bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractLinear 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

AbstractAn 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 SummaryMedicaid 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

AbstractConcentration 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

AbstractBreast 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

AbstractHere 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.
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

AbstractThe 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

AbstractIn 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

AbstractThis 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

AbstractIm 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

AbstractChagas 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.
Special issue: 2016 International Conference on Information Technology in Medicine and Education (ITME2016)
Authors: Chen Jinjun 
Published: July 2019

SummaryThis 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

AbstractNiFeOx 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

AbstractMolybdenum 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

SummaryThe 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

SummaryIn 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.