bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible microprocessor simulation
Authors: Gamrat B. A.
Published: April 2014

This article presents a method for describing microprocessors that allows a single simulator to support many microprocessors. The article begins with a discussion of the importance of flexible simulation software, then describes a current implementation. Specific educational applications and advantages are also discussed.
Interactive neural‐network simulation: A textbook pattern‐recognition problem yields to art‐enhanced counterpropagation
Authors: Korn Granino A.
Published: April 2014

We explain our motivation for truly interactive dynamic‐system simulation and apply DESIRE/NEUNET software to a classical textbook problem in neural‐network pattern recognition. Neural‐network designs which can distinguish two closely spaced spirals must discriminate precisely between complicated, nonconvex pattern clusters. This classical textbook problem is quite difficult. It was finally solved by an unconventional back‐propagation network using ad hoc layer skipping and, more accurately, by Boston University's ARTMAP algorithm. We discuss competitive learning and present a new accurate solution using a counterpropagation network whose novel competitive layer separates closely spaced patterns cleanly with the CLEARN algorithm, a very fast computer routine which emulates simplified adaptive‐resonance functionality.
Development of multimedia modules for education
Authors: Iskander Magdy F. , Catten J. Corey , Jameson Rex , Jones Antony , Balcells Albert
Published: April 2014

Development of multimedia modules and courses for engineering education present a significant opportunity to modernize curricula and improve the effectiveness of teaching and learning. In this article we review the various hardware and software components required to develop multimedia lessons and discuss the role of each component in the structure of a multimedia module. Examples of multimedia lessons developed for CD‐ROM distribution by the Center for Multimedia Education and Technology (CAEME) at the University of Utah are described. These include multimedia lessons in electromagnetics, the Calculus Castle, and the Physics Museum. It is shown that although extensive resources and expertise are often needed to develop these modules, development software and associated technologies are readily available and educators are encouraged to take advantage of these opportunities to reform, restructure, and improve engineering education.
ProDIM: Educational software for digital image processing
Authors: Ramírez Juan Manuel , García‐Aguilar Ramón A. , Báez‐López David
Published: April 2014

We present the educational software package ProDIM, created with the idea of supporting courses on digital image processing techniques. This package was implemented in Visual Basic, which is a visual programming language to create applications in a Windows environment. Operations available in ProDIM include manipulation in the space and frequency domains, such as 2‐D convolution, gray‐level transformations, linear filtering, histogram equalization, and morphologic filtering. Examples show how the package can be useful as a lecture aid and as a lab assistance tool. The image to be processed can be generated using the editor included, or can be imported using images in a BMP format. A graphical interface allows the user to activate available operations through a menu selection.
Experiments in machine learning using artificial neural networks for control and image compression
Authors: Watta Paul B. , Hassoun Mohamad H.
Published: April 2014

This article presents two computer projects which can be incorporated in an undergraduate course in artificial neural networks. These projects allow students to explore both the exciting possibilities and practical limitations of machine learning using the popular back‐prop algorithm. In the first project, a neural net is trained in real‐time to control a ball balanced on a beam by observing the actions of a human operator. In the second project, a bottle‐neck—type neural net is trained for the task of image compression. Once completed, both these projects can be used to visually demonstrate both the process and power of machine learning to a nontechnical audience, including, for example, non‐engineering undergraduate students, and even high‐school students.
A spreadsheet educational tool for microprocessor system
Authors: El‐Hajj Ali , Kabalan Karim Y. , Diab Hassan
Published: April 2014

This article presents a spreadsheet simulation of a user‐defined central processing unit. The tool allows users to emulate their own instructions and visualize the graphical animation of the operation involved. The simulation environment, which is ideal for educational use, is characterized by its low cost, flexibility, and simplicity.
Regulation of endothelial progenitor cell differentiation and function by dimethylarginine dimethylaminohydrolase 2 in an asymmetric dimethylarginine‐independent manner
Authors: Yuan Qiong , Bai Yong‐Ping , Shi Rui‐Zheng , Liu Si‐Yu , Chen Xu‐Meng , Chen Lei , Li Yuan‐Jian , Hu Chang‐Ping
Published: April 2014

Endothelial progenitor cells (EPCs) are involved in the repair of vessels and angiogenesis and are useful in the treatment of ischemic diseases. The dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is regulated by silent information regulator 1 (SIRT1), leading to the senescence of endothelial cells (ECs). Here, we demonstrated that peripheral blood EPCs predominantly expressed DDAH2 that increased with EPC differentiation. EPC senescence and dysfunction were induced on interruption of DDAH2 expression, whereas the mRNA expression of vascular endothelial growth factor (VEGF) and kinase‐domain insert containing receptor (KDR) were downregulated. Moreover, SIRT1 expression increased with EPC differentiation. Interruption of SIRT1 inhibited DDAH2, VEGF, and KDR expression, but had no effect on the level of ADMA. From our data, we concluded that DDAH2 is involved in the differentiation of EPCs and regulates the senescence and function of EPCs through the VEGF/KDR pathway by activation of SIRT1.
A new bioassay identifies proliferation ratios of fibroblasts and myofibroblasts
Authors: Vaughan Melville B. , Odejimi Tobi D. , Morris Tracy L. , Sawalha Dima , Spencer Chelsea L.
Published: April 2014

Myofibroblasts are resident cells of wound healing, contractures and fibroses; these tissues are often referred to as fibroproliferative. Whether myofibroblasts themselves proliferate is of interest. Since many in vitro cultures are heterogeneous, staining in situ is required to identify the myofibroblast. We have tested a newly available fluorescent staining kit using ethynyl deoxyuridine (EdU) and click chemistry to identify EdU incorporation into the replicated DNA of proliferative cells. The proliferation stain was combined with the definitive myofibroblast immunostain for alpha smooth muscle actin (α‐sma). Fibroblasts were grown on coverslips and within attached collagen lattices. Cultures were pulsed with EdU 4 h prior to fixation. Different standard methods of fixation and permeabilization were used to test the effects of these variables on EdU and α‐sma labeling. Images of the stained samples were quantified as the total percentage of proliferative cells, as well as the proportion of fibroblasts and myofibroblasts that were proliferating. Proliferative myofibroblasts were identified in both culture conditions and with all preparation methods tested. Proliferation within the fibroblast population was greater than within the myofibroblast population in both culture conditions. Fixation and permeabilization had little effect on EdU or α‐sma labeling. This method of identifying proliferative myofibroblasts will be useful in future studies of myofibroblast proliferation within heterogeneous populations.
Multisynchro: a novel approach for batch synchronization in scenarios of multiple asynchronisms
Authors: González‐Martínez José M. , de Noord Onno E. , Ferrer Alberto
Published: April 2014

Batch synchronization has been widely misunderstood as being only needed when variable trajectories have uneven length. Batch data are actually considered not synchronized when the key process events do not occur at the same point of process evolution, irrespective of whether the batch duration is the same for all batches or not. Additionally, a single synchronization procedure is usually applied to all batches without taking into account the nature of asynchronism of each batch, and the presence of abnormalities. This strategy may distort the original trajectories and decrease the signal‐to‐noise ratio, affecting the subsequent multivariate analyses. The approach proposed in this paper, named multisynchro, overcomes these pitfalls in scenarios of multiple asynchronisms. The different types of asynchronisms are effectively detected by using the warping information derived from synchronization. Each set of batch trajectories is synchronized by appropriate synchronization procedures, which are automatically selected based on the nature of asynchronisms present in data. The novel approach also includes a procedure that performs abnormality detection and batch synchronization in an iterative manner. Data from realistic simulations of a fermentation process of the Saccharomyces cerevisiae cultivation are used to illustrate the performance of the proposed approach in a context of multiple asynchronisms.Copyright © 2014 John Wiley & Sons, Ltd.
Metal‐Free Reduction of CO2 with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO2 to Methanol
Authors: Das Neves Gomes Christophe , Blondiaux Enguerrand , Thuéry Pierre , Cantat Thibault
Published: April 2014

Guanidines and amidines prove to be highly efficient metal‐free catalysts for the reduction of CO2 to methanol with hydroboranes such as 9‐borabicyclo[3.3.1]nonane (9‐BBN) and catecholborane (catBH). Nitrogen bases, such as 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), 7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (Me‐TBD), and 1,8‐diazabicycloundec‐7‐ene (DBU), are active catalysts for this transformation and Me‐TBD can catalyze the reduction of CO2 to methoxyborane at room temperature with TONs and TOFs of up to 648 and 33 h−1 (25 °C), respectively. Formate HCOOBR2 and acetal H2C(OBR2)2 derivatives have been identified as reaction intermediates in the reduction of CO2 with R2BH, and the first CH‐bond formation is rate determining. Experimental and computational investigations show that TBD and Me‐TBD follow distinct mechanisms. The NH bond of TBD is reactive toward dehydrocoupling with 9‐BBN and affords a novel frustrated Lewis pair (FLP) that can activate a CO2 molecule and form the stable adduct 2, which is the catalytically active species and can facilitate the hydride transfer from the boron to the carbon atoms. In contrast, Me‐TBD promotes the reduction of CO2 through the activation of the hydroborane reagent. Detailed DFT calculations have shown that the computed energy barriers for the two mechanisms are consistent with the experimental findings and account for the reactivity of the different boron reductants.
A Transition‐Metal‐Free Synthesis of Fluorinated Naphthols
Authors: Hammann Jeffrey M. , Unzner Teresa A. , Magauer Thomas
Published: April 2014

Herein, we describe a transition‐metal‐free protocol for the conversion of simple 2‐allyl‐3‐(trifluoromethyl)phenols into substituted 5‐fluoronaphthalen‐1‐ols. The key events of this reaction include the selective activation of two CF bonds and formation of an intermediate hexatriene system, which undergoes a 6π electrocyclization, followed by rearomatization. This concept enables the rapid conversion (three steps) of various commercially available 3‐(trifluoromethyl)phenols into novel fluorine‐containing naphthols, which are difficult to prepare by previous methods. The reported sequence was also extended to a one‐pot transformation of 3‐(trifluoromethyl)phenols into 5‐fluoronaphthalen‐1‐ols.
Chloride‐Induced Aufbau of Perchlorinated Cyclohexasilanes from Si2Cl6: A Mechanistic Scenario
Authors: Tillmann Jan , Meyer Lioba , Schweizer Julia I. , Bolte Michael , Lerner Hans‐Wolfram , Wagner Matthias , Holthausen Max C.
Published: April 2014

A surprisingly simple preparative procedure, addition of Si2Cl6 to a solution of [nBu4N]Cl in CH2Cl2, leads to the formation of the chloride‐complexed cyclic dianions [Si6Cl12⋅2Cl]2−, [(SiCl3)Si6Cl11⋅2Cl]2−, or [1,y‐(SiCl3)2Si6Cl10⋅2Cl]2− (y=1, 3, 4), depending on the stoichiometric ratio of the reactants and the reaction temperature (25–85 °C). Below −40 °C the open‐chain oligosilane chloride adducts [Si3Cl9]−, [Si3Cl10]2−, [Si4Cl11]−, and [Si6Cl15]− are formed, again depending on the reaction conditions chosen. All species were characterized by X‐ray crystallography. The underlying reaction mechanism is elucidated by DFT calculations. It incorporates all experimental findings and involves a few key elementary steps: 1) chloride‐induced liberation of SiCl3− or higher silanides, 2) their addition to neutral silanes yielding larger oligosilane chloride adducts, 3) dimerization of larger silanides to (substituted) cyclohexasilane dichloride adducts with inverse sandwich structure.
Decomposition and Carbon and Nitrogen Dynamics of Phragmites australis Litter as Affected by Flooding Periods in Coastal Wetlands
Authors: Zhao Qingqing , Bai Junhong , Liu Peipei , Gao Haifeng , Wang Junjing
Published: April 2014

To investigate the effects of flooding periods on decomposition and carbon and nitrogen return of Phragmites australis litter, we examined the dynamic of P. australis litter decomposition in short‐, medium‐, and long‐flooding coastal wetlands (HN, HS, and LL wetlands, respectively) in the Yellow River Delta, China. Our results showed that the percentage of dry weight loss of P. australis litter increased gradually as the decomposition proceeded and the percentage of dry weight loss was highest in LL wetland, followed by HS wetland, while the percentage of dry weight loss was lowest in HN wetland. Similar to the percentage of dry weight loss, the relative return indices (RRIs) of carbon of P. australis litter also increased with the increasing days of decomposition, following the order LL wetland > HS wetland > HN wetland. With the exception of little accumulation in both HS and HN wetlands in a certain period, the RRIs of nitrogen increased generally with increasing days of decomposition. However, the C/N ratios decreased rapidly in the first 40 days and retained steady after 40 days.
Minimization of self‐quenching fluorescence on dyes conjugated to biomolecules with multiple labeling sites via asymmetrically charged NIR fluorophores
Authors: Zhegalova Natalia G. , He Shawn , Zhou Haiying , Kim David M. , Berezin Mikhail Y.
Published: April 2014

Self‐aggregation of dyes even at low concentrations poses a considerable challenge in preparing sufficiently bright molecular probes forin vivoimaging, particularly in the conjugation of near infrared cyanine dyes to polypeptides with multiple labeling sites. Such self‐aggregation leads to a significant energy transfer between the dyes, resulting in severe quenching and low brightness of the targeted probe. To address this problem, we designed a novel type of dye with an asymmetrical distribution of charge. Asymmetrical distribution prevents the chromophores fromπ‐stacking thus minimizing the energy transfer and fluorescence quenching. The conjugation of the dye to polypeptides showed only a small presence of an H‐aggregate band in the absorption spectra and, hence, a relatively high quantum efficiency. Copyright © 2014 John Wiley & Sons, Ltd.
Three‐dimensional imaging of the mouse heart and vasculature using micro‐CT and whole‐body perfusion of iodine or phosphotungstic acid
Authors: Dunmore‐Buyze P. Joy , Tate Elsbeth , Xiang Fu‐li , Detombe Sarah A. , Nong Zengxuan , Pickering J. Geoffrey , Drangova Maria
Published: April 2014

Recent studies have investigated histological staining compounds as micro‐computed tomography (micro‐CT) contrast agents, delivered by soaking tissue specimens in stain and relying on passive diffusion for agent uptake. This study describes a perfusion approach using iodine or phosphotungstic acid (PTA) stains, delivered to an intact mouse, to capitalize on the microvasculature as a delivery conduit for parenchymal staining and direct contact for staining artery walls. Twelve C57BL/6 mice, arterially perfused with either 25% Lugol's solution or 5% PTA solution were scanned intact and reconstructed with 26 µm isotropic voxels. The animals were fixed and the heart and surrounding vessels were excised, embedded and scanned; isolated heart images were reconstructed with 13 µm isotropic voxels. Myocardial enhancement and artery diameters were measured. Both stains successfully enhanced the myocardium and vessel walls. Interestingly, Lugol's solution provided a significantly higher enhancement of the myocardium than PTA [2502 ± 437 vs 656 ± 178 Hounsfield units (HU); p < 0.0001], delineating myofiber architecture and orientation. There was no significant difference in vessel wall enhancement (Lugol's, 1036 ± 635 HU; PTA, 738 ± 124 HU; p = 0.29), but coronary arteries were more effectively segmented from the PTA‐stained hearts, enabling segmented imaging of fifth‐ order coronary artery branches. The combination of whole mouse perfusion delivery and use of heavy metal‐containing stains affords high‐resolution imaging of the mouse heart and vasculature by micro‐CT. The differential imaging patterns of Lugol's‐ and PTA‐stained tissues reveals new opportunities for micro‐analyses of cardiac and vascular tissues. Copyright © 2014 John Wiley & Sons, Ltd.
Targeting human prostate cancer with 111In‐labeled D2B IgG, F(ab′)2 and Fab fragments in nude mice with PSMA‐expressing xenografts
Authors: Lütje Susanne , van Rij Catharina M. , Franssen Gerben M. , Fracasso Giulio , Helfrich Wijnand , Eek Annemarie , Oyen Wim J. , Colombatti Marco , Boerman Otto C.
Published: April 2014

D2B is a new monoclonal antibody directed against an extracellular domain of prostate‐specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab′)2 and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing subcutaneous prostate cancer xenografts. The optimal time point for imaging was determined in biodistribution and microSPECT imaging studies with 111In‐D2B IgG, 111In‐capromab pendetide, 111In‐D2B F(ab′)2 and 111In‐D2B Fab fragments in mice with PSMA‐expressing LNCaP and PSMA‐negative PC3 tumors at several time points after injection. All 111In‐labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of 111In‐D2B IgG and 111In‐capromab pendetide at 168 h p.i. (94.8 ± 19.2% injected dose per gram (ID/g) and 16.7 ± 2.2% ID/g, respectively), whereas uptake of 111In‐D2B F(ab′)2 and 111In‐D2B Fab fragments peaked at 24 h p.i. (12.1 ± 3.0% ID/g and 15.1 ± 2.9% ID/g, respectively). Maximum LNCaP tumor‐to‐blood ratios were 13.0 ± 2.3 (168 h p.i.), 6.2 ± 0.7 (24 h p.i.), 23.0 ± 4.0 (24 h p.i.) and 4.5 ± 0.6 (168 h p.i.) for 111In‐D2B IgG, 111In‐F(ab′)2, 111In‐Fab and 111In‐capromab pendetide, respectively. LNCaP tumors were clearly visualized with microSPECT with all antibody formats. This study demonstrates the feasibility of D2B IgG, F(ab′)2 and Fab fragments for targeting PSMA‐expressing prostate cancer xenografts. Copyright © 2014 John Wiley & Sons, Ltd.
Concept and viability of androgen annihilation for advanced prostate cancer
Authors: Mohler James L.
Published: April 2014

There remains no standard of care for patients with a rising prostate‐specific antigen level after radical prostatectomy or radiotherapy but who have no radiographic metastases, even though this is the second largest group of patients with prostate cancer (CaP) in the United States. Androgen deprivation therapy (ADT) may cure some men with advanced CaP based on single‐institution series and a randomized clinical trial of immediate versus delayed ADT for men found to have pelvic lymph node metastasis at the time of radical prostatectomy. ADT may be more effective when initiated for minimal disease burden, which can be detected using PSA after radical prostatectomy or radiotherapy, and if more complete disruption of the androgen axis using newer agents decreases the chance that androgen‐sensitive cells survive to adapt to a low‐androgen environment. Androgens may be “annihilated” simultaneously using a luteinizing hormone‐releasing hormone antagonist or agonist to inhibit testicular production of testosterone, a P45017A1 (CYP17A1) inhibitor to diminish metabolism of testosterone via the adrenal pathway and dihydrotestosterone (DHT) via the backdoor pathway, a 5α‐reductase (SRD5A) inhibitor to diminish testosterone reduction to DHT and backdoor metabolism of progesterone substrates to DHT, and a newer antiandrogen to compete better with DHT for the androgen receptor ligand‐binding domain. Early initiation of androgen annihilation for induction as part of planned intermittent ADT should be safe, may reduce tumor burden below a threshold that allows eradication by the immune system, and may cure many men who have failed definitive local therapy. Cancer 2014;120:2628–2637. © 2014 American Cancer Society.
Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project
Authors: Carson Kenneth R. , Newsome Scott D. , Kim Ellen J. , Wagner‐Johnston Nina D. , von Geldern Gloria , Moskowitz Craig H. , Moskowitz Alison J. , Rook Alain H. , Jalan Pankaj , Loren Alison W. , Landsburg Daniel , Coyne Thomas , Tsai Donald , Raisch Dennis W. , Norris LeAnn B. , Bookstaver P. Brandon , Sartor Oliver , Bennett Charles L.
Published: April 2014

BACKGROUND

Brentuximab vedotin (BV) is an anti‐CD30 monoclonal antibody‐drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus‐induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. In the current study, the authors reported 5 patients who developed BV‐associated PML, including 2 immunocompetent patients.

METHODS

Case information was obtained from clinicians (4 patients) or a US Food and Drug Administration database (1 patient).

RESULTS

All 5 patients had lymphoid malignancies. Two patients with cutaneous T‐cell lymphomas had not previously received chemotherapy. PML developed after a median of 3 BV doses (range, 2 doses‐6 doses) and within a median of 7 weeks after BV initiation (range, 3 weeks‐34 weeks). Presenting findings included aphasia, dysarthria, confusion, hemiparesis, and gait dysfunction; JC virus in the cerebrospinal fluid (2 patients) or central nervous system biopsy (3 patients); and brain magnetic resonance imaging scans with white matter abnormalities (5 patients). Four patients died at a median of 8 weeks (range, 6 weeks‐16 weeks) after PML diagnosis. The sole survivor developed immune reconstitution inflammatory syndrome.

CONCLUSIONS

PML can develop after a few BV doses and within weeks of BV initiation. Clinicians should be aware of this syndrome, particularly when neurologic changes develop after the initiation of BV treatment. The decision to administer BV to patients with indolent cutaneous lymphomas should be based on consideration of risk‐benefit profiles and of alternative options. Cancer 2014;120:2464–2471. © 2014 American Cancer Society.
Gastroenteropancreatic high‐grade neuroendocrine carcinoma
Authors: Sorbye Halfdan , Strosberg Jonathan , Baudin Eric , Klimstra David S. , Yao James C.
Published: April 2014

Gastroenteropancreatic (GEP) neuroendocrine neoplasms are classified as low‐grade, intermediate‐grade, and high‐grade tumors based on morphologic criteria and the proliferation rate. Most studies have been conducted in patients with well differentiated (low‐grade to intermediate‐grade) neuroendocrine tumors. Data are substantially scarcer on poorly differentiated, high‐grade neuroendocrine carcinoma (NEC), which includes the entities of small cell carcinoma and large cell NEC. A literature search of GEP‐NEC was performed. Long‐term survival was poor even among patients who presented with localized disease. Several studies highlighted heterogeneity within the high‐grade NEC category and a need for the further identification of discreet prognostic and predictive groups. Tumors with a Ki‐67 proliferation index <55% were less responsive to platinum‐based chemotherapy, and patients with such tumors or with well differentiated morphology had better survival than patients who had tumors with poorly differentiated morphology or a higher Ki‐67 index. Treatment options beyond platinum‐based chemotherapy are emerging. A revision of the World Health Organization high‐grade NEC classification seems to be necessary based on recent data. Platinum‐based chemotherapy may not be the optimal treatment for patients who have GEP‐NEC with a moderately high proliferation rate. Adequate diagnostic and prognostic stratifications constitute the basis for future progress. Cancer 2014;120:2814–2823. © 2014 American Cancer Society.
Two‐graph analysis of pathological equivalent networks
Authors: Shi Guoyong
Published: April 2014

Recently, abstract current mirror and voltage mirror elements have been proposed for behavioral modeling of active analog blocks. Such artificial elements and the traditionally used nullor element together are called pathological elements in the literature. Pathological elements are very useful in modeling and analysis of active network. Hence, researchers have been motivated to study symbolic analysis methods for networks containing pathological elements. However, so far, only nodal admittance matrix analysis has been formulated. In this work, an alternative two‐graph method is formulated, which has the advantage of providing a compact intermediate form for subsequent symbolic term generation. With a compact two‐graph representation, either a matrix method or a tree enumeration method can be employed. For completeness, the classical two‐graph theory has been extended in this paper to encompass all four types of dependent sources and all pathological elements. Illustrative examples are presented to demonstrate the principle of compact symbolic term generation by the presented two‐graph method. Copyright © 2014 John Wiley & Sons, Ltd.
Neurobiology of attachment to an abusive caregiver: Short‐term benefits and long‐term costs
Authors: Perry Rosemarie , Sullivan Regina M.
Published: April 2014

Childhood maltreatment is associated with adverse brain development and later life psychiatric disorders, with maltreatment from the caregiver inducing a particular vulnerability to later life psychopathologies. Here we review two complementary rodent models of early life abuse, which are used to examine the infant response to trauma within attachment and the developmental trajectories that lead to later life neurobehavioral deficits. These rodent models include being reared with an abusive mother, and a more controlled attachment‐learning paradigm using odor‐shock conditioning to produce a new maternal odor. In both of these rodent models, pups learn a strong attachment and preference to the maternal odor. However, both models produce similar enduring neurobehavioral deficits, which emerge with maturation. Importantly, cues associated with our models of abuse serve as paradoxical safety signals, by normalizing enduring neurobehavioral deficits following abuse. Here we review these models and explore implications for human interventions for early life maltreatment. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 56: 1626–1634, 2014.
Identification and characterization by LC‐UV‐MS/MS of melanotan II skin‐tanning products sold illegally on the Internet
Authors: Breindahl Torben , Evans‐Brown Michael , Hindersson Peter , McVeigh Jim , Bellis Mark , Stensballe Allan , Kimergård Andreas
Published: April 2014

New methods were developed and validated to determine the identity, contents, and purity of samples of melanotan II, a synthetic melanocortin receptor agonist, sold in vials as injectable skin‐tanning products that were purchased from three online shops. Methods were based on liquid chromatography with ultra‐violet detection (LC‐UV) at wavelength 218 nm, and tandem mass spectrometric detection (MS/MS) after collision‐induced fragmentation of the double charged [M+2H]2+ precursor ion (m/z 513). Identification of melanotan II was verified by correct chromatographic retention time, and relative abundance ratios of five qualifying fragment ions. LC‐UV was used to quantify melanotan II as well as impurities. Method validation was performed with reference to guidelines for assessing active substances in authorized medicinal products to reach acceptable accuracy and precision. Vials from two shops contained unknown impurities ranging from 4.1 to 5.9%; impurities from one shop were below the quantification limit. The total amount of melanotan II in vials ranged between 4.32 and 8.84 mg, although each shop claimed that vials contained 10 mg melanotan II. A broad range of drugs used for enhancement purposes can be obtained from the illicit market. However, users of these drugs may be exposed to a range of potential harms, as shown in this study, given that these products are manufactured, distributed and supplied from an illicit market. Copyright © 2014 John Wiley & Sons, Ltd.
Artificial light at night causes diapause inhibition and sex‐specific life history changes in a moth
Authors: van Geffen Koert G. , van Grunsven Roy H. A. , van Ruijven Jasper , Berendse Frank , Veenendaal Elmar M.
Published: April 2014

Rapidly increasing levels of light pollution subject nocturnal organisms to major alterations of their habitat, the ecological consequences of which are largely unknown. Moths are well‐known to be attracted to light at night, but effects of light on other aspects of moth ecology, such as larval development and life‐history, remain unknown. Such effects may have important consequences for fitness and thus for moth population sizes. To study the effects of artificial night lighting on development and life‐history of moths, we experimentally subjected Mamestra brassicae (Noctuidae) caterpillars to low intensity green, white, red or no artificial light at night and determined their growth rate, maximum caterpillar mass, age at pupation, pupal mass and pupation duration. We found sex‐specific effects of artificial light on caterpillar life‐history, with male caterpillars subjected to green and white light reaching a lower maximum mass, pupating earlier and obtaining a lower pupal mass than male caterpillars under red light or in darkness. These effects can have major implications for fitness, but were absent in female caterpillars. Moreover, by the time that the first adult moth from the dark control treatment emerged from its pupa (after 110 days), about 85% of the moths that were under green light and 83% of the moths that were under white light had already emerged. These differences in pupation duration occurred in both sexes and were highly significant, and likely result from diapause inhibition by artificial night lighting. We conclude that low levels of nocturnal illumination can disrupt life‐histories in moths and inhibit the initiation of pupal diapause. This may result in reduced fitness and increased mortality. The application of red light, instead of white or green light, might be an appropriate measure to mitigate negative artificial light effects on moth life history.
Integration of palaeohydrological proxies into a peatland model: a new tool for palaeoecological studies
Authors: Quillet Anne , Garneau Michelle , van Bellen Simon , Frolking Steve , Tuittila Eeva‐Stiina
Published: April 2014

To assess the response of northern peatlands to hydrological changes, we analysed the response of a model designed to simulate peatland development at a millennial timescale, the Holocene Peat Model, to two hydrological drivers. The study is performed on two open ombrotrophic peatlands located in the James Bay region in North‐eastern Canada. For both sites, two simulations were realized: one based on a precipitation reconstruction from pollen data, used as input in the model, and a second using a water‐table depth reconstruction derived from testate amoebae to apply a forcing on the model. Simulated variations in carbon accumulation rates (CARs) and vegetation composition were analysed against palaeoecological datasets.

In both sites and for the two hydrological drivers, modelling results in CARs showed periods of net carbon loss that coincided with fluctuations in observed CARs, although net carbon loss cannot be traced in palaeoecological datasets per se. The comparison between plant macrofossil records and simulated vegetation distributions highlighted differences between precipitation and water‐table depth‐driven simulations. Thus, the methodology used was found useful to analyse the origin of vegetation shifts in macrofossil datasets. Copyright © 2014 John Wiley & Sons, Ltd.
International differences in clinical characteristics, management, and outcomes in acute heart failure patients: better short‐term outcomes in patients enrolled in Eastern Europe and Russia in the PROTECT trial
Authors: Mentz Robert J. , Cotter Gad , Cleland John G.F. , Stevens Susanna R. , Chiswell Karen , Davison Beth A. , Teerlink John R. , Metra Marco , Voors Adriaan A. , Grinfeld Liliana , Ruda Mikhail , Mareev Viacheslav , Lotan Chaim , Bloomfield Daniel M. , Fiuzat Mona , Givertz Michael M. , Ponikowski Piotr , Massie Barry M. , O'Connor Christopher M.
Published: April 2014

Aims

The implications of geographical variation are unknown following adjustment for hospital length of stay (LOS) in heart failure (HF) trials that included patients whether or not they had systolic dysfunction. We investigated regional differences in an international acute HF trial.

Methods and results

The PROTECT trial investigated 2033 patients with acute HF and renal dysfunction hospitalized at 173 sites in 17 countries with randomization to rolofylline or placebo. We grouped enrolling countries into six regions. Baseline characteristics, in‐hospital management, and outcomes were explored by region. The primary study outcome was 60‐day mortality or cardiovascular/renal hospitalization. Secondary outcomes included 180‐day mortality. Of 2033 patients, 33% were from Eastern Europe, 19% from Western Europe, 16% from Israel, 15% from North America, 14% from Russia, and 3% from Argentina. Marked differences in baseline characteristics, HF phenotype, in‐hospital diuretic and vasodilator strategies, and LOS were observed by region. LOS was shortest in North America and Israel (median 5 days) and longest in Russia (median 15 days). Regional event rates varied significantly. Following multivariable adjustment, region was an independent predictor of the risk of mortality/hospitalization at 60 days, with the lowest risk in Russia (hazard ratio 0.39, 95% confidence interval 0.23–0.64 vs. Western Europe) due to lower rehospitalization; mortality differences were attenuated by 180 days.

Conclusions

In an international HF trial, there were differences in baseline characteristics, treatments, LOS, and rehospitalization amongst regions, but little difference in longer term mortality. Rehospitalization differences exist independent of LOS. This analysis may help inform future trial design and should be externally validated.
PAHs, nitro-PAHs, hopanes, and steranes in lake trout from Lake Michigan
Authors: Huang Lei , Chernyak Sergei M. , Batterman Stuart A.
Published: April 2014

The present study examines concentrations and risks of polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), steranes, and hopanes in lake trout collected in Lake Michigan. A total of 74 fish were collected in 2 seasons at 3 offshore sites. The total PAH concentration (Σ9PAH) in whole fish ranged from 223 pg/g to 1704 pg/g wet weight, and PAH concentrations and profiles were similar across season, site, and sex. The total NPAH (Σ9NPAH) concentrations ranged from 0.2 pg/g to 31 pg/g wet weight, and carcinogenic compounds, including 1-nitropyrene and 6-nitrochrysene, were detected. In the fall, NPAH concentrations were low at the Illinois site (0.2–0.5 pg/g wet wt), and site profiles differed considerably; in the spring, concentrations and profiles were similar across sites, possibly reflecting changes in fish behavior. In the fall, the total sterane (Σ5Sterane) and total hopane (Σ2Hopane) levels reached 808 pg/g and 141 pg/g wet weight, respectively, but concentrations in the spring were 10 times lower. Concentrations in eggs (fall only) were on the same order of magnitude as those in whole fish. These results demonstrate the presence of target semivolatile organic compounds in a top predator fish, and are consistent with PAH biodilution observed previously. Using the available toxicity information for PAHs and NPAHs, the expected cancer risk from consumption of lake trout sampled are low. However, NPAHs contributed a significant portion of the toxic equivalencies in some samples. The present study provides the first measurements of NPAHs in freshwater fish, and results suggest that additional assessment is warranted. Environ Toxicol Chem 2014;33:1792–1801. © 2014 SETAC
Using ordination and clustering techniques to assess multimetric fish health response following a coal ash spill
Authors: Bevelhimer Mark S. , Adams S. Marshall , Fortner Allison M. , Greeley Mark S. , Brandt Craig C.
Published: April 2014

The effect of coal ash exposure on fish health in freshwater communities is largely unknown. Given the large number of possible pathways of effects (e.g., toxicological effect of exposure to multiple metals, physical effects from ash exposure, and food web effects), measurement of only a few health metrics is not likely to give a complete picture. The authors measured a suite of 20 health metrics from 1100+ fish collected from 5 sites (3 affected and 2 reference) near a coal ash spill in east Tennessee over a 4.5-yr period. The metrics represented a wide range of physiological and energetic responses and were evaluated simultaneously using 2 multivariate techniques. Results from both hierarchical clustering and canonical discriminant analyses suggested that for most species × season combinations, the suite of fish health indicators varied more among years than between spill and reference sites within a year. In a few cases, spill sites from early years in the investigation stood alone or clustered together separate from reference sites and later year spill sites. Outlier groups of fish with relatively unique health profiles were most often from spill sites, suggesting that some response to the ash exposure may have occurred. Results from the 2 multivariate methods suggest that any change in the health status of fish at the spill sites was small and appears to have diminished since the first 2 to 3 yr after the spill. Environ Toxicol Chem 2014;33:1903–1913. Published 2014 Wiley Periodicals, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.
Theoretical investigations on C60–ionic liquid interactions and their impacts on C60 dispersion behavior
Authors: Wang Zhuang , Tang Lili , Peijnenburg Willie J.G.M.
Published: April 2014

Increased use and production of carbon nanomaterials (e.g., fullerene C60) and ionic liquids (ILs) may result in their concomitant releases into the environment. Inevitably there will be interactions between carbon nanoparticles (CNPs) and ILs. However, experimental data on the interaction of CNPs with ILs are not readily available, and the mechanism behind the interactions is still elusive. To contribute to an understanding of the molecular interactions established between CNPs and ILs, theoretical investigations at multiple levels were performed to determine the interactions of C60 with 6 different imidazolium-based ILs. The results indicate that C60 mainly interacts with the IL molecules through the van der Waals, π–cation, and hydrophobic interactions. Mulliken population analysis suggests that charge transfer occurs from the IL to C60 during the C60–IL interaction. The self-diffusion coefficient (D) of C60 in [C60 + IL] systems reaches the maximum in the case of moderate C60–IL interaction (interaction energy, EINT), implying that in this case a good dispersion of an agglomerate species of C60 is obtained. The D value of C60 in [C60 + IL + water] systems increases with an increase of the EINT, implying that the presence of ILs can play an important role in the aqueous dispersion of the C60 agglomerate. Environ Toxicol Chem 2014;33:1802–1808. © 2014 SETAC
Energy‐aware load adaptive framework for LTE heterogeneous network
Authors: Abdulkafi Ayad Atiyah , Chieng David , Kiong Tiong Sieh , Ting Alvin , Koh Johnny , Ghaleb Abdulaziz M.
Published: April 2014

One of the main approaches for improving the network energy efficiency (EE) is through the introduction of load adaptive techniques, where the network's components/subsystems are switched off when the network is lightly loaded. Optimising such a dynamic operation in a heterogeneous network (HetNet) remains an active topic of research. In this paper, a traffic load‐adaptive model that aims to evaluate the EE of base stations in Long Term Evolution (LTE) HetNet is presented. First, a model that simulates the load‐adaptive power consumption behaviour of LTE HetNet is developed. In this regard, a load adaptation factor is introduced to assess the network's EE performance. The model also adapts and predicts the achievable data rate of each base station with respect to the traffic load. Our study shows that the fully load‐adaptive LTE HetNet can significantly improve network's EE up to 10%, 40%, and 80% for high, medium, and low loads, respectively, as compared to the conventional non load‐adaptive HetNet. In addition, we show that the full adaptive network operation can achieve significant EE gains under a realistic daily traffic profile up to 86%. The proposed evaluation model is essential to assess the network EE and can be used in future studies that focus on improving the adaptation level of the already installed network equipments. Copyright © 2014 John Wiley & Sons, Ltd.
Tumor genetics and survival of thymic neuroendocrine neoplasms: A multi‐institutional clinicopathologic study
Authors: Ströbel Philipp , Zettl Andreas , Shilo Konstantin , Chuang Wen‐Yu , Nicholson Andrew G. , Matsuno Yoshihiro , Gal Anthony , Laeng Rolf Hubert , Engel Peter , Capella Carlo , Marino Mirella , Chan John Kwok-Cheung , Rosenwald Andreas , Travis William , Franks Teri J. , Ellenberger David , Schaefer Inga‐Marie , Marx Alexander
Published: April 2014

Thymic neuroendocrine tumors (TNET) are rare primary epithelial neoplasms of the thymus. This study aimed to determine clinically relevant parameters for their classification and for therapeutic decisions. We performed a comprehensive histological, clinical, and genetic study of 73 TNET cases (13 thymic typical carcinoids [TTC], 40 thymic atypical carcinoids [TAC], and 20 high‐grade neuroendocrine carcinomas [HGNEC] of the thymus), contributed by multiple institutions. The mean number of chromosomal imbalances per tumor was 0.8 in TTC (31% aberrant cases) versus 1.1 in TAC (44% aberrant cases) versus 4.7 in HGNEC (75% aberrant cases). Gains of 8q24 (MYC gene locus) were the most frequent alteration and one of the overlapping features between carcinoids and HGNEC. The 5‐year survival rates for TTC, TAC, and HGNEC were 100, 60, and 30%. The 10‐year survival rates for TTC and TAC were 50 and 30% (P = 0.002). Predictive mitotic cut‐off values for TTC versus TAC were 2.5 per 10 high‐power fields (HPF; indicating a higher death rate, P = 0.062) and 15 per 10 HPF (indicating higher risk of recurrence, P = 0.036) for separating HGNEC from TAC. We conclude that the current histopathologic classifications of TNET reflect tumor biology and provide important information for therapeutic management. © 2014 Wiley Periodicals, Inc.
Acute and late side effects to salivary glands and oral mucosa after head and neck radiotherapy in children and adolescents. Results of the “Registry for the evaluation of side effects after radiotherapy in childhood and adolescence”
Authors: Bölling Tobias , Weege Julia , Eich Hans Theodor , Timmermann Beate , Meyer Frank‐Michal , Rübe Christian , Kortmann Rolf‐Dieter , Fischedick Karin , Rödel Claus , Koch Raphael , Willich Normann
Published: April 2014

Background

The registry for the evaluation of side effects after radiotherapy in childhood and adolescence (RiSK) was established to prospectively characterize radiation‐associated side effects. The purpose of this analysis was to characterize side effects after radiotherapy to the head and neck in children and adolescents.

Methods

Radiation doses have been collected across Germany since 2001. Acute and late side effects were characterized.

Results

Until January 2010, 133 patients (median age, 12.7 years) were recruited who had received radiotherapy to the salivary glands. Toxicity evaluation was available for 114 patients (median follow‐up, 2.9 years). Acute and late toxicity significantly depended on the maximum radiation dose to the salivary glands. An increase of the mean value of maximum dose of 1 Gray (Gy) to the submandibular glands resulted in an odds ratio of 1.04 (range, 1.00–1.08; p = .039) for acute toxicities of the salivary glands and 1.08 (range, 1.03–1.13; p = .001) for acute mucosal toxicities.

Conclusion

These data can be used for an individual risk assessment in pediatric head and neck radiotherapy. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1137–1141, 2015
Nodal metastasis and survival in oral cancer: Association with protein expression of SLPI, not with LCN2, TACSTD2, or THBS2
Authors: Noorlag Rob , van der Groep Petra , Leusink Frank K. J. , van Hooff Sander R. , Frank Michaël H. , Willems Stefan M. , van Es Robert J. J.
Published: April 2014

Background

Gene expression profiling revealed a strong signature predicting lymph node metastases in oral squamous cell carcinoma (OSCC). Four of the most predictive genes are secretory leukocyte protease inhibitor (SLPI), lipocalin‐2 (LCN2), thrombospondin‐2 (THBS2), and tumor‐associated calcium signal transducer 2 (TACSTD2). This study correlates their protein expression with lymph node metastases, overall survival (OS), and disease‐specific survival (DSS).

Methods

Two hundred twelve patients with OSCC were included for protein expression analysis by immunohistochemistry.

Results

SLPI expression correlates with lymph node metastases in the whole cohort, not in a subgroup of cT1 to 2N0. SLPI expression correlates with OS (hazard ratio [HR] = 0.61) and DSS (HR = 0.47) in multivariate analysis. LCN2, THBS2, and TACSTD2 show no correlation with lymph node metastases, OS, or DSS.

Conclusion

Although SLPI expression correlates with lymph node metastases, it has no additional value in determining lymph node metastases in early oral cancer. However, it is an independent predictor for both OS and DSS and therefore a relevant prognostic biomarker in OSCC. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1130–1136, 2015