovascular events in prevalent peritoneal dialysis patients. DMP1 might be a potential factor contributing to cardiovascular complications in dialysis patients. © 2016 American Society for Bone and Mineral Research.
FAK Promotes Osteoblast Progenitor Cell Proliferation and Differentiation by Enhancing Wnt Signaling
Authors: Sun Chunhui , Yuan Hebao , Wang Li , Wei Xiaoxi , Williams Linford , Krebsbach Paul H , Guan Jun-Lin , Liu Fei
Published: July 2016

Decreased bone formation is often associated with increased bone marrow adiposity. The molecular mechanisms that are accountable for the negative correlation between bone mass and bone marrow adiposity are incompletely understood. Focal adhesion kinase (FAK) has critical functions in proliferation and differentiation of many cell types; however, its roles in osteoblast lineage cells are largely unknown. We show herein that mice lacking FAK in Osterix-expressing cells exhibited decreased osteoblast number and low bone mass as well as increased bone marrow adiposity. The decreased bone mass in FAK-deficient mice was accounted for by decreased proliferation, compromised osteogenic differentiation, and increased adipogenic differentiation of bone marrow Osterix-expressing cells resulting from downregulation of Wnt/β-catenin signaling due to the reduced expression of canonical Wnt ligands. In contrast, FAK loss in calvarial preosteoblasts had no adverse effect on their proliferation and osteogenic differentiation and these cells had intact Wnt/β-catenin signaling. © 2016 American Society for Bone and Mineral Research.
Interpersonal Circumplex Profiles Of Persistent Depression: Goals, Self‐Efficacy, Problems, And Effects Of Group Therapy
Authors: Locke Kenneth D. , Sayegh Liliane , Penberthy J. Kim , Weber Charlotte , Haentjens Katherine , Turecki Gustavo
Published: July 2016

Objectives

We assessed severely and persistently depressed patients’ interpersonal self‐efficacy, problems, and goals, plus changes in interpersonal functioning and depression during 20 weeks of group therapy.

Method

Outpatients (32 female, 26 male, mean age = 45 years) completed interpersonal circumplex measures of goals, efficacy, and problems before completing 20 weeks of manualized group therapy, during which we regularly assessed depression and interpersonal style.

Results

Compared to normative samples, patients lacked interpersonal agency, including less self‐efficacy for expressive/assertive actions; stronger motives to avoid conflict, scorn, and humiliation; and more problems with being too submissive, inhibited, and accommodating. Behavioral Activation and especially Cognitive Behavioral Analysis System of Psychotherapy interventions produced improvements in depression and interpersonal agency, with increases in “agentic and communal” efficacy predicting subsequent decreases in depression.

Conclusions

While severely and persistently depressed patients were prone to express maladaptive interpersonal dispositions, over the course of group therapy, they showed increasingly agentic and beneficial patterns of cognitions, motives, and behaviors.
Impact of Transporter Polymorphisms on Drug Development: Is It Clinically Significant?
Authors: McLean Cheynne , Wilson Aze , Kim Richard B.
Published: July 2016

Drug transporters are becoming increasingly recognized as relevant to the drug development process. This may be a reflection of increasing target complexity and the need for high‐affinity interaction with drug targets that minimize off‐target side effects. Moreover, as new molecular entities (NMEs) become larger in size and amphipathic in nature, interaction with drug transporters, both uptake as well as efflux, becomes increasingly likely. In some cases transporters may limit the absorption or organ‐specific entry of NMEs, whereas in other cases transporters may enhance their absorption or tissue accumulation. Indeed, in some cases, transporters may prove to be a therapeutic target. Accordingly, a better understanding of potentially clinically relevant drug transporter polymorphisms earlier in the drug development process is highly desirable. In this review we examine key transporters that are important to the absorption, distribution, and excretion of a large number of drugs in clinical use. Importantly, we provide our assessment of the potential impact of known polymorphisms in such transporters and discuss whether there is sufficient evidence to incorporate these polymorphisms in the drug development process.
Role of Hepatic Drug Transporters in Drug Development
Authors: Liu Houfu , Sahi Jasminder
Published: July 2016

Hepatic drug transporters can play an important role in pharmacokinetics and the disposition of therapeutic drugs and endogenous substances. Altered function of hepatic drug transporters due to drug‐drug interactions (DDIs), genetic polymorphisms, and disease states can often result in a change in systemic and/or tissue exposure and subsequent pharmacological/toxicological effects of their substrates. Regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japan Pharmaceuticals and Medical Devices Agency have issued guidance for industry on drug interaction studies, which contain comprehensive recommendations on in vitro and in vivo study tools and cutoff values to evaluate the DDI potential of new molecular entities mediated by hepatic drug transporters. In this report we summarize the latest regulatory and scientific progress of hepatic drug transporters in clinical DDIs, pharmacogenetics, drug‐induced liver injury (DILI), as well as methods for predicting transporter‐mediated pharmacokinetics and DDIs.
Use of PET Imaging to Evaluate Transporter‐Mediated Drug‐Drug Interactions
Authors: Langer Oliver
Published: July 2016

Several membrane transporters belonging to the adenosine triphosphate‐binding cassette (ABC) and solute carrier (SLC) families can transport drugs and drug metabolites and thereby exert an effect on drug absorption, distribution, and excretion, which may potentially lead to transporter‐mediated drug‐drug interactions (DDIs). Some transporter‐mediated DDIs may lead to changes in organ distribution of drugs (eg, brain, liver, kidneys) without affecting plasma concentrations. Positron emission tomography (PET) is a noninvasive imaging method that allows studying of the distribution of radiolabeled drugs to different organs and tissues and is therefore the method of choice to quantitatively assess transporter‐mediated DDIs on a tissue level. There are 2 approaches to how PET can be used in transporter‐mediated DDI studies. When the drug of interest is a potential perpetrator of DDIs, it may be administered in unlabeled form to assess its influence on tissue distribution of a generic transporter‐specific PET tracer (probe substrate). When the drug of interest is a potential victim of DDIs, it may be radiolabeled with carbon‐11 or fluorine‐18 and used in combination with a prototypical transporter inhibitor (eg, rifampicin). PET has already been used both in preclinical species and in humans to assess the effects of transporter‐mediated DDIs on drug disposition in different organ systems, such as brain, liver, and kidneys, for which examples are given in the present review article. Given the growing importance of membrane transporters with respect to drug safety and efficacy, PET is expected to play an increasingly important role in future drug development.
Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans
Authors: Momper Jeremiah D. , Tsunoda Shirley M. , Ma Joseph D.
Published: July 2016

Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter‐mediated drug–drug interactions. The transporters are P‐glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter‐mediated drug–drug interaction study is needed. Phenotyping is a methodology that evaluates real‐time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.
Differentiation of digestive system cancers by using serum protein‐based surface‐enhanced Raman spectroscopy
Authors: Lin Juqiang , Wang Jing , Xu Chaoxian , Zeng Yongyi , Chen Yanping , Li Ling , Huang Zufang , Li Buhong , Chen Rong
Published: July 2016

The aim of this study is to develop a more robust surface‐enhanced Raman spectroscopy method for the simultaneous differentiation of two or more different types of cancer. For this, the periodical reversal of current directions is imposed on electrophoresis for the fast purification of serum proteins, and the serum proteins were then mixed with silver nanoparticles for surface‐enhanced Raman spectroscopy spectral measurement. The Raman spectra of serum proteins from healthy subjects (n = 85) and three types of digestive system cancer – colorectal cancer (n = 109), gastric cancer (n = 133), and liver cancer (n = 38) – were measured for analyses. Principal component analysis and linear discriminant analysis yield diagnostic sensitivities of 94.5, 97.0, and 89.1% and specificities of 98.1, 92.7, and 99.2% in the differentiation of colorectal, gastric, and liver cancers, respectively. This work marks a promising step toward the potential applications of Raman spectroscopic blood analysis in multi‐type cancer screening. Copyright © 2016 John Wiley & Sons, Ltd.
Bayesian network meta‐analysis for cluster randomized trials with binary outcomes
Authors: Uhlmann Lorenz , Jensen Katrin , Kieser Meinhard
Published: July 2016

Network meta‐analysis is becoming a common approach to combine direct and indirect comparisons of several treatment arms. In recent research, there have been various developments and extensions of the standard methodology. Simultaneously, cluster randomized trials are experiencing an increased popularity, especially in the field of health services research, where, for example, medical practices are the units of randomization but the outcome is measured at the patient level. Combination of the results of cluster randomized trials is challenging. In this tutorial, we examine and compare different approaches for the incorporation of cluster randomized trials in a (network) meta‐analysis. Furthermore, we provide practical insight on the implementation of the models. In simulation studies, it is shown that some of the examined approaches lead to unsatisfying results. However, there are alternatives which are suitable to combine cluster randomized trials in a network meta‐analysis as they are unbiased and reach accurate coverage rates. In conclusion, the methodology can be extended in such a way that an adequate inclusion of the results obtained in cluster randomized trials becomes feasible. Copyright © 2016 John Wiley & Sons, Ltd.
Effect of technological factors on the activity and losses of cathepsins B, D and L during the marinating of Atlantic and Baltic herrings
Authors: Szymczak Mariusz
Published: July 2016

BACKGROUND

This study analyzes the effect of salt and acetic acid concentration, time, temperature and fish freezing on the activity and losses of cathepsins during the marinating of Atlantic and Baltic herrings.

RESULTS

The highest contribution to meat general proteolytic activity was found for cathepsin D‐like activity. This contribution decreased during the marinating process as a result of, among other things, cathepsin losses to brine. The methods of marinating had a significant impact on cathepsin activity losses. The average ratio of cathepsin D‐like activity to L and B in brine accounted for 15:3.5:1.5, respectively. Depending on the method of calculation, cathepsin activity in brine was similar (per gram of tissue/milliliter of brine) or multiply higher (per gram protein in tissue/brine) than in the marinated herring meat. Statistical analysis demonstrated that the extent and structure of cathepsin losses were significantly correlated with the quantitative and qualitative composition of protein hydrolysis products in marinades.

CONCLUSION

The presented results depict new phenomena of cathepsin losses and explain their impact on the process of fish marinating. Results allow better optimization of the process of meat ripening. The high activity of aspartyl and cysteine cathepsins in brine indicates the real feasibility of their application in the food industry for novel food design. © 2016 Society of Chemical Industry
Outcomes of vascularized versus non‐vascularized lymph node transplant in animal models for lymphedema. Review of the literature
Authors: Cornelissen Anouk J.M. , Qiu Shan Shan , Lopez Penha Tiara , Keuter Xavier , Piatkowski de Grzymala Andrzej , Tuinder Stefania , van der Hulst Rene
Published: July 2016

Lymph node transfer has been performed to treat lymphedema for several years. The goal of this procedure is to provide a bridge between the lymphatic system distal and proximal to the lymph node dissection. There is a lack of consensus about the necessity of an additional vascular anastomosis for the transplanted lymph nodes. A systematic literature search in Cochrane Library database CENTRAL, MEDLINE, and EMBASE of animal studies using lymph node transplantation with and without additional vascularization was performed in March 2016. The strategy used for the search was: ((“Models, Animal”[Mesh]) AND ((“Lymphedema”[Mesh]) OR “Lymph Nodes”[Mesh]) OR “Lymph Node Excision”[Mesh])) AND ((vascularized lymph node transfer) OR ((non‐vascularized lymph node transfer) OR lymph node graft)). The primary outcomes were: survival of transplanted lymph node and lymphatic vessel regeneration. Sixteen studies were included. Vascularization and the use of growth factors were significantly associated with lymph node survival. Lymphatic vessels regeneration was independent from vascularization. According to the results of the current study, additional vascular anastomosis might improve the transplanted lymph node survival. Further studies in both experimental and clinical setting are needed in order to support it. J. Surg. Oncol. 2017;115:32–36. © 2016 Wiley Periodicals, Inc.
Characterization of the pigment fraction in sweet bell peppers (Capsicum annuum L.) harvested at green and overripe yellow and red stages by offline multidimensional convergence chromatography/liquid chromatography–mass spectrometry
Authors: Bonaccorsi Ivana , Cacciola Francesco , Utczas Margita , Inferrera Veronica , Giuffrida Daniele , Donato Paola , Dugo Paola , Mondello Luigi
Published: July 2016

Offline multidimensional supercritical fluid chromatography combined with reversed‐phase liquid chromatography was employed for the carotenoid and chlorophyll characterization in different sweet bell peppers (Capsicum annuum L.) for the first time. The first dimension consisted of an Acquity HSS C18 SB (100 × 3 mm id, 1.8 μm particles) column operated with a supercritical mobile phase in an ultra‐performance convergence chromatography system, whereas the second dimension was performed in reversed‐phase mode with a C30 (250 × 4.6 mm id, 3.0 μm particles) stationary phase combined with photodiode array and mass spectrometry detection. This approach allowed the determination of 115 different compounds belonging to chlorophylls, free xanthophylls, free carotenes, xanthophyll monoesters, and xanthophyll diesters, and proved to be a significant improvement in the pigments determination compared to the conventional one‐dimensional liquid chromatography approach so far applied to the carotenoid analysis in the studied species. Moreover, the present study also aimed to investigate and to compare the carotenoid stability and composition in overripe yellow and red bell peppers collected directly from the plant, thus also evaluating whether biochemical changes are linked to carotenoid degradation in the nonclimacteric investigated fruits, for the first time.
Simultaneous quantitation and comparison of eight components in Jiao‐ai decoction and Si‐wu decoction by ultra high performance liquid chromatography with triple quadrupole tandem mass spectrometry
Authors: Yao Weifeng , Li Hui , Liu Qinan , Gao Ye , Dai Jin , Bao Beihua , Zhang Li , Ding Anwei , Tang Yuping , Duan Jinao
Published: July 2016

An ultra high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry method has been established to evaluate the variations of multiple components of Chinese herbal preparations, Jiao‐ai decoction and Si‐wu decoction, through the simultaneous determination of eight major active compounds with a huge difference in the level of content. Chromatographic separation was achieved on a Waters Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) with a mobile phase consisting of acetonitrile (0.1% formic acid) and water (0.1% formic acid) under gradient elution. A triple quadrupole tandem mass spectrometer was operated in positive and negative ionization modes, respectively, with multiple reaction monitoring for the detection of the eight compounds. All calibration curves showed excellent linear regressions (r > 0.99) within the test range. The precision, repeatability, and stability of the eight compounds were below 5.0% in terms of relative standard deviation. The recoveries were 97.0–102.4% with a relative standard deviation of 1.21–3.65% for all samples. In conclusion, a rapid, sensitive, precise, accurate, and reliable method has been developed for the simultaneous detection of eight active compounds in the pharmaceutical samples of Jiao‐ai decoction and Si‐wu decoction, which can be applied for the multicomponent comparison and further quality control.
Novel use of non‐ablative fractional photothermolysis for café‐au‐lait macules in darker skin types
Authors: Balaraman Brundha , Ravanfar‐Jordan Parisa , Friedman Paul M.
Published: July 2016

Importance

The removal of café‐au‐lait macules (CALMs) in patients with darker skin phototypes poses a significant challenge due to limited available therapeutic options and increased risk of adverse effects, including permanent scarring and further dyspigmentation. Herein, we demonstrate the novel use of non‐ablative fractional photothermolysis for the safe removal of CALMs in individuals with Fitzpatrick skin type (FST) IV–V.

Observations

Retrospective analysis of four patients (FST IV–V) with CALMs revealed that three of these patients had greater than 50% clearance after multiple treatment sessions with the non‐ablative fractional 1,550‐nm erbium‐doped fiber laser.

Conclusions and Relevance

This report demonstrates the utility and safety of non‐ablative fractional resurfacing in the treatment of CALMs in darker skin phototypes. Lasers Surg. Med. 49:84–87, 2017. © 2016 Wiley Periodicals, Inc.
Enhancement of light absorption by blood to Nd:YAG laser using PEG‐modified gold nanorods
Authors: Xing Linzhuang , Li Dong , Chen Bin , Dai Yuze , Wu Wenjuan , Wang Guoxiang
Published: July 2016

Background and Objective

On the basis of the principle of selective photothermolysis, laser therapy has been the most effective treatment strategy for Port‐wine stains (PWSs) caused by the expansion of dermal capillaries. Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser at 1064 nm wavelength has great potential for deeply buried PWS, although its application is limited because of its weak absorption by blood. The purpose of this study is to investigate the effect of PEG‐modified gold nanorods (NRs) on the blood absorption enhancement for Nd:YAG laser.

Materials and Methods

PEG‐modified gold nanorods (NRs) were synthesized via the seeded growth method. Then, the effect of PEG‐modified gold NRs on blood light absorbance was investigated through adding different concentration of PEG‐modified gold NRs to 1 ml of blood at room temperature. Finally, the optical properties of whole mice blood with or without PEG‐modified gold NRs under slow heating were investigated.

Results

The average length and width of PEG‐modified gold NRs are 79.5 ± 10.5 and 13.5 ± 0.9 nm, respectively, with the aspect ratio of 5.89, and a strong absorption peak exists at ∼1050 nm in the near‐infrared range. A linear correlation between the blood absorbance at 1064 nm and the amount of PEG‐modified gold NRs was obtained. The absorbance at 1064 nm increased 17.6, 33.0, 48.3, and 65.4 times when 0.4, 0.8, 1.2, and 1.6 mg of PEG‐modified gold NRs was added to 1 ml of blood at room temperature, respectively. After adding 0.8 mg of PEG‐modified gold NRs to 1 ml of blood, blood absorbance at 1064 nm at different temperatures increased by an average of 24.0 times. After intravenously injecting PEG‐modified gold NRs (0.87 mg/ml) into Sprague–Dawley mice, the blood absorbance at 1064 nm increased from 0.014 to 0.5.

Conclusion

Our findings suggest that PEG‐modified gold NRs injection is an efficient way to enhance light absorption by blood to Nd:YAG laser. Lasers Surg. Med. 48:790–803, 2016. © 2016 Wiley Periodicals, Inc.
Achievement of Release Mode under Combinational Stimuli by Acid and Reduction for Reduced Adverse Effect in Antitumor Efficacy
Authors: Song Meifang , Xue Yanan , Lin Xiao , Xia Xiaoyang , Chen Lidi , Zhang Liujie , Yu Bo , Long Sihui , Huang Shiwen , Yu Faquan
Published: July 2016

To reduce the adverse effect in antitumor therapy, a superparamagnetic doxorubicin (DOX)‐loaded nanogel with the release mode under the combinational stimuli present in intracellular environments of solid tumors is presented. Dextran is first modified to involve both thiol groups and carboxyl groups. The dextran derivative is then covalently coupled with previously thiolated and aminated magnetic iron oxide nanoparticles through both the linkage of disulfide bond and electrostatic interaction. Upon the optimal conditions, a nanogel is fabricated via the dual cross‐linking. The nanogel features the targeting release under combinational stimuli by acid and reduction environment with low release level in healthy tissues. In vitro release profiles reveal these release modes as expected. Cytotoxicity assay exhibits a much lower toxicity of the DOX‐loaded nanogel to COS‐7 cells than free DOX. Prussian blue staining and confocal laser scanning microscopy observation reveal the cellular uptake and subcellular release in nuclei of the nanogel. In vivo study exhibits that the nanogel presented 67.3% of inhibition rate of tumor growth and a healthy appearance. The present nanogel expresses high efficacy with low systemic adverse effect and is thus believed to offer a promising candidate for highly effective cancer therapy.

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Nanomarketing: A New Frontier for Neuromarketing
Authors: Mileti Antonio , Guido Gianluigi , Prete M. Irene
Published: July 2016

The emergence of neuromarketing has significantly advanced conventional marketing research, illuminating how unconscious responses and emotions impact consumers’ perceptions and decision‐making processes. Neuromarketing is founded on the assumption that individual sensory and motor systems can be identified in specific networks of brain cells, the observation of which can reveal the unconscious or emotional characteristics of consumer decision making. Yet, neuromarketing technologies present several limitations that can impede the extension and validation of their application: (i) the development of high‐priced and time‐restricted neuroimaging experiments; (ii) the employment of large and immovable devices confined to artificial laboratory environments; (iii) the use of a single neuroimaging technology at a time (usually the functional magnetic resonance imaging); (iv) the use of a single nonneuroimaging device at a time; and (v) the potentially unethical manipulation of research subjects. One way to address these issues involves nanotechnologies, which present a ground‐breaking opportunity for neuromarketing research. These technologies encompass not only the traditional notion of structures, devices, and systems created by limiting shape and size at the nanometer scale, but also the new miniaturized tools based on one or more nanocomponents. The integration of neuromarketing and nanotechnologies could start a new field of research, which is termed here nanomarketing. Nanomarketing makes it possible to: (i) carry out noninvasive and nonintrusive experiments in shopping places; (ii) monitor consumers’ mental processes in real time; (iii) combine different technologies to corroborate results obtained by different neuroscientific tools; (iv) integrate neurophysiological field indicators with laboratory neuroimaging results; and (v) highlight ethical issues raised by the use of these novel, portable, and easy‐to‐use nanodevices. This study thus has a twofold aim: (i) investigating both the limitations and opportunities, for researchers and practitioners, that accompany the miniaturization process and application of nanotechnologies to neuromarketing; and (ii) providing a critical review of the aforementioned limitations, highlighting the theoretical and managerial implications, and summarizing the discussion for future research.