bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing Impunity for Serious Crimes: The Imperative for Domesticating the Rome Statute of the ICC in Nigeria
Authors: Ibe Stanley
Published: March 2016

Addressing Impunity for Serious Crimes: The Imperative for Domesticating the Rome Statute of the ICC in Nigeria

Over the last decade, Nigeria has witnessed several high-intensity conflicts. It became a country under preliminary investigation by the International Criminal Court (ICC) following allegations of serious crimes. In 2013, the boko haram insurgency was classified as a “non-international armed conflict.” Commentators appear divided over the capacity and willingness of domestic institutions to manage crimes arising from or connected with conflicts in Nigeria. Those who argue for unwillingness often point to the struggle to domesticate the Rome Statute of the International Criminal Court (Rome Statute) as one of the clearest indication that there is not sufficient interest. This article interrogates the question of seeming impunity for serious crimes in Nigeria and makes a case for domesticating the Rome Statute through an amendment to the Crimes against Humanity, War Crimes, Genocide and Related Offences Bill, 2012 pending before the National Assembly.
On Technological Rationality and the Lack of Authenticity in the Modern Age
Authors: Maboloc Christopher Ryan ,   Philosophy Documentation Center
Published: March 2016

I will argue in this paper that Andrew Feenberg has erred in his claim on technological adaptability. Adapting to modern technology may not always be liberating. Drawing from his reflections on Heidegger and Marcuse, I will explain why Feenberg thinks that adaptability has a redemptive role in the midst of technological domination. I will also show why technological domination still characterizes human relations in the modern age. Advanced technologies including social media, have continued to manipulate people and as such, diminish rather than deepen the authenticity of human life. For instance, two people in a café sometimes spend more time on their smartphones rather than valuing their face-to-face encounter; here, one can point out the lack of authenticity in human relations. This clearly manifests how consumer culture has taken over human life. In addition, it can be said that the notion of adaptability also fails to account for the hegemonic social relations created by modern technological innovations, since these gadgets remain beyond the reach of the masses, thus broadening the divide between classes of people in society. In order to address this, I propose that people should use technology in a socially sensitive way in order to truly give meaning to their lives and to effectively resist the totalitarian tendency of the modern age.
Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci
Authors: Philippe Claude , Vargas-Landin Dulce B , Doucet Aurélien J , van Essen Dominic , Vera-Otarola Jorge , Kuciak Monika , Corbin Antoine , Nigumann Pilvi , Cristofari Gaël
Published: March 2016

LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants.
Two types of volcanic tremor changed with eruption style during 1986 Izu‐Oshima eruption
Authors: Kurokawa Aika , Takeo Minoru , Kurita Kei
Published: March 2016

Volcanic tremor provides clues to magma migration pathways so that tremor source location is expected to be an efficient tool for tracking dynamic behavior of magma in evolution of eruptive activity. However, clear evidence, which connects between temporal variation in volcanic tremor and evolution of eruption style, is still lacking. We have analyzed volcanic tremors occurred during 1986 Izu‐Oshima eruption using recently digitized data. The results present a clear link between eruption styles, waveform variations and source locations of the tremors. Moreover, precursory activity of the tremors that indicates injection of magma below fissures has been clarified 5 days prior to the fissure eruptions. This demonstrates predominance of tremor activity as an adaptive monitoring tool in volcanic eruption.
Injection‐induced seismicity on basement faults including poroelastic stressing
Authors: Chang K. W. , Segall P.
Published: March 2016

Most significant induced earthquakes occur on faults within the basement beneath sedimentary cover. In this two‐dimensional plane strain numerical study, we examine the full poroelastic response of basement faults to fluid injection into overlying strata, considering both (1) the permeability of the fault zone and (2) the hydraulic connectivity of the faults to the target horizon. Given hydraulic and mechanical properties, we compute the spatiotemporal change in Coulomb stress, which we separate into (1) the change in poroelastic stresses Δτs+fΔσn, where Δτs and Δσn are changes in shear and normal stress (Δτs>0 and Δσn>0 both favor slip), and (2) the change in pore pressure fΔp. Pore pressure diffusion into hydraulically connected, permeable faults dominates their mechanical stability. For hydraulically isolated or low‐permeability faults, however, poroelastic stresses transmitted to deeper basement levels can trigger slip, even without elevated pore pressure. The seismicity rate on basement fault zones is predicted using the model of Dieterich (1994). High seismicity rates can occur on permeable, hydraulically connected faults due to direct pore pressure diffusion. Lower rates are predicted on isolated steeply dipping normal faults, caused solely by poroelastic stressing. In contrast, seismicity on similarly oriented reverse faults is inhibited.
Gravity Models and Asymmetric Exchange Rate Effects: Insights from German Beer Exports
Authors: Dreyer Heiko , Fedoseeva Svetlana
Published: March 2016

Recent developments in trade literature suggest that in the presence of strategic pricing in some markets and an incomplete exchange rate pass‐through resulting from it, the standard gravity model has to be augmented with an exchange rate variable. As symmetry of pass‐through has been questioned in new pricing‐to‐market (PTM) studies, we argue that this asymmetric impact of the exchange rate on trade should be explicitly modeled within the gravity framework. This consideration of asymmetric effects of exchange rate appreciations and depreciations on export values and quantities might provide insights into the driving forces of PTM in a particular market (or group of markets) given that the existing literature emphasizes two main hypotheses that explain the occurrence of an asymmetric PTM (market share hypothesis and marketing bottleneck hypothesis). In this paper, we propose a way to integrate individual (asymmetric) long‐run effects of currency appreciations and depreciations on trade flows into the gravity model and empirically investigate which of the driving forces is relevant for the case of German beer exports. PTM studies often argue that the market share protection is a reason for local currency price stabilization mechanisms applied in the most important markets. Yet, the results of our analysis reveal that this might no longer be the case when all trading partners are considered. [EconLit citations: C33; F14; L66].
N‐Heterocyclic carbenes derived from imidazo‐[1,5‐a]pyridines related to natural products: synthesis, structure and potential biological activity of some corresponding gold(I) and silver(I) complexes
Authors: Mihorianu Monica , Franz M Heiko , Jones Peter G , Freytag Matthias , Kelter Gerhard , Fiebig Heinz‐Herbert , Tamm Matthias , Neda Ion
Published: March 2016

A series of Au(I) complexes (12, 13, 14, 15, 16) and Ag(I) complexes (17, 18, 19, 20) derived from imidazo[1,5‐a]pyridin‐3‐ylidenes were synthesized from AuCl(SMe2) or by reacting silver(I) acetate with 2,5‐dimethylimidazo[1,5‐a]pyridin‐2‐ium iodide or imidazo[1,5‐a]pyridin‐2‐ium salts, and were characterized using NMR spectroscopy, mass spectrometry and elemental analyses. In addition, the Au(I) complex 13 and the Ag(I) complex 19 were characterized using single‐crystal X‐ray diffraction. Using paclitaxel as a standard, all Au(I) and Ag(I) N‐heterocyclic carbene complexes were evaluated for their in vitro anti‐tumour activity against 12 cell lines using a monolayer cell survival and proliferation assay. The highest anticancer activity was found for complexes 15, 13 and 14 with mean IC50 values of 10.09, 10.42 and 12.28 μM, respectively. Copyright © 2016 John Wiley & Sons, Ltd.
Beyond university rankings? Generating new indicators on universities by linking data in open platforms
Authors: Daraio Cinzia , Bonaccorsi Andrea
Published: March 2016

The need for new indicators on universities is growing enormously. Governments and decision makers at all levels are faced with the huge opportunities generated by the availability of new knowledge and information and, simultaneously, are pressed by tight budget constraints. University rankings, in particular, are attracting policy and media attention, but at the same time receive harsh methodological criticism. After summarizing the main criticisms of rankings, we describe 2 trends in the user requirements for indicators; namely, granularity and cross‐referencing. We then suggest that a change in the paradigm of the design and production of indicators is needed. The traditional approach is one that not only leverages on the existing data but also suggests heavy investment to integrate existing databases and to build up tailored indicators. We show, based on the European universities case, how theintelligentintegration of existing data may lead to an open‐linked data platform which permits the construction of new indicators. The power of the approach derives from the ability to combine heterogeneous sources of data to generate indicators that address a variety of user requirements without the need to design indicators on a custom basis.
Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype
Authors: Cinci Lorenzo , Luceri Cristina , Bigagli Elisabetta , Carboni Ilaria , Paccosi Sara , Parenti Astrid , Guasti Daniele , Coronnello Marcella
Published: March 2016

The major cause of failure in cancer chemotherapy is the development of multidrug resistance (MDR), and the characterization of biological factors involved in this response to therapy is particularly needed. A doxorubicin‐resistant HCT‐8/R clone was selected from sensitive parental cells and characterized analyzing several parameters (cell cycle phase distribution, apoptotic activity, expression, distribution and functionality of the P‐gp efflux pump, the response to other chemotherapy agents, its ultrastructural features, invasiveness, and transcriptomic profile). HCT‐8/R cells showed a peculiar S phase distribution, characterized by a single pulse of proliferation, resistance to drug‐mediated apoptosis, increased expression and functionality of P‐gp and overexpression of stem cell markers (CD44 and aldehyde dehydrogenase 1A2). At the ultrastructural level, HCT‐8/R presented a greater cell volume and several intracytoplasmic vesicles respect to HCT‐8. Moreover, the resistant clone was characterized by cross resistance to other cytotoxic drugs and a greater capacity for migration and invasion, compared to parental cells. Our data reinforce the concept that the MDR phenotype in HCT‐8/R cells is multifactorial and involves multiple mechanisms, representing an interesting tool to understand the biological basis of MDR and to test strategies that overcome resistance to chemotherapy.
Binary classification model to predict developmental toxicity of industrial chemicals in zebrafish
Authors: Ghorbanzadeh Mehdi , Zhang Jin , Andersson Patrik L.
Published: March 2016

The identification of industrial chemicals, which may cause developmental effects, is of great importance for an early detection of hazardous chemicals. Accordingly, categorical quantitative structure‐activity relationship (QSAR) models were developed, based on developmental toxicity profile data for zebrafish from the ToxCast Phase I testing, to predict the toxicity of a large set of high and low production volume chemicals (H/LPVCs). QSARs were created using linear (LDA), quadratic, and partial least squares‐discriminant analysis with different chemical descriptors. The predictions of the best model (LDA) were compared with those obtained by the freely available QSAR model VEGA, created based on a dataset with a different chemical domain. The results showed that despite similar accuracy (AC) of both models, the LDA model is more specific than VEGA and shows a better agreement between sensitivity (SE) and specificity (SP). Applying a 90% confidence level on the LDA model led to even better predictions showing SE of 0.92, AC of 0.95, and geometric mean of SE and SP (G) of 0.96 for the prediction set. The LDA model predicted 608 H/LPVCs as toxicants among which 123 chemicals fall inside the AD of the VEGA model, which predicted 112 of those as toxicants. Among the 112 chemicals predicted as toxic H/LPVCs, 23 have been previously reported as developmental toxicants. The here presented LDA model could be used to identify and prioritize H/LPVCs for subsequent developmental toxicity assessment, as a screening tool of potential developmental effects of new chemicals, and to guide synthesis of safer alternative chemicals. © 2016 The Authors Journal of Chemometrics Published by John Wiley & Sons Ltd
Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia
Authors: Spencer Nick J. , Kyloh Melinda , Beckett Elizabeth A , Brookes Simon , Hibberd Tim
Published: March 2016

In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran‐amine were made into thoracic DRGs (T8–T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene‐related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple‐type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064–3083, 2016. © 2016 Wiley Periodicals, Inc.
Evolution of the northern Tethyan Helvetic Platform during the late Berriasian and early Valanginian
Authors: Morales Chloe , Spangenberg Jorge E. , Arnaud‐Vanneau Annie , Adatte Thierry , Föllmi Karl B.
Published: March 2016

The Early Cretaceous period is characterized by widespread carbonate production in tropical and subtropical epicontinental seas, which was modulated by changes in sea‐level, detrital and nutrient fluxes, and the global carbon cycle. As a result, carbonate platforms were sensitive recorders of environmental change, which often anticipated global environmental perturbations. A good example is provided by the northern Tethyan carbonate platform, which is presently preserved in the central European Helvetic Alps. There, the latest early to late Valanginian Weissert episode of global change, which is defined by the first important positive shift in δ13C records of the Cretaceous, is expressed by a prolonged, stepwise drowning phase. In this contribution, a detailed reconstruction of palaeoenvironmental change before and during the Weissert episode is provided based on three representative sections of the Helvetic platform. The sections are placed along a deepening transect and correlated by means of ammonite and microfossil biostratigraphy, sequence stratigraphy and δ13C chemostratigraphy. In a first phase of palaeoenvironmental change during the latest Berriasian, photozoan carbonate production was stopped by a major and hitherto undetected drowning episode, which was followed by a phase of renewed carbonate production by heterozoan biota. This phase was linked to major sea‐level rise, a change to a more humid climate and strong regional subsidence associated with tectonic block tilting. During the Valanginian, the circulation of nutrient‐enriched sea waters prevented a return to oligotrophic conditions and two further drowning episodes occurred, which are both documented by condensed phosphate‐rich beds and dated as middle early Valanginian and late Valanginian to early Hauterivian. The exact causes of the three‐step deterioration in carbonate production are not established but a link to episodic volcanic activity is likely, eventually related to the formation of the Paranà‐Etendeka large igneous province.
Bitter taste perception and TAS2R38 genotype: effects on taste sensitivity, food consumption and anthropometry in Mexican adults
Authors: Barajas‐Ramírez Jahir A. , Quintana‐Castro Rodolfo , Oliart‐Ros Rosa M. , Angulo-Guerrero Ofelia
Published: March 2016

Differences in sensitivity to 6‐n‐propylthiouracil (PROP) are associated with TAS2R38 genotypes. Those differences allow the classification in “nontasters” (NT), “tasters” (MT) and “supertasters” (ST), which have been related to differences in taste acuity and nutritional status, although there is controversy in the results obtained by different research groups. The aim of this study was to determine the frequencies of NT, MT and ST, TAS2R38 genotypes and to analyze its relationship with taste sensitivity, food consumption and anthropometric measures in healthy Mexican adults. Body Mass Index (BMI), Waist Circumference (WC), TAS2R38 genotype, detection thresholds for sucrose, capsaicin, PROP and linoleic acid as well as intensity perceived for sucrose, capsaicin and PROP suprathreshold solutions were performed in 76 Mexican adults. Food restriction was assessed and two seven‐day food consumption records from 66 individuals were analyzed. The proportion of subjects with genotype AVI/AVI, and its associated phenotype NT, was close to 10%; the proportion of MT and ST was 54.6 and 31.8 respectively. Genotypes associated with ST were present in 38%, while those associated with MT accounted for 41% of the population. PROP sensitivity was associated with linoleic acid sensitivity, consumption of vegetables, grains and dairy foods. BMI and WC were negatively correlated to carbohydrate intake and linoleic acid detection threshold. PROP taster status and TAS2R38 genotypes were related. PROP and linoleic acid sensitivity influences food consumption in unrestrained eaters and could produce differences in long‐term nutritional status. Copyright © 2016 John Wiley & Sons, Ltd.
Epigenetic mediated silencing of EYA4 contributes to tumorigenesis in oral dysplastic cells
Authors: Towle Rebecca , Truong Danielle , Garnis Cathie
Published: March 2016

Five‐year survival rates for oral squamous cell carcinoma (OSCC) have remained at a dismal 50% for the past several decades. Molecular analyses of premalignant tissues are a key means of identifying early foundational drivers of disease, which may be exploitable as biomarkers or therapeutic targets for improving disease outcomes. We previously identified EYA4 as frequently hypermethylated and silenced in premalignant disease based on an analysis of lesion‐adjacent normal, dysplasia, and carcinoma in situ/squamous cell carcinoma tissues from the oral cavity. Herein, we further evaluate the role of this putative tumor suppressor gene in transformation of oral tissues and OSCC. By an initial assessment, EYA4 promoter hypermethylation was found in 24/32 (75%) of paired tumor samples in The Cancer Genome Atlas oral cancer data set, with significant correlation noted between methylation status and relative gene expression. To assess the impact of EYA4 in oral tumorigenesis, we overexpressed EYA4 in two oral dysplasia cell lines. Expression of EYA4 caused an increase in cell proliferation, DNA damage repair capabilities, and increased the level of apoptosis. Taken together, we find evidence that EYA4 is a novel tumor suppressor in oral cancer, which becomes methylated and silenced at the premalignant stage and appears to be epigenetically regulated. Further studies are warranted to investigate its role as a marker for progression in oral cancer. © 2016 Wiley Periodicals, Inc.
Adrenergic activation attenuates astrocyte swelling induced by hypotonicity and neurotrauma
Authors: Vardjan Nina , Horvat Anemari , Anderson Jamie E. , Yu Dou , Croom Deborah , Zeng Xiang , Lužnik Zala , Kreft Marko , Teng Yang D. , Kirov Sergei A. , Zorec Robert
Published: March 2016

Edema in the central nervous system can rapidly result in life‐threatening complications. Vasogenic edema is clinically manageable, but there is no established medical treatment for cytotoxic edema, which affects astrocytes and is a primary trigger of acute post‐traumatic neuronal death. To test the hypothesis that adrenergic receptor agonists, including the stress stimulus epinephrine protects neural parenchyma from damage, we characterized its effects on hypotonicity‐induced cellular edema in cortical astrocytes by in vivo and in vitro imaging. After epinephrine administration, hypotonicity‐induced swelling of astrocytes was markedly reduced and cytosolic 3'‐5'‐cyclic adenosine monophosphate (cAMP) was increased, as shown by a fluorescence resonance energy transfer nanosensor. Although, the kinetics of epinephrine‐induced cAMP signaling was slowed in primary cortical astrocytes exposed to hypotonicity, the swelling reduction by epinephrine was associated with an attenuated hypotonicity‐induced cytosolic Ca2+ excitability, which may be the key to prevent astrocyte swelling. Furthermore, in a rat model of spinal cord injury, epinephrine applied locally markedly reduced neural edema around the contusion epicenter. These findings reveal new targets for the treatment of cellular edema in the central nervous system. GLIA 2016;64:1034–1049
Patterns and persistence of behavioural and psychological symptoms in those with cognitive impairment: the importance of apathy
Authors: van der Linde Rianne M , Matthews Fiona E , Dening Tom , Brayne Carol
Published: March 2016

Objective

To study the stability and emergence of a range of behavioural and psychological symptoms (BPS), their association with mortality and the effect of covariates on these transitions in a population‐based study of cognitively impaired older people with a long follow‐up period and large sample size, with a particular focus on apathy.

Methods

Data were from a population‐based, longitudinal cohort study of ageing. Interviews were conducted at 0, 2, 6, 8 and 10 years with 3626 participants aged 65+. The persistence of 11 BPS and their association with mortality in those with cognitive impairment (MMSE 25 or below) was investigated using multi‐state models, allowing us to take into account estimations of the probability of transitions that occurred in the time between interviews.

Results

Most BPS were persistent. Apathy was one of the most stable symptoms; in those with apathy, the probability of still having apathy after 1 year is 62%. Apathy, sleep problems, depression, irritability and wandering were most likely to develop. BPS are associated with mortality; in those with apathy, mortality is 3.1 times more likely than in those without apathy. Low cognitive function and dementia were associated with emergence of new symptoms.

Conclusions

This population‐based, multi‐centre study with a follow‐up period of 10 years showed that BPS are associated with mortality and most symptoms are persistent. Apathy was characterised by a high prevalence, a high persistence and a strong association with mortality, and has a negative impact on disability, management of other disease and caregiver burden.
Dynamic regional phase synchrony (DRePS)
Authors: Omidvarnia Amir , Pedersen Mangor , Walz Jennifer M. , Vaughan David N. , Abbott David F. , Jackson Graeme D.
Published: March 2016

Dynamic functional brain connectivity analysis is a fast expanding field in computational neuroscience research with the promise of elucidating brain network interactions. Sliding temporal window based approaches are commonly used in order to explore dynamic behavior of brain networks in task‐free functional magnetic resonance imaging (fMRI) data. However, the low effective temporal resolution of sliding window methods fail to capture the full dynamics of brain activity at each time point. These also require subjective decisions regarding window size and window overlap. In this study, we introduce dynamic regional phase synchrony (DRePS), a novel analysis approach that measures mean local instantaneous phase coherence within adjacent fMRI voxels. We evaluate the DRePS framework on simulated data showing that the proposed measure is able to estimate synchrony at higher temporal resolution than sliding windows of local connectivity. We applied DRePS analysis to task‐free fMRI data of 20 control subjects, revealing ultra‐slow dynamics of local connectivity in different brain areas. Spatial clustering based on the DRePS feature time series reveals biologically congruent local phase synchrony networks (LPSNs). Taken together, our results demonstrate three main findings. Firstly, DRePS has increased temporal sensitivity compared to sliding window correlation analysis in capturing locally synchronous events. Secondly, DRePS of task‐free fMRI reveals ultra‐slow fluctuations of ∼0.002–0.02 Hz. Lastly, LPSNs provide plausible spatial information about time‐varying brain local phase synchrony. With the DRePS method, we introduce a framework for interrogating brain local connectivity, which can potentially provide biomarkers of human brain function in health and disease. Hum Brain Mapp 37:1970–1985, 2016. © 2016 Wiley Periodicals, Inc.
Cell Polarity Proteins in Breast Cancer Progression
Authors: Rejon Carlis , Al‐Masri Maia , McCaffrey Luke
Published: March 2016

Breast cancer, one of the leading causes of cancer related death in women worldwide, is a heterogeneous disease with diverse subtypes that have different properties and prognoses. The developing mammary gland is a highly proliferative and invasive tissue, and some of the developmental programs may be aberrantly activated to promote breast cancer progression. In the breast, luminal epithelial cells exhibit apical–basal polarity, and the failure to maintain this organizational structure, due to disruption of polarity complexes, is implicated in promoting hyperplasia and tumors. Therefore, understanding the mechanisms underlying loss of polarity will contribute to our knowledge of the early stages leading to the pathogenesis of the disease. In this review, we will discuss recent findings that support the idea that loss of apical–basal cell polarity is a crucial step in the acquisition of the malignant phenotype. Oncogene induced loss of tissue organization shares a conserved cellular mechanism with developmental process, we will further describe the role of the individual polarity complexes, the Par, Crumbs, and Scribble, to couple cell division orientation and cell growth. We will examine symmetric or asymmetric cell divisions in mammary stem cell and their contribution to the development of breast cancer subtypes and cancer stem cells. Finally, we will highlight some of the recent advances in our understanding of the molecular mechanisms by which changes in epithelial polarity programs promote invasion and metastasis through single cell and collective cell modes. J. Cell. Biochem. 117: 2215–2223, 2016. © 2016 Wiley Periodicals, Inc.
Oxidation of amaranth dye by persulfate and peroxymonosulfate activated by ferrocene
Authors: Lin Kun‐Yi Andrew , Lin Jyun‐Ting , Jochems Andrew P
Published: March 2016

Background

Readily‐available and efficient catalysts are preferable for activating oxidants such as persulfate (PSF) and peroxymonosulfate (PMS) for environmental remediation. Ferrocene (Fc), a stable and non‐toxic Fe2+‐bearing compound, is a promising heterogeneous catalyst for activation of PSF/PMS, that has not been previously investigated. In this study, the activation of PSF/PMS by Fc is evaluated using the oxidation of toxic amaranth dye as a model reaction.

Results

While an insignificant amount of amaranth dye was removed by Fc or PSF/PMS separately, the combination of Fc and the oxidants completely decolorized amaranth dye, indicating that Fc activated PSF/PMS. Fc‐activated PMS was found to be much more effective than Fc‐activated PSF for degrading amaranth. Elevated temperatures improved the degradation efficiency and kinetics, while the activation of PSF/PMS remained consistent under acidic conditions. Through examining the effects of inhibitors and electron paramagnetic resonance analyses, Fc was proven to activate PSF/PMS to generate sulfate radicals. Fc could also be re‐used for multiple cycles to activate PSF and PMS.

Conclusion

Fc remained intact after the activation according to X‐ray diffraction, FT‐IR and X‐ray photoelectron spectroscopy analyses. These features make Fc an effective and readily‐available heterogeneous catalyst to activate PSF and PMS for advanced oxidation processes (AOPs). © 2016 Society of Chemical Industry
Sustained release of neurotrophin‐3 via calcium phosphate‐coated sutures promotes axonal regeneration after spinal cord injury
Authors: Hanna Amgad , Thompson Daniel L. , Hellenbrand Daniel J. , Lee Jae‐Sung , Madura Casey J. , Wesley Meredith G. , Dillon Natalie J. , Sharma Tapan , Enright Connor J. , Murphy William L.
Published: March 2016

Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin‐3 (NT‐3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT‐3 binding and release were characterized in vitro. Then, the NT‐3‐loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP‐coated sutures exhibited a burst release of NT‐3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT‐3‐loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT‐3‐loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT‐3‐loaded sutures had significantly more axons per graft than rats treated with an NT‐3 injection and rats without NT‐3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP‐coated sutures can efficiently release NT‐3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc.
Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration
Authors: Tang Xinyan , Jing Liufang , Richardson William J. , Isaacs Robert E. , Fitch Robert D. , Brown Christopher R. , Erickson Melissa M. , Setton Lori A. , Chen Jun
Published: March 2016

Previous study claimed that disc degeneration may be preceded by structure and matrix changes in the intervertebral disc (IVD) which coincide with the loss of distinct notochordally derived nucleus pulposus (NP) cells. However, the fate of notochordal cells and their molecular phenotype change during aging and degeneration in human are still unknown. In this study, a set of novel molecular phenotype markers of notochordal NP cells during aging and degeneration in human IVD tissue were revealed with immunostaining and flow cytometry. Furthermore, the potential of phenotype juvenilization and matrix regeneration of IVD cells in a laminin‐rich pseudo‐3D culture system were evaluated at day 28 by immunostaining, Safranin O, and type II collagen staining. Immunostaining and flow cytometry demonstrated that transcriptional factor Brachyury T, neuronal‐related proteins (brain abundant membrane attached signal protein 1, Basp1; Neurochondrin, Ncdn; Neuropilin, Nrp‐1), CD24, and CD221 were expressed only in juvenile human NP tissue, which suggested that these proteins may be served as the notochordal NP cell markers. However, the increased expression of CD54 and CD166 with aging indicated that they might be referenced as the potential biomarker for disc degeneration. In addition, 3D culture maintained most of markers in juvenile NP, and rescued the expression of Basp1, Ncdn, and Nrp 1 that disappeared in adult NP native tissue. These findings provided new insight into molecular profile that may be used to characterize the existence of a unique notochordal NP cells during aging and degeneration in human IVD cells, which will facilitate cell‐based therapy for IVD regeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1316–1326, 2016.
Farmland Conversion Decreases Regional and National Land Quality in China
Authors: Song Wei , Liu Mingliang
Published: March 2016

Maintaining sufficient farmland to ensure food security and a strong rural economy is crucial for China. At the national as well as regional levels, we compared the quality of the land converted from and to farmland during the period 1986–2005, thus quantifying the change in farmland quality directly attributable to land‐use conversion. Specifically, we compared land cover maps compiled for the initial and final years of the study period at a 1:250,000 scale by institutes of the Chinese Academy of Sciences, and combined this with national land quality assessment data compiled at the beginning of the period. Comparison of the land cover maps revealed that over the 20‐year period 12·9 Mha of farmland were converted to other land uses and 14·0 Mha of new farmland were brought under cultivation. Large net increases in farmland area occurred in Heilongjiang, Jilin, Liaoning, Xinjiang, and Inner Mongolia, together contributing 3·5 Mha of the net increase in farmland area. Several developed provinces, e.g. Beijing (−21·20%), Shanghai (−15·81%), Zhejiang (−9·85%), Guangdong (−7·79%), and Tianjin (−6·35%), experienced rapid farmland decreases. Although there was a net increase in farmland, the most suitable and productive farmland decreased by 1·8% while low‐quality farmland increased by 1·4%. Thus, focusing solely on maintaining the total farmland area did not prevent overall loss of a substantial amount of high‐quality farmland. Farmland protection policies should therefore take into account both farmland quantity and quality. Copyright © 2016 John Wiley & Sons, Ltd.
Accelerating fully phase‐encoded MRI near metal using multiband radiofrequency excitation
Authors: Artz Nathan S. , Wiens Curtis N. , Smith Matthew R. , Hernando Diego , Samsonov Alexey , Reeder Scott B.
Published: March 2016

Purpose

To develop a multiband radiofrequency (RF) excitation strategy for simultaneous excitation of multiple RF offsets to accelerate fully phase‐encoded imaging near metallic prostheses.

Methods

Multiband RF excitation was designed and incorporated into a spectrally resolved fully phase‐encoded (SR‐FPE) imaging scheme. A triband (−6, 0, 6 kHz) acquisition was compared with three separate single‐band acquisitions at the corresponding RF offsets with a phantom containing the head of a hip prosthesis. In vivo multiband data with continuous spectral coverage were acquired in the knee of a healthy volunteer with the head of a hip prosthesis placed posteriorly and in a volunteer with a total knee prosthetic implant.

Results

Phantom images acquired with triband excitation were essentially identical to the composite of three single‐band excitations, but with an acceleration factor of three. In vivo multiband images of the healthy knee with adjacent metal demonstrated very good depiction of knee anatomy. In vivo images of the total knee replacement were successfully acquired, allowing visualization of native tissue with far less signal dropout than 2D‐FSE.

Conclusions

FPE imaging with multiband excitation is feasible in the presence of extreme off‐resonance. This approach can reduce scan time and/or increase off‐resonance coverage, enabling in vivo FPE imaging near metallic prostheses over a broad off‐resonance spectrum. Magn Reson Med 77:1223–1230, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Quantitative susceptibility mapping detects abnormalities in cartilage canals in a goat model of preclinical osteochondritis dissecans
Authors: Wang Luning , Nissi Mikko J. , Toth Ferenc , Johnson Casey P. , Garwood Michael , Carlson Cathy S. , Ellermann Jutta
Published: March 2016

Purpose

To use quantitative susceptibility mapping (QSM) to investigate changes in cartilage canals in the distal femur of juvenile goats after their surgical transection.

Methods

Chondronecrosis was surgically induced in the right medial femoral condyles of four 4‐day‐old goats. Both the operated and control knees were harvested at 2, 3, 5, and 10 weeks after the surgeries. Ex vivo MRI scans were conducted at 9.4 Tesla using TRAFF (relaxation time along a fictitious field)‐weighted fast spin echo imaging and QSM to detect areas of chondronecrosis and investigate cartilage canal abnormalities. Histological sections from these same areas stained with hematoxylin and eosin and safranin O were evaluated to assess the affected tissues.

Results

Both the histological sections and the TRAFF‐weighted images of the femoral condyles demonstrated focal areas of chondronecrosis, evidenced by pyknotic chondrocyte nuclei, loss of matrix staining, and altered MR image contrast. At increasing time points after surgery, progressive changes and eventual disappearance of abnormal cartilage canals were observed in areas of chondronecrosis by using QSM.

Conclusion

Abnormal cartilage canals were directly visualized in areas of surgically induced chondronecrosis. Quantitative susceptibility mapping enabled investigation of the vascular changes accompanying chondronecrosis in juvenile goats. Magn Reson Med 77:1276–1283, 2017. © 2016 International Society for Magnetic Resonance in Medicine
A low‐communication, parallel algorithm for solving PDEs based on range decomposition
Authors: Appelhans David J. , Manteuffel Tom , McCormick Steve , Ruge John
Published: March 2016

This paper proposes a new, low‐communication algorithm for solving PDEs on massively parallel computers. The range decomposition (RD) algorithm exposes coarse‐grain parallelism by applying nested iteration and adaptive mesh refinement locally before performing a global communication step. Just a few such steps are observed to be sufficient to obtain accuracy within a small multiple of discretization error. The target applications are petascale and exascale machines, where hierarchical parallelism is required and traditional parallel numerical PDE communication patterns are costly because of message latency. The RD algorithm uses a partition of unity to equally distribute the error, and thus, the work. The computational advantages of this approach are that the decomposed problems can be solved in parallel without any communication until the partitioned solutions are summed. This offers potential advantages in the paradigm of expensive communication but very cheap computation. This paper introduces the method and explains the details of the communication step. Two performance models are developed, showing that the latency cost associated with a traditional parallel implementation of nested iteration is proportional to log(P)2, whereas the RD method reduces the communication latency to log(P), while maintaining similar bandwidth costs. Numerical results for two problems, Laplace and advection diffusion, demonstrate the enhanced performance, and a heuristic argument explains why the method converges quickly. Copyright © 2016 John Wiley & Sons, Ltd.
Combined homotopy and neighboring extremal optimal control
Authors: Gupta Rohit , Bloch Anthony M. , Kolmanovsky Ilya V.
Published: March 2016

This paper presents a new approach to trajectory optimization for nonlinear systems. The method exploits homotopy between a linear system and a nonlinear system and neighboring extremal optimal control, in combination with few iterations of a convergent optimizer at each step, to iteratively update the trajectory as the homotopy parameter changes. To illustrate the proposed method, a numerical example of a three‐dimensional orbit transfer problem for a spacecraft is presented. Copyright © 2016 John Wiley & Sons, Ltd.
Viscoelastic properties of amaranth starch gels and pastes. Creep compliance modeling with Maxwell model
Authors: Villarreal Myriam E. , Iturriaga Laura B.
Published: March 2016

In this work, the morphological, thermal, and crystalline properties of starches isolated from two amaranth cultivars, Amaranthus cruentus (ACr) and Amaranthus caudatus (ACa); the viscoelastic properties of their pastes and gels, through oscillatory and creep‐recovery tests and the adjustment to the Maxwell mechanical model, were studied. Both starches presented type A crystalline patterns with high crystallinity degree (CD), 41.84% for ACr and 40.70% for ACa, associated to their low apparent amylose content (AAM) (1.06 g/100 g for ACr and 7.39 g/100 g for ACa). The ACr starch showed the highest values for temperature of gelatinization (Tg) (74.50°C) and ΔH (16.15 W/g). Amaranth gelatinized starches exhibited rheological behavior that corresponds to concentrated macromolecular solutions for ACr while ACa starches showed a gel‐type behavior. The ACa gels behaved as a viscoelastic solid with smaller values of instantaneous compliance (0.006 Pa−1 < J0 < 0.0002 Pa−1), retarded compliances (0.0005 Pa−1 < J1 < 0.000006 Pa−1; 0.0016 Pa−1 < J2 < 0.00008 Pa−1) and higher values of newtonian viscosities (33.4 × 105 Pa · s ≤ η0 ≤ 357.1 × 105Pa · s) than ACr, which facilitated their later structural recovery (75.8% ≤ final recovery ≤ 85.1%). The gels exhibited a small contribution of viscous flow's compliance (t/η0) brought about by the dashpot of the Maxwell's simple element, while in the ACr pastes, this element acquired importance. The Maxwell model of six‐parameters adjusted satisfactorily (R2 ≥ 0.986; RSS ≤ 3 × 10−4) the results of creep curves.
Mesenchymal Stromal Cells Induce Peculiar Alternatively Activated Macrophages Capable of Dampening Both Innate and Adaptive Immune Responses
Authors: Chiossone Laura , Conte Romana , Spaggiari Grazia Maria , Serra Martina , Romei Cristina , Bellora Francesca , Becchetti Flavio , Andaloro Antonio , Moretta Lorenzo , Bottino Cristina
Published: March 2016

Mesenchymal stromal cells (MSCs) support hematopoiesis and exert immunoregulatory activities. Here, we analyzed the functional outcome of the interactions between MSCs and monocytes/macrophages. We showed that MSCs supported the survival of monocytes that underwent differentiation into macrophages, in the presence of macrophage colony-stimulating factor. However, MSCs skewed their polarization toward a peculiar M2-like functional phenotype (MMSC), through a prostaglandin E2-dependent mechanism. MMSC were characterized by high expression of scavenger receptors, increased phagocytic capacity, and high production of interleukin (IL)-10 and transforming growth factor-β. These cytokines contributed to the immunoregulatory properties of MMSC, which differed from those of typical IL-4-induced macrophages (M2). In particular, interacting with activated natural killer (NK) cells, MMSC inhibited both the expression of activating molecules such as NKp44, CD69, and CD25 and the production of IFNγ, while M2 affected only IFNγ production. Moreover, MMSC inhibited the proliferation of CD8+ T cells in response to allogeneic stimuli and induced the expansion of regulatory T cells (Tregs). Toll-like receptor engagement reverted the phenotypic and functional features of MMSC to those of M1 immunostimulatory/proinflammatory macrophages. Overall our data show that MSCs induce the generation of a novel type of alternatively activated macrophages capable of suppressing both innate and adaptive immune responses. These findings may help to better understand the role of MSCs in healthy tissues and inflammatory diseases including cancer, and provide clues for novel therapeutic approaches.
Heterologous expression and characterization of a new heme-catalase in Bacillus subtilis 168
Authors: Philibert Tuyishime , Rao Zhiming , Yang Taowei , Zhou Junping , Huang Genshu , Irene Komera , Samuel Niyomukiza
Published: March 2016

Reactive oxygen species (ROS) is an inherent consequence to all aerobically living organisms that might lead to the cells being lethal and susceptible to oxidative stress. Bacillus pumilus is characterized by high-resistance oxidative stress that stimulated our interest to investigate the heterologous expression and characterization of heme-catalase as potential biocatalyst. Results indicated that recombinant enzyme significantly exhibited the high catalytic activity of 55,784 U/mg expressed in Bacillus subtilis 168 and 98.097 µmol/min/mg peroxidatic activity, the apparent K  m of catalytic activity was 59.6 ± 13 mM with higher turnover rate (K  cat = 322.651 × 103 s−1). The pH dependence of catalatic and peroxidatic activity was pH 7.0 and pH 4.5 respectively with temperature dependence of 40 °C and the recombinant heme-catalase exhibited a strong Fe2+ preference. It was further revealed that catalase KatX2 improved the resistance oxidative stress of B. subtilis. These findings suggest that this B. pumilus heme-catalase can be considered among the industrially relevant biocatalysts due to its exceptional catalytic rate and high stability and it can be a potential candidate for the improvement of oxidative resistance of industrially produced strains.