bluuebunny/crossref_metadata_2025 huggingface dataset:
RuIII Complexes for Anticancer Therapy: The Importance of Being Nucleolipidic
Authors: Riccardi Claudia , Musumeci Domenica , Irace Carlo , Paduano Luigi , Montesarchio Daniela
Published: December 2016

Ruthenium complexes are attracting increasing attention as second‐generation metal‐based anticancer agents, with NAMI‐A and KP1019 as the major representatives of this class having undergone clinical trials. Our recent interest has been focused on the synthesis and characterization of new amphiphilic derivatives of nucleosides (nucleolipids). These compounds have been selected as core scaffolds linked to RuIII complexes and capable of self‐assembly into stable nanostructures in aq. solutions so to transport the metal ions efficiently into the cell. Through the use of ribo‐ and deoxyribonucleosides as starting building blocks, a mini‐library of nucleolipidic RuIII complexes decorated with diverse hydrophilic and lipophilic chains and incorporating the NAMI‐A analogue AziRu has been prepared. When co‐aggregated with biocompatible lipids, these RuIII‐containing nucleolipids proved to be stable for months under physiological conditions. Detailed microstructural characterization, carried out by a combined approach including different physico‐chemical techniques, allowed their stability, size and shape to be determined. Tested on a panel of human and non‐human cells, all of the studied RuIII complexes showed potent in vitro anticancer activity, significantly higher than that of NAMI‐A‐like analogues, and minimal toxicity. Here we summarize the design and synthetic procedures developed to prepare these new Ru‐containing candidate drugs, discussing the beneficial effects achievable through exploiting nucleolipid appendages in the delivery of metal‐based drugs.
High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study
Authors: Rusiecki Jennifer A. , Beane Freeman Laura E. , Bonner Matthew R. , Alexander Melannie , Chen Ligong , Andreotti Gabriella , Barry Kathryn H. , Moore Lee E. , Byun Hyang‐Min , Kamel Freya , Alavanja Michael , Hoppin Jane A. , Baccarelli Andrea
Published: December 2016

Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE‐1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p‐interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE‐1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non‐specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE‐1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19–29, 2017. © 2016 Wiley Periodicals, Inc.
Sustainion Imidazolium‐Functionalized Polymers for Carbon Dioxide Electrolysis
Authors: Kutz Robert B. , Chen Qingmei , Yang Hongzhou , Sajjad Syed D. , Liu Zengcai , Masel I. Richard
Published: December 2016

CO2 electrolysis is a key step in CO2 conversion into fuels and chemicals as a way of mitigating climate change. We report the synthesis and testing of a series of new anion‐conductive membranes (tradenamed Sustainion™) for use in CO2 electrolysis. These membranes incorporate the functional character of imidazolium‐based ionic liquids as co‐catalysts in CO2 reduction into a solid membrane with a styrene backbone. We find that the addition of an imidazolium group onto the styrene side‐chains increases the selectivity of the reaction from approximately 25 % to approximately 95 %. The current at 3 V is increased by a factor of 14. So far we have been able to tune these parameters to achieve stable cells that provide current densities higher than 100 mA cm−2 at 3 V cell potential with a CO product selectivity over 98 %. Stable performance was observed for 6 months of continuous operation (>150 000 000 turnovers). These results demonstrate that imidazolium polymers are ideal membranes for CO2 electrolysis.
A window of opportunity for climate‐change adaptation: easing tree mortality by reducing forest basal area
Authors: Bradford John B , Bell David M
Published: December 2016

Increasing aridity as a result of climate change is expected to exacerbate tree mortality. Reducing forest basal area – the cross‐sectional area of tree stems within a given ground area – can decrease tree competition, which may reduce drought‐induced tree mortality. However, neither the magnitude of expected mortality increases, nor the potential effectiveness of basal area reduction, has been quantified in dryland forests such as those of the drought‐prone Southwest US. We used thousands of repeatedly measured forest plots to show that unusually warm and dry conditions are related to high tree mortality rates and that mortality is positively related to basal area. Those relationships suggest that while increasing high temperature extremes forecasted by climate models may lead to elevated tree mortality during the 21st century, future tree mortality might be partly ameliorated by reducing stand basal area. This adaptive forest management strategy may provide a window of opportunity for forest managers and policy makers to guide forest transitions to species and/or genotypes more suited to future climates.
Oil sands and the marine environment: current knowledge and future challenges
Authors: Green Stephanie J , Demes Kyle , Arbeider Michael , Palen Wendy J , Salomon Anne K , Sisk Thomas D , Webster Margot , Ryan Maureen E
Published: December 2016

The environmental consequences of bitumen extraction from oil sands deposits are at the center of North American natural resource and energy policy debate, yet impacts on ocean environments have received little attention. Using a quantitative framework, we identify knowledge gaps and research needs related to the effects of oil sands development on marine biota. Fifteen sources of stress and disturbance – varying greatly in spatial and temporal scale – are generated via two pathways: (1) the coastal storage and oceanic transport of bitumen products, and (2) the contribution of industry‐derived greenhouse gases to climate change in the ocean. Of highest research priority are the fate, behavior, and biological effects of bitumen in the ocean. By contrast, climate‐change impacts are scientifically well established but not considered in key regulatory processes. Most stressors co‐occur and are generated by other industries, yet cumulative effects are so far unaccounted for in decision making associated with new projects. Our synthesis highlights priority research needed to inform future energy development decisions, and opportunities for policy processes to acknowledge the full scope of potential and realized environmental consequences.
Longitudinal imaging reveals subhippocampal dynamics in glutamate levels associated with histopathologic events in a mouse model of tauopathy and healthy mice
Authors: Crescenzi Rachelle , DeBrosse Catherine , Nanga Ravi P. R. , Byrne Matthew D. , Krishnamoorthy Guruprasad , D'Aquilla Kevin , Nath Hari , Morales Knashawn H. , Iba Michiyo , Hariharan Hari , Lee Virginia M. Y. , Detre John A. , Reddy Ravinder
Published: December 2016

Tauopathies are neurodegenerative disorders characterized by abnormal intracellular aggregates of tau protein, and include Alzheimer's disease, corticobasal degeneration, frontotemporal dementia, and traumatic brain injury. Glutamate metabolism is altered in neurodegenerative disorders manifesting in higher or lower concentrations of glutamate, its transporters or receptors. Previously, glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) demonstrated that glutamate levels are reduced in regions of synapse loss in the hippocampus of a mouse model of late‐stage tauopathy. We performed a longitudinal GluCEST imaging experiment paired with a cross‐sectional study of histologic markers of tauopathy to determine whether (1) early GluCEST changes are associated with synapse loss before volume loss occurs in the hippocampus, and whether (2) subhippocampal dynamics in GluCEST are associated with histopathologic events related to glutamate alterations in tauopathy. Live imaging of the hippocampus in three serial slices was performed without exogenous contrast agents, and subregions were segmented based on a k‐means cluster model. Subregions of the hippocampus were analyzed (cornu ammonis CA1, CA3, dentate gyrus DG, and ventricle) in order to associate local MRI‐observable changes in glutamate with histological measures of glial cell proliferation (GFAP), synapse density (synaptophysin, VGlut1) and glutamate receptor (NMDA–NR1) levels. Early differences in GluCEST between healthy and tauopathy mice were measured in the CA1 and DG subregions (30% reduction, P ≤ 0.001). Synapse density was also significantly reduced in every subregion of the hippocampus in tauopathy mice by 6 months. Volume was not significantly reduced in any subregion until 13 months. Further, a gradient in glutamate levels was observed in vivo along hippocampal axes that became polarized as tauopathy progressed. Dynamics in hippocampal glutamate levels throughout lifetime were most closely correlated with combined changes in synaptophysin and GFAP, indicating that GluCEST imaging may be a surrogate marker of glutamate concentration in glial cells and at the synaptic level. © 2016 Wiley Periodicals, Inc.
Activin‐SMAD signaling is required for maintenance of porcine iPS cell self‐renewal through upregulation of NANOG and OCT4 expression
Authors: Yang Fan , Wang Ning , Wang Yaxian , Yu Tong , Wang Huayan
Published: December 2016

Porcine induced pluripotent stem cells (piPSCs) retain the enormous potential for farm animal reproduction and translational medicine, and have been reported by many laboratories worldwide. Some piPSC lines were bFGF‐dependence and showed mouse EpiSC‐like morphology; other lines were LIF‐dependence and showed mouse ESC‐like morphology. Metastable state of piPSC line that required both LIF and bFGF was also reported. Because bona fide pig embryonic stem cells were not available, uncovering piPSC state‐specific regulatory circuitries was the most important task. In this study, we explored the function of Activin‐SMAD signaling pathway and its downstream activated target genes in piPSCs. Transcriptome analysis showed that genes involved in Activin‐SMAD signaling pathway were evidently activated during porcine somatic cell reprogramming, regardless piPSCs were LIF‐ or bFGF‐dependent. Addition of Activin A and overexpression of SMAD2/3 significantly promoted expressions of porcine NANOG and OCT4, whereas inhibition of Activin‐SMAD signaling by SB431542 and SMAD7 reduced NANOG and OCT4 expressions, and induced piPSCs differentiation exiting from pluripotent state. Our data demonstrate that activation of Activin‐SMAD signaling pathway by addition of Activin A in culture medium is necessary for maintenance of self‐renewal in porcine pluripotent stem cells.
Bevacizumab chemotherapy for management of pulmonary and laryngotracheal papillomatosis in a child
Authors: Zur Karen B. , Fox Elizabeth
Published: December 2016

Recurrent laryngeal papillomatosis (RRP) can be a devastating condition for a child to endure, and pulmonary involvement may have terminal consequences. Adjuvant therapies have been trialed and reported over the years; however, these chemotherapy options have not been successful. Bevacizumab (Avastin, Genetech Inc., South San Francisco, CA) is a vascular endothelial factor (VEGF) inhibitor that has shown promise in the management of papillomatosis. Most research has focused on intralesional injections of this antiangiogenic drug. The systemic use of bevacizumab is not as well described. This is a case report of a 12‐year‐old female diagnosed with severe laryngotracheal papillomatosis near birth who underwent a tracheostomy tube placement at 1 year of age. She required weekly debridements to prevent tracheal obstruction. When lung involvement was diagnosed at 1 year of age, cidofovir was started intravenously. Over the course of the past 10 years, the patient was managed with celecoxib (Celebrex, Pfizer, New York, NY), anti‐reflux medications, zithromycin, propranolol, Gardasil (Merck and Co., Kenilworth, NJ), and a 7‐year course of interferon‐alpha. Intravenous bevacizumab was started when the patient's pulmonary status deteriorated. There was remarkable improvement in her laryngotracheal disease within 6 weeks of therapy. Following 3 months of bevacizumab, the patient's disease was completely resolved at the laryngeal level and nearly gone in the trachea, and she was decannulated. A computed scan was performed following 5 months of intravenous bevacizumab, and the pulmonary RRP nodules completely resolved. The patient had no major or minor complication from the chemotherapy to date. Systemic Bevacizumab is a promising modality of adjuvant therapy for significant papillomatosis. Laryngoscope, 127:1538–1542, 2017
Beyond the Usefulness of Branded Applications: Insights from Consumer–Brand Engagement and Self‐construal Perspectives
Authors: Fang Yu‐Hui
Published: December 2016

Branded mobile applications (apps) present one of the most promising opportunities for marketers to reach current and potential customers, sell products or services, and facilitate customer engagement with brands. This study aims to explore how branded apps influence consumers’ brand repurchase intention and continuance usage intention. Integrating the utilitarian view from information systems research and the view of consumer–brand engagement from marketing research, a complementary engagement path alongside the utilitarian path was devised and tested in order to elucidate consumer perceptions toward branded apps. Independent self‐construal and interdependent self‐construal moderate relationships along the utilitarian path and engagement path, respectively. Data collected from 637 respondents support most of the proposed hypotheses. Results show that the engagement path has more influence on continuance intention and equal influence on repurchase intention when compared to the utilitarian path. Findings show that apps users have different thoughts along each of the two paths, depending on their self‐construal. The study's findings also provide app designers and marketers with new perspectives on how to better design branded apps.
Digitalization Capabilities as Enablers of Value Co‐Creation in Servitizing Firms
Authors: Lenka Sambit , Parida Vinit , Wincent Joakim
Published: December 2016

As manufacturing companies pursue a servitization strategy, they are increasingly relying on developing digitalization capabilities to interact and co‐create value with their customers. However, many lack an understanding of what constitutes digitalization capabilities and how they can create value with customers. To address these questions, the study builds on qualitative data from four industrial manufacturing firms to conceptualize three underlying subcomponents of digitalization capabilities, namely, intelligence capability, connect capability, and analytic capability. The study identifies and explains how digitalization capabilities enable value co‐creation with customers through perceptive and responsive mechanisms. This study contributes to the servitization literature by showcasing how digitalization capabilities are enabling value co‐creation in a business‐to‐business context.
Effect of NR5A2 inhibition on pancreatic cancer stem cell (CSC) properties and epithelial‐mesenchymal transition (EMT) markers
Authors: Luo Zhaofan , Li Yanan , Zuo Mingxin , Liu Chang , Yan Dong , Wang Huamin , Li Donghui
Published: December 2016

NR5A2 (aka LRH‐1) has been identified as a pancreatic cancer susceptibility gene with missing biological link. This study aims to demonstrate expression and potential role of NR5A2 in pancreatic cancer. NR5A2 expression was quantified in resected pancreatic ductal adenocarcinomas and the normal adjacent tissues of 134 patients by immunohistochemistry. The intensity and extent of NR5A2 staining was quantified and analyzed in association with overall survival (OS). The impact of NR5A2 knockdown on pancreatic cancer stem cell (CSC) properties and epithelial‐mesenchymal transition (EMT) markers was examined in cancer cells using RT‐PCR and Western Blot. NR5A2 was overexpressed in pancreatic tumors, the IHC‐staining H score (mean ± SE) was 96.4 ± 8.3 in normal versus 137.9 ± 8.2 in tumor tissues (P < 0.0001). Patients with a higher NR5A2 expression had a median survival time 18.4 months compared to 23.7 months for those with low IHC H scores (P = 0.019). The hazard ratio of death (95% confidence interval) was 1.60 (1.07‐2.41) after adjusting for disease stage and tumor grade (P = 0.023). NR5A2 was highly expressed in pancreatic cancer sphere forming cells. NR5A2‐inhibition by siRNA was associated with reduced sphere formation and decreased levels of CSCs markers NANOG, OCT4, LIN28B, and NOTCH1. NR5A2 knockdown also resulted in reduced expression of FGB, MMP2, MMP3, MMMP9, SNAIL, and TWIST, increased expression of epithelial markers E‐cadherin and β‐catenin, and a lower expression of mesenchymal marker Vimentin. Taken together, our findings suggest that NR5A2 could play a role in CSC stemness and EMT in pancreatic cancer, which may contribute to the worse clinical outcome.
Chemopreventive potential of in vitro fermented nuts in LT97 colon adenoma and primary epithelial colon cells
Authors: Schlörmann Wiebke , Lamberty Julia , Lorkowski Stefan , Ludwig Diana , Mothes Henning , Saupe Christian , Glei Michael
Published: December 2016

Due to their beneficial nutritional profile the consumption of nuts contributes to a healthy diet and might reduce colon cancer risk. To get closer insights into potential mechanisms, the chemopreventive potential of different in vitro fermented nut varieties regarding the modulation of genes involved in detoxification (CAT, SOD2, GSTP1, GPx1) and cell cycle (p21, cyclin D2) as well as proliferation and apoptosis was examined in LT97 colon adenoma and primary epithelial colon cells. Fermentation supernatants (FS) of nuts significantly induced mRNA expression of CAT (up to 4.0‐fold), SOD2 (up to 2.5‐fold), and GSTP1 (up to 2.3‐fold), while GPx1 expression was significantly reduced by all nut FS (0.8 fold on average). Levels of p21 mRNA were significantly enhanced (up to 2.6‐fold), whereas all nut FS significantly decreased cyclin D2 expression (0.4‐fold on average). In primary epithelial cells, expression of CAT (up to 3.5‐fold), GSTP1 (up to 3.0‐fold), and GPx1 (up to 3.9‐fold) was increased, whereas p21 and cyclin D2 levels were not influenced. Nut FS significantly inhibited growth of LT97 cells and increased levels of early apoptotic cells (8.4% on average) and caspase 3 activity (4.6‐fold on average), whereas caspase 3 activity was not modulated in primary colon cells. The differential modulation of genes involved in detoxification and cell cycle together with an inhibition of proliferation and induction of apoptosis in adenoma cells might contribute to chemopreventive effects of nuts regarding colon cancer.
Peroxisome proliferator‐activated receptor‐β/δ inhibits human neuroblastoma cell tumorigenesis by inducing p53‐ and SOX2‐mediated cell differentiation
Authors: Yao Pei‐Li , Chen Liping , Dobrzański Tomasz P. , Zhu Bokai , Kang Boo‐Hyon , Müller Rolf , Gonzalez Frank J. , Peters Jeffrey M.
Published: December 2016

Neuroblastoma is a common childhood cancer typically treated by inducing differentiation with retinoic acid (RA). Peroxisome proliferator‐activated receptor‐β/δ, (PPARβ/δ) is known to promote terminal differentiation of many cell types. In the present study, PPARβ/δ was over‐expressed in three human neuroblastoma cell lines, NGP, SK‐N‐BE(2), and IMR‐32, that exhibit high, medium, and low sensitivity, respectively, to retinoic acid‐induced differentiation to determine if PPARβ/δ and retinoic acid receptors (RARs) could be jointly targeted to increase the efficacy of treatment. All‐trans‐RA (atRA) decreased expression of SRY (sex determining region Y)‐box 2 (SOX2), a stem cell regulator and marker of de‐differentiation, in NGP and SK‐N‐BE(2) cells with inactive or mutant tumor suppressor p53, respectively. However, atRA did not suppress SOX2 expression in IMR‐32 cells carrying wild‐type p53. Over‐expression and/or ligand activation of PPARβ/δ reduced the average volume and weight of ectopic tumor xenografts from NGP, SK‐N‐BE(2), or IMR‐32 cells compared to controls. Compared with that found with atRA, PPARβ/δ suppressed SOX2 expression in NGP and SK‐N‐BE(2) cells and ectopic xenografts, and was also effective in suppressing SOX2 expression in IMR‐32 cells that exhibit higher p53 expression compared to the former cell lines. Combined, these observations demonstrate that activating or over‐expressing PPARβ/δ induces cell differentiation through p53‐ and SOX2‐dependent signaling pathways in neuroblastoma cells and tumors. This suggests that combinatorial activation of both RARα and PPARβ/δ may be suitable as an alternative therapeutic approach for RA‐resistant neuroblastoma patients.
Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice
Authors: Rusli Fenni , Lute Carolien , Boekschoten Mark V. , van Dijk Miriam , van Norren Klaske , Menke Aswin L. , Müller Michael , Steegenga Wilma T.
Published: December 2016

Scope

Calorie restriction (CR) has been shown to extend life‐ and health‐span in model species. For most humans, a life‐long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can (1) provide long‐term beneficial effects and (2) counteract diet‐induced obesity in male aging mice.

Methods and results

In this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate‐fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight, and liver health markers in 24‐month‐old male mice. Hepatic gene expression profiles of INT‐exposed animals appeared much more comparable to CR‐ than to MF‐exposed mice. At 12 months of age, a subgroup of MF‐exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24‐month‐old diet switch mice were highly similar to the INT‐exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.

Conclusion

Weekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.
Specific joint angle dependency of voluntary activation during eccentric knee extensions
Authors: Doguet Valentin , Rivière Valentin , Guével Arnaud , Guilhem Gaël , Chauvet Lucile , Jubeau Marc
Published: December 2016

Introduction

This study compared voluntary activation during isometric, concentric, and eccentric maximal knee extensions at different joint angles.

Methods

Fifteen participants performed isometric, concentric, and eccentric protocols (9 contractions each). For each protocol, the central activation ratio (CAR) was randomly measured at 50°, 75°, or 100° of knee joint angle (0° = full knee extension) using superimposed supramaximal paired nerve stimulations during contractions.

Results

CAR increased between 50° and 100° during isometric (93.6 ± 3.1 vs. 98.5 ± 1.4%), concentric (92.4 ± 5.4 vs. 99.2 ± 1.2%), and eccentric (93.0 ± 3.5 vs. 96.6 ± 3.8%) contractions. CAR was lower during eccentric than both isometric and concentric contractions at 75° and 100°, but similar between contraction types at 50°.

Conclusions

The ability to activate muscle maximally is impaired during eccentric contractions compared with other contraction types at 75° and 100°, but not at 50°. Muscle Nerve 56: 750–758, 2017
Disparity in neural and subjective responses to food images in women with obesity and normal‐weight women
Authors: Carbine Kaylie A. , Larson Michael J. , Romney Lora , Bailey Bruce W. , Tucker Larry A. , Christensen William F. , LeCheminant James D.
Published: December 2016

Objective

Self‐reports tend to differ from objective measurements of food intake, particularly in adults with obesity; however, no studies have examined how neural responses to food (an objective measure) and subjective ratings of food differ by BMI status. This study tested normal‐weight women (NWW) and women with obesity (OBW) for group differences in neural indices of attention towards food pictures, subjective ratings of these pictures, and the disparity between objective and subjective measurements.

Methods

Twenty‐two NWW (21.8 ± 1.7 kg/m2) and 22 OBW (37.0 ± 5.7 kg/m2) viewed food and flower pictures while late positive potential amplitude, an event‐related potential, was recorded. Participants rated pictures for arousal and valence.

Results

Late positive potential amplitude was larger toward food than flower pictures. OBW self‐reported flower pictures as more pleasant than food; NWW showed no difference for pleasantness. There were no significant main effects or interactions for arousal. Standardized scores showed that only on subjective, but not objective, measures did OBW compared with NWW disproportionately indicate food pictures as less pleasant than flowers.

Conclusions

Compared with NWW, OBW showed larger discrepancies between neural and subjective reports of attention towards food. Inaccurate self‐reports of attention towards food may reduce the efficiency of health interventions.
Poly(lactic acid)‐based nanocomposites
Authors: Basu Arijit , Nazarkovsky Michael , Ghadi Rohan , Khan Wahid , Domb Abraham J.
Published: December 2016

Classic plastics accumulate in nature causing environmental pollution, yet as a counterbalance they benefit society in many ways. They are versatile, cost‐effective, and can be tailored to have desired properties. The global environment has led to the fabrication of commodity plastics from environmentally degradable polymers. Poly(lactic acid) (PLA) is the most promising among the environmentally friendly polymers available. PLA‐based plastics have mechanical, thermal, and transparency similar to traditional plastics, and they can be molded and fabricated using the same equipment and procedures. Their material properties are enhanced through nanocomposites, compatibilizers, plasticizers, and other fillers (flame retardant, ultraviolet filter, etc.). This review summarizes mass production techniques and property reinforcements (focusing on nanocomposites and plasticizers) for PLA‐based plastics for commodity use. Copyright © 2016 John Wiley & Sons, Ltd.
Compliance with Procalcitonin Algorithm Antibiotic Recommendations for Patients in Medical Intensive Care Unit
Authors: Ammar Abdalla A. , Lam Simon W. , Duggal Abhijit , Neuner Elizabeth A. , Bass Stephanie N. , Guzman Jorge A. , Wang Xiao‐Feng , Han Xiaozhen , Bauer Seth R.
Published: December 2016

Study Objectives

To describe compliance with antibiotic recommendations based on a previously published procalcitonin (PCT)‐guided algorithm in clinical practice, to comparePCTalgorithm compliance rates betweenPCTassays ordered in the antibiotic initiation setting (PCTconcentration measured less than 24 hours after antibiotic initiation or before antibiotic initiation) with those in the antibiotic continuation setting (PCTconcentration measured 24 hours or more after antibiotic initiation), and to evaluate patient‐ andPCT‐related factors independently associated with algorithm compliance in patients in the medical intensive care unit (MICU).

Design

Single‐center retrospective cohort study.

Setting

Large MICUin a tertiary care academic medical center.

Patients

A total of 527 adults admitted to the MICUunit over a 2‐year period (November 1, 2011–October 31, 2013) who had a total of 957PCTassays performed.PCTassays whose results were determined in the MICUwere allocated retrospectively to either the initiation setting cohort or the continuation setting cohort based on timing of thePCTassay.

Measurements and Main Results

EachPCTassay was treated as a separate episode. Antibiotic regimens were compared between the 24‐hour periods before and after the results of eachPCTassay and evaluated against an algorithm to determine compliance. Clinical, laboratory,PCT‐related, and microbiologic variables were assessed during the 24‐hour period after thePCTassay results to determine their influence onPCTalgorithm compliance. A larger proportion ofPCTepisodes occurred in the initiation setting (540 [56.4%]) than in the continuation setting (417 [43.5%]). Overall, compliance withPCTalgorithm recommendations was low (48.5%) and not significantly different between the initiation setting and the continuation setting (49.1% vs 47.7%, p=0.678). No patient‐related orPCT‐related factors were independently associated withPCTalgorithm compliance on multivariable logistic regression.

Conclusion

Compliance withPCTalgorithm antibiotic recommendations in both the initiation and continuation settings was lower than that reported in published randomized studies. No factors were independently associated withPCTalgorithm compliance. Institutions usingPCTassays to guide antibiotic use should assess compliance with algorithm antibiotic recommendations. Inclusion of a formalized antimicrobial stewardship program along with aPCT‐guided algorithm is highly recommended.
Contribution of proteomics to our understanding of periodontal inflammation
Authors: Bostanci Nagihan , Bao Kai
Published: December 2016

Periodontal diseases entail the inflammatory destruction of the tooth supporting (periodontal) tissues and may eventually lead tooth loss. Severe periodontal disease (or periodontitis) affects approximately 10% of the global population. Periodontitis not only severely deteriorates people's quality of life by impairing the dentition but also adversely affects systemic health. The present review paper highlights the advancements made in our understanding of inflammatory periodontal diseases by the use of proteomic technologies. The novel information comes from both clinical and in vitro studies, the former investigating samples of saliva and gingival crevicular fluid in patients with periodontal disease, whereas the latter utilizing host cell/tissue–bacteria/biofilm interaction models of relevance to periodontal disease. A broad range of information on protein profiles can be obtained, which is useful, however needs to be individually validated by golden‐standard sensitive antibody‐based methods. The development of the employed proteomic platform technologies will help complete in breadth and in depth the protein profiles of periodontal disease. The so‐far collected data highlights the importance of moving away from the concept of a handful of proteins being responsible for the pathogenesis of the disease, and start to accept that there are “signatures” of proteins and associated pathways that lead to this.
Modular toxin from the lynx spider Oxyopes takobius: Structure of spiderine domains in solution and membrane‐mimicking environment
Authors: Nadezhdin Kirill D. , Romanovskaia Daria D. , Sachkova Maria Y. , Oparin Peter B. , Kovalchuk Sergey I. , Grishin Eugene V. , Arseniev Alexander S. , Vassilevski Alexander A.
Published: December 2016

We have recently demonstrated that a common phenomenon in evolution of spider venom composition is the emergence of so‐called modular toxins consisting of two domains, each corresponding to a “usual” single‐domain toxin. In this article, we describe the structure of two domains that build up a modular toxin named spiderine or OtTx1a from the venom of Oxyopes takobius. Both domains were investigated by solution NMR in water and detergent micelles used to mimic membrane environment. The N‐terminal spiderine domain OtTx1a‐AMP (41 amino acid residues) contains no cysteines. It is disordered in aqueous solution but in micelles, it assumes a stable amphiphilic structure consisting of two α‐helices separated by a flexible linker. On the contrary, the C‐terminal domain OtTx1a‐ICK (59 residues) is a disulfide‐rich polypeptide reticulated by five S–S bridges. It presents a stable structure in water and its core is the inhibitor cystine knot (ICK) or knottin motif that is common among single‐domain neurotoxins. OtTx1a‐ICK structure is the first knottin with five disulfide bridges and it represents a good reference for the whole oxytoxin family. The affinity of both domains to membranes was measured with NMR using titration by liposome suspensions. In agreement with biological tests, OtTx1a‐AMP was found to show high membrane affinity explaining its potent antimicrobial properties.
The presence of non‐native helical structure in the unfolding of a beta‐sheet protein MPT63
Authors: Kundu Amrita , Kundu Sangeeta , Chattopadhyay Krishnananda
Published: December 2016

MPT63, a major secreted protein from Mycobacterium tuberculosis, has been shown to have immunogenic properties and has been implicated in virulence. MPT63 is a β‐sandwich protein containing 11 β strands and a very short stretch of 310 helix. The detailed experimental and computational study reported here investigates the equilibrium unfolding transition of MPT63. It is shown that in spite of being a complete β‐sheet protein, MPT63 has a strong propensity toward helix structures in its early intermediates. Far UV‐CD and FTIR spectra clearly suggest that the low‐pH intermediate of MTP63 has enhanced helical content, while fluorescence correlation spectroscopy suggests a significant contraction. Molecular dynamics simulation complements the experimental results indicating that the unfolded state of MPT63 traverses through intermediate forms with increased helical characteristics. It is found that this early intermediate contains exposed hydrophobic surface, and is aggregation prone. Although MPT63 is a complete β‐sheet protein in its native form, the present findings suggest that the secondary structure preferences of the local interactions in early folding pathway may not always follow the native conformation. Furthermore, the Gly25Ala mutant supports the proposed hypothesis by increasing the non‐native helical propensity of the protein structure.
Does a long‐term orientation create value? Evidence from a regression discontinuity
Authors: Flammer Caroline , Bansal Pratima
Published: December 2016

Research summary: In this paper, we theorize and empirically investigate how a long‐term orientation impacts firm value. To study this relationship, we exploit exogenous changes in executives' long‐term incentives. Specifically, we examine shareholder proposals on long‐term executive compensation that pass or fail by a small margin of votes. The passage of such “close call” proposals is akin to a random assignment of long‐term incentives and hence provides a clean causal estimate. We find that the adoption of such proposals leads to (1) an increase in firm value and operating performance—suggesting that a long‐term orientation is beneficial to companies—and (2) an increase in firms' investments in long‐term strategies such as innovation and stakeholder relationships. Overall, our results are consistent with a “time‐based” agency conflict between shareholders and managers.

Managerial summary: This paper shows that corporate short‐termism is hampering business success. We show clear, causal evidence that imposing long‐term incentives on executives—in the form of long‐term executive compensation—improves business performance. Long‐term executive compensation includes restricted stocks, restricted stock options, and long‐term incentive plans. Firms that adopted shareholder resolutions on long‐term compensation experienced a significant increase in their stock price. This stock price increase foreshadowed an increase in operating profits that materialized after two years. We unpack the reasons for these improvements in performance, and find that firms that adopted these shareholder resolutions made more investments in R&D and stakeholder engagement, especially pertaining to employees and the natural environment. Copyright © 2016 John Wiley & Sons, Ltd.
There and back again: Can you compile that snapshot?
Authors: Tufano Michele , Palomba Fabio , Bavota Gabriele , Di Penta Massimiliano , Oliveto Rocco , De Lucia Andrea , Poshyvanyk Denys
Published: December 2016

A broken snapshot represents a snapshot from a project's change history that cannot be compiled. Broken snapshots can have significant implications for researchers, as they could hinder any analysis of the past project history that requires code to be compiled. Noticeably, while some broken snapshots may be observable in change history repositories (e.g., no longer available dependencies), some of them may not necessarily happen during the actual development. In this paper, we systematically study the compilability of broken snapshots in 219 395 snapshots belonging to 100 Java projects from the Apache Software Foundation, all relying on Maven as an automated build tool. We investigated broken snapshots from 2 different perspectives: (1) how frequently they happen and (2) likely causes behind them. The empirical results indicate that broken snapshots occur in most (96%) of the projects we studied and that they are mainly due to problems related to the resolution of dependencies. On average, only 38% of the change history of the analyzed systems is currently successfully compilable.
Curcuma treatment prevents cognitive deficit and alteration of neuronal morphology in the limbic system of aging rats
Authors: Vidal Blanca , Vázquez‐Roque Rubén A. , Gnecco Dino , Enríquez Raúl G. , Floran Benjamin , Díaz Alfonso , Flores Gonzalo
Published: December 2016

Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment. In this regard, there is a need to use alternative therapies that delay the onset of morphologies and behavioral characteristics of aging. Therefore, the objective of this study was to evaluate the effect of curcuma on cognitive processes and dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 and CA3 regions of the dorsal hippocampus, the dentate gyrus, and the basolateral amygdala (BLA) of aged rats. 18‐month‐old rats were administered curcuma (100 mg/kg) daily for 60 days. After treatment, recognition memory was assessed using the novel object recognition test. Curcuma‐treated rats showed a significant increase in the exploration quotient. Dendritic morphology was assessed by Golgi–Cox staining and followed by Sholl analysis. Curcuma‐treated rats showed a significant increase in dendritic spine density and dendritic length in pyramidal neurons of the PFC, the CA1 and CA3, and the BLA. The preservation of dendritic morphology was positively correlated with cognitive improvements. Our results suggest that curcuma induces modification of dendritic morphology in the aforementioned regions. These changes may explain how curcuma slows the aging process that has already begun in these animals, preventing deterioration in neuronal morphology of the limbic system and recognition memory.
Distribution of type I corticotropin‐releasing factor (CRF1) receptors on GABAergic neurons within the basolateral amygdala
Authors: Calakos Katina C. , Blackman Dakota , Schulz Alexandra M. , Bauer Elizabeth P.
Published: December 2016

The neuropeptide corticotropin‐releasing factor (CRF) plays a critical role in mediating anxiety‐like responses to stressors, and dysfunction of the CRF system has been linked to the etiology of several psychiatric disorders. Extra‐hypothalamic CRF can also modulate learning and memory formation, including amygdala‐dependent learning. The basolateral nucleus of the amygdala (BLA) contains dense concentrations of CRF receptors, yet the distribution of these receptors on specific neuronal subtypes within the BLA has not been characterized. Here, we quantified the expression of CRF receptors on three nonoverlapping classes of GABAergic interneurons: those containing the calcium‐binding protein parvalbumin (PV), and those expressing the neuropeptides somatostatin (SOM) or cholecystokinin (CCK). While the majority of PV+ neurons and roughly half of CCK+ neurons expressed CRF receptors, they were expressed to a much lesser extent on SOM+ interneurons. Knowledge of the distribution of CRF receptors within the BLA can provide insight into how manipulations of the CRF system modulate fear and anxiety‐like behaviors.
Lethal Repetition
Authors: Dyer Richard
Published: December 2016

Shifting the focus away from the US, which is often seen as the home of the serial killer, expression of characteristic aspects of humanity, masculinity, or our times.

Richard Dyer investigates this paradox, focusing on the notion at its heart: seriality. He considers the aesthetics of the repetition of nastiness and how this relates to the perceptions and anxieties that images of serial killing highlight in the societies that produce them.

Shifting the focus away from the US, which is often seen as the home of the serial killer, Lethal Repetition instead examines serial killing in European culture and cinema – ranging from Scandinavia to the Mediterranean and from Britain to Romania. Spanning all brows of cinema – including avant-garde, art, mainstream and trash – Dyer provides case studies on Jack the Ripper, the equation of Nazism with serial killing, and the Italian giallo film to explore what this marginal and uncommon crime is being made to mean on European screens.
High-yield production of aryl alcohol oxidase under limited growth conditions in small-scale systems using a mutant Aspergillus nidulans strain
Authors: Pardo-Planas Oscar , Prade Rolf A , Wilkins Mark R
Published: December 2016

Aryl alcohol oxidase (MtGloA) is an enzyme that belongs to the ligninolytic consortium and can play an important role in the bioenergy industry. This study investigated production of an MtGloA client enzyme by a mutant strain of Aspergillus nidulans unable to synthesize its own pyridoxine. Pyridoxine limitation can be used to control cell growth, diverting substrate to protein production. In agitated culture, enzyme production was similar when using media with 1 mg/L and without pyridoxine (26.64 ± 6.14 U/mg mycelia and 26.14 ± 8.39 U/mg mycelia using media with and without pyridoxine, respectively). However, the treatment lacking pyridoxine had to be supplemented with pyridoxine after 156 h of fermentation to sustain continued enzyme production. Use of extremely diluted pyridoxine levels allowed reduced fungal growth while maintaining steady enzyme production. Concentrations of 9 and 13.5 µg/L pyridoxine allowed MtGloA production with a growth rate of only 5% of that observed when using the standard 1 mg/L pyridoxine media.
Allometric and growth data of an evergreen oak, Quercus glauca, in a secondary broadleaved forest
Authors: Itô Hiroki , Sumida Akihiro
Published: December 2016

The evergreen oak Quercus glauca often dominates secondary broadleaved forests in Western Japan. It is regarded as a mid‐successional species, whose diameter and height growth fall between those of early‐ and late‐successional species. Despite the ecological importance of this evergreen oak in the secondary succession of the evergreen broadleaved forest zone in Japan, tree‐felling data that allow estimations of tree mass and leaf area from non‐destructive measurements are lacking. This paper provides stem growth data, read from tree rings on disks sampled from 13 Q. glauca stems, and their allometric data. The samples were collected in 1994 from the Ginkakuji‐san National Forest, Kyoto City, Japan. Allometric data comprised data on stem age, diameter at breast height, diameter at 10% height, tree height, height of the lowest living branch, height of the lowest living leaf in the crown, volume of the main stem, squared stem diameter just below the lowest living branch, total leaf area of the stem, dry weight of the total leaves, dry weight of all branches, dry weight of the main stem, total aboveground dry weight, mean relative photosynthetic photon flux density (PPFD) above the crown, mean relative PPFD below the crown, crown projection area, and specific leaf area. These data can be helpful for estimating the biomass and leaf area index of a Q. glauca stand by enabling the derivation of allometric relationships between non‐destructive measurements (such as stem diameter at breast height, and tree height) and tree mass or leaf area. Diameters (including bark thickness) at ground height and above (at 0.5‐ or 1‐m intervals) for each stem are also provided. Stem growth data were based on tree‐ring reads from disks taken from heights of 0.0 and 0.3 m, and at 0.5‐m (stem height <7 m) or 1.0‐m (stem height ≥7 m) intervals above that. Stem volume growth derived from these tree‐ring data can be converted into stem mass growth if combined with an analysis of the allometric data, which may serve as a useful resource for the estimation of carbon fixation by evergreen oaks in relation to global climate change.
Bias and Imprecision in the Determination of Free Glycerin in Biodiesel: The Unexpected Role of Limitations in Solubility
Authors: Heiden Richard W. , Schober Sigurd , Mittelbach Martin
Published: December 2016

Residual free glycerin (FG) is a critical marker of fatty acid methyl ester (biodiesel) fuel quality. Yet, routine determinations by standard methods display excessive imprecision, and the uncertainties undermine confidence in the data. Various degrees of agitation are used here to evaluate the possibility of heterophase formation as a contributor to imprecision and potential bias. Statistical markers from the analysis of 13 biodiesel samples reveal that seven contain unexpected heterophases, which, due to settling, cause underestimates of 15–68%. Agitation alone re‐suspends heterophases for brief periods, easing potential biases, but also increases imprecision. A promising new sample pretreatment is presented, which reduces the deleterious effects of heterophases. Solubility limitations are explored as possible contributing factors, and measurements made at 23 °C in purified soy FAME reveal an equilibrium solubility which is more than 80% below previously published estimates. Strong interactions of liquid FG with small amounts of moisture reduce solubility to below international quality limits, while interactions of initially dissolved forms of moisture and FG produce bias‐inducing heterophases at 0.02% FG. The unexpected low solubility of FG, exacerbated by interactions with impurities, is seen as an important contributor to underestimates and imprecision, and a strong influencing factor on the fate of residual FG in commercial biodiesel fuels.