bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational design of peptide affinity ligands for the purification of therapeutic enzymes
Authors: Trasatti John P. , Woo James , Ladiwala Asif , Cramer Steven , Karande Pankaj
Published: April 2018

Non‐mAb biologics represent a growing class of therapeutics under clinical development. Although affinity chromatography is a potentially attractive approach for purification, the development of platform technologies, such as Protein A for mAbs, has been challenging due to the inherent chemical and structural diversity of these molecules. Here, we present our studies on the rapid development of peptide affinity ligands for the purification of biologics using a prototypical enzyme therapeutic in clinical use. Employing a suite of de novo rational and combinatorial design strategies we designed and screened a library of peptides on microarray platforms for their ability to bind to the target with high affinity and selectivity in cell culture fluid. Lead peptides were evaluated on resin in batch conditions and compared with a commercially available resin to evaluate their efficacy. Two lead candidates identified from microarray studies provided high binding capacity to the target while demonstrating high selectivity against culture contaminants and product variants compared to a commercial resin system. These findings provide a proof‐of‐concept for developing affinity peptide‐based bioseparations processes for a target biologic. Peptide affinity ligand design and screening approaches presented in this work can also be easily translated to other biologics of interest. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:987–998, 2018
Bio‐preparation of (R)‐DMPM using whole cells of Pseudochrobactrum asaccharolyticum WZZ003 and its application on kilogram‐scale synthesis of fungicide (R)‐metalaxyl
Authors: Zhang Yinjun , Fan Yicheng , Zhang Wei , Wu Guanzhong , Wang Jinghong , Cheng Feng , Zheng Jianyong , Wang Zhao
Published: April 2018

Methyl (R)‐N‐(2,6‐dimethylphenyl)alaninate ((R)‐DMPM) is a key chiral intermediate for the production of (R)‐metalaxyl, which is one of the best‐selling fungicides. A new strain, Pseudochrobactrum asaccharolyticum WZZ003, was identified as a biocatalyst for the enantioselective hydrolysis of (R,S)‐DMPM. The key parameters including pH, temperature, rotation speed and substrate concentrations were optimized in the enantioselective hydrolysis of (R,S)‐DMPM. After the 48 h hydrolysis of 256 mM (R,S)‐DMPM under the optimized reaction conditions, the enantiomeric excess of product (e.e.p) was up to 99% and the conversion was nearly 50%. Subsequently, the unhydrolyzed (S)‐DMPM was converted to (R,S)‐DMPM through the n‐butanal‐catalyzed racemization. Furthermore, stereoselective hydrolysis of (R,S)‐DMPM catalyzed by whole cells of P. asaccharolyticum WZZ003 was scaled up to kilogram‐scale, offering (R)‐MAP‐acid with 98.6% e.e.p and 48.0% yield. Moreover, (R)‐metalaxyl was prepared at kilogram scale after subsequent esterification and coupling reactions. Therefore, a practical production process of (R)‐DMPM and (R)‐metalaxyl with the prospect of industrialization was developed in this study. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:921–928, 2018
Effect of nanoparticle on cellular growth and lipid production in Chlorella vulgaris culture
Authors: Ahn Bohye , Park So Eun , Oh Byung‐Keun , Kim Young‐Kee
Published: April 2018

Magnetic cobalt ferrite/silica nanoparticles (MSNs) and methyl functionalized MSNs (methyl‐MSNs) were used to enhance lipid production in Chlorella vulgaris culture through enhancement of gas‐water mass transfer and increased dissolved concentration of CO2. Methyl‐MSNs enhanced CO2–water mass transfer rate better than MSNs, and 0.3 wt% methyl‐MSNs are more effective than 0.1 wt% MSNs. In the cultivation experiment, 0.3 wt% methyl‐MSNs yielded the highest dry cell weight and subsequently, the highest mass transfer rate. However, enhancement of mass transfer rate did not increase lipid content. The volumetric lipid productivity in C. vulgaris culture depends not only on intracellular lipid content but also on the cell mass concentration. Consequently, 0.1 wt% methyl‐MSNs yielded the highest volumetric lipid productivity in C. vulgaris cultivation. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:929–933, 2018
Analytical subcloning of a clonal cell line demonstrates cellular heterogeneity that does not impact process consistency or robustness
Authors: Scarcelli John J. , Hone Megan , Beal Kathryn , Ortega Alejaida , Figueroa Bruno , Starkey Jason A. , Anderson Karin
Published: April 2018

During development of a cell line intended to support production of an IgG2 monoclonal antibody, a sequence variant caused by a genetic mutation was identified in the bulk drug substance. Gene copy number analysis together with the level of the observed variant in genomic DNA indicated that the master cell bank was a mixed population of cells; some harboring the variant copy and some mutation free. Since the cell bank had been single‐cell cloned, this variant could be used as a biomarker to demonstrate either that the bank was not derived from a single cell, or that the variant was a result of a post‐cloning genetic event, leading to a mixed population of cells. The sequence variant was only present in a small percentage of subclones, confirming the hypothesis that the cell bank was indeed a mixed population. Interrogation of subclones via Southern blot analysis revealed that almost all subclones had very similar transgene integrant structures, suggesting that the cell bank was likely derived from a single cell, and the cellular event that yielded the sequence variant was a post‐cloning event. Further, there were likely several other post‐cloning events that impacted transgene loci, leading to a population of related, yet genetically distinct cells comprising the cell bank. Despite this, the heterogeneous bank performed consistently in a bioprocess across generational age with comparable product quality. These results experimentally demonstrate the heterogeneity of a cell bank derived from a single cell, and its relationship to process consistency. © 2018 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 34:602–612, 2018
An approach to STFT and CWT learning through music hands‐on labs
Authors: Ortiz‐Echeverri César J. , Rodríguez‐Reséndiz Juvenal , Garduño‐Aparicio Mariano
Published: April 2018

This work presents a series of lectures and activities for Digital Signal Processing (DSP) teaching, based upon music and their principal elements such as melody, pitch, timbre, beat, and metric, to explain the time‐frequency analysis and its repercussions in other areas of engineering. DSP courses are difficult to the students due to a high mathematical content and high level of abstraction, for this reason, the primary objective of this work is to create a pedagogical tool that allows the improvement on the teaching process in Signal Processing courses. There are two popular approaches: Short‐Time Fourier Transform (STFT) and Continuous Wavelet Transform (CWT) which have been used to find time‐frequency maps. The student roll was designed for active participation by creating melodies from real instruments as well as synthetic generators, and by implementing the codes of STFT and CWT in MATLAB. The results demonstrate that in general terms, after carrying out these laboratory activities the students are more motivated to learn Signal Processing theory, and some of them become interested in the new research line on Music Information Retrieval (MIR), which would benefit the continuity of the Accreditation Board for Engineering and Technologies ABET, obtained for the Automation Engineering program at Universidad Autónoma de Querétaro (UAQ) since 2016.
Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities
Authors: Pham Thi‐Anh , Shair Mohammad Imran , Vu Van‐Tuan , Hu Xiao‐Long , Birendra Chaurasiya , Ulah Aftab , Guo Cui , Lü Xian‐Yu , Ye Wen‐Cai , Wang Hao
Published: April 2018

A new phloroglucinol derivative, named eucalyptin B (1), along with five related known compounds (2 – 6), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D‐ and 2D‐NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds (1 – 6) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B (1) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B (1), the apoptosis factor proteins (Bcl2 and Bax) and caspase‐3 levels in A549 cells were also determined by Western‐blot analysis. By cytotoxic assay, eucalyptin B (1) exhibited potent cytotoxicity against A549 cells with an IC50 value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B (1) inhibited 5‐fold and increased 10‐folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11‐fold increase in the level of caspase‐3 confirmed eucalyptin B (1) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B (1) has promising cytotoxic activity in tumor cells, especially in A549.
Simultaneous kissing stents to treat unprotected left main stem coronary artery bifurcation disease; stent expansion, vessel injury, hemodynamics, tissue healing, restenosis, and repeat revascularization
Authors: Morris Paul D. , Iqbal Javaid , Chiastra Claudio , Wu Wei , Migliavacca Francesco , Gunn Julian P.
Published: April 2018

Objectives

To perform detailed analysis of stent expansion, vessel wall stress, hemodynamics, re‐endothelialization, restenosis, and repeat PCI in the simultaneous kissing stents (SKS) technique of bifurcation left main stem (LMS) stenting.

Background

The SKS technique is useful to treat patients with true bifurcation disease of the LMS but remains controversial.

Methods and Results

Computational structural analysis of SKS expansion demonstrated undistorted and evenly expanded stents. Computational fluid dynamics modelling revealed largely undisturbed blood flow. 239 PCI procedures were performed on 217 patients with unprotected bifurcation LMS disease with SKS using DES (2004‐2017). We electively studied 13 stable patients from baseline to 10 years post‐SKS with repeat angiography and optical coherence tomography, and demonstrated tissue coverage of the stent struts at the carina, with no evidence of lacunae behind the stents. We studied all patients with symptomatic recurrence. Target lesion revascularization rate was 3.2% at 1 year and 4.6% at 2 years. Of all 20 patients with restenosis, the site was the LMS‐Cx stent in 7, the LMS‐LAD stent in 2 and both in 11. Two‐year recurrence rate was 7/32 (5.3%) for first, and 4/108 (3.7%) for second generation DES. Treatment with repeat kissing techniques was undertaken in 19/20, with sustained clinical results with re‐SKS.

Conclusion

The SKS technique for treating unprotected LMS bifurcation disease does not distort the stents, is associated with favorable hemodynamics, tissue coverage of the exposed struts, and a low restenosis rate when performed with contemporary stents. Re‐PCI with repeat SKS appears feasible, safe, and durable.
Gout tophi on the soles resembling viral warts
Authors: Bossart Simon , Sidler Daniel , Blum Roland , Hunger Robert E.
Published: April 2018

Key Clinical Message

This case highlights the need to consider tophaceous gout in patients with post‐transplant renal insufficiency, chronic immunosuppression, and hypertension, who develop atypical papules or nodules on the soles, which can cause problems in differentiation from other skin diseases.
Study of Ni, Pt, and Ru Catalysts on Wood‐based Activated Carbon Supports and their Activity in Furfural Conversion to 2‐Methylfuran
Authors: Mäkelä Eveliina , Lahti Riikka , Jaatinen Salla , Romar Henrik , Hu Tao , Puurunen Riikka L. , Lassi Ulla , Karinen Reetta
Published: April 2018

Bio‐based chemicals can be produced from furfural through hydrotreatment. In this study, 2‐methylfuran (MF), a potential biofuel component, was produced with Pt, Ru, and Ni catalysts supported on wood‐based activated carbons. The catalytic hydrotreatment experiments were conducted in a batch reactor at 210–240 °C with 2‐propanol as solvent and 40 bar H2 pressure. Two types of activated carbon supports were prepared by carbonization and activation of lignocellulosic biomass (forest‐residue‐based birch and spruce from Finland). Both types of activated carbons were suitable as catalyst supports, giving up to 100 % furfural conversions. The most important factors affecting the MF yield were the metal dispersion and particle size as well as reaction temperature. The highest observed MF yields were achieved with the noble metal catalysts with the highest dispersions at 240 °C after 120 min reaction time: 3 wt % Pt on spruce (MF yield of 50 %) and 3 wt % Ru on birch (MF yield of 49 %). Nickel catalysts were less active most likely owing to lower dispersions and incomplete metal reduction. Interesting results were obtained also with varying the metal loadings: the lower Pt loading (1.5 wt %) achieved almost the same MF yield as the 3 wt % catalysts, which can enable the production of MF with high yields and reduced catalyst costs. Based on this study, biomass‐based renewable activated carbons can be used as catalyst supports in furfural hydrotreatment with high conversions.
Introducing Molecular Functionalities within High Surface Area Nanostructured ITO Electrodes through Diazonium Electrografting
Authors: Kim Yee‐Seul , Fournier Sophie , Lau‐Truong Stéphanie , Decorse Philippe , Devillers Charles H. , Lucas Dominique , Harris Kenneth D. , Limoges Benoît , Balland Véronique
Published: April 2018

Efficient and homogeneous functionalization of 3D nanostructured transparent ITO electrodes was reproducibly achieved by electrochemical reduction of in‐situ generated free‐base porphyrin diazonium salts. The resulting modified electrodes were characterized by cyclic voltammetry and voltabsorptometry, UV‐visible absorption, resonance Raman and XPS. The overall results strongly support the formation of covalently linked electroactive porphyrin oligomers on the ITO surface, that are highly stable towards desorption or hydrolysis in organic as well as mild hydrolytic conditions. Further metalation by zinc ions was quantitatively achieved, thus opening new opportunities for the preparation of robust high‐surface area photoelectrodes with adjustable properties.
Fabrication of Miniaturised Screen‐printed Glucose Biosensors, Using a Water‐based Ink, and the Evaluation of their Electrochemical Behaviour
Authors: Hughes G. , Pemberton R. M. , Nicholas P. , Hart J. P.
Published: April 2018

This paper describes a simple, convenient approach to the fabrication of microband electrodes and microband biosensors based on screen printing technology. These devices were printed in a three‐electrode configuration on one strip; a silver/silver chloride electrode and carbon counter electrode served as reference and counter electrodes respectively. The working electrodes were fabricated by screen‐printing a water‐based carbon ink containing cobalt phthalocyanine for hydrogen peroxide detection. These were converted into a glucose microband biosensor by the addition of glucose oxidase into the carbon ink. In this paper, we discuss the fabrication and application of glucose microband electrodes for the determination of glucose in cell media. The dimensions (100–400 microns) of the microband electrodes result in radial diffusion, which results in steady state responses in the absence of stirring. The microband biosensors were investigated in cell media containing different concentrations of glucose using chronoamperometry. The device shows linearity for glucose determination in the range 0.5 mM to 2.5 mM in cell media. The screen‐printed microband biosensor design holds promise as a generic platform for future applications in cell toxicity studies.
The new wave of equality legislation: States move to create pay parity by banning inquiries into candidate's prior salary history
Authors: Barnett Anne Cherry
Published: April 2018

State‐by‐state survey on current laws prohibiting employers from inquiring into job candidate's prior salary history.
Ecological risk assessment of perfluooroctane sulfonate to aquatic fauna from a bayou adjacent to former fire training areas at a US Air Force installation
Authors: Salice Christopher J. , Anderson Todd A. , Anderson Richard H. , Olson Adric D.
Published: April 2018

Per- and polyfluoroalkyl substances (PFASs) continue to receive significant attention, with particular concern for PFASs such as perfluorooctane sulfonate (PFOS), which was a constituent of aqueous film-forming foam used widely as a fire suppressant for aircraft since the 1970s. We were interested in the potential for risk to ecological receptors inhabiting Cooper Bayou, which is adjacent to 2 former fire-training areas at Barksdale Air Force Base (LA, USA). Previous research showed higher PFOS concentrations in surface water and biota from Cooper Bayou compared to reference sites. To estimate risk, we compared surface water concentrations from multiple sites within Cooper Bayou with several PFOS chronic toxicity benchmarks for freshwater aquatic organisms (∼0.4–5.1 μg PFOS/L) and showed probability of exceedances from 0.04 to 0.5, suggesting a potential for adverse effects in the most contaminated habitats. A tissue-residue assessment similarly showed some exceedance of benchmarks but with a lower probability (maximum = 0.17). Both fire-training areas have been inactive for more than a decade, so exposures (and, thus, risks) are expected to decline. Several uncertainties limit confidence in our risk estimates including highly dynamic surface water concentrations and limited chronic toxicity data for relevant species. Also, we have little data concerning organisms higher in the food chain which may receive higher lifetime exposures given the potential for PFOS to bioaccumulate and the longevity of many of these organisms. Overall, the present study suggests that PFOS can occur at concentrations that may cause adverse effects to ecological receptors, although additional, focused research is needed to reduce uncertainties. Environ Toxicol Chem 2018;37:2198–2209. © 2018 SETAC
Call options with concave payoffs: An application to executive stock options
Authors: Bae Kwangil , Kang Jangkoo , Kim Hwa‐Sung
Published: April 2018

We observe that the incentive effects of traditional stock options can be improved by making the option's payoff concave in the region of a high stock price at maturity. To reflect the concave property, we propose two types of executive stock options: a generalized power option and an ordinary bull spread. Under the [Hall and Murphy (): American Economic Review 209‐214, Hall and Murphy () Journal of Accounting and Economics 33: 3‐42] framework, we show that the generalized power option with high concavity and the ordinary bull spread generate greater incentive effects than those of traditional options or the [Bernard, Boyle, and Chen (): The Journal of Derivatives 23: 9‐20] power executive options.
Cultivating Nonfiction Readers Open to Challenge and Change
Authors: Kerr Kristine Rodriguez
Published: April 2018

This forum reviews a mix of resources (written texts, graphic novels, documentaries, and mixed‐media pieces) to inform pedagogy and related educational practices that foreground representations of youths and their literacy practices within and outside of school.
The Hidden Burden of Fractures in People Living With HIV
Authors: Premaor Melissa O , Compston Juliet E
Published: April 2018

The survival of people living with human immunodeficiency virus (HIV) has increased markedly since the advent of antiretroviral therapy (ART). However, other morbidities have emerged, including osteoporosis. The estimated incidence of fractures at any site in people living with HIV ranges from 0.1 per 1000 person‐years to 8.4 per 1000 person‐years: at least twice that of people without HIV. This increased risk seems to be related to HIV itself and its treatment. Risk factors for bone disease in HIV‐positive (HIV+) subjects include both classical risk factors for osteoporosis and fracture and factors linked to HIV itself, such as inflammation, reconstitution syndrome, low CD4, ART, and co‐infection with hepatitis B and C viruses. The risk of fractures in these individuals can be at least partially assessed by measurement of BMD and the Fracture Risk Assessment Tool (FRAX™). Only alendronate and zoledronic acid have been studied in HIV+ individuals; both show beneficial effects on BMD, although data on fracture reduction are not available. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
The mental nose and the Pinocchio effect: Thermography, planning, anxiety, and lies
Authors: Moliné A. , Dominguez E. , Salazar‐López E. , Gálvez‐García G. , Fernández‐Gómez J. , De la Fuente J. , Iborra O. , Tornay F.J. , Gómez Milán E.
Published: April 2018

We applied thermography to cognitive neuropsychology, particularly as a somatic marker of subjective experience during cognitive and emotional tasks. We found significant correlations between changes in facial temperature and mental set. Specifically, the temperature of the nose tended to decrease during emotional tasks and increase during cognitive tasks. However, for stress tests or high arousal reactions to emotional stimuli, the direction of the thermal change depended on the nature of the setting, real or simulated. Detection of deception is a mixed field where cognitive effort, physiological stress, and empathy have evolved, affecting the direction of the thermal variation—higher or lower temperature of the tip of the nose and forehead. We found that the temperature change of the nose and forehead may enable detecting when people lie about facts (the Pinocchio effect markers). In general, one important contribution is to recover mental thermometry as a potent tool for neurocognitive studies.
Resilience to shading influenced by differential allocation of biomass inThalassia testudinum
Authors: Barry Savanna C. , Jacoby Charles A. , Frazer Thomas K.
Published: April 2018

Seagrasses are marine plants with fully developed leaves, roots, and rhizomes and a high degree of phenotypic plasticity. In the shallow waters along Florida's central Gulf of Mexico coast, leaf morphology of the dominant seagrass,Thalassia testudinum, varies along a spatial gradient in concentrations of total phosphorus (TP) in the water column. We examined ratios of aboveground to belowground biomass (AG : BG) forT. testudinumalong this gradient to determine if they varied consistently with TP. Ratios were positively correlated with TP, indicatingT. testudinumallocated more carbon to leaf biomass relative to belowground biomass as TP increased. To determine if this variation in AG : BG influenced resilience to shading, we carried out an 8‐week, comparative shading experiment in threeT. testudinummeadows that spanned the range of recorded ratios. The experiment showed that seagrasses employing a range of AG : BG strategies persisted for 5 weeks with ambient light reduced by ∼ 93%.Thalassia testudinumwith intermediate AG : BG exhibited the least severe impacts and strongest recovery when compared toT. testudinumwith either high or low AG : BG. Seagrasses with high AG : BG ratios showed the most severe responses and weakest recovery. These results suggestT. testudinumallocates biomass such that growth and survival are maximized under the local, long‐term nutrient regime, which affects the direction and magnitude of a response to a short‐term reduction in light availability. In addition, we suggest that AG : BG is an important metric to monitor inT. testudinummeadows because of its potential to identify areas of high and low resilience.
Bottom‐up influences on tropical freshwater food web structure support the “environmental filtering” hypothesis
Authors: Liew J. H. , Jardine T. D. , Lim R. B. H. , Kwik J. T. B. , Tan H. H. , Kho Z. Y. , Yeo D. C. J.
Published: April 2018

Studies of ecosystem functions are gaining traction in the scientific community along with a growing consensus that losses in ecosystem functions have widespread consequences. Food webs, which are networks comprising all trophic interactions (represented by links) between taxa present in a community (represented by nodes), are important aspects of ecosystem functioning, yet a clear understanding of the factors and mechanisms influencing their assembly and structure is lacking. In our study, we addressed this fundamental question by investigating the respective roles of (1) environmental filtering and (2) biotic filtering, in governing food web structure. We did this by assessing the relationship between the network structure of five high‐resolution empirical tropical food webs and associated environmental and biotic covariates. Our data suggest that only environmental filtering is important in shaping food webs. Further, we found that the underlying ecological mechanism is a function of bottom‐up influences comprising resource levels, and to a lesser degree, resource type (i.e., terrestrial organic matter) available. Specifically, our data suggest high‐nutrient environments favor greater food web complexity. In the general context of community assembly, our findings add to existing knowledge of the process by demonstrating that environmental conditions previously shown to influence species assemblages can also drive trends in prevailing species interactions.
Synthesis and in vitro PDT evaluation of new porphyrins containing meso‐epoxymethylaryl cationic groups
Authors: Carneiro Jaqueline , Gonçalves Alan , Zhou Zehua , Griffin Kaitlin E. , Kaufman Nichole E.M. , Vicente Maria da Graça Henriques
Published: April 2018

Objectives

Photodynamic therapy (PDT) is an effective cancer treatment that uses photosensitizers, light, and oxygen to destroy malignant cells. Porphyrins, and in particular the cationic derivatives, are the most investigated photosensitizers for PDT. In this context, it is important to study new methodologies to develop efficient cationic photosensitizers for use in PDT.

Materials and Methods

New porphyrins bearing cationic epoxymethylaryl groups were synthesized and characterized. Their cellular uptake, intracellular localization, and phototoxicity were evaluated in human HEp2 cells, and compared with their methylated analogs.

Results

All cationic porphyrins were efficient generators of singlet oxygen, with quantum yields in the range 0.35–0.61. The two methylated derivatives (3 and 4) accumulated the most within cells at all times investigated, up to 24 hours. Of these two porphyrins, 4 was the most phototoxic to the cells (LD50 = 2.4 μM at 1.5 J/cm2); however, porphyrin 3 also showed high phototoxicity (LD50 = 7.4 μM at 1.5 J/cm2). The epoxymethyl‐containing porphyrins were found to be less phototoxic than the methylated derivatives, with LD50 > 38 μM. The neutral porphyrins showed no phototoxicity up to the 100 μM concentrations investigated, and had the lowest singlet oxygen quantum yields. All cationic porphyrins localized mainly in the cell ER, Golgi apparatus, and lysosomes.

Conclusion

Our results suggest that cationic methylated porphyrin derivatives are promising PDT photosensitizing agents. The epoxymethyl‐containing derivatives showed increased efficacy relative to the neutral analogs, and are good candidates for further investigation. Lasers Surg. Med. 50:566–575, 2018. © 2018 Wiley Periodicals, Inc.
Access to hematopoietic stem cell transplant for patients with sickle cell anemia
Authors: Meier Emily Riehm , Johnson Theodore , Pinkney Kerice , Velez Maria C. , Kamani Naynesh , Odame Isaac
Published: April 2018

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for patients with phenotypically severe sickle cell anemia, and survival rates following matched‐sibling HSCT are very high. However, despite cure rates much higher than HSCT for malignant diseases, the field has been slow to adopt this treatment modality for sickle cell anemia. This article explores some of the social forces that may contribute to this dichotomy.
Autologous stem cell transplantation for refractory opsoclonus myoclonus ataxia syndrome
Authors: Johnston Donna L. , Murray Sean , Irwin Meredith S. , Doyle John , Schechter Tal
Published: April 2018

Opsoclonus, myoclonus, ataxia syndrome (OMA) is a severe neurologic disorder often associated with neuroblastoma. It is challenging to treat and can have long‐term neurologic sequelae. Current recommended therapies include intravenous immunoglobulin, corticosteroids, rituximab, and chemotherapy (cyclophosphamide). We present two cases who were refractory to conventional therapy and underwent autologous stem cell transplantation (ASCT). One patient had complete resolution of symptoms following ASCT and the other patient had minimal change in symptoms with this therapy. These findings support consideration of ASCT as a therapeutic option for patients with refractory OMA after failure of known effective therapies.
The Role of N–Si–O Defect States in Optical Gain from an a‐SiNxOy/SiO2 Waveguide and in Light Emission from an n‐a‐SiNxOy/p‐Si Heterojunction LED
Authors: Lin Zewen , Chen Kunji , Zhang Pengzhan , Xu Jun , Dong Hengping , Li Wei , Ji Yang , Huang Xinfan
Published: April 2018

Amorphous silicon oxynitride (a‐SiNxOy) film is a kind of new luminescent material, which exhibits highly efficient light emission from luminescent N–Si–O defect states. In this work, the measurements of steady‐state photoluminescence (SSPL), temperature‐dependent photoluminescence (TDPL), and nanosecond time‐resolved photoluminescence (ns‐TRPL) are combined to further verify the role of luminescent N–Si–O defect states on the performance of photoluminescence (PL), electro‐luminescence (EL), and optical gain, etc., for both intrinsic and doped a‐SiNxOy films. The results indicate that both PL and EL originate from luminescent N–Si–O defect states, which is totally different behavior from that observed from band tail states in normal amorphous semiconductors. In the case of device applications, the properties of optical gain in an a‐SiNxOy/SiO2 waveguide are investigated. Based on the signal of amplified spontaneous emission (ASE) coming from the edge of the waveguide, an optical gain coefficient higher than 100 cm−1 is obtained by using variable stripe length (VSL) measurements. For another application example, it is found that radiative recombination via luminescent N–Si–O defect states can also contribute to the EL observed from an n‐a‐SiNxOy/p‐Si heterojunction LED, in which the light emission power efficiency is determined to be five times higher than that in an a‐SiNxOy MIS LED.
Correlation Between Electrocaloric Response and Polarization Behavior: Slim‐Like and Square‐Like Hysteresis Loop
Authors: Nie Xin , Yan Shiguang , Chen Xuefeng , Guo Shaobo , Cao Fei , Yao Chunhua , Mao Chaoliang , Dong Xianlin , Wang Genshui
Published: April 2018

Electrocaloric response in slim‐like (Ba0.9Ca0.1)(Zr0.2Ti0.8)O3 and square‐like Pb(Zr0.95Ti0.05)O3 hysteresis loops are observed by cycling samples between positive and negative values of electric field, respectively. The slim‐like (Ba0.9Ca0.1)(Zr0.2Ti0.8)O3 ceramics represent a typical electrocaloric response, while the square‐like Pb(Zr0.95Ti0.05)O3 ceramics depict an unusual electrocaloric response. It is worth noting that the unusual electrocaloric response (inverse electrocaloric effect) can be induced by inverse electric field. Furthermore, the highest value of inverse electrocaloric effect is not obtained at negative coercive field but at values that are half of it. With the increase in inverse electric field, the value of induced unusual electrocaloric effect becomes weaker and only positive electrocaloric response is present at higher magnitudes of inverse field. In the present work, the relationship between electrocaloric response and polarization behavior of these two kinds of samples are discussed.
A Novel Modular Device for Biological Impedance Measurements: The Differential Impedimetric Sensor Cell (DISC)
Authors: Cornelis Peter , Wackers Gideon , Thomas Isabelle , Brand Max , Putzeys Tristan , Gennaro Alessia , Wübbenhorst Michael , Ingebrandt Sven , Wagner Patrick
Published: April 2018

For medical diagnostics, food‐safety analysis, and detection of environmental pollutants, simultaneous detection and quantification of multiple target molecules can be a great advantage. Impedimetric measurements using molecularly imprinted polymers (MIPs), antibodies or aptamers as biomimetic sensors are becoming a well‐established technique for detecting, quantifying, and analyzing various biological targets such as DNA, proteins, and small molecules. The most commonly implemented systems use non‐Faradaic impedance spectroscopy. Adding a redox probe such as silver/silver chloride allows for the use of Faradaic impedance spectroscopy techniques using redox‐active molecules such as ferricyanide thereby extending the range of possible applications. Furthermore, the ability to perform differential measurements allows for the use of undiluted patient samples which significantly simplifies sample preparation. Therefore, adapting this low‐cost technique to simultaneously perform differential measurements on multiple targets and making it easy to use has great potential in a wide range of applications. In this work, a system that meets these requirements is successfully designed and fabricated. Up to eight different targets can be quasi‐simultaneously analyzed. Furthermore, the system is validated against a high‐resolution dielectric spectrometer (Novocontrol, Alpha analyzer) using well‐characterized samples at different temperatures over the whole frequency range (10 Hz–100 kHz).
Structure and Electrochemical Properties of Ball‐Milled La15Fe2Ni72Mn7B2Al2 Hydrogen Storage Alloys with Graphene
Authors: Li Shucun , Guo Chengxiao , Yin Weiqiang , Sha Ou , Wang Jiahao
Published: April 2018

In order to improve the electrochemical properties of the La‐Fe−B system hydrogen storage alloy, graphene was synthesized and added into the hydrogen storage alloy La15Fe2Ni72Mn7B2Al2. The La15Fe2Ni72Mn7B2Al2 alloy was prepared by arc‐melting and the La15Fe2Ni72Mn7B2Al2+ x wt. % graphene (x=1, 3, 5) composites were obtained by mechanical ball‐milling method. The effects of graphene addition on their electrochemical properties and dynamic performances have been discussed. Structure analyses showed that the La15Fe2Ni72Mn7B2Al2 alloy was composed of LaNi5 phase, La3Ni13B2 phase and (Fe, Ni) phase. The electrochemical experimental results demonstrate that the discharge capacity of ball‐milled La15Fe2Ni72Mn7B2Al2 hydrogen storage alloys with graphene was significantly improved. With 3 wt. % graphene addition, the maximum discharge capacity can reach 288.4 mAh⋅g−1, which is much higher than that of norm alloy (215.3 mAh⋅g−1). Moreover, the high‐rate dischargeability (HRD) and self‐discharge characteristics were also increased with graphene addition.
A Dienyl Boronate‐Aryl Nitroso Ene Reaction Entry to C‐Pyrrolyl Nitrones and Subsequent Conversion to Isoxazolidines
Authors: Eberlin Ludovic , Macé Aurélie , Batsanov Andrei S. , Carboni Bertrand , Whiting Andrew
Published: April 2018

A new cascade reaction to access C‐pyrrolyl nitrones en route to isoxazolidines is reported; a process that involves four successive steps, the first key step being an ene‐reaction of a 3‐methyl‐1,3‐dienylboronate ester with an aryl nitroso compounds to derive uncommon 1,3‐dipoles which react with various alkenes to access isoxazolidines. The scope and mechanism of the cascade sequence is discussed.
A disaster multiagent coordination simulation system to evaluate the design of a first‐response team
Authors: Hashemipour Mehdi , Stuban Steven , Dever Jason
Published: April 2018

Identifying the best design configuration for a first‐response team is important for minimizing total operation time and reducing the human cost of natural and manmade disasters. This paper presents ongoing research that focuses on a disaster multiagent coordination simulation (DMCsim) system that is able to optimally design the first‐response team and evaluate the team design configuration before initiation of a search and rescue operation. We developed an agent‐based simulation system that uses machine learning techniques and design of experiments methods to test different configuration setups and determine the effects of various factors on operation completion time. The evaluation of a team design for a disaster‐response operation revealed that some design factors have a significant effect on operation outcome. Removing the effects of uncontrollable factors, such as damage level and robot reliability, yielded a robust team design that could function in a particular disaster environment regardless of the effects of such factors. The DMCsim assists decision makers to evaluate an emergency‐response operation, revise the current strategy based on resources on hand, redesign the available team, and visually track operation performance before launching the actual team in the disaster field. This research extends previous disaster response coordination systems by proposing a new simulation model and evaluating a first‐response team design.
Alternative‐splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics
Authors: Urbanski Laura M. , Leclair Nathan , Anczuków Olga
Published: April 2018

Defects in alternative splicing are frequently found in human tumors and result either from mutations in splicing‐regulatory elements of specific cancer genes or from changes in the regulatory splicing machinery. RNA splicing regulators have emerged as a new class of oncoproteins and tumor suppressors, and contribute to disease progression by modulating RNA isoforms involved in the hallmark cancer pathways. Thus, dysregulation of alternative RNA splicing is fundamental to cancer and provides a potentially rich source of novel therapeutic targets. Here, we review the alterations in splicing regulatory factors detected in human tumors, as well as the resulting alternatively spliced isoforms that impact cancer hallmarks, and discuss how they contribute to disease pathogenesis. RNA splicing is a highly regulated process and, as such, the regulators are themselves tightly regulated. Differential transcriptional and posttranscriptional regulation of splicing factors modulates their levels and activities in tumor cells. Furthermore, the composition of the tumor microenvironment can also influence which isoforms are expressed in a given cell type and impact drug responses. Finally, we summarize current efforts in targeting alternative splicing, including global splicing inhibition using small molecules blocking the spliceosome or splicing‐factor‐modifying enzymes, as well as splice‐switching RNA‐based therapeutics to modulate cancer‐specific splicing isoforms.

This article is categorized under:

RNA in Disease and Development > RNA in Disease

RNA Processing > Splicing Regulation/Alternative Splicing
Studying superconformal symmetry enhancement through indices
Authors: Evtikhiev Mikhail
Published: April 2018

Abstract

In this note we classify the necessary and the sufficient conditions that an index of a superconformal theory in 3 ≤ d ≤ 6 must obey for the theory to have enhanced supersymmetry. We do that by noting that the index distinguishes a superconformal multiplet contribution to the index only up to a certain equivalence class it lies in. We classify the equivalence classes in d = 4 and build a correspondence between

$$ \mathcal{N}=1 $$

N
=
1

and

$$ \mathcal{N}>1 $$

N
>
1

equivalence classes. Using this correspondence, we find a set of necessary conditions and a sufficient condition on the d = 4

$$ \mathcal{N}=1 $$

N
=
1

index for the theory to have

$$ \mathcal{N}>1 $$

N
>
1

SUSY. We also find a necessary and sufficient condition on a d = 4

$$ \mathcal{N}>1 $$

N
>
1

index to correspond to a theory with

$$ \mathcal{N}>2 $$

N
>
2

. We then use our results to study some of the d = 4 theories described by Agarwal, Maruyoshi and Song, and find that the theories in question have only

$$ \mathcal{N}=1 $$

N
=
1

SUSY despite having rational central charges. In d = 3 we classify the equivalence classes, and build a correspondence between

$$ \mathcal{N}>2 $$

N
>
2

and

$$ \mathcal{N}>2 $$

N
>
2

equivalence classes. Using this correspondence, we classify all necessary or sufficient conditions on an

$$ 1\le \mathcal{N}\le 3 $$

1
≤
N
≤
3

superconformal index in d = 3 to correspond to a theory with higher SUSY, and find a necessary and sufficient condition on an

$$ \mathcal{N}=4 $$

N
=
4

index to correspond to an

$$ \mathcal{N}=4 $$

N
=
4

theory. Finally, in d = 6 we find a necessary and sufficient condition for an

$$ \mathcal{N}=1 $$

N
=
1

index to correspond to an

$$ \mathcal{N}>2 $$

N
>
2

theory.
Anomalous Z′ and diboson resonances at the LHC
Authors: Ismail Ahmed , Katz Andrey
Published: April 2018

Abstract

We propose novel collider searches which can significantly improve the LHC reach to new gauge bosons Z′ with mixed anomalies with the electroweak (EW) gauge group. Such a Z′ necessarily acquires a Chern-Simons coupling to the EW gauge bosons and these couplings can drive both exotic Z decays into Z′γ if the new gauge boson is sufficiently light, as well as Z′ decays into EW gauge bosons. While the exotic decay rate of the heavy Z into Z′γ is too small to be observed at the LHC, for a light Z′, we show the potential of a lepton jet search in association with a photon to probe the rare decay Z → Z′γ.
Compact, singular G2-holonomy manifolds and M/heterotic/F-theory duality
Authors: Braun Andreas P. , Schäfer-Nameki Sakura
Published: April 2018

Abstract

We study the duality between M-theory on compact holonomyG2-manifolds and the heterotic string on Calabi-Yau three-folds. The duality is studied for K3-fiberedG2-manifolds, called twisted connected sums, which lend themselves to an application of fiber-wise M-theory/Heterotic Duality. For a large class of suchG2-manifolds we are able to identify the dual heterotic as well as F-theory realizations. First we establish this chain of dualities for smoothG2-manifolds. This has a natural generalization to situations with non-abelian gauge groups, which correspond to singularG2-manifolds, where each of the K3-fibers degenerates. We argue for their existence through the chain of dualities, supported by non-trivial checks of the spectra. The corresponding 4d gauge groups can be both Higgsable and non-Higgsable, and we provide several explicit examples of the general construction.
New form of the exact NSVZ β-function: the three-loop verification for terms containing Yukawa couplings
Authors: Kazantsev A. E. , Shakhmanov V. Yu. , Stepanyantz K. V.
Published: April 2018

Abstract

We investigate a recently proposed new form of the exact NSVZ β-function, which relates the β-function to the anomalous dimensions of the quantum gauge superfield, of the Faddeev-Popov ghosts, and of the chiral matter superfields. Namely, for the general renormalizable

$$ \mathcal{N} $$

N

= 1 supersymmetric gauge theory, regularized by higher covariant derivatives, the sum of all three-loop contributions to the β-function containing the Yukawa couplings is compared with the corresponding two-loop contributions to the anomalous dimensions of the quantum superfields. It is demonstrated that for the considered terms both new and original forms of the NSVZ relation are valid independently of the subtraction scheme if the renormalization group functions are defined in terms of the bare couplings. This result is obtained from the equality relating the loop integrals, which, in turn, follows from the factorization of the integrals for the β-function into integrals of double total derivatives. For the renormalization group functions defined in terms of the renormalized couplings we verify that the NSVZ scheme is obtained with the higher covariant derivative regularization supplemented by the subtraction scheme in which only powers of ln Λ/μ are included into the renormalization constants.
Routine Pathology and Postoperative Follow‐Up are Not Cost‐Effective in Cholecystectomy for Benign Gallbladder Disease
Authors: Olthof Pim B. , Metman Madelon J. H. , de Krijger Ronald R. , Scheepers Joris J. , Roos Daphne , Dekker Jan Willem T.
Published: April 2018

Introduction

The incidence of gallstone disease is increasing and represents a strain on healthcare systems worldwide. Following cholecystectomy, gallbladder specimens are generally submitted for histopathologic examination and the diagnostic yield of this strategy remains questionable. This study aimed to evaluate the usefulness of routine pathologic examination of the gallbladder specimens and investigate the results of routine postoperative follow‐up visits.

Methods

All cholecystectomies performed between January 2011 and July 2017 at a single center were evaluated. All gallbladder specimens were routinely pathologically examined. The outcome parameters were the macro‐ and microscopic gallbladder anomalies at pathology and the reported symptoms during routine follow‐up visits 2–6 weeks after surgery.

Results

In the study period a total of 2763 patients underwent cholecystectomy, of which 2615 had a postoperative visit in the outpatient clinic. Seventy‐three patients (3%) complained of persistent abdominal pain, and 29 of these patients were referred for further treatment, resulting in a resolution of symptoms in 97%. Of all gallbladder specimens, 199 (7%) displayed macroscopic anomalies and in four (2%) of these, gallbladder carcinoma was diagnosed.

Discussion

Selective pathologic examination of gallbladder specimens in case of macroscopic anomalies appears justified. Also routine follow‐up after cholecystectomy appears not useful since 97% of patients do not report any symptoms at follow‐up. A selective pathology and follow‐up strategy could save significant healthcare costs.
Poland’s conception of European security and Russia
Authors: Lisiakiewicz Rafał
Published: April 2018

This article examines the problem of contemporary bilateral relations between Poland and Russia. Its thesis largely attributes the rivalry of these two states in Eastern Europe to conceptions relating to the balancing and bandwagoning of power. This rivalry can be put down to the fact that Polish-Russian relations are being developed within broader global processes such as Russia’s relations with NATO, the USA and European Union. The greatest obstacle to the maintenance of mutually beneficial relations is the sensitive issue of security. In recent years Poland has consistently underlined its willingness to reinforce NATO’s mutual defense mechanisms by supporting the organization’s continued presence in Central-Eastern Europe. This issue has been compounded by Poland’s striving to bring the countries of Eastern Europe (especially Ukraine) into closer affiliation with Western institutions favoring European integration, which is evidently perceived as interference in what is regarded by Moscow to be a sphere of Russian influence. This has provoked a number of serious crises in bilateral relations between Poland and Russia since the Euro-Maidan Revolution in Ukraine. Russian plans to install new (Iskander) missile systems close to the Polish border and Poland’s effective attempts post-2014 to extend NATO presence within its own country testify to the scale of conflicts of interest between the two states and the lack of trust afforded by both sides. The issues highlighted in this paper are of great importance, since they not only enable the complexity of Central European issues to be more fully comprehended but also help to elucidate other global actors’ conceptions relating to cooperation with Europe.