bluuebunny/crossref_metadata_2025 huggingface dataset:
AVPR1b variation and the emergence of adaptive phenotypes in Platyrrhini primates
Authors: Fam Bibiana S. O. , Reales Guillermo , Vargas‐Pinilla Pedro , Paré Pamela , Viscardi Lucas H. , Sortica Vinicius A. , Felkl Aline B. , de O. Franco Álvaro , Lucion Aldo B. , Costa‐Neto Claudio M. , Pissinatti Alcides , Salzano Francisco M. , Paixão‐Côrtes Vanessa R. , Bortolini Maria Cátira
Published: July 2019

Platyrrhini (New World monkeys, NWm) are a group of primates characterized by behavioral and reproductive traits that are otherwise uncommon among primates, including social monogamy, direct paternal care, and twin births. As a consequence, the study of Platyrrhine primates is an invaluable tool for the discovery of the genetic repertoire underlying these taxon‐specific traits. Recently, high conservation of vasopressin (AVP) sequence, in contrast with high variability of oxytocin (OXT), has been described in NWm. AVP and OXT functions are possible due to interaction with their receptors: AVPR1a, AVPR1b, AVPR2, and OXTR; and the variability in this system is associated with the traits mentioned above. Understanding the variability in the receptors is thus fundamental to understand the function and evolution of the system as a whole. Here we describe the variability of AVPR1b coding region in 20 NWm species, which is well‐known to influence behavioral traits such as aggression, anxiety, and stress control in placental mammals. Our results indicate that 4% of AVPR1b sites may be under positive selection and a significant number of sites under relaxed selective constraint. Considering the known role of AVPR1b, we suggest that some of the changes described here for the Platyrrhini may be a part of the genetic repertoire connected with the complex network of neuroendocrine mechanisms of AVP–OXT system in the modulation of the HPA axis. Thus, these changes may have promoted the emergence of social behaviors such as direct paternal care in socially monogamous species that are also characterized by small body size and twin births.
Assessment of different sperm functional tests in golden‐headed lion tamarins (Leontopithecus chrysomelas)
Authors: Arakaki Paloma Rocha , Salgado Paula Andrea Borges , de Agostini Losano João Diego , Blank Marcel Henrique , Nichi Marcílio , Pereira Ricardo José Garcia
Published: July 2019

The golden‐headed lion tamarin (Leontopithecus chrysomelas) is an endangered species endemic to Brazil's Atlantic Forest, a shrinking biodiversity hotspot. As in other Neotropical primates, its semen characteristics and freezability are poorly studied. Hence, reproductive technologies for callitrichids would greatly benefit from reliable methods of semen analysis. In a bid to promote reproductive research in tamarins, we validated simple and inexpensive sperm function tests that can be used to monitor sperm‐egg binding, plasma membrane and acrosome integrity, mitochondrial activity, and DNA fragmentation. Ejaculates from adult males were individually diluted and divided into control and damage‐induced aliquots, and then samples comprising assorted amounts of damaged spermatozoa were examined by organelle‐specific tests. Our findings showed that sperm‐binding in chicken egg perivitelline membrane (EPM) positively correlated with the number of spermatozoa injured by snap‐freezing. Eosin‐nigrosin (EN) and propidium iodide readings were correlated with each other, and both provided robust measurements of plasma membrane integrity. A high correlation between expected and measured amounts of acrosome‐intact spermatozoa was found using Fast Green‐Rose Bengal (FG‐RB), Coomassie Blue (CB), and FITC‐PSA stains, and all three methods exhibited comparable results. Likewise, different percentages of UV‐irradiated spermatozoa were accurately assessed for DNA integrity by Toluidine Blue (TB) and sperm chromatin dispersion (SCD) tests. Comparisons between 3,3′‐diaminobenzidine (DAB) and JC‐1 stains also indicated the reliability of the former assay to ascertain gradual increases in spermatozoa with greater mitochondrial function. These data confirmed that different parts of the tamarin spermatozoa can be simply and consistently evaluated by EPM, EN, FG‐RB, CB, TB, and DAB protocols.
Total Synthesis of Leuconoxine, Melodinine E, and Mersicarpine through a Radical Translocation–Cyclization Cascade
Authors: Kim Ryan , Ferreira Andrew J. , Beaudry Christopher M.
Published: July 2019

The Aspidosperma alkaloids leuconoxine, melodinine E, and mersicarpine were synthesized. The approach features a key cascade radical reaction. A 1,5‐hydrogen atom transfer is followed by spontaneous 5‐exo‐trig cyclization to construct the central indoline architecture. Late‐stage differentiation of the radical cyclization product by chemoselective oxidation allows production of either the leuconoxine/melodinine E or mersicarpine structure.
Introduction of Ag/CuO/MCM‐48 as an efficient catalyst for the one‐pot synthesis of novel pyran‐pyrrole hybrids
Authors: Tavakoli Fateme , Mamaghani Manouchehr , Sheykhan Mehdi
Published: July 2019

Bimetallic silver and copper incorporated mesoporous MCM‐48 (Ag/CuO/MCM‐48) was synthesized by simple wet‐impregnation method. The knowledge about its structural properties was gathered by means of Fourier transform‐infrared, energy‐dispersive X‐ray, X‐ray diffraction, field emission‐scanning electron microscopy, transmission electron microscopy and Brunauer–Emmett–Teller analyses. The catalytic activity of Ag/CuO/MCM‐48 was examined in the one‐pot three‐component reaction of 3‐(1‐methyl‐1H‐pyrrol‐2‐yl)‐3‐oxopropanenitrile, malononitrile and various aromatic aldehydes leading to novel pyran‐pyrrole hybrid derivatives in reduced reaction times (5–10 min) and excellent yields (88–97%). Application of Ag/CuO/MCM‐48 as a potent heterogeneous catalyst with good reusability up to five times, use of ethanol as an eco‐compatible medium and chromatography‐free work‐up are some crucial green aspects of this procedure.
Synthesis, spectra, crystal structures and anticancer studies of 26‐membered macrocyclic dibutyltin(IV) dithiocarbamate complexes: Single‐source precursors for tin sulfide nanoparticles
Authors: Selvaganapathi Pandurangan , Thirumaran Subbiah , Ciattini Samuele
Published: July 2019

Four new macrocyclic dinuclear dibutyltin(IV) dithiocarbamate complexes of the type [Bu2Sn(dtc)]2, where dtc = hexane‐1,6‐diylbis(4‐fluorobenzyldithiocarbamate) anion (1), hexane‐1,6‐diylbis(4‐chlorobenzyldithiocarbamate) anion (2), hexane‐1,6‐diylbis(furfuryldithiocarbamate) anion (3) and hexane‐1,6‐diylbis(pyrrole‐2‐ylmethyldithiocarbamate) anion (4), have been prepared. The dithiocarbamate ligands efficiently self‐assemble with Bu2Sn(IV) to form bimetallic 26‐membered macrocycles. All the complexes have been characterized using elemental analysis, infrared and NMR (1H and 13C) spectroscopies and X‐ray crystallography. Single‐crystal X‐ray diffraction analysis of all the complexes confirms the formation of the dinuclear metallomacrocycles in which dithiocarbamate ligands are asymmetrically bound to the tin atoms. The coordination sphere around the tin atom in 1–4 can be described as a skew trapezoidal bipyramid. The dimensions of the cavity of the macrocycles of 1–4 are ca 8.0 × 9.0 Å2. Complexes 1–4 were evaluated for their in vitro anticancer activity against MCF‐7 and HL‐60 cells. Complexes 1 and 2 are more active against MCF‐7 and HL‐60. Thermal decomposition of 1 and 4 yielded tin sulfides. They were characterized using powder X‐ray diffraction (PXRD), high‐resolution transmission electron microscopy and UV diffuse reflectance and energy‐dispersive X‐ray spectroscopies. PXRD studies reveal that the as‐prepared tin sulfides are composed of orthorhombic phase of SnS.
Bio‐based benzoxazines based on sesamol: Synthesis and properties
Authors: Liu Xiaoyun , Li Ziying , Zhan Guozhu , Wu Yuting , Zhuang Qixin
Published: July 2019

Sesamol was used with furfurylamine, dehydroabietylamine, and stearylamine to prepare three fully‐bio‐based benzoxazines: S‐fa, S‐da, and S‐sa, respectively. Their structures were confirmed by Fourier transform infrared spectroscopy (FTIR),1H‐NMR, and13C‐NMR. FTIR and differential scanning calorimetry were performed to monitor the curing behaviors of S‐fa, S‐da, and S‐sa. The thermal stability of the corresponding polybenzoxazines was supported by thermogravimetric analysis, and all polymers showed high thermal stability. The limiting oxygen indexes of all three polybenzoxazines were higher than 30, suggestive of good flame retardancy. The use of polybenzoxazine for the corrosion protection of Q235 low‐carbon steel was also studied. The results of OCP curves and Tafel plots demonstrate that the polymer coatings provide good corrosion resistance and can be applied to this purpose. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 48255.
Design, synthesis and biological evaluation of peptide‐NSAID conjugates for targeted cancer therapy
Authors: Shokri Bahareh , Zarghi Afshin , Shahhoseini Soraya , Mohammadi Reza , Kobarfard Farzad
Published: July 2019

Linear arginine‐glycine‐aspartic acid (RGD) and asparagine‐glycine‐arginine (NGR) peptide‐nonsteroidal anti‐inflammatory drug conjugates were synthesized to evaluate their anticancer effect. Two well‐known targeting peptide sequences, RGD and NGR, were conjugated with naproxen and ibuprofen. It is expected that the RGD peptide selectively binds to αv‐integrin receptors, which are highly expressed in cancer cells, and that the NGR peptide selectively targets aminopeptidase N (APN/CD13, EC 3.4.11.2), which is overexpressed in blood vessels of tumors. To investigate the impact of possible steric hindrance due to the attachment of the drug to the peptide, a linear six‐carbon linker (hexanoic acid) was also used as a spacer. Cytotoxic effects of the synthesized compounds were evaluated against several cancer cell lines, including MCF‐7, A2780 (αvβ3 positive), OVCAR3 (high αvβ3), HT‐1‐80, and SKOV‐3 cells (CD13 positive). The NGR conjugate forms of both ibuprofen and naproxen showed better activity against the SKOV‐3 tumor cell line. The improved binding of these conjugates to their receptors was confirmed by docking studies.
Radical C−H Acylation of Nitrogen Heterocycles Induced by an Aerobic Oxidation of Aldehydes
Authors: Paul Subhasis , Bhakat Manotosh , Guin Joyram
Published: July 2019

An aerobic radical approach for the synthesis of unsymmetrical heteroaryl ketones is described herein. The reaction involves cross‐dehydrogenative coupling between aldehydes and heteroaromatic bases with molecular oxygen (O2). The key aspect of the method is the generation of reactive acyl radical via homolytic activation of aldehyde C−H bond using O2 as the sole oxidant. The reaction has a good substrate scope with respect to aldehydes and functionalized nitrogen heterocycles. Based on our mechanistic studies, a radical chain pathway is suggested for the reaction. A synthetic application of the method is demonstrated in the formal synthesis of natural alkaloid (±) angustureine.
Is the Autism Boom Headed for Medicaid? Patterns in the Enrollment of Autistic Adults in Wisconsin Medicaid, 2008–2018
Authors: Rubenstein Eric , Bishop Lauren
Published: July 2019

Our primary objective was to describe demographic characteristics and enrollment patterns in a unique 11‐year full sample of adult Wisconsin Medicaid beneficiaries with identified autism spectrum disorder (ASD) or intellectual disability (ID). We obtained de‐identified Medicaid claims data for adults with a recorded ASD or ID diagnosis aged 21 and older with any Medicaid fee‐for‐service claims between January 1, 2008 and December 31, 2018. We assessed enrollment, age, number of visits, and paid amount per year using generalized linear models with a random intercept for each beneficiary. We identified claims for 4,775 autistic adults without ID, 2,738 autistic adults with ID, 14,945 adults with ID, and 3,484 adults with Down syndrome. The age distribution of the diagnostic group with ASD diagnoses was right skewed with a majority of beneficiaries less than age 30. The ASD without ID diagnostic group had the least visits and paid amount per person per year compared to other groups. In each age category, the ASD with ID diagnostic group had the most paid amount per person per year compared to other groups. It is urgent that we identify the health and health service needs of autistic adults from young adulthood through old age. Our findings have implications for ensuring adequate health coverage across the lifespan and highlight the importance of a strong and accessible health care system for autistic people. Autism Res 2019, 12: 1541–1550. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Medicaid provides health insurance to disabled people who meet income requirements. We assessed patterns of enrollment and service use among autistic adults and adults with developmental disabilities in Wisconsin Medicaid. We found a consistent influx of new young autistic adults without intellectual disability into the Medicaid system, with fewer visits and lower paid amounts compared to other developmental disability groups. The changing population of autistic people using Medicaid has implications for providing health care to autistic adults in the future.
A model‐based framework for parallel scale‐down fed‐batch cultivations in mini‐bioreactors for accelerated phenotyping
Authors: Anane Emmanuel , García Ángel Córcoles , Haby Benjamin , Hans Sebastian , Krausch Niels , Krewinkel Manuel , Hauptmann Peter , Neubauer Peter , Cruz Bournazou Mariano Nicolas
Published: July 2019

Concentration gradients that occur in large industrial‐scale bioreactors due to mass transfer limitations have significant effects on process efficiency. Hence, it is desirable to investigate the response of strains to such heterogeneities to reduce the risk of failure during process scale‐up. Although there are various scale‐down techniques to study these effects, scale‐down strategies are rarely applied in the early developmental phases of a bioprocess, as they have not yet been implemented on small‐scale parallel cultivation devices.

In this study, we combine mechanistic growth models with a parallel mini‐bioreactor system to create a high‐throughput platform for studying the response of Escherichia coli strains to concentration gradients. As a scaled‐down approach, a model‐based glucose pulse feeding scheme is applied and compared with a continuous feed profile to study the influence of glucose and dissolved oxygen gradients on both cell physiology and incorporation of noncanonical amino acids into recombinant proinsulin. The results show a significant increase in the incorporation of the noncanonical amino acid norvaline in the soluble intracellular extract and in the recombinant product in cultures with glucose/oxygen oscillations. Interestingly, the amount of norvaline depends on the pulse frequency and is negligible with continuous feeding, confirming observations from large‐scale cultivations. Most importantly, the results also show that a larger number of the model parameters are significantly affected by the scale‐down scheme, compared with the reference cultivations.

In this example, it was possible to describe the effects of oscillations in a single parallel experiment. The platform offers the opportunity to combine strain screening with scale‐down studies to select the most robust strains for bioprocess scale‐up.
Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor
Authors: Novak Caymen M. , Horst Eric N. , Taylor Charles C. , Liu Catherine Z. , Mehta Geeta
Published: July 2019

Breast cancer cells experience a range of shear stresses in the tumor microenvironment (TME). However most current in vitro three‐dimensional (3D) models fail to systematically probe the effects of this biophysical stimuli on cancer cell metastasis, proliferation, and chemoresistance. To investigate the roles of shear stress within the mammary and lung pleural effusion TME, a bioreactor capable of applying shear stress to cells within a 3D extracellular matrix was designed and characterized. Breast cancer cells were encapsulated within an interpenetrating network hydrogel and subjected to shear stress of 5.4 dynes cm−2 for 72 hr. Finite element modeling assessed shear stress profiles within the bioreactor. Cells exposed to shear stress had significantly higher cellular area and significantly lower circularity, indicating a motile phenotype. Stimulated cells were more proliferative than static controls and showed higher rates of chemoresistance to the anti‐neoplastic drug paclitaxel. Fluid shear stress‐induced significant upregulation of the PLAU gene and elevated urokinase activity was confirmed through zymography and activity assay. Overall, these results indicate that pulsatile shear stress promotes breast cancer cell proliferation, invasive potential, chemoresistance, and PLAU signaling.
Development of a bio‐MEMS device for electrical and mechanical conditioning and characterization of cell sheets for myocardial repair
Authors: Roberts Erin G. , Kleptsyn Vladimir F. , Roberts Gregory D. , Mossburg Katherine J. , Feng Bei , Domian Ibrahim J. , Emani Sitaram M. , Wong Joyce Y.
Published: July 2019

Here we propose a bio‐MEMS device designed to evaluate contractile force and conduction velocity of cell sheets in response to mechanical and electrical stimulation of the cell source as it grows to form a cellular sheet. Moreover, the design allows for the incorporation of patient‐specific data and cell sources. An optimized device would allow cell sheets to be cultured, characterized, and conditioned to be compatible with a specific patient's cardiac environment in vitro, before implantation. This design draws upon existing methods in the literature but makes an important advance by combining the mechanical and electrical stimulation into a single system for optimized cell sheet growth. The device has been designed to achieve cellular alignment, electrical stimulation, mechanical stimulation, conduction velocity readout, contraction force readout, and eventually cell sheet release. The platform is a set of comb electrical contacts consisting of three‐dimensional walls made of polydimethylsiloxane and coated with electrically conductive metals on the tops of the walls. Not only do the walls serve as a method for stimulating cells that are attached to the top, but their geometry is tailored such that they are flexible enough to be bent by the cells and used to measure force. The platform can be stretched via a linear actuator setup, allowing for simultaneous electrical and mechanical stimulation that can be derived from patient‐specific clinical data.
Saving Democracy: Good Governance to the Rescue
Authors: Mogensen Susan
Published: July 2019

Susan Mogensen is president of Brown Dog Consulting, which educates board members, senior executives, and staff on the theory and practice of Policy Governance® principles. In this article, she illustrates three ways in which excellence in board leadership today can help preserve and shape the democracy of tomorrow.
The link between advanced glycation end products and apoptosis in delayed wound healing
Authors: Shaikh‐Kader Asma , Houreld Nicolette Nadene , Rajendran Naresh Kumar , Abrahamse Heidi
Published: July 2019

Advanced glycation end products (AGEs) are naturally occurring molecules that start to accumulate from embryonic developmental stages and form as part of normal ageing. When reducing sugars interact with and modify proteins or lipids, AGE production occurs. AGE formation accelerates in chronic hyperglycemic conditions, and high AGE levels have been associated with the pathogenesis of various diseases. In addition, enhanced levels of AGEs have been linked to delayed wound healing as seen in patients with diabetes mellitus. Research has provided numerous ways in which a high AGE concentration results in impaired wound healing, including oxidative stress, structural and functional changes to proteins important in wound repair, an enhanced inflammatory response by activation of transcription factors, and possible exaggerated apoptosis of cells necessary to the wound repair process. Apoptosis is a naturally occurring cell death process that is significant for normal tissue functioning and plays an important role in wound repair by preventing a prolonged inflammatory response and excessive scar formation. Abnormal apoptosis affects wound healing, resulting in slow healing wounds. This review will summarize the role of AGEs in wound healing, focusing on the mechanisms by which AGEs lead to apoptosis in various cell types. The review provides the way forward for medical research and molecular studies as it focuses on the mechanisms by which AGEs induce apoptosis in various cell types, including fibroblasts, osteoblasts, neuronal cells, and endothelial cells. Reviewing the mechanisms of AGE‐linked apoptosis is important in understanding the impact of high AGE levels in delayed wound healing in diabetic patients due to abnormal apoptosis of cells necessary to the wound healing process.
Design, Synthesis, and Self‐Assembly Studies of a Suite of Monodisperse, Facially Amphiphilic, Protein–Dendron Conjugates
Authors: Sandanaraj Britto S. , Bhandari Pavankumar Janardhan , Reddy Mullapudi Mohan , Lohote Akshay Bhagwan , Sahoo Bankanidhi
Published: July 2019

The custom design of protein–dendron amphiphilic macromolecules is at the forefront of macromolecular engineering. Macromolecules with this architecture are very interesting because of their ability to self‐assemble into various biomimetic nanoscopic structures. However, to date, there are no reports on this concept due to technical challenges associated with the chemical synthesis. Towards that end, herein, a new chemical methodology for the modular synthesis of a suite of monodisperse, facially amphiphilic, protein–dendron bioconjugates is reported. Benzyl ether dendrons of different generations (G1–G4) are coupled to monodisperse cetyl ethylene glycol to form macromolecular amphiphilic activity‐based probes (AABPs) with a single protein reactive functionality. Micelle‐assisted protein labeling technology is utilized for site‐specific conjugation of macromolecular AABPs to globular proteins to make monodisperse, facially amphiphilic, protein–dendron bioconjugates. These biohybrid conjugates have the ability to self‐assemble into supramolecular protein nanoassemblies. Self‐assembly is primarily mediated by strong hydrophobic interactions of the benzyl ether dendron domain. The size, surface charge, and oligomeric state of protein nanoassemblies could be systematically tuned by choosing an appropriate dendron or protein of interest. This chemical method discloses a new way to custom‐make monodisperse, facially amphiphilic, protein–dendron bioconjugates.
Self‐Indicative Gold Nanozyme for H2O2 and Glucose Sensing
Authors: Chen Jinxing , Wu Weiwei , Huang Liang , Ma Qian , Dong Shaojun
Published: July 2019

In addition to superior enzyme‐mimicking abilities, nanozymes also have intrinsic physicochemical properties. Integrating the enzyme‐like activities and tunable physicochemical properties into a single nanoparticle is a promising strategy for versatile nanozyme design and application. Herein, a composite nanozyme in which Au nanoparticles are encapsulated by Au nanoclusters (AuNP@AuNCs) is presented. By integrating the peroxidase‐mimicking ability of fluorescent Au NCs with the glucose oxidase‐like activity of Au NPs, the composite nanozyme realized cascade assay of glucose without the aid of external indicators. Compared to traditional multistep colorimetric methods, the analytical process was highly simplified by using the self‐responsive nanozyme. This synthetic strategy provided valuable insights into exploring talented nanozymes for sensing diverse targets.
Two‐layer model predictive control for chemical process model with integrating controlled variables
Authors: Yang Yuanqing , Ding Baocang
Published: July 2019

This paper proposes an overall solution to the two‐layer model predictive control (MPC) for the integrating controlled variables in the process model. The scheme includes three modules, that is, the open‐loop prediction module, the steady‐state target calculation (SSTC) module, and the dynamic control module. Based on the real‐time output measurements and past inputs, the open‐loop prediction module predicts the future outputs in the presence of disturbances. The economic optimization of SSTC is comprised of the feasibility stage and the economics stage, considering constraints of multi‐priority ranks. The dynamic control module receives the steady‐state targets from SSTC and calculates the control signals. The optimization problems of SSTC and dynamic control operate with the same frequency. This overall method guarantees the consistency of three modules with respect to the model, the constraints, and the targets. The simulation example illustrates that steady‐state targets are adjusted dynamically after the occurrence of disturbances, and offset‐free control is achieved.
Teaching ionic bonding – a plea for introducing the term “ion” before explaining ion formation
Authors: Herdt Christian
Published: July 2019

Im Chemieunterricht bereitet sowohl das Thema „Ionen“ als auch das Thema „Bindungen“ chemiedidaktische Probleme, beispielsweise hinsichtlich der optimalen zeitlichen Abfolge der Einführung dieser Begriffe oder der Visualisierung. Beide Begriffe zielen klar auf die Modellebene, d. h. es lassen sich zwar unterrichtliche Experimente durchführen, Ionenbindungen bleiben aber ein theoretisches Konstrukt und sollten durch Modelle veranschaulicht werden. Traditionell wurde im Chemieunterricht erst die Reaktion von Metallen mit Nichtmetallen unterrichtet, um nach der Bildung von Ionen die ionische Bindung zu erläutern. Dieser künstlich hergestellte Zusammenhang führt bei den Lernenden nachweislich zu Fehlvorstellungen, denn die Elektronenübertragung wird als entscheidend für die Ionenbindung angesehen – und nicht das Gleichgewicht zwischen ungerichteten anziehenden und abstoßenden Kräften der unterschiedlich geladenen Ionen in der Gitterstruktur.
Identification of Phenylpyrazolone Dimers as a New Class of Anti‐Trypanosoma cruzi Agents
Authors: Sijm Maarten , Siciliano de Araújo Julianna , Ramos Llorca Alba , Orrling Kristina , Stiny Lydia , Matheeussen An , Maes Louis , de Esch Iwan J. P. , de Nazaré Correia Soeiro Maria , Sterk Geert Jan , Leurs Rob
Published: July 2019

Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in‐house library led to the identification of 2,2′‐methylenebis(5‐(4‐bromophenyl)‐4,4‐dimethyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′‐methylenebis(5‐(3‐bromo‐4‐methoxyphenyl)‐4,4‐dimethyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one (NPD‐0228) as the most potent analogue. NPD‐0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC‐5 cell line and murine cardiac cells.
ESR1 mutations in breast cancer
Authors: Dustin Derek , Gu Guowei , Fuqua Suzanne A. W.
Published: July 2019

The acquisition of ligand‐independent ESR1 mutations during aromatase inhibitor therapy in metastatic estrogen receptor (ER)‐positive breast cancer is a common mechanism of hormonal therapy resistance. Preclinical and clinical studies have demonstrated that ESR1 mutations can preexist in primary tumors and can be enriched during metastasis. Furthermore, ESR1 mutations express a unique transcriptional profile that favors tumor progression, suggesting that selected ESR1 mutations may influence metastasis. Several groups have used sensitive detection methods using patient liquid biopsies to track ESR1 or truncal somatic mutations to predict treatment outcome and tumor progression, and some of these techniques may eventually be used to guide sequential treatment options in patients. Further development and standardization of mutation tracking in circulating tumor DNA is ongoing. Clinically, patients with ESR1 mutations derive clinical benefit when treated with fulvestrant and CDK4/6‐targeted therapies, but the development of more potent selective ER degraders and/or new targeted biotherapies are needed to overcome the endocrine‐resistant phenotype of ESR1 mutant–bearing tumors. In this review, we discuss the mechanisms of resistance and dissemination of ESR1 mutations as well as the detection methods for ESR1 mutation tracking, newly discovered potential therapeutic targets, and the clinical implications and treatment options for treating patients with ESR1 mutant–bearing tumors.
Special issue: 2016 International Conference on Information Technology in Medicine and Education (ITME2016)
Authors: Chen Jinjun
Published: July 2019

This special issue contains selected high‐quality papers from the 2016 International Conference on Information Technology in Medicine and Education (ITME2016), which was held on December 23‐25, 2016 in Fuzhou, China. The ITME conference series aims to provide an international forum for the presentation and discussion of research and development trends regarding information technology in medicine and education. The ITME2016 attracted many international attendants, allowing deep discussion and the exchange of ideas and results related to ongoing research among attendants. This special issue contains nine papers based on those that were presented at ITME2016. Among these are those by Liu et al, Lin et al, Zhang et al, Lin et al, Zhou et al, Cai et al, Li et al, Zheng et al, and Dai et al, 2018. Research problems in these papers have been analyzed systematically, and for specific approaches or models, evaluation has been performed to demonstrate their feasibility and advantages. The papers were selected on this basis and also peer reviewed thoroughly. The nine papers reflect a vision of the area in state‐of‐art fashion.
Efficient and Highly Transparent Ultra‐Thin Nickel‐Iron Oxy‐hydroxide Catalyst for Oxygen Evolution Prepared by Successive Ionic Layer Adsorption and Reaction
Authors: Garcia‐Torregrosa Ivan , Goryachev Andrey , Hofmann Jan P. , Hensen Emiel J. M. , Weckhuysen Bert M.
Published: July 2019

NiFeOx thin films prepared by successive ionic layer adsorption and reaction (SILAR) were deposited onto nanostructured hematite (Fe2O3) photoanodes and their effect on the current density and photo‐onset potential was studied. After optimization of bath concentration, immersion times, and number of SILAR cycles, very conformal and active NiFeOx films with controlled Fe/Ni content ratios were obtained. Upon the incorporation of Fe2+ species in the NiCl2 solution bath, a cathodic shift in the overpotential required for the oxygen evolution reaction (OER) by more than 200 mV with no decrease in current density was observed after 40 SILAR cycles. We demonstrate that by fine‐tuning the film composition and thickness, NiFeOx can be employed as an efficient OER catalyst with very low absorbance in the visible spectrum. By doing so, we demonstrate that this material has great potential for incorporation in semiconductor photoelectrodes for direct solar‐driven water electrolysis. Being a simple water‐based layer‐by‐layer growth method, SILAR offers promise for the synthesis of catalyst coatings in nano‐structured and high surface area electrodes.
The Origin of High Activity of Amorphous MoS2 in the Hydrogen Evolution Reaction
Authors: Wu Longfei , Longo Alessandro , Dzade Nelson Y. , Sharma Akhil , Hendrix Marco M. R. M. , Bol Ageeth A. , de Leeuw Nora H. , Hensen Emiel J. M. , Hofmann Jan P.
Published: July 2019

Molybdenum disulfide (MoS2) and related transition metal chalcogenides can replace expensive precious metal catalysts such as Pt for the hydrogen evolution reaction (HER). The relations between the nanoscale properties and HER activity of well‐controlled 2H and Li‐promoted 1T phases of MoS2, as well as an amorphous MoS2 phase, have been investigated and a detailed comparison is made on Mo−S and Mo−Mo bond analysis under operando HER conditions, which reveals a similar bond structure in 1T and amorphous MoS2 phases as a key feature in explaining their increased HER activity. Whereas the distinct bond structure in 1T phase MoS2 is caused by Li+ intercalation and disappears under harsh HER conditions, amorphous MoS2 maintains its intrinsic short Mo−Mo bond feature and, with that, its high HER activity. Quantum‐chemical calculations indicate similar electronic structures of small MoS2 clusters serving as models for amorphous MoS2 and the 1T phase MoS2, showing similar Gibbs free energies for hydrogen adsorption (ΔGH*) and metallic character.
A generalized service deployment framework for OSPF networks using multi‐topology routing: Modeling and methodology
Authors: Li Ke , Fan Pingzhi
Published: July 2019

The exponential growth of various applications requires deploying an ever‐growing number of network services. A generalized service deployment framework for Open Shortest Path First (OSPF) networks is proposed in this paper. The framework includes placing programmable routers, distributing different types of services on these routers, and leading traffic flow through them according to the predetermined sequence order requirement. However, it is not possible to direct all the traffic flows through the required service nodes along the shortest path with a single and suitable set of link weights. To address the issue, multiple topology routing (MTR) technique is incorporated to have various logical topologies with multiple sets of link weights. Correspondingly, the problem of jointly optimizing Placement of programmable routers, Distribution of different types of services among these routers, and Link Weights setting based on MTR (shortened to PD‐LW‐MTR) and its mixed integer linear programming formulation are presented in this paper. A novel decomposition algorithm is also proposed to address this problem efficiently. Experiment results validate the correctness and feasibility of our algorithm. It is also shown that the optimization algorithm can obtain near‐optimal solution and just only a few logical topologies over multiple sets of link weights are necessary for traffic flows to guarantee service order requirements.
SYN‐Guard: An effective counter for SYN flooding attack in software‐defined networking
Authors: Mohammadi Reza , Conti Mauro , Lal Chhagan , Kulhari Satish C.
Published: July 2019

In software‐defined networking (SDN), TCP SYN flooding attack is considered as one of the most effective attacks to perform control plane and target server saturation. In this attack, an attacker generates a large number of malicious SYN requests, and because of the absence of the forwarding rules, the data plane switches have to forward these SYN messages to the controller. This excessive forwarding causes congestion over the communication channel between a data plane and control plane, and it also exhausts computational resources at both the planes. In this paper, we propose a novel countermeasure called SYN‐Guard to detect and prevent SYN flooding in SDN networks. We fully implement SYN‐Guard on the SDN controller to validate the incoming TCP connection requests. The controller installs forwarding rules for the SYN requests that successfully clear the validation test of SYN‐Guard. The host of the fake SYN request is detected, and SYN‐Guard prevents it from sending any further SYN requests to the data plane switch. The performance evaluation done using the simulation results shows that SYN‐Guard exhibits low side effect for genuine TCP requests, and when compared with standard SDN and state‐of‐art proposals, it reduces the average response time up to 21% during an ongoing SYN flooding attack.
Follow these tips for successful meetings
Authors: Hodges Dawn Z.
Published: July 2019

I worked for a president whose senior leadership meetings dragged on for four to five hours, usually straight through lunchtime. The agenda included 30 to 40 items and never seemed to change much. By the end of the marathon, we were so hungry and mentally drained, we weren't thinking clearly or creatively.
Past, present and future of latent autoimmune diabetes in adults
Authors: Liu Bingwen , Xiang Yufei , Liu Zhenqi , Zhou Zhiguang
Published: July 2019

Latent autoimmune diabetes in adults (LADA) is the most common form of autoimmune diabetes diagnosed in adults. Similar to type 1 diabetes, the prevalence of LADA is impacted by ethnicity and geography. LADA is characterized by β cell loss due to autoimmunity and insulin resistance and has highly heterogeneous clinical features, autoimmunity, and genetics in a glutamic acid decarboxylase antibody (GADA) titre‐dependent manner, suggesting LADA is part of a continuum spectrum between type 1 and type 2 diabetes. Although LADA is the most frequent form of autoimmune diabetes diagnosed in adults, clinical trials involving LADA are scarce. Here we review the recent advancements in LADA epidemiology, clinical features, pathogenesis, and interventions. We also highlight the environmental factors that are thought to play an important role in addition to genetics in the pathogenesis of LADA. In the future, high‐throughput molecular profiles might shed light on the nature of LADA among the wide spectrum of diabetes and offer new opportunities to identify novel LADA‐specific biomarkers.
Colonization and extinction dynamics among the plant species at tree bases in Paris (France)
Authors: Omar Mona , Schneider‐Maunoury Laure , Barré Kévin , Al Sayed Nazir , Halwani Jalal , Machon Nathalie
Published: July 2019

In cities, trees planted along streets could play an important ecological role for spontaneous plants growing at their bases. For example, these trees could represent corridors by potentially connecting large green spaces (e.g., parks, gardens), which allow species to move within the urban matrix. We considered sets of urban trees in 15 streets in Paris, France, as metapopulations for 15 plant species. Our objective was to determine the factors influencing the dynamics of colonization and extinction of populations based on the distance of the streets to green spaces and biological traits of each species.

Plant species in 1,324 tree bases of the Bercy District of Paris were surveyed annually from 2009 to 2015. For each species and each street, we used SPOMSIM software to identify the best‐fit metapopulation model between four models with different colonization and extinction functions: propagule rain model (PRM) and Levins’ model with or without rescue effect.

Results demonstrated that species more often conformed to the PRM in streets near green spaces, which suggested that green spaces could act as sources for the populations in those streets. Species with seeds with long‐term persistence more often conformed to the PRM, indicating that a soil seed bank helps species invade entire streets. Finally, a higher percentage of species with a short height conformed to models with a rescue effect, which indicated that those small species resisted the effects of weeding by the city technical services better than taller species.

Synthesis and applications. This study showed how biological traits of species and geography of the district determine the dynamics of plants in the streets, and these results may provide important information for biodiversity management in cities.
Niche differentiation in rainforest ant communities across three continents
Authors: Grevé Michael E. , Houadria Mickal , Andersen Alan N. , Menzel Florian
Published: July 2019

A central prediction of niche theory is that biotic communities are structured by niche differentiation arising from competition. To date, there have been numerous studies of niche differentiation in local ant communities, but little attention has been given to the macroecology of niche differentiation, including the extent to which particular biomes show distinctive patterns of niche structure across their global ranges. We investigated patterns of niche differentiation and competition in ant communities in tropical rainforests, using different baits reflecting the natural food spectrum. We examined the extent of temporal and dietary niche differentiation and spatial segregation of ant communities at five rainforest sites in the neotropics, paleotropics, and tropical Australia. Despite high niche overlap, we found significant dietary and temporal niche differentiation in every site. However, there was no spatial segregation among foraging ants at the community level, despite strong competition for preferred food resources. Although sucrose, melezitose, and dead insects attracted most ants, some species preferentially foraged on seeds, living insects, or bird feces. Moreover, most sites harbored more diurnal than nocturnal species. Overall niche differentiation was strongest in the least diverse site, possibly due to its lower number of rare species. Both temporal and dietary differentiation thus had strong effects on the ant assemblages, but their relative importance varied markedly among sites. Our analyses show that patterns of niche differentiation in ant communities are highly idiosyncratic even within a biome, such that a mechanistic understanding of the drivers of niche structure in ant communities remains elusive.
Encapsulation of Chaotropic closo‐Decahydrodecaborate Clusters Within Cyclodextrins: Synthesis, Solution Studies, and DFT Calculations
Authors: Diab Manal , Floquet Sébastien , Haouas Mohamed , Abramov Pavel A. , López Xavier , Landy David , Damond Aurélie , Falaise Clément , Guérineau Vincent , Touboul David , Naoufal Daoud , Cadot Emmanuel
Published: July 2019

This paper deals with the formation of host‐guest systems between cyclodextrins and the closo‐decahydrodecaborate cluster. The inclusion processes, although involving weak interaction, were evidenced in solution by ESI‐MS and various NMR techniques. ITC measurements provided thermodynamic parameters, and DFT calculations gave some elements that help in understanding these processes.
A Ghost Trapped: Realization of the 1‐Titanacyclobuta‐2,3‐diene as the First Four‐Membered Group 4 Metallacycloallene
Authors: Rosenthal U.
Published: July 2019

Very recently the synthesis of the first four‐membered metallacycloallene of a group 4 metal, the very unusual 1‐titanacyclobuta‐2,3‐diene [rac‐(ebthi)Ti[‐C(SiMe3)=C=C(SiMe3)‐] (rac‐ebthi = rac‐1,2‐ethylene‐1,1′‐bis(η5‐tetrahydroindenyl)) was reported by Reiß and Beweries. This complex has its own story since 2004 when the five‐membered metallacycloallene was proposed, for which later many examples were described. Over the years several studies have described preparative and computational attempts to stabilize and describe such a complex, before the successful synthesis of the above mentioned smaller four‐membered metallacycloallene. Only by appropriate variation of the cyclopentadienyl ligand of the titanocene complex it was possible now to realize this highly strained compound.
An Expeditious and Environmentally‐Benign Approach to 2‐Aryl/Heteroaryl Selenopyridines via Ruthenium Catalyzed [2+2+2] Cycloadditions
Authors: Kalaramna Pratibha , Bhatt Divya , Sharma Himanshu , Goswami Avijit
Published: July 2019

A highly efficient protocol for the synthesis of 2‐aryl/ hetero aryl selenopyridines has been developed via a ruthenium(II)‐catalyzed cycloaddition reaction of 1,6‐diynes with aryl/heteroaryl selenocyanates with good to excellent yields. It was found that various diynes and selenocyanates expediently underwent the reaction under open‐flask conditions. This atom‐economical catalytic strategy offers a mild and practical approach to access a variety of such cycloadducts with excellent regioselectivities.
Reactive and Nonreactive Ball Milling of Tin‐Antimony (Sn‐Sb) Composites and Their Use as Electrodes for Sodium‐Ion Batteries with Glyme Electrolyte
Authors: Brehm Wolfgang , Buchheim Johannes Rolf , Adelhelm Philipp
Published: July 2019

Tin (Sn), antimony (Sb), as well as their intermetallic compound SnSb are potential high‐capacity negative electrodes for lithium‐ or sodium‐ion batteries. Starting from bulk Sn and Sb, the effect of ball milling in sodium‐ion half cells with a diglyme‐based electrolyte is studied. Nonreactive ball milling of Sn, Sb, and carbon leads to intimately mixed but largely phase‐separated composites (Sn + Sb) with electrochemical sodiation behavior being the sum of the individual phases. Thereby, Sb shows an unusual and rapid capacity fade in the chosen electrolyte which is unexpected, considering the usually excellent compatibility of diglyme‐based electrolytes with negative electrodes. Reactive ball milling of Sn and Sb using a planetary ball mill leads to the phase‐pure intermetallic compound β‐SnSb. Compared with Sn + Sb, SnSb shows excellent performance with a specific capacity exceeding 400 mAh g−1 after 190 cycles and a high rate capability (around 400 mAh g−1 at 5 C). Hence, herein, Sb is largely inactive as a pure phase but active when bound in the β‐SnSb intermetallic compound. Using in situ electrochemical dilatometry, the “breathing” of the electrodes during charging/discharging is minimized by optimizing ball‐milling time, which improves cycle life.
Aligned Electrospun Carbon Nanofibers as Electrodes for Vanadium Redox Flow Batteries
Authors: Zhang Zhihui , Bai Bofeng , Zeng Lin , Wei Lei , Zhao Tianshou
Published: July 2019

Electrospun carbon nanofibers (CNFs) are regarded as potential electrode materials for vanadium redox flow batteries (VRFBs) due to the advantages of a large surface area and good electrochemical activity. However, woven CNFs with randomly distributed fibers are limited by poor permeability of the electrolyte, thus leading to a large mass‐transport polarization during battery operation. To address this issue, aligned carbon nanofiber (ACNF) webs are fabricated and applied in the battery with fibers parallel to the flow channel. Cyclic voltammogram results show that the as‐prepared aligned electrode exhibits better electrochemical activity for both the VO2+/VO2+ and V2+/V3+ redox reactions than that of commercial carbon paper (CP) and random electrodes, attributing to its higher surface area and favorable surface activity. The battery with the ACNF electrode achieves higher voltage efficiency (87%, 60 mA cm−2) than that of CP and random electrodes. Moreover, the ordered structure of the aligned electrode further enhances mass transport effectively, thus lowering the concentration loss. The polarization curve measurements also show that the limiting current density of the aligned electrode is 25% higher than that of the random electrode. All these results demonstrate that the aligned electrode is promising in VRFBs.