bluuebunny/crossref_metadata_2025 huggingface dataset:
Plurality in biomedical research: Multiple institutional affiliations are associated with improved research output
Authors: Sanfilippo Paul , Hewitt Alex W , Mackey David A
Published: March 2018

Background. The institutional affiliations and associated collaborative networks that scientists foster during their research careers are salient in the production of high quality science. The phenomenon of multiple institutional affiliations and its relationship to research output remains relatively unexplored in the literature.

Methods. We examined 27,612 scientific articles, modelling the citation counts received against the number of authors and affiliations held.

Results. In agreement with previous research, we found that teamwork is an important factor in high impact papers, with average citations received increasing concordant with the number of co-authors listed. For articles with more than five co-authors, we noted an increase in average citations received when authors with more than one institutional affiliation contributed to the research.

Discussion. Multiple author affiliations may play a positive role in the production of high-impact science. This ‘polygamous’ behavior, sometimes shunned by institutional board, should instead be viewed as meritorious in the pursuit of scientific discovery.
The Role of Shoe and Sock Sanitization in the Management of Superficial Fungal Infections of the Feet
Authors: Gupta Aditya K. , Versteeg Sarah G.
Published: March 2018

Because of the ubiquitous nature of dermatophytes and a lack of an adaptive immune response in the nail plate, recurrence and relapse rates associated with superficial fungal infections are high (10%–53%). Cured or improved dermatophytosis patients could become reinfected if exposed to fungal reservoirs, such as an infected shoe, sock, or textile. To prevent this, footwear, sock, and textile sanitization methods can be used. To provide insight into effective sanitization options, the focus of this article is to review footwear, sock, and textile sanitization studies conducted throughout history (1920–2016). Thirty-three studies are covered in this review, encompassing techniques ranging from formaldehyde fumigation and foot powder application, to more modern approaches such as UV light and silver-light irradiation technologies. Older sanitization methods (eg, boiling, use of chlorine and salts) are quite limited in their practicality, as they can result in health complications and ruin shoe integrity. Newer approaches to shoe and sock sanitization, such as ozone application and UV irradiation, have shown very promising results. Further research is still needed with these modern techniques, as knowledge gaps and cost prevent the creation of standardized parameters for successful use. By combining sanitization methods with other preventative measures, protection against reinfection may be enhanced.
A compartmentalized signaling network mediates crossover control in meiosis
Authors: Zhang Liangyu , Köhler Simone , Rillo-Bohn Regina , Dernburg Abby F
Published: March 2018

During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation.
CRISPR-based herd immunity can limit phage epidemics in bacterial populations
Authors: Payne Pavel , Geyrhofer Lukas , Barton Nicholas H , Bollback Jonathan P
Published: March 2018

Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity.
Myotubularin related protein-2 and its phospholipid substrate PIP2 control Piezo2-mediated mechanotransduction in peripheral sensory neurons
Authors: Narayanan Pratibha , Hütte Meike , Kudryasheva Galina , Taberner Francisco J , Lechner Stefan G , Rehfeldt Florian , Gomez-Varela David , Schmidt Manuela
Published: March 2018

Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes in DRG appeared largely unaffected by Mtmr2. Experiments with catalytically inactive Mtmr2, pharmacological blockers of PI(3,5)P2 synthesis, and osmotic stress suggest that Mtmr2-dependent Piezo2 inhibition involves depletion of PI(3,5)P2. Further, we identified a PI(3,5)P2 binding region in Piezo2, but not Piezo1, that confers sensitivity to Mtmr2 as indicated by functional analysis of a domain-swapped Piezo2 mutant. Altogether, our results propose local PI(3,5)P2 modulation via Mtmr2 in the vicinity of Piezo2 as a novel mechanism to dynamically control Piezo2-dependent mechanotransduction in peripheral sensory neurons.
Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
Authors: Schürmann Sabine , Steffes Georg , Manikowski Dominique , Kastl Philipp , Malkus Ursula , Bandari Shyam , Ohlig Stefanie , Ortmann Corinna , Rebollido-Rios Rocio , Otto Mandy , Nüsse Harald , Hoffmann Daniel , Klämbt Christian , Galic Milos , Klingauf Jürgen , Grobe Kay
Published: March 2018

Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3–4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3–4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions.
Activation of CD4 and CD8 T cell receptors and regulatory T cells in response to human proteins
Authors: Arneth Borros M.
Published: March 2018

This study assessed in detail the influence of four different human proteins on the activation of CD4+ and CD8+ T lymphocytes and on the formation of regulatory T cells. Human whole-blood samples were incubated with four different human proteins. The effects of these proteins on the downstream immune-system response, on the expression of extracellular activation markers on and intracellular cytokines in T lymphocytes, and on the number of regulatory T cells (T-reg cells) were investigated via flow cytometry. Incubation with β-actin or glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which are cytoplasmic proteins, increased the expression of both extracellular activation markers (CD69 and HLA-DR) and intracellular cytokines but did not significantly affect the number of T-reg cells. In contrast, incubation with human albumin or insulin, which are serum proteins, reduced both extracellular activation markers and intracellular cytokine expression and subsequently increased the number of T-reg cells. These findings may help to explain the etiological basis of autoimmune diseases.
Presumptive Color Tests of Seized Drugs
Authors: Hafer Kaitlin E. , Brettell Thomas A.
Published: March 2018

Chemical color tests have been used in the field of forensic science for quite some time. They have proven particularly useful in the screening process of unknown seized drugs in the field, as well as in a laboratory setting. The colors produced by these quick, sensitive, and inexpensive tests can indicate both the presence and the absence of a controlled substance. In most recent years, new psychoactive substances have quickly become available on the market. Due to the frequency at which these substances are developed, newer chemical tests and the manners in which they are interpreted have also evolved. This article provides a discussion on color, color tests, and some of the color test reagents that are most commonly used. Recent developments within the field, as well as examples of the role that color test results play in court, is also discussed.
Neutron Diffraction and Neutron Imaging with Compact Neutron Source
Authors: Otake Yoshie
Published: March 2018

A compact neutron source using a particle accelerator is a promising tool for practical material analysis, infrastructural diagnostics, nuclear detection, and medical treatment. We have been operating the neutron source RANS (RIKEN accelerator‐driven compact neutron source) with 7 MV proton linac and a beryllium target for 5 years and learned a lot about experiment, maintenance, and safety management. In recent years, imaging with fast neutrons, engineering diffraction for texture evolution estimation and austenite volume fraction, and prompt‐gamma neutron analysis (PGA) are the major activities.

Here, neutron diffraction and imaging methods with compact neutron source will be explained.
Fluorescence Spectroscopy to Probe Ionic Liquid‐Based Systems
Authors: Pandey Siddharth , Trivedi Shruti , Pandey Shubha
Published: March 2018

Owing to its inherent sensitivity coupled with multidimensionality, fluorescence spectroscopy has established itself as a versatile tool to investigate complex chemical systems in analytical chemistry. Ionic liquids, for the last couple of decades or so, have emerged as intriguing modern materials in science and technology that display an array of useful and sometimes unconventional features. Steady‐state fluorescence intensity and anisotropy and time‐resolved excited‐state emission intensity and anisotropy decays along with other advanced fluorescence techniques have been employed effectively to analyze, characterize, and explore ionic liquids and ionic liquid‐based systems. The extent of dipolarity afforded by ionic liquids as well as cosolvent/supercritical fluid‐added ionic liquid systems is readily manifested through the response of judiciously selected fluorescence polarity probes. Transient solvation measurements carried out by means of time‐resolved fluorescence measurements are particularly powerful for their ability to parameterize the kinetics of the solvation process within ionic liquids. Dynamic Stokes' shift of appropriate fluorescence probes reveals the presence of several components, thus highlighting the complexity of solvation within ionic liquids and ionic liquid‐based media. Various fluorescence spectroscopic tools are used to establish and characterize macromolecular (surfactant and polymer) and dye aggregation within ionic liquids and ionic liquid‐based media along with aggregation of surface‐active ionic liquids (SAILs) in water.
Optimizing the target detectability of cone beam CT performed in image‐guided radiation therapy for patients of different body sizes
Authors: Yang Ching‐Ching , Yu Pei‐Chieh , Ruan Jau‐Ming , Chen Yu‐Cheng
Published: March 2018

Purpose

The target detectability of cone beam computed tomography (CBCT) performed in image‐guided radiation therapy (IGRT) was investigated to achieve sufficient image quality for patient positioning over a course of treatment session while maintaining radiation exposure from CBCT imaging as low as reasonably achievable (ALARA).

Methods

Body CBCT scans operated in half‐fan mode were acquired with three different protocols: CBCTlowD, CBCTmidD, and CBCThighD, which resulted in weighted CT dose index (CTDIw) of 0.36, 1.43, and 2.78 cGy, respectively. An electron density phantom that is 18 cm in diameter was covered by four layers of 2.5‐cm‐thick bolus to simulate patients of different body sizes. Multivariate analysis was used to examine the impact of body size, radiation exposure, and tissue type on the target detectability of CBCT imaging, quantified as contrast‐to‐noise ratio (CNR).

Results

CBCTmidD allows sufficient target detection of adipose, breast, muscle, liver in a background of water for normal‐weight adults with cross‐sectional diameter less than 28 cm, while CBCThighD is suitable for adult patients with larger body sizes or body mass index over 25 kg/m2. Once the cross‐sectional diameter of adult patients is larger than 35 cm, the CTDIw of CBCT scans should be higher than 2.78 cGy to achieve required CNR. As for pediatric and adolescent patients with cross‐sectional diameter less than 25 cm, CBCTlowD is able to produce images with sufficient target detection.

Conclusion

The target detectability of soft tissues in default CBCT scans may not be sufficient for overweight or obese adults. Contrary, pediatric and adolescent patients would receive unnecessarily high radiation exposure from default CBCT scans. Therefore, the selection of acquisition parameters for CBCT scans optimized according to patient body size was proposed to ensure sufficient image quality for daily patient positioning in radiation therapy while achieving the ALARA principle.
Functional lifespans of xylem vessels: Development, hydraulic function, and post‐function of vessels in several species of woody plants
Authors: Jacobsen Anna L. , Valdovinos‐Ayala Jessica , Pratt R. Brandon
Published: March 2018

Premise of the Study

Xylem vessels transition through different stages during their functional lifespan, including expansion and development of vessel elements, transition to vessel hydraulic functionality, and eventual transition to post‐functionality. We used information on vessel development and function to develop a model of vessel lifespan for woody plants.

Methods

We examined vessel functional lifespan using repeated anatomical sampling throughout the growing season, combined with active‐xylem staining to evaluate vessel hydraulic transport functionality. These data were combined with a literature review. The transitions between vessel functional lifespans for several species are illustrated, including grapevine (Vitis vinifera L., Vitaceae), English oak (Quercus robur L., Fagaceae), American chestnut [Castanea dentata (Marshall) Borkh.; Fagaceae], and several arid and semi‐arid shrub species.

Key Results

In intact woody plants, development and maturation of vessel elements may be gradual. Once hydraulically functional, vessel elements connect to form a vessel network that is responsible for bulk hydraulic flow through the xylem. Vessels become nonfunctional due to the formation of gas emboli. In some species and under some conditions, vessel functionality of embolized conduits may be restored through refilling. Blockages, such as tyloses, gels, or gums, indicate permanent losses in hydraulic functional capacity; however, there may be some interesting exceptions to permanent loss of functionality for gel‐based blockages.

Conclusions

The gradual development and maturation of vessel elements in woody plants, variation in the onset of functionality between different populations of vessels throughout the growing season, and differences in the timing of vessel transitions to post‐functionality are important aspects of plant hydraulic function.
Anwendung der analytischen Pyrolyse zur Untersuchung organischer Materialien in Kulturgütern
Authors: Degano Ilaria , Modugno Francesca , Bonaduce Ilaria , Ribechini Erika , Colombini Maria Perla
Published: March 2018

Bei der molekulare Charakterisierung von organischen Materialien in Proben von Kunstwerken und historischen Objekten wird traditionell die qualitative und quantitative Analyse mittels HPLC und GC durchgeführt. Heutige Ansätze, basierend auf analytischer Pyrolyse, ermöglichen die Analyse von Proben ohne chemische Vorbehandlung. Die Pyrolyse, die bisher oft als Screening‐Methode angesehen wurde, birgt bisher unerkannte Möglichkeiten dank jüngster Entwicklungen in der instrumentellen Analytik. Organische Materialien makromolekularer Natur oder solche, die während des Trocknens und Alterns polymerisieren, können nun besser untersucht werden. Farbschichten und archäologische organische Substanzen beinhalten oft als Hauptbestandteil unlösliche und chemisch nicht‐hydrolisierbare Bestandteile, die durch GC und HPLC nicht zugänglich sind. Bis zum heutigen Tage haben sich die wissenschaftlichen Untersuchungen organischer Bestandteile von Kunstgegenständen und historischen Objekten vor allem auf die löslichen Nebenbestandteile beschränkt. Dieser Kurzaufsatz präsentiert die jüngsten Fortschritte bei qualitativen und semiquantitativen Analysen von organischen Materialien in Kulturgütern, basierend auf analytischer Pyrolyse gekoppelt mit Massenspektrometrie.
Synthesis, characterization, density functional theory, X‐ray study, thermal stability, and biological and MOE relevance of metal complexes of griseofulvin
Authors: Mahmoud Walaa H. , Mahmoud Nessma F. , Mohamed Gehad G.
Published: March 2018

Metal(II) and metal(III) coordination compounds of griseofulvin (GFV) drug were synthesized. The structure of the ligand was determined on the basis of elemental analyses, infrared and 1H NMR spectroscopies and thermal studies. GFV behaved as a neutral tridentate chelating agent and coordinated to metal ions through three oxygen atoms: two methoxy groups and oxygen atom of furan ring. Metal complexes were characterized by means of elemental analyses and molar conductance, spectral (infrared, electron spin resonance) and thermal studies. All the complexes showed molar conductance behaviour corresponding to an electrolytic nature. All the complexes showed octahedral geometry, except [Zn(GFV)Cl]Cl that showed tetrahedral geometry. Density functional theory (DFT) calculations were employed to understand and estimate the contribution of each interaction in the formation of the assembly using several theoretical models. The computed parameters from DFT calculations for structure optimizations and vibrational frequencies were in good agreement with the experimental data. Newly synthesized metal complexes in addition to GFV were examined against opportunistic pathogens. The biological applications of complexes were studied with two Gram‐positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram‐negative bacteria (Escherichia coli and Neisseria gonorrhoeae) as well as their antifungal activity against Candida albicans. Results suggested that metal complexes were more biologically sensitive than free ligand. The complexes showed a moderate inhibition of MCF7 breast cancer cell line growth. Molecular docking studies further helped in understanding the mode of action of the compounds through their various interactions with the crystal structures of: human serum albumin (PDB: 5FUO), Staphylococcus aureus nucleoside (PDB: 3Q8U), human acetylcholinesterase (PDB: 1B41) and the human DNA–Topo I complex (PDB: 1SC7).
Impact of cobalt as dopant on surface morphologies of undoped ZnO nanostructured thin films
Authors: Ali Arshid M. , Mahpudz Aishah , Basahel Abdulrahman , Saeed Usman , Taimoor Aqeel Ahmad , Rather Sami U. , Zhang Hui
Published: March 2018

This study is aimed to investigate the effect of cobalt, as dopant, on the surface morphologies of nanostructured ZnO thin films. Four different cobalt‐doped ZnO morphologies were prepared by low‐temperature hydrothermal solution deposition, on 2 different substrates—clean glass (CG) and direct‐current magnetron‐sputtered (MS) ZnO glass. An inverse relationship between dopant concentration and grain size was obtained in morphologies obtained from the mixture of solution Zn(NO3)2 + HMT + Co(NO)3.6H2O. No specific relationship exists for those obtained from the mixture of solution Zn(NO3)2 + HMT + PEI + Co(NO)3.6H2O. In general, morphologies obtained from a mixture Zn(NO3)2 + HMT + Co(NO)3.6H2O and Zn(NO3)2 + HMT + PEI + Co(NO)3.6H2O, on MS and CG substrate, vary in grain size (both in length and diameter), crystal population, morphology, film thickness, and crystallinity on films grown on both MS and CG substrates. An increased volumetric size is observed with the increased concentration of cobalt. Lowering the pH—even by 1 magnitude—makes the MS template less effective at aligning the growth of ZnO crystals, giving a decreased crystal packing density.
Poly(hexane succinate) plasticizer designed for poly(vinyl chloride) with a high efficiency, nontoxicity, and improved migration resistance
Authors: Gao Chuanhui , Zhang Xinhua , Sun Jiawen , Yuan Zhen , Han Shijian , Liu Yuetao , Ji Shufang
Published: March 2018

Poly(hexane succinate) (PHS) was designed as an alternative type of polyester plasticizer for the modification of poly(vinyl chloride) (PVC). The plasticizing effect of PHS was studied and compared with the traditional dioctyl phthalate (DOP) plasticizer. The results show that the PVC plasticized by PHS had the lowest tensile strength of 15.3 MPa and the highest elongation at break of 105.1% when 35 phr PHS was added. It also exhibited a lower glass‐transition temperature than PVC plasticized by DOP (PVC–DOP); this could be explained by the improvement of free volume for the amorphous part of PVC enhanced by high‐molecular‐weight PHS. The migration‐resistant properties of PVC–PHS was greatly superior to those of PVC–DOP. All of these results illustrate that PHS had a higher plasticizing efficiency than DOP for PVC. PHS could be used as an alternative plasticizer to remove the potential health risks of phthalates migrating out during applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46388.
Electrostatic and mechanical properties of extrusion spun PTFE monofilament with integration of microtourmaline particles
Authors: Mao Haiwen , Ma Pibo , Jiang Gaoming
Published: March 2018

This study reports on polytetrafluoroethylene (PTFE) monofilaments prepared by extrusion spinning with the integration of tourmaline particles. The resultant PTFE monofilaments have excellent electrostatic properties and contain different amounts and sizes of tourmaline particles. Tensile tests show that the PTFE monofilaments with 7 wt % and 1 wt % of 5 μm particles possessed tensile strengths of 1175 N and 1026 N, which were 12.5% and 23.6% lower than those of the pure PTFE monofilament, respectively. In electrostatic properties, there was 14.3% growth in surface voltage compared with the original PTFE monofilament in the series of monofilaments with varying content of tourmaline particles. When the particle size was 5 μm, the voltage was 14.7% higher than that of pure PTFE monofilament in the series of monofilaments with varying sizes of tourmaline particles. In addition, a model of electric field distribution around the monofilament was proposed based on a static electricity test. Successful research on such an intriguing monofilament might provide a novel application of the PTFE and tourmaline. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46401.
Crystallinity of poly(arylene ether nitrile) copolymers containing hydroquinone and bisphenol A segments
Authors: Tu Ling , You Yong , Tong Lifen , Wang Yajie , Hu Weibin , Wei Renbo , Liu Xiaobo
Published: March 2018

The hydroquinone (HQ) and bisphenol A (BPA) type poly(arylene ether nitrile) (PEN) (HQ/BPA‐PEN) were synthesized through nucleophilic aromatic substitution polymerization from HQ, BPA, and 2,6‐dichlorobenzonitrile (DCBN). The prepared copolymers were characterized by intrinsic viscosity, Fourier transform infrared (FTIR), and dynamic rheological analysis. The properties of resultant copolymers were studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and mechanical testing. The results showed that the PEN copolymers exhibited crystallization performance with excellent thermal and mechanical properties. HQ/BPA‐PEN10 was made into films by solution‐casting process and then were treated at different temperatures (200, 260, 280, 300, 310, and 320 °C) for different times (1, 2, 3, 4, and 5 h) to investigate the crystallinity. Results showed that when isothermal treatment temperature is 310 °C and isothermal treating time is 4 h, HQ/BPA‐PEN10 showed best properties. At this condition, the melting enthalpy, crystallinity, tensile strength, and elongation at break of the sample is 17.7 J/g, 14.11%, 132.9 MPa, and 6.1%, respectively. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2018,135, 46412.
Metal‐Nitrogen‐doped Porous Carbons Derived from Metal‐Containing Ionic Liquids for Oxygen Reduction Reaction
Authors: Wang Cancan , Guo Jiangna , Xu Dan , Zhang Juewen , Chen Muzi , Yan Feng
Published: March 2018

This study describes a self‐doping and additive‐free strategy for the synthesis of metal‐nitrogen‐doped porous carbon materials (CMs) via carbonizing well‐tailored precursors, metal‐containing ionic liquids (M‐ILs). The organic skeleton in M‐ILs serves as both carbon and nitrogen sources, while metal ions acts as porogen and metallic dopants. A high nitrogen content, appropriate content of metallic species and hierarchical porosity synergistically endow the resultant CMs (MIBA‐M‐T) as effective electrocatalysts for the oxygen reduction reaction (ORR). MIBA‐Fe‐900 with a high specific surface area of 1567 m2 g−1 exhibits an activity similar to that of Pt/C catalyst, a higher tolerance to methanol than Pt/C, and long‐term durability. This work supplies a simple and convenient route for the preparation of metal‐containing carbon electrocatalysts.
Design and Experimental Evaluation of a Discrete‐time ASPR‐based Adaptive Output Feedback Control System Using FRIT
Authors: Guan Zhe , Wakitani Shin , Mizumoto Ikuro , Yamamoto Toru
Published: March 2018

This paper describes the design of an adaptive output feedback control system in discrete‐time, based on almost strictly positive real (ASPR)‐ness with a feedforward input. It is well‐known that an adaptive output feedback control system based on ASPR conditions can achieve asymptotic stability via a constant feedback gain. Unfortunately, most realistic systems are not ASPR because of the severe conditions. The introduction of a parallel feedforward compensator (PFC) is an efficient way to alleviate such restrictions. However, the problem remains that there exists a steady state error between the output of the augmented system and the output of the original system. The proposed scheme provides a strategy wherein the feedforward input is utilized such that the steady state error is removed. Furthermore, the fictitious reference iterative tuning (FRIT) approach is employed to determine the control parameters using one‐shot input/output experimental data directly, without prior information about the control system. This paper explains how the FRIT approach is applied in designing an adaptive output feedback control system. The effectiveness of the proposed scheme is confirmed experimentally, by using a motor application.
Loss and Rebirth of the Animal Microtubule Organizing Center: How Maternal Expression of Centrosomal Proteins Cooperates with the Sperm Centriole in Zygotic Centrosome Reformation
Authors: Inoue Daigo , Wittbrodt Joachim , Gruss Oliver J.
Published: March 2018

Centrosomes are the main microtubule organizing centers in animal cells. In particular during embryogenesis, they ensure faithful spindle formation and proper cell divisions. As metazoan centrosomes are eliminated during oogenesis, they have to be reassembled upon fertilization. Most metazoans use the sperm centrioles as templates for new centrosome biogenesis while the egg's cytoplasm re‐prepares all components for on‐going centrosome duplication in rapidly dividing embryonic cells. We discuss our knowledge and the experimental challenges to analyze zygotic centrosome reformation, which requires genetic experiments to enable scrutinizing respective male and female contributions. Male and female knockout animals and mRNA injection to mimic maternal expression of centrosomal proteins could point a way to the systematic molecular dissection of the process. The most recent data suggest that timely expression of centrosome components in oocytes is the key to zygotic centrosome reformation that uses male sperm as coordinators for de novo centrosome production.
Lipidomics of CHO Cell Bioprocessing: Relation to Cell Growth and Specific Productivity of a Monoclonal Antibody
Authors: Ali Amr S. , Raju Ravali , Ray Somak , Kshirsagar Rashmi , Gilbert Alan , Zang Li , Karger Barry L.
Published: March 2018

As the demand for biological therapeutic proteins rises, there is an increasing need for robust and highly efficient bioprocesses, specifically, maximizing protein production by controlling the cellular nutritional and metabolic needs. A comprehensive lipidomics analysis has been performed, for the first time, over the time course of CHO cells producing an IgG1 monoclonal antibody (mAb) with fed batch 5 L bioreactors. The dynamic nature and importance of the CHO lipidome, especially on cellular growth and specific productivity, is demonstrated. A robust LC‐MS method using positive and negative mode ESI was developed for lipid identification and quantitation of 377 unique lipids. The analysis revealed large changes in lipid features between the different days in bioprocessing including accumulation of triacylglycerol (TG) and lysophospholipid species with depletion of diacylglycerol (DG) species. Exploring pathway analysis where the lipid data was combined with polar metabolites and transcriptomics (RNA sequencing) revealed differences in lipid metabolism between the various stages of cellular growth and highlighted the role of key features of lipid metabolism on cell growth and specific productivity. The study demonstrates the importance of lipidomics in the expanding role of ‘Omics methodologies in gaining insight into cellular behavior during protein production in a fed batch bioprocess.
Relationship of employment status and socio‐economic factors with distress levels and counselling outcomes during a recession
Authors: Berzins Sandy , Babins‐Wagner Robbie , Hyland Kathleen
Published: March 2018

Background

Social inequalities may be magnified during times of economic growth and recession when unemployment levels increase and income opportunities diminish. During a recession with high regional unemployment levels, can therapists expect the same improvements from therapy as they could in good economic times? The aim of this naturalistic study was to use routinely collected outcome measurement data to explore the relationships between unemployment status and client level of distress at the start and completion of counselling.

Methods

The sample included 20,690 clients from Calgary Counselling Centre (CCC) who received counselling between January 2013 and December 2016, and completed the Outcome Questionnaire‐45.2 (OQ) (Lambert, Gregersen & Burlingame, 2004) at both the first and last sessions. Relationships between employment status and level of distress at first and last counselling sessions for these clients were assessed using cross‐tabulations, chi‐square and one‐way analysis of variance tests of significance.

Results

Less improvement was gained from counselling during the recession period than during the boom, and outcomes were affected by age, gender and income level differentially for employed and unemployed clients.

Discussion

Routine outcome data can be utilised at an agency/community level to illustrate the effect of socio‐economic factors on mental health status and treatment outcomes in the general population as well as on community mental health service utilisation. Employment status affects the sociodemographic profile of clients attending a community mental health centre, which in turn affects counselling outcomes overall.
Anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS), fractional flow reserve‐ and intravascular ultrasound‐guided management in adult patients
Authors: Driesen Bart W. , Warmerdam Evangeline G. , Sieswerda Gert‐Jan T. , Schoof Paul H. , Meijboom Folkert J. , Haas Felix , Stella Pieter R. , Kraaijeveld Adriaan O. , Evens Fabiola C. M. , Doevendans Pieter A. F. M. , Krings Gregor J. , van Dijk Arie P. J. , Voskuil Michiel
Published: March 2018

Objectives

To describe the use of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) in the evaluation of patients with anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS).

Background

ACAOS of the right and left coronary are rare, but may lead to symptoms and impose a risk for sudden cardiac death, depending on several anatomical features. Assessment and risk estimation is challenging in (nonathlete) adults, especially if they present without symptoms or with atypical complaints.

Methods

The team retrospectively studied 30 consecutive patients with ACAOS with interarterial course, who received IVUS‐ and FFR‐guided treatment at our institution between October 2010 and September 2017.

Results

FFR was abnormal in only seven patients. IVUS showed the typical slit‐like anatomy of the orifice in 23 patients. Based on FFR and/or IVUS results, in conjunction with the clinical presentation, clinical decision was made. A decision for intervention was made if at least two out of three entities were abnormal. Intervention implied unroofing of the coronary artery (n = 10) or coronary artery bypass grafting (n = 1). In all other patients a conservative strategy was followed. No adverse events occurred in the total population after a median of 37 (0–62) months of follow‐up.

Conclusions

Conservative treatment may be justifiable in adult patients with ACAOS in the presence of normal FFR and nonsuspicious symptoms, despite the presence of an interarterial course and/or slitlike orifice on IVUS. We recommend the use of FFR and IVUS in the standard work‐up for adult patients with ACAOS and propose the use of a flowchart to aid in decision‐making.
Generalized tetanus in adults without antitetanus booster vaccination in southern Mauritania
Authors: Boushab Boushab Mohamed , Fall‐Malick Fatim‐Zahra , Savadogo Mamoudou , Basco Leonardo K.
Published: March 2018

Key Clinical Message

Tetanus has become rare in countries with high levels of vaccination coverage and hygiene but may still occur in adults without booster vaccination. In addition to the expanded program on immunization for children and maternal immunization against neonatal tetanus, a systematic vaccination of the population, including boosters, is recommended.
Electrospun BiOCl/Bi2Ti2O7 Nanorod Heterostructures with Enhanced Solar Light Efficiency in the Photocatalytic Degradation of Tetracycline Hydrochloride
Authors: Xu Yuxian , Lin Daifeng , Liu Xinping , Luo Yongjin , Xue Hun , Huang Baoquan , Chen Qinghua , Qian Qingrong
Published: March 2018

Bismuth titanates (BTs) can be fabricated by electrospinning combined with calcination at different temperatures. BiOCl/Bi2Ti2O7 nanorod heterostructures were obtained at 500 °C. They possess excellent photocatalytic efficiency and stability for tetracycline hydrochloride (TC‐HCl) degradation under simulated solar light. The excellent catalytic activity is predominantly attributed to the heterostructure between BiOCl and Bi2Ti2O7, which accelerates the separation of photogenerated carriers while the narrow band gap of Bi2Ti2O7 enhances solar energy utilization. On the basis of energy band engineering, scavenger tests, and LC‐HRMS analysis, a possible degradation pathway of TC‐HCl and photocatalytic mechanism were proposed. Our work can predict a facile route for achieving high photocatalytic performance of Bi2Ti2O7‐based materials in the application of TC‐HCl degradation.
Investigation of the Redox and Acid‐Base properties of TCNQF and TCNQF2: Electrochemistry, Vibrational Spectroscopy, and Substituent Effects
Authors: Vo Nguyen , Haworth Naomi L. , Bond Alan M. , Martin Lisandra L.
Published: March 2018

The electrochemistry and acid‐base chemistry of TCNQF and TCNQF2 (TCNQ=7,7,8,8‐tetracyanoquinodimethane) are described, and the results are compared to those reported previously for TCNQ and TCNQF4. In acetonitrile solution, both mono‐ and di‐fluorinated TCNQ derivatives show two well‐resolved, diffusion‐controlled chemically and electrochemically reversible one‐electron‐transfer processes under the conditions of cyclic voltammetry. The reversible potentials of the mono‐ and difluoro‐TCNQ were determined for both the monoanionic and dianionic processes, that is, TCNQF0/1−/2− and TCNQF20/1−/2−. A Hammett plot shows a linear relationship of the potential differences between the three fluorinated derivatives and TCNQ with the sum of the Hammett constants for fluoro substitution. A significant positive shift in the reversible potential is found by increasing the number of fluoro substituents. Although the first TCNQFn0/1− (n=1,2) reduction process is not affected by addition of trifluoroacetic acid (TFA), the dianions are more basic and rapidly protonate to form H2TCNQFn. This explains the significant change detected in the electrochemistry of the second TCNQFn1−/2− redox process. The addition of TFA to solutions of the monoanionic form also gives rise to the disproportionation of TCNQFn1− to TCNQFn and H2TCNQFn, as proven electrochemically and spectroscopically. Furthermore, a higher number of fluoro substituents results in the reduced form of the molecule being more stable, as evidenced by both UV/Vis spectra and voltammetric measurements. Finally, we performed DFT calculations for TCNQF2 and TCNQF2 to produce a spectroscopic library of characteristic IR and Raman bands for these species. These data are used for comparisons with earlier calculations for TCNQF4, and we report the experimental and calculated infrared and Raman spectra for TCNQF and TCNQF2. The vibrational frequencies of the trifluorinated species, TCNQF3, were also calculated to complete the series.
Simulation of kinetic behavior of natural surfactants adsorption using a new robust approach
Authors: Daryasafar Navid , Borazjani Omid , Daryasafar Amin
Published: March 2018

Surfactant‐based enhanced oil recovery techniques are known as promising methods for mobilizing the trapped oil in porous media. Surfactants can improve oil recovery by modifying the wettability of rock minerals and also by reducing the interfacial tension between injected water and the trapped oil. Natural surfactants have been introduced as good candidates for enhanced oil recovery applications. In addition, they are less expensive and also have less detrimental environmental effects in comparison with the industrial surfactants. Various empirical models have been proposed for simulating the kinetic behavior of surfactants adsorption, but these models suffer from overestimation and underestimation and they cannot be generalized for even a type of surfactant. Therefore, it is crucial to develop a new model that can overcome these issues. In this study, a new simple, rapid, and accurate model based on least square support vector machines (LSSVMs) was developed for predicting the kinetic adsorption density of natural surfactants on both sandstone and carbonate minerals. Coupled simulated annealing algorithm (CSA) is used for tuning the parameters of the model. Predicted values by this model were in an excellent agreement with experimental values with a coefficient of determination of 0.990. The results demonstrated that the proposed LSSVM‐CSA model has the best performance in comparison with the other well‐established kinetic models. Furthermore, the model reliability was investigated over input parameters changes and showed the acceptable efficiency of the proposed model.
Influence of symptom typicality for predicting MACE in patients without obstructive coronary artery disease: From the CONFIRM Registry (Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry)
Authors: Lee Ji Hyun , Han Donghee , Hartaigh Bríain ó , Gransar Heidi , Lu Yao , Rizvi Asim , Park Mahn Won , Roudsari Hadi Mirhedayati , Stuijfzand Wijnand J. , Berman Daniel S. , Callister Tracy Q. , DeLago Augustin , Hadamitzky Martin , Hausleiter Joerg , Al‐Mallah Mouaz H. , Budoff Matthew J. , Kaufmann Philipp A. , Raff Gilbert , Chinnaiyan Kavitha , Cademartiri Filippo , Maffei Erica , Villines Todd C. , Kim Yong‐Jin , Leipsic Jonathon , Feuchtner Gudrun , Pontone Gianluca , Andreini Daniele , Marques Hugo , Rubinshtein Ronen , Achenbach Stephan , Shaw Leslee J. , Chang Hyuk‐Jae , Bax Jeroen , Chow Benjamin , Cury Ricardo C. , Gomez Millie , Jones Erica C. , Lin Fay Y. , Min James K. , Peña Jessica M.
Published: March 2018

Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (<50% CCTA stenosis). CAD severity was categorized as nonobstructive (1%–49%) and none (0%). Based upon the Diamond‐Forrester criteria for angina pectoris, symptom typicality was classified as asymptomatic, nonanginal, atypical, and typical. Multivariable Cox proportional hazards models were used to assess the risk of major adverse cardiac events (MACE), comprising all‐cause mortality, myocardial infarction, unstable angina, and late revascularization, according to symptom typicality. Mean patient age was 57.0 ±12.0 years (54.9% male). During a median follow‐up of 5.3 years (interquartile range, 4.6–5.9 years), MACE were reported in 312 (7.4%) patients. Among patients with nonobstructive CAD, there was an association between symptom typicality and MACE (P for interaction = 0.05), driven by increased risk of MACE among those with typical angina and nonobstructive CAD (hazard ratio: 1.62, 95% confidence interval: 1.06–2.48, P = 0.03). No consistent relationship was found between symptom typicality and MACE among patients without any CAD (hazard ratio: 0.73, 95% confidence interval: 0.34–1.57, P = 0.08). In the CONFIRM registry, patients who presented with concomitant typical angina and nonobstructive CAD had a higher rate of MACE than did asymptomatic patients with nonobstructive CAD. However, the presence of typical angina did not appear to portend worse prognosis in patients with no CAD.
Design, Synthesis, and in vitro Evaluation of Multivalent Drug Linkers for High‐Drug‐Load Antibody–Drug Conjugates
Authors: Chen Bo , Gianolio Diego A. , Stefano James E. , Manning Charlene M. , Gregory Richard C. , Busch Michelle M. , Brondyk William H. , Miller Robert J. , Dhal Pradeep K.
Published: March 2018

A series of novel multivalent drug linkers (MDLs) containing cytotoxic agents were synthesized and conjugated to antibodies to yield highly potent antibody–drug conjugates (ADCs) with drug/antibody ratios (DARs) higher than those typically reported in the literature (10 vs. ≈4). These MDLs contain two copies of a cytotoxic agent attached to biocompatible scaffolds composed of a branched peptide core and discrete polyethylene glycol (PEG) chains to enhance solubility and decrease aggregation. These drug linkers produced well‐defined ADCs, whose DARs could be accurately determined by LC–MS. Using this approach, ADCs with significantly lower aggregation and higher DAR than those of conventional drug linker design were obtained with highly hydrophobic cytotoxic agents such as monomethyldolastatin 10 (MMAD). The in vitro potencies of the MDL‐derived conjugates matched that of ADCs of similar DAR with conventional linkers, and the potency increased proportionally with drug loading. This approach may provide a means to prepare highly potent ADCs from a broader range of drugs, including those with lower cytotoxicity or poor solubility, which otherwise limits their use for antibody–drug conjugates. This may also provide a means to further improve the potency achievable with cytotoxins currently used in ADCs.
A (+)‐Larixol Congener with High Affinity and Subtype Selectivity toward TRPC6
Authors: Häfner Stephanie , Burg Finn , Kannler Martina , Urban Nicole , Mayer Peter , Dietrich Alexander , Trauner Dirk , Broichhagen Johannes , Schaefer Michael
Published: March 2018

Natural products have many health benefits, and their application can improve the quality of life. Recently, the diterpene (+)‐larixol and its acetylated congeners demonstrated selective inhibition of the second‐messenger‐gated cation channel transient receptor potential canonical 6 (TRPC6) over its close isoforms TRPC3 and TRPC7. Building on this knowledge, we expanded these findings by chemical diversification of (+)‐larixol mostly at position C6. Implementing high‐throughput Ca2+ FLIPR screening assays and electrophysiological patch‐clamp recordings, we showcase larixyl N‐methylcarbamate, termed SH045, as a compound with nanomolar affinity and 13‐fold subtype selectivity over TRPC3 in stably expressing HEK293 cells. Expanding on this finding, TRPC6 inhibition was also observed in rat pulmonary smooth muscle cells. Furthermore, treatment of isolated perfused lung preparations with SH045 led to a decrease in lung ischemia‐reperfusion edema (LIRE), a life‐threatening condition associated with TRPC6 that may occur after organ transplantation. Taken together, and given the inexpensive, straightforward, and scalable preparation of SH045, we report a TRPC6 blocker that holds promise for the translational treatment of LIRE.