bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying Design Thinking Principles to Curricular Development in Medical Education
Authors: Gottlieb Michael , Wagner Emilie , Wagner Alexei , Chan Teresa
Published: October 2016

Medical education is an ever‐evolving field, resulting in numerous changes and modifications to curricular structure, learner assessment, feedback, and remediation. To best meet the needs of the individual learners, it is important to design curricula that meet their real needs. Design thinking (DT) first gained popularity in the 1960s and, since then, has been applied to problem solving within business, primary education, and medicine. The process involves five stages: discovery, interpretation, ideation, experimentation, and evolution, which are targeted toward empathizing with end‐users to uncover and design for unmet needs. In this paper, we describe the five‐stage DT approach with specific application to medical education and discuss future directions within the medical education field.
Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management
Authors: Pardanani Animesh
Published: October 2016

Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra‐cutaneous organs.

Diagnosis: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.

Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD) and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.

Management: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (±corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KITD816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting; there is a role for allogeneic stem cell transplantation in select cases.

Investigational drugs: Recent data confirms midostaurin's significant anti‐MC activity in patients with advanced SM. Am. J. Hematol. 91:1147–1159, 2016. © 2016 Wiley Periodicals, Inc.
A novel fecal stable isotope approach to determine the timing of age‐related feeding transitions in wild infant chimpanzees
Authors: Bădescu Iulia , Katzenberg M. Anne , Watts David P. , Sellen Daniel W.
Published: October 2016

Objectives

Determining nutritional development in wild primates is difficult through observations because confirming dietary intake is challenging. Physiological measures are needed to determine the relative contributions of maternal milk and other foods at different ages, and time of weaning. We used fecal stable carbon and nitrogen isotopes (δ13C, δ15N) and fecal nitrogen concentrations (%N) from wild chimpanzees at Ngogo, Uganda, to derive physiological dietary indicators during the transition from total reliance on maternal milk to adult foods after weaning.

Materials and Methods

We analyzed 560 fecal samples collected non‐invasively from 48 infants, their mothers, and 6 juvenile siblings. Most infant and juvenile samples (90%) were matched to samples collected from mothers on the same day. Isotopic assessments were compared with observations of nursing and feeding.

Results

Infants ≤1 year old showed average δ15N, δ13C and %N ratios that were 2.0‰, 0.8‰ and 1.3% greater than their mothers, respectively, interpreted as trophic level effects. Although data collected on newborns were few, results suggest that solid foods were consumed within 2–5 months after birth. Trophic level differences decreased steadily after 1 year, which indicates a decreasing relative contribution of milk to the diet. Isotopic results indicated infants were weaned by 4.5 years old—more than a year earlier than observations of nipple contacts ceased, which revealed the occurrence of “comfort nursing.” Juvenile isotopic signatures indicate no nursing overlap between siblings.

Discussion

Our results resemble the stable isotope differences of human babies. This study contributes to a model of chimpanzee nutritional development required to understand early life history patterns in hominins.
Early lipofuscin accumulation in frontal lobe epilepsy
Authors: Liu Joan Y.W. , Reeves Cheryl , Diehl Beate , Coppola Antonietta , Al‐Hajri Aliya , Hoskote Chandrashekar , Mughairy Salim al , Tachrount Mohamed , Groves Michael , Michalak Zuzanna , Mills Kevin , McEvoy Andrew W. , Miserocchi Anna , Sisodiya Sanjay M. , Thom Maria
Published: October 2016

Objective

This study reports on a novel brain pathology in young patients with frontal lobe epilepsy (FLE) that is distinct from focal cortical dysplasia (FCD).

Methods

Surgical specimens from 20 young adults with FLE (mean age, 30 years) were investigated with histological/immunohistochemical markers for cortical laminar architecture, mammalian target of (mTOR) pathway activation and inhibition, cellular autophagy, and synaptic vesicle‐mediated trafficking as well as proteomics analysis. Findings were correlated with pre‐/postoperative clinical, imaging, and electrophysiological data.

Results

Excessive lipofuscin accumulation was observed in abnormal dysmorphic neurones in 6 cases, but not in seven FCD type IIB and 7 pathology‐negative cases, despite similar age and seizure histories. Abnormal dysmorphic neurones on proteomics analysis were comparable to aged human brains. The mTOR pathway was activated, as in cases with dysplasia, but the immunoreactivities of nucleoporin p62, DEP‐domain containing protein 5, clathrin, and dynamin‐1 were different between groups, suggesting that enhanced autophagy flux and abnormal synaptic vesicle trafficking contribute to early lipofuscin aggregation in these cases, compared to suppression of autophagy in cases with typical dysplasia. Cases with abnormal neuronal lipofuscin showed subtle magnetic resonance imaging cortical abnormalities that localized with seizure onset zone and were more likely to have a family history.

Interpretation

We propose that excess neuronal lipofuscin accumulation in young patients with FLE represents a novel pathology underlying this epilepsy; the early accumulation of lipofuscin may be disease driven, secondary to as‐yet unidentified drivers accelerating autophagic pathways, which may underpin the neuronal dysfunction in this condition. Ann Neurol 2016;80:882–895
Carboxylierte photoschaltbare Diarylethene als Biomarkierungen für hochauflösende RESOLFT‐Mikroskopie
Authors: Roubinet Benoît , Bossi Mariano L. , Alt Philipp , Leutenegger Marcel , Shojaei Heydar , Schnorrenberg Sebastian , Nizamov Shamil , Irie Masahiro , Belov Vladimir N. , Hell Stefan W.
Published: October 2016

Reversibel photoschaltbares 1,2‐Bis(2‐ethyl‐6‐phenyl‐1‐benzothiophen‐1,1‐dioxid‐3‐yl)perfluorcyclopenten (EBT) mit fluoreszierender “geschlossener” Form wurde mit vier oder acht Carboxygruppen versehen und an Antikörper gebunden. Die carboxylierten Derivate wiesen geringe Aggregation, effizientes Photoschalten in wässrigen Puffern, gezieltes Färben von zellulären Strukturen und gute photophysikalische Eigenschaften auf. Abwechselnde Bestrahlung mit UV und blauem Licht relativ geringer Intensität führte zu reversibler photochemischer Isomerisierung zwischen zwei stabilen Strukturen über mehrere dutzend Schaltzyklen. Dies ermöglichte die Verwendung der Farbstoffe für hochauflösende RESOLFT‐Mikroskopie (“reversible switchable optical linear fluorescence transitions”). Hierbei konnte eine optische Auflösung von 75 nm an zellulären Tubulin‐Filamenten erzielt werden.
Structural studies and quantum chemical calculations of Cr(III), Fe(III) and Ru(III) bromazepam complexes
Authors: Mansour Ahmed M. , Shehab Ola R.
Published: October 2016

The reaction of bromazepam (7‐bromo‐1,3‐dihydro‐5‐(2‐pyridyl)‐2H‐1,4‐benzodiazepin‐2‐one, BZM) with Cr(III) (1), Fe(III) (2) and Ru(III) (3) salts gives complexes of the type [M(BZM)3]⋅3X (X = Cl or NO3). Structural characterization was extensively carried out using various analytical and spectral tools such as infrared, 1H NMR and UV–visible spectroscopies and magnetic, conductance, elemental and thermal analyses. BZM is a bidentate ligand and interacts with the metal ions via the pyridine and benzodiazepin‐2‐one nitrogen atoms. The magnetic and electronic properties of 2 and 3 are consistent with low‐spin octahedral complexes. The three BZM molecules are non‐isoenergetically coordinated to the metal ions and this is reflected in the values of the second‐order interaction energy. The antibacterial activity was studied using Staphylococcus aureus and Escherichia coli. Coordination of BZM to Cr(III) or Ru(III) ions leads to a marked increase in toxicity with respect to the inactive Fe(III) complex 2.
Diffusion mechanism of byproducts resulting from the peroxide crosslinking of polyethylene
Authors: Sahyoun J. , Crepet A. , Gouanve F. , Keromnes L. , Espuche E.
Published: October 2016

In this study, a polyethylene grade used for applications in the insulation of energy cables was crosslinked by the peroxide crosslinking route. The impact of dicumyl peroxide (DCP) crosslinking on the polymer microstructure was studied. The different byproducts formed during the crosslinking reaction [acetophenone, α‐cumyl alcohol, and α‐methyl styrene (aMS)] were identified and quantified. Another molecule, 2,4‐diphenyl‐4‐methyl‐1‐pentene, regarded as an aMS dimer, was detected for the first time. Some amounts of residual DCP were also detected. A detailed study of the diffusion mechanism of each byproduct under different desorption conditions (e.g., samples exposed to vacuum or atmospheric conditions) and temperatures was performed. The diffusion coefficient values were determined and are discussed as a function of the desorption conditions and byproduct characteristics. Through this study, essential diffusion parameters were provided as a first step for further modeling development to allow the definition of optimized desorption conditions for a large range of sample geometries and thicknesses. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44525.
Improvement of impact strength and hydrolytic stability of PC/ABS blend using reactive polymer
Authors: Nishino Kohhei , Shindo Yuichi , Takayama Tetsuo , Ito Hiroshi
Published: October 2016

Polycarbonate/acrylonitrile–butadiene–styrene (PC/ABS) blends have been used widely for specific applications such as in automotive interior and exterior parts, and for office automation equipment parts. This study was conducted to investigate the effects of a reactive polymer as a modifier on properties such as the impact strength of PC/ABS blends. A reaction between PC and maleic anhydride group cannot usually be expected because the end hydroxyl group of PC is capped with an end‐capping agent such as t‐butylphenol to improve PC properties such as fluidity, thermal resistance, and impact strength. However, a reactive polymer that has a maleic anhydride group reacts with the end hydroxyl group of PC hydrolyzed with metal salts. Results show that PC/ABS with a reactive polymer exhibits improved impact strength. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44550.
Genetic backgrounds and modifier genes of NTD mouse models: An opportunity for greater understanding of the multifactorial etiology of neural tube defects
Authors: Leduc Renee Y.M. , Singh Parmveer , McDermid Heather E.
Published: October 2016

Neurulation, the early embryonic process of forming the presumptive brain and spinal cord, is highly complex and involves hundreds of genes in multiple genetic pathways. Mice have long served as a genetic model for studying human neurulation, and the resulting neural tube defects (NTDs) that arise when neurulation is disrupted. Because mice appear to show mostly single gene inheritance for NTDs and humans show multifactorial inheritance, mice sometimes have been characterized as a simpler model for the identification and study of NTD genes. But are they a simple model? When viewed on different genetic backgrounds, many genes show significant variation in the penetrance and expressivity of NTD phenotypes, suggesting the presence of modifier loci that interact with the target gene to affect the phenotypic expression. Looking at mutations on different genetic backgrounds provides us with an opportunity to explore these complex genetic interactions, which are likely to better emulate similar processes in human neurulation. Here, we review NTD genes known to show strain‐specific phenotypic variation. We focus particularly on the gene Cecr2, which is studied using both a hypomorphic and a presumptive null mutation on two different backgrounds: one susceptible (BALB/c) and one resistant (FVB/N) to NTDs. This strain difference has led to a search for genetic modifiers within a region on murine chromosome 19. Understanding how genetic variants alter the phenotypic outcome in NTD mouse models will help to direct future studies in humans, particularly now that more genome wide sequencing approaches are being used. Birth Defects Research 109:140–152, 2017. © 2016 Wiley Periodicals, Inc.
The chemiluminescence immunoassay for aflatoxin B1 based on functionalized magnetic nanoparticles with two strategies of antigen probe immobilization
Authors: Yao Manwen , Wang Linyu , Fang Chengzhi
Published: October 2016

A rapid and sensitive chemiluminescence immunoassay (CLIA) based on magnetic nanoparticles (MNPs) was developed to detect aflatoxin B1 (AFB1), which is a potent carcinogen in nature. We prepared monodisperse MNPs (300 nm in diameter) according to the solvothermal synthesis reaction and the MNPs were coated with silica by the Stöber method. Triethox was used as a one‐step carboxylation reagent, and 3‐aminopropyltriethoxysilane (APTES) an amination reagent, to modify the MNPs. We prepared two types of solid phase antigens using the above synthesized functionalized MNPs coupled with the later prepared AFB1‐oxime active ester and the purchased BSA–AFB1 respectively. 2′,6′‐dimethylcarbonylphenyl‐10‐sulfopropylacridinium‐9‐carboxylate 4′‐N‐hydroxysuccinimide (4′‐NHS) ester (NSP–DMAE–NHS), as a novel luminescent reagent, was used to label anti‐AFB1 antibodies. The two CLIA calibration curves based on the two types of solid phase antigens were obtained and compared. The acquired limit of detection (LOD) was about 0.001 ng/mL for the two functionalized MNPs‐based immunoassays, and the half maximal inhibitory concentration (IC50) was 0.51 ng/mL for the MNPs–AFB1‐based method and 0.72 ng/mL for the MNPs–BSA–AFB1‐based method.
Fluoride‐Catalyzed Methylation of Amines by Reductive Functionalization of CO2 with Hydrosilanes
Authors: Liu Xiao‐Fang , Ma Ran , Qiao Chang , Cao Han , He Liang‐Nian
Published: October 2016

An effective and inexpensive organocatalyst tetrabutylammonium fluoride (TBAF) was developed for the reductive functionalization of CO2 with amines to selectively afford formamides or methylamines by employing hydrosilanes. Hydrosilanes with different substituents show discriminatory reducing activity. Thus, the formation of formamides and further reduction products, that is, methylamines could be controlled by elegantly tuning hydrosilane types. Formamides were obtained exclusively under an atmospheric pressure of CO2 with triethoxysilane. Using phenylsilane as a reductant, methylamines were attained with up to 99 % yield at 50 °C coupled to a complete deoxygenation of CO2. The crucial intermediate silyl formate in the formylation step was identified and thereby a tentative mechanism involving the fluoride‐promoted hydride transfer from the hydrosilane to CO2/formamide was proposed. Striking features of this metal‐free protocol are formylation and methylation of amines by reductive functionalization of CO2 with hydrosilanes and mild reaction conditions.
Quantifying the Tunable Conjugated Area of Graphene Oxide by Using Pyrene as a Fluorescent Probe
Authors: Liu Jingquan , Ma Hongjing , Zhu Huihui , Liu Zhen , Jiang Degang , Zhang Jizhen , Yang Wenrong
Published: October 2016

The determination of oxygenous groups, conjugated area ratio, and reduction efficiency of graphene oxide (GO) is a difficult task because of its heterogeneous structure. Herein, a novel approach is described for a detailed understanding of the surface chemistry of GO by using pyrene as a fluorescent probe through π–π stacking interactions.
Preparation of an 18F‐Labeled Hydrocyanine Dye as a Multimodal Probe for Reactive Oxygen Species
Authors: Al‐Karmi Salma , Albu Silvia A. , Vito Alyssa , Janzen Nancy , Czorny Shannon , Banevicius Laura , Nanao Max , Zubieta Jon , Capretta Alfredo , Valliant John F.
Published: October 2016

Hydrocyanine dyes are sensitive “turn‐on” type optical probes that can detect reactive oxygen species (ROS). We have developed a method to prepare an 18F‐labeled hydrocyanine dye as a multi‐modal PET and optical “turn‐on” probe. A commercially available near infrared (NIR) dye was modified with a fluorinated prosthetic group that did not alter its ROS sensing properties in the presence of superoxide and hydroxyl radicals. The 18F‐labeled analogue was produced using a single‐step terminal fluorination procedure. Positron emission tomography (PET) imaging and quantitative in vivo biodistribution studies indicated this novel probe had remarkably different pharmacokinetics compared to the oxidized cyanine analogue. The chemistry reported enables the use of quantitative and dynamic PET imaging for the in vivo study of hydrocyanine dyes as ROS probes.
Quantum Computation using Arrays of N Polar Molecules in Pendular States
Authors: Wei Qi , Cao Yudong , Kais Sabre , Friedrich Bretislav , Herschbach Dudley
Published: October 2016

We investigate several aspects of realizing quantum computation using entangled polar molecules in pendular states. Quantum algorithms typically start from a product state
and we show that up to a negligible error, the ground states of polar molecule arrays can be considered as the unentangled qubit basis state
. This state can be prepared by simply allowing the system to reach thermal equilibrium at low temperature (<1 mK). We also evaluate entanglement, characterized by concurrence of pendular state qubits in dipole arrays as governed by the external electric field, dipole–dipole coupling and number N of molecules in the array. In the parameter regime that we consider for quantum computing, we find that qubit entanglement is modest, typically no greater than 10−4, confirming the negligible entanglement in the ground state. We discuss methods for realizing quantum computation in the gate model, measurement‐based model, instantaneous quantum polynomial time circuits and the adiabatic model using polar molecules in pendular states.
Cell size assays for mass cytometry
Authors: Stern Alan D. , Rahman Adeeb H. , Birtwistle Marc R.
Published: October 2016

Mass cytometry offers the advantage of allowing the simultaneous measurement of a greater number parameters than conventional flow cytometry. However, to date, mass cytometry has lacked a reliable alternative to the light scatter properties that are commonly used as a cell size metric in flow cytometry (forward scatter intensity—FSC). Here, we report the development of two plasma membrane staining assays to evaluate mammalian cell size in mass cytometry experiments. One is based on wheat germ agglutinin (WGA) staining and the other on Osmium tetroxide (OsO4) staining, both of which have preferential affinity for cell membranes. We first perform imaging and flow cytometry experiments to establish a relationship between WGA staining intensity and traditional measures of cell size. We then incorporate WGA staining in mass cytometry analysis of human whole blood and show that WGA staining intensity has reproducible patterns within and across immune cell subsets that have distinct cell sizes. Lastly, we stain PBMCs or dissociated lung tissue with both WGA and OsO4 ; mass cytometry analysis demonstrates that the two staining intensities correlate well with one another. We conclude that both WGA and OsO4 may be used to acquire cell size‐related parameters in mass cytometry experiments, and expect these stains to be broadly useful in expanding the range of parameters that can be measured in mass cytometry experiments. © 2016 International Society for Advancement of Cytometry
Fluorescence‐free flow cytometry for measurement of shape index distribution of resting, partially activated, and fully activated platelets
Authors: Litvinenko A.L. , Moskalensky A.E. , Karmadonova N.A. , Nekrasov V.M. , Strokotov D.I. , Konokhova A.I. , Yurkin M.A. , Pokushalov E.A. , Chernyshev A.V. , Maltsev V.P.
Published: October 2016

Whereas commercially available hematological analyzers measure volume of individual platelets, angle‐resolved light‐scattering provides unique ability to additionally measure their shape index. We utilized the scanning flow cytometer to measure light‐scattering profiles (LSPs) of individual platelets taken from 16 healthy donors and the solution of the inverse light‐scattering problem to retrieve the volume and shape index of each platelet. In normal conditions, the platelet shape index distribution (PSID) demonstrates three peaks, which relate to resting, partially activated, and fully activated platelets. We developed an algorithm, based on fitting PSID by a sum of three peak functions, to determine the percentage, mean platelet shape index, and distribution width of each platelet fraction. In total, this method gives eight additional parameters of platelet morphology and function to be used in clinical hematological analysis. We also stimulated the platelets with adenosine diphosphate (ADP) and measured the dependence of equilibrium PSID, including the total percentage of activated platelets, on ADP concentration. © 2016 International Society for Advancement of Cytometry
An improved cooperative spectrum sensing of femtocells with hybrid TDD access scheme in massive MIMO system
Authors: Bai Zhiquan , Gao Peng , Su Yingyan , Han Tao , Kwak Kyungsup , Park Daeyoung
Published: October 2016

To improve the sensing performance and achieve higher throughput of the femtocells (FCs) while alleviating the influence to the macrocell in the cognitive massive multiple‐input and multiple‐output system (MIMO), we propose in this paper a hybrid time‐division duplex (TDD) access scheme of the FCs with confidence factor–based weighted cooperative spectrum sensing (CSS). A first, we present an efficient hybrid TDD access scheme for better spectrum reuse of the FCs based on the typical TDD and reversed TDD schemes. Furthermore, confidence factor–based weighted CSS has been used for better spectrum sensing and interference alleviation. In the cognitive massive MIMO system, FC base stations will form dynamical clustering based on the channel conditions, sense the spectrum through cooperative scheme, and decide whether to access the spectrum or not. After information exchange within each FC cluster, the FC base stations can obtain and update their confidence factors and weight factors based on the sensing results and reliability. Numerical results and theoretical analysis show that the proposed scheme can get more accurate sensing results, increase the throughput and the spectrum access opportunity of the FCs, and efficiently alleviate the interference to the macrocell tier.
From Gutenberg to Open Science: An Unfulfilled Odyssey
Authors: Triggle Chris R. , Triggle David J.
Published: October 2016

Preclinical Research

With the almost global availability of the Internet comes the expectation of universal accessibility to knowledge, including scientific knowledge‐particularly that generated by public funding. Currently this is not the case. In this Commentary we discuss access to this knowledge, the politics that govern peer review and publication, and the role of this knowledge as a public good in medicine.

 Gutenberg's invention of the printing press in 1440 opened an avenue for the distribution of scholarly information to the entire world. The scientific literature first appeared in 1665 with Le Journal des Sçavans followed in the same year by Philosophical Transactions. Today there are more than 5000 scientific publishing companies, 25,000 journals and 1.5 million articles published/year generating revenue of $25 billion USD.

 The European Union and the Organization for Economic Cooperation and Development have argued for open access (OA) to scientific data for all publicly funded research by 2020 with a similar initiative in the USA via the Fair Access to Science and Technology Research Act (FASTR). However, OA to published science is but one step in this odyssey. If the products of science are not openly available then it can be argued that the norms of science as defined by Merton including “universalism” and “communalism” have yet to be accomplished. Nowhere is this more apparent than in the delivery of medicines to the poor and for rare diseases, the attempts to privatize human genetic information and, not least, dealing with the challenges of antibiotic resistance and new disease pandemics exacerbated by climate change. Drug Dev Res 78 : 3–23, 2017.   © 2016 Wiley Periodicals, Inc.
The relative importance of tree and stand properties in susceptibility to spruce beetle outbreak in the mid‐20th century
Authors: Bakaj Felicia , Mietkiewicz Nathan , Veblen Thomas T. , Kulakowski Dominik
Published: October 2016

Tree susceptibility to potentially lethal agents is determined not only by attributes of individual trees, but also by neighborhood effects at a range of scales. For example, effects of disturbances on individual trees are often contingent on the size, configuration, and other properties of neighboring trees. Wildfires can modify postfire properties of individual trees as well as of entire forest stands, both of which can affect subsequent ecological processes, including subsequent disturbances. In recent years, much has been learned about how disturbances interact, but numerous questions concerning underlying mechanisms remain unresolved. For example, the relative importance of forest properties at different spatial scales in determining how fires affect forest susceptibility to subsequent disturbances is not well understood. This study explicitly compares the relative importance of tree vs. fine‐scale neighborhood effects (e.g., stand properties at <7 m radii), on susceptibility to a 1940s' spruce beetle outbreak. Attributes of individual trees and of stand structure were spatially reconstructed at five 250‐m2 sites that were partly burned in the late 19th century and then affected by spruce beetle outbreak in the 1940s. Random Forest models and classification trees were used to compare the relative importance of variables for susceptibility to spruce beetle attack. Individual tree properties (diameter at breast height and age) were the most important predictors of susceptibility to the outbreak across all sites combined and at each of the sites individually. In contrast, neighborhood effects were poor predictors of susceptibility. This study suggests wildfires reduce susceptibility to outbreaks primarily by reducing the size of postfire live trees and only secondarily by modifying stand structure. One implication of this is that management strategies that aim to modify stand structure over large areas in order to reduce susceptibility to spruce beetle outbreaks may be unnecessarily intensive.
Local site conditions drive climate–growth responses ofPicea marianaandPicea glaucain interior Alaska
Authors: Nicklen E. Fleur , Roland Carl A. , Ruess Roger W. , Schmidt Joshua H. , Lloyd Andrea H.
Published: October 2016

The growth response of boreal forest trees to projected changes in climate will have wide ranging and cascading impacts on disturbance regimes, climate feedbacks, carbon storage, and habitat ranges for flora and fauna. Recent findings in Alaska suggest the boreal biome is shifting in response to changes in climate. It is unlikely such a shift will occur in a uniform manner over a landscape variable in topography and site conditions, although there is little consensus of how local site characteristics will interact with climate to alter tree growth patterns. Few studies of tree growth responses to climate in the boreal forest have used randomized study designs encompassing the full range of site conditions, leaving open the question of whether observed patterns in tree growth at local scales are wholly representative of the boreal forest. We addressed these issues using a systematic sampling design to quantify the landscape‐scale patterns in annual growth forPicea marianaandPicea glauca, the two most abundant tree species in interior Alaska. We used measurements of annual tree growth based on increment cores taken from trees distributed across a 1.28 million‐ha study area in Denali National Park and Preserve. We found site‐specific variables, namely near‐surface permafrost, slope angle, and elevation, strongly modified the magnitude, shape, and, in some cases, the direction of growth response to climatic conditions for both species. With predicted warming, our results suggest bothP. marianaandP. glaucawill decrease growth in areas underlain by shallow permafrost.P. marianagrowth may increase on flat terrain, but decrease on steep slopes, whileP. glaucagrowth will show the greatest increases at high elevations during very warm summers. Our results suggest future shifts in these species distributions in response to a changing climate will be conditional on variation in site factors operating at local scales.
Age distributions of Greenlandic dwarf shrubs support concept of negligible actuarial senescence
Authors: Dahlgren Johan P. , Rizzi Silvia , Schweingruber Fritz H. , Hellmann Lena , Büntgen Ulf
Published: October 2016

Many plants and sessile animals may not show actuarial senescence, the increase in mortality with age predicted to be ubiquitous by classic evolutionary theories of aging. Age‐structured demographic information is, however, limited for most organisms. We assessed the age distributions of nine dwarf shrub species from 863 taproot samples collected in coastal east Greenland. Penalized composite link models (pclm) were used to fill gaps in the observed age ranges, caused by low species‐specific sample sizes in relation to life span. Resulting distributions indicate that mortality patterns are independent of age. Actuarial senescence is thus negligible in these dwarf shrub populations. We suggest that smoothing techniques such as pclm enable consideration of noisy age data for determining age distributions. These distributions may, in turn, reveal age effects on demographic rates. Moreover, age determination from the root collars of small plants constitutes a powerful technique to further investigate age dependency of the demography of many plant species, including eudicot herbs. Using these methods for long‐lived plants where long‐term monitoring is unrealistic, we show that age is unlikely to be an important variable for making population projections and determining extinction risks.
Variability of biomarkers in patients with chronic heart failure and healthy controls
Authors: Meijers Wouter C. , van der Velde A. Rogier , Muller Kobold Anneke C. , Dijck‐Brouwer Janneke , Wu Alan H. , Jaffe Allan , de Boer Rudolf A.
Published: October 2016

Aims

Biomarkers can be used for diagnosis, risk stratification, or management of patients with heart failure (HF). Knowledge about the biological variation is needed for proper interpretation of serial measurements. Therefore, we aimed to determine and compare the biological variation of a large panel of biomarkers in healthy subjects and in patients with chronic HF.

Methods and results

The biological variability of established biomarkers [NT‐proBNP and high‐sensitivity troponin T (hsTnT)], novel biomarkers [galectin‐3, suppression of tumorigenicity 2 (ST2), and growth differentiation factor 15 (GDF‐15)], and renal/neurohormonal biomarkers (aldosterone, phosphate, parathyroid hormone, plasma renin concentration, and creatinine) was determined in 28 healthy subjects and 83 HF patients, over a period of 4 months and 6 weeks, respectively. The analytical (CVa), intraindividual (CVi), and interindividual (CVg) variations were calculated, as well as the reference change value (RCV), which reflects the percentage of change that may indicate a ‘relevant’ change. All crude biomarker levels were significantly increased or decreased in HF patients compared with controls (all P < 0.01). Variation indices were comparable in healthy individuals and HF patients. CVi was not influenced by the individual levels of the biomarker itself. NT‐proBNP and GDF‐15 had relatively high CVi (21.8% and 16.6%) and RCV (61.7% and 64.3%), whereas ST2 (CVi, 15.0; RCV, 42.9%), hsTnT (CVi, 11.1; RCV, 31.4%), and galectin‐3 (CVi, 8.1; RCV, 25.0%) had lower indices of variation.

Conclusion

Biological variation indices are comparable between healthy subjects and HF patients for a broad spectrum of biomarkers. NT‐proBNP and GDF‐15 have substantial variation, with lower variation for ST2, hsTnT, and galectin‐3. These data are instrumental in proper interpretation of biomarker levels in HF patients.
Cationic Ru(η6‐p‐cymene) Complexes of 3‐Hydroxy‐4‐pyr(id)ones – Lipophilic Triphenylphosphine as Co‐Ligand Is Key to Highly Stable and Cytotoxic Anticancer Agents
Authors: Parveen Shahida , Hanif Muhammad , Movassaghi Sanam , Sullivan Matthew P. , Kubanik Mario , Shaheen Muhammad Ashraf , Söhnel Tilo , Jamieson Stephen M. F. , Hartinger Christian G.
Published: October 2016

Ru(arene)[3‐hydroxy‐4(1H)‐pyr(id)one]Cl complexes are known to be converted intodinuclear Ru(arene) compounds with three hydroxido bridges in aqueous solution. In an attempt to obtain anticancer Ru(arene) complexes of 3‐hydroxy‐4(1H)‐pyr(id)one ligands that are stable in aqueous solution, triphenylphosphine (PPh3) and 1,3,5‐triaza‐7‐phoshatricyclo[3.3.1.1]decane (pta) were introduced as co‐ligands instead of the chlorido ligand. This led to a series of cationic complexes that were characterized by using standard methods and X‐ray diffraction analysis. The pta complexes were found to be highly stable in aqueous solution for up to 120 h. While they were unreactive in the presence of l‐histidine (His) and l‐methionine (Met), l‐cysteine (Cys) induced cleavage of the 3‐hydroxy‐4(1H)‐pyr(id)one ligands from the Ru center. In vitro cytotoxicity assays against human cancer cell lines revealed that the complexes with the more lipophilic phosphine ligand were cytotoxic in the low‐micromolar concentration range, while the analogous pta compounds did not significantly inhibit cell proliferation.
An Efficient One‐Pot Protocol for the Synthesis of Polysubstituted 4‐Amino‐iminocoumarins and 4‐Aminoquinolines by a Copper‐Catalyzed Three‐Component Reaction
Authors: Yi Fengping , Zhang Songxing , Huang Ying , Zhang Lirong , Yi Weiyin
Published: October 2016

A simple and efficient synthetic approach is reported for the synthesis of highly functionalized 4‐amino‐iminocoumarins 4 and 4‐aminoquinolines 6 in moderate to excellent yields, through a copper‐catalyzed multicomponent reaction. The reaction is carried out in a one‐pot manner, using readily available terminal alkynes 1, sulfonyl azides 2, and 2‐hydroxybenzonitriles 3 or 2‐aminobenzonitrile (5) as substrates at a slightly elevated temperature under N2. The protocol is operationally simple and has a good substrate scope. The overall process involves a nucleophilic addition to a ketenimine, and isomerization of the intermediate.
Cavitand Chemistry – Towards Metallocapsular Catalysts
Authors: Chavagnan Thierry , Sémeril David , Matt Dominique , Toupet Loïc
Published: October 2016

Two diphosphanes with widely separated P centres and cores that consists of two covalently linked resorcinarene cavitands were synthesised. Their ability to bind transition‐metal ions in a chelating fashion with the concomitant formation of capsular complexes was shown in their reactions with metal centres with two available binding sites. The solid‐state structure of one of the complexes, a capsule with a partially embedded “trans‐PtCl2” unit, was determined by single‐crystal X‐ray diffraction. Upon reaction with SnCl2, this complex developed good activity for the hydroformylation of styrene. Its activity and selectivity towards the branched aldehyde were significantly superior to those observed for the reference complex trans‐PtCl2L2, in which L is a monophosphane monocavitand ligand. The higher activity is likely to reflect the initial formation of a hydrido intermediate with a somewhat distorted trigonal‐bipyramidal structure that facilitates the intracapsular olefin/PtH insertion step. The observed aldehyde selectivity is probably controlled by the shape of the capsule, which is sterically better suited for hosting a branched Pt–alkyl unit than a linear one.
Mechanistic modeling of pesticide exposure: The missing keystone of honey bee toxicology
Authors: Sponsler Douglas B. , Johnson Reed M.
Published: October 2016

The role of pesticides in recent honey bee losses is controversial, partly because field studies often fail to detect effects predicted by laboratory studies. This dissonance highlights a critical gap in the field of honey bee toxicology: there exists little mechanistic understanding of the patterns and processes of exposure that link honey bees to pesticides in their environment. The authors submit that 2 key processes underlie honey bee pesticide exposure: 1) the acquisition of pesticide by foraging bees, and 2) the in-hive distribution of pesticide returned by foragers. The acquisition of pesticide by foraging bees must be understood as the spatiotemporal intersection between environmental contamination and honey bee foraging activity. This implies that exposure is distributional, not discrete, and that a subset of foragers may acquire harmful doses of pesticide while the mean colony exposure would appear safe. The in-hive distribution of pesticide is a complex process driven principally by food transfer interactions between colony members, and this process differs importantly between pollen and nectar. High priority should be placed on applying the extensive literature on honey bee biology to the development of more rigorously mechanistic models of honey bee pesticide exposure. In combination with mechanistic effects modeling, mechanistic exposure modeling has the potential to integrate the field of honey bee toxicology, advancing both risk assessment and basic research. Environ Toxicol Chem 2017;36:871–881. © 2016 SETAC
Captagon: use and trade in the Middle East
Authors: AL‐Imam Ahmed , Santacroce Rita , Roman‐Urrestarazu Andres , Chilcott Robert , Bersani Giuseppe , Martinotti Giovanni , Corazza Ornella
Published: October 2016

Background

Fenetheylline, a psychostimulant drug, often branded as Captagon, is a combination of amphetamine and theophylline. Since the cessation of its legal production in 1986, counterfeited products have been produced illicitly in south‐east Europe and far‐east Asia. Its profitable trade has been linked to terrorist organizations, including Islamic State of Iraq and the Levant. This study aims to reach up‐to‐date data, concerning the Captagon e‐commerce and use in the Middle East.

Methods

A multi‐staged and multi‐lingual literature search was carried out. A list of prespecified keywords was applied across medical and paramedical databases, web and Dark web, search engines, social communication media, electronic commerce websites, media networks, and the Global Public Health Intelligence Network database.

Results

The use of Captagon as a stimulant in terrorist settings has been marginally covered in the literature. Data can widely be retrieved from Google and AOL search engines, YouTube, and Amazon e‐commerce websites, and to a lesser extent from Alibaba and eBay. On the contrary, Middle Eastern e‐commerce websites yielded almost no results. Interestingly, the Dark web generated original data for Captagon e‐commerce in the Middle East.

Conclusion

Further investigations are needed on the role that psychoactive drugs play in terrorist attacks and civil war zones. Unless a comprehensive methodological strategy, inclusive of unconventional methods of research, is implemented, it will not be feasible to face such a threat to humanity.
Induction of the Acrosome Reaction and Zona‐Free Hamster Oocyte Penetration by a Bull With Complete Teratospermia Versus a Half Brother With Normal Sperm
Authors: HOUGH SHELLEY R. , KAPROTH MICHAEL T. , FOOTE ROBERT H.
Published: October 2016

ABSTRACT: A fertile bull producing normal sperm and a sterile half brother exhibiting 100% teratospermia were available to study an induced sperm acrosome reaction and oocyte penetration. Pedigree analysis indicated that this condition was inherited. Experiments were undertaken to study the induction of the acrosome reaction using di‐laurylphosphatidylcholine (PC12) liposomes, because this procedure was previously established to be highly correlated with bull fertility. The sperm from each bull were incubated with several PC12 concentrations for varying time periods. The initial percentages ofsperm from the sterile bull with intact, partially intact, and lost acrosomes were 67%, 18%, and 14%, respectively, vs 82%, 13%, and 5% forthe fertile bull (P < .05). After incubation for 15 minutes with 50 μM PC12 liposomes the corresponding values were, respectively, 51%, 26%, and 19%; and 60%, 28%, and 12%. Thus, the differences after induction of the acrosome reaction, although significant (P < .05), were small. The number of sperm adhered to each oocyte averaged 22 and 10, respectively, for the fertile and sterile bulls, whereas 74% of the fertile bull sperm and only 11% of the sterile bull sperm penetrated oocytes. Mixing the sperm‐oocyte complex during incubation and increasing the sperm concentration during incubation to compensate for differences in sperm motility did not markedly affect oocyte penetration by teratogenic sperm, which is consistent with this bull being sterile. In other studies, microinjection of this type of sperm was demonstrated to induce fertilization, so the consequences of using sperm with hereditary defects in assisted reproductive programs to overcome human male sterility may be a concern.
Detection of DNA Damage in Response to Cooling Injury in Equine Spermatozoa Using Single‐Cell Gel Electrophoresis
Authors: LINFOR JENNIFER J. , MEYERS STUART A.
Published: October 2016

ABSTRACT: Single‐cell gel electrophoresis (SCGE), or comet assay, has the ability to detect damage at the single cell level and has not been reported for equine sperm. The ability to detect nuclear damage at the single cell level could aid in the advancement of protocols for optimal semen preservation. The goals of these experiments were to adapt this assay for use with equine sperm and to utilize the assay for determining the integrity of equine sperm DNA following treatments with storage at various decreased temperatures (‐20°C and 5°C). Results from experiments in which sperm were frozen (‐20°C) in the absence of cryoprotectants revealed that significantly more cells with fragmented tails of DNA, or comets, occurred among those exposed to 1, 3, and 5 freeze‐thaw cycles (65% ± 6%, 76% ± 11%, 92% ± 6%, respectively) compared with fresh, untreated sperm (19% ± 16%, P < .05). In addition, DNA damage was different (P < .05) between the three freeze‐thaw treatments. Sensitivity of SCGE on equine sperm was further tested with known ratios of frozen‐thawed and fresh cells. The amount of detectable DNA damage was positively correlated with the percentage of cryo‐damaged cells in each treatment (r2 = 0.92, P < .05). Potential damage as a result of cooled storage was also investigated and results revealed that sperm stored for 48 hours (at 5°C) had a higher percentage of comets than that of fresh sperm (63% ± 13.9% and 28% ± 15.6%, respectively, P < .05). The percentage of viable sperm also decreased linearly over time and was inversely correlated with percent of comets (r2 = 0.805, P < .001). Detection of sublethal and/or uncompensable fertility factors in semen, such as DNA fragmentation, could be useful for detecting male differences in semen for cooling or cryopreservation potential and could provide a tool for monitoring and preserving fertility for individual stallions.
Localization of Peripheral Dopamine D1 and D2 Receptors in Rat and Human Seminal Vesicles
Authors: HYUN JAE‐SEOG , BAIG MASOOD R. , YANG DAE‐YUL , LEUNGWATTANAKIJ SOMBOON , KIM KYUNG‐DO , ABDEL‐MAGEED ASIM B. , BIVALACQUA TRINITY J. , HELLSTROM WAYNE J.G.
Published: October 2016

ABSTRACT: Dopamine, an established neurotransmitter in the central nervous system, is recognized for its role in penile erection and ejaculation in rats. However, its complete mechanism of action in the genitourinary tract is unknown. The objective of this study was to investigate the existence and expression of peripheral dopamine D1 and D2 receptor messenger RNAs (mRNAs) and corresponding proteins in rat and human seminal vesicles. The seminal vesicle tissues of male Sprague‐Dawley rats and human radical prostatectomy specimens were used to extract total RNA and proteins, and to prepare slide sections. Rat hypothalamus tissue served as a control for dopamine D1 and D2 receptors. Testing for the presence and expression of peripheral dopamine D1 and D2 receptor mRNAs in rat and human seminal vesicle tissues was performed by reverse transcription‐polymerase chain reaction. Western blotting was used to detect corresponding proteins of D1 and D2 receptors. Immunohistochemical staining using rabbit antipeptide polyclonal antibodies was employed to identify and anatomically localize dopamine D1 and D2 receptor proteins in rat and human seminal vesicles. Do‐pamine D1 and D2 receptor transcripts were detected in both human and rat seminal vesicle tissues. Western blot analysis demonstrated that peripheral dopamine D1 and D2 receptor proteins exist in both human and rat seminal vesicle tissues. Immunohistochemical analysis demonstrated the localization of peripheral dopamine D1 and D2 receptors to the smooth muscle layer of human and rat seminal vesicles. The results of this study demonstrate that peripheral dopamine D1 and D2 receptors are present in the seminal vesicle tissue in both rats and humans. Although these results suggest that seminal emission may be mediated in part by the stimulation of peripheral dopamine receptors located in the seminal vesicles, the functional significance of dopamine in male reproductive tract has yet to be fully defined.