bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometric Gait Design for a Starfish‐Inspired Robot Using a Planar Discrete Elastic Rod Model
Authors: Scott William L. , Paley Derek A.
Published: February 2020

A starfish‐inspired robotic platform consisting of multiple soft fluidic bending actuator arms arranged with radial symmetry about a rigid hub is described. Intrinsic properties of the soft actuators are estimated via computer vision for varying input fluid pressures. The dynamic motion of individual arms and the full robot are modeled using the planar discrete elastic rod (PDER) theory. Locomotion gaits (periodic shape changes) that result in translation in the plane, separately considering fixed or rotating anchors at the end of each arm, are derived. Gait efficiency is defined as the displacement magnitude divided by a measure of the input control effort over each gait cycle, including a cost for anchor attachment. Through numerical computation, optimally efficient gaits are found and the desired motion with a pneumatic hardware prototype is demonstrated.
MECP2 duplication syndrome in a patient from Cameroon
Authors: Tekendo‐Ngongang Cedrik , Dahoun Sophie , Nguefack Séraphin , Moix Isabelle , Gimelli Stefania , Zambo Huguette , Morris Michael A. , Sloan‐Béna Frédérique , Wonkam Ambroise
Published: February 2020

MECP2 duplication syndrome (MDS; OMIM 300260) is an X‐linked neurodevelopmental disorder caused by nonrecurrent duplications of the Xq28 region involving the gene methyl‐CpG‐binding protein 2 (MECP2; OMIM 300005). The core phenotype of affected individuals includes infantile hypotonia, severe intellectual disability, very poor‐to‐absent speech, progressive spasticity, seizures, and recurrent infections. The condition is 100% penetrant in males, with observed variability in phenotypic expression within and between families. Features of MDS in individuals of African descent are not well known. Here, we describe a male patient from Cameroon, with MDS caused by an inherited 610 kb microduplication of Xq28 encompassing the genes MECP2, IRAK1, L1CAM, and SLC6A8. This report supplements the public data on MDS and contributes by highlighting the phenotype of this condition in affected individuals of African descent.
Prenatal diagnosis of cerebro‐oculo‐facio‐skeletal syndrome: Report of three fetuses and review of the literature
Authors: Le Van Quyen Pauline , Calmels Nadège , Bonnière Maryse , Chartier Suzanne , Razavi Féréchté , Chelly Jamel , El Chehadeh Salima , Baer Sarah , Boutaud Lucile , Bacrot Séverine , Obringer Cathy , Favre Romain , Attié‐Bitach Tania , Laugel Vincent , Antal Maria C.
Published: February 2020

Cerebro‐oculo‐facio‐skeletal syndrome (COFS) is a rare autosomal recessive neurodegenerative disease belonging to the family of DNA repair disorders, characterized by microcephaly, congenital cataracts, facial dysmorphism and arthrogryposis. Here, we describe the detailed morphological and microscopic phenotype of three fetuses from two families harboring ERCC5/XPG likely pathogenic variants, and review the five previously reported fetal cases. In addition to the classical features of COFS, the fetuses display thymus hyperplasia, splenomegaly and increased hematopoiesis. Microencephaly is present in the three fetuses with delayed development of the gyri, but normal microscopic anatomy at the supratentorial level. Microscopic anomalies reminiscent of pontocerebellar hypoplasia are present at the infratentorial level. In conclusion, COFS syndrome should be considered in fetuses when intrauterine growth retardation is associated with microcephaly, arthrogryposis and ocular anomalies. Further studies are needed to better understand XPG functions during human development.
Recent Advances in Total Synthesis of Bioactive Furo[3,2‐b]furanone Natural Products
Authors: Bhat Bilal A. , Rashid Showkat , Sengupta Saumitra , Mehta Goverdhan
Published: February 2020

The ubiquitous presence of highly oxygenated furo[3,2‐b]furanone fragments in diverse natural products with wide range of biological activities such as anti‐cancer, anti‐HIV, anti‐microbial activities, etc., has augmented their appeal both for synthetic and medicinal chemistry campaigns. Enticed by their potent biological activities and challenging polycyclic architecture, total synthesis of furo[3,2‐b]furanone natural products has witnessed intense activity in recent years with many notable achievements in the synthesis of structurally embellished family of bioactive metabolites such as plakortones, lactonamycines, schisanartanes, etc. While presenting a comprehensive account of post‐2000 syntheses of these natural products, through strategic and nuanced use of modern tools of organic synthesis, this review also aims to stimulate interest in exploring the diversity space around these natural products for newer applications.
ZnS Nanospheres for Optical Modulator in an Erbium‐Doped Fiber Laser
Authors: Liu Jie , Li Xiaohui , Feng Jiangjiang , Zheng Chuang , Wang Yamin , Wang Aocheng , Liu Xinfeng
Published: February 2020

Zinc sulfide (ZnS), which belongs to transition metal monochalcogenides, is a semiconductor material with wide direct band gap. It can potentially show some special applications (such as luminescence, phosphor, sensors, infrared window materials, photocatalysis) by changing the morphology, size, and crystal structure of semiconductor materials. However, ZnS nanospheres have not been studied as optical modulators until now. Herein, ZnS nanospheres are synthesized by the hydrothermal method and are used to realize optical modulators in an Er‐doped fiber laser. The evanescent field effect is utilized to incorporate the ZnS nanospheres on a tapered fiber. Furthermore, with the increase in pump power, the modulation interval gradually decreases to a minimum of 34.36 ns corresponding to the modulation frequency of 29.1 MHz, which is the highest modulation frequency to our knowledge in a ring cavity all‐fiber laser. These results demonstrate ZnS nanospheres together with the interaction of dispersion and nonlinearity in optical fibers can modulate the proposed lasers. This not only provides a new method for controlling the power and frequency of all optical modulators, but also marks an important step for ZnS materials in optics research and device applications.
A Stable All‐Thiophene‐Based Core‐Modified [38]Octaphyrin Diradicaloid: Conformation and Aromaticity Switch at Different Oxidation States
Authors: Ni Yong , Gopalakrishna Tullimilli Y. , Wu Shaofei , Wu Jishan
Published: February 2020

A soluble and stable core‐modified [38]octaphyrin, MC‐T8, containing eight thiophene rings was synthesized by Yamamoto coupling followed by oxidative dehydrogenation. X‐ray crystallographic analysis revealed a nearly planar backbone, and the molecule is globally aromatic with a dominant 38π conjugation pathway. The dication MC‐T82+ is antiaromatic, and the backbone is distorted, with a different orientation of the thiophene rings. The tetracation MC‐T84+ becomes aromatic again, with a shallow‐bowl‐shaped geometry. Both the neutral compound and the dication demonstrated open‐shell diradical character with a small singlet–triplet energy gap (−2.70 kcal mol−1 for MC‐T8 and −3.78 kcal mol−1 for MC‐T82+), and they are stable owing to effective spin delocalization.
Supramolecular Fluorescence Resonance Energy Transfer in Nucleobase‐Modified Fluorogenic RNA Aptamers
Authors: Steinmetzger Christian , Bäuerlein Carmen , Höbartner Claudia
Published: February 2020

RNA aptamers form compact tertiary structures and bind their ligands in specific binding sites. Fluorescence‐based strategies reveal information on structure and dynamics of RNA aptamers. Herein, we report the incorporation of the universal emissive nucleobase analog 4‐cyanoindole into the fluorogenic RNA aptamer Chili, and its application as a donor for supramolecular FRET to the bound ligands DMHBI+ or DMHBO+. The photophysical properties of the new nucleobase–ligand‐FRET pair revealed structural restraints for the overall RNA aptamer organization and identified nucleotide positions suitable for FRET‐based readout of ligand binding. This strategy is generally suitable for binding‐site mapping and may also be applied for responsive aptamer devices.
A Modular Synthetic Strategy for Functional Macrocycles
Authors: Xu Kaidi , Zhang Zhi‐Yuan , Yu Chengmao , Wang Bin , Dong Ming , Zeng Xianqiang , Gou Rui , Cui Lei , Li Chunju
Published: February 2020

Reported here is a molecule‐Lego synthetic strategy for macrocycles with functional skeletons, involving one‐pot and high‐yielding condensation between bis(2,4‐dimethoxyphenyl)arene monomers and paraformaldehyde. By changing the blocks, variously functional units (naphthalene, pyrene, anthraquinone, porphyrin, etc.) can be conveniently introduced into the backbone of macrocycles. Interestingly, the macrocyclization can be tuned by the geometrical configuration of monomeric blocks. Linear (180°) monomer yield cyclic trimers and pentamers, while V‐shaped (120°, 90° and 60°) monomers tend to form dimers. More significantly, even heterogeneous macrocycles are obtained in moderate yield by co‐oligomerization of different monomers. This series of macrocycles have the potential to be prosperous in the near future.
Synthesis of epichlorohydrin from 1,3‐dichlorohydrin with solid catalysts using γ‐Al2O3 as carrier material
Authors: Zhang Rong , Yang Huimin , Li Fuxiang , Ma Yao
Published: February 2020

Alkaline earth metal‐based catalysts applied in the process of dichlorohydrin cyclization into epichlorohydrin were studied. A series of solid catalysts were prepared by the equivalent‐volume impregnation method using γ‐Al2O3 as a carrier, whereas nitrates and chlorides of the three alkaline earth metals (Mg, Ca, and Ba) were employed as precursors. Their catalytic performance was investigated and compared, taking into account the main factors influencing the catalytic efficiency, such as X‐ray diffraction (XRD), N2 adsorption–desorption, energy dispersive spectrometry (EDS) coupled with TEM, and CO2 temperature‐programmed desorption (CO2‐TPD). The results have shown that the specific surface area and the number of active base sites are the main factors that are affecting the catalytic efficiency. Among the series of as‐prepared catalysts, 10BaO/γ‐Al2O3 had improved catalytic performance. Based on the obtained results for the characterization of catalysts, the increased catalytic activity could be mainly attributed to the increase in base strength resulting from BaO loading onto the surface of γ‐Al2O3. Under optimized conditions, 98.4% conversion of 1,3‐DCH and approximately 90% of ECH selectivity were achieved using 10BaO/γ‐Al2O3 with a reaction temperature of 270°C. During the reaction process, the catalytic activity of 10BaO/γ‐Al2O3 remained consistently high, and its catalytic stability was excellent.
Choline ameliorates ethanol induced alterations in tyrosine phosphorylation and distribution in detergent‐resistant membrane microdomains of L1 cell adhesion molecule in vivo
Authors: Davis Natalie L. , Tang Ningfeng , He Min , Lee Daniel , Bearer Cynthia F.
Published: February 2020

Background

Exposure to ethanol during pregnancy is the cause of fetal alcohol spectrum disorder. The function of L1 cell adhesion molecule (L1), critical for proper brain development, is dependent on detergent‐resistant membrane microdomains (DRM). Ethanol at low concentrations disrupts L1 function measured by inhibition of downstream signaling and alterations in L1‐DRM distribution in cerebellum in vivo and in cerebellar granule neurons (CGN) in vitro. We have previously shown that choline pretreatment of CGN partially prevents ethanol toxicity through improving L1 function in vitro. Here we show that choline supplementation reduces the impact of ethanol on L1 in cerebellum in vivo.

Methods

Pregnant rat dams were placed on choline free diet on gestational Day 5 (G5). Pups were treated with saline or choline from postnatal day (P) 1–5. On P5, pups were intubated twice 2 hr apart with ethanol or Intralipid® for a total dose of 6 g/kg/d and sacrificed 1 hr after the last intubation. The cerebella were harvested and L1 phosphorylation/dephosphorylation status and distribution in DRM were analyzed.

Results

Ethanol reduced L1 tyrosine phosphorylation and L1‐Y1176 dephosphorylation in cerebella, and caused an increase in the percent of L1 in DRM. Choline supplementation of pups reduced the ethanol‐induced changes in L1 phosphorylation status and ameliorated ethanol‐induced redistribution of L1 into DRM.

Conclusion

Choline supplementation before an acute dose of ethanol ameliorates changes in L1 in vivo.
Construction and assessment of prediction rules for binary outcome in the presence of missing predictor data using multiple imputation and cross‐validation: Methodological approach and data‐based evaluation
Authors: Mertens Bart J. A. , Banzato Erika , de Wreede Liesbeth C.
Published: February 2020

We investigate calibration and assessment of predictive rules when missing values are present in the predictors. Our paper has two key objectives. The first is to investigate how the calibration of the prediction rule can be combined with use of multiple imputation to account for missing predictor observations. The second objective is to propose such methods that can be implemented with current multiple imputation software, while allowing for unbiased predictive assessment through validation on new observations for which outcome is not yet available.

We commence with a review of the methodological foundations of multiple imputation as a model estimation approach as opposed to a purely algorithmic description. We specifically contrast application of multiple imputation for parameter (effect) estimation with predictive calibration. Based on this review, two approaches are formulated, of which the second utilizes application of the classical Rubin's rules for parameter estimation, while the first approach averages probabilities from models fitted on single imputations to directly approximate the predictive density for future observations. We present implementations using current software that allow for validation and estimation of performance measures by cross‐validation, as well as imputation of missing data in predictors on the future data where outcome is missing by definition.

To simplify, we restrict discussion to binary outcome and logistic regression throughout. Method performance is verified through application on two real data sets. Accuracy (Brier score) and variance of predicted probabilities are investigated. Results show substantial reductions in variation of calibrated probabilities when using the first approach.
Extracellular laccase from Monilinia fructicola: isolation, primary characterization and application
Authors: Demkiv Olga M. , Gayda Galina Z. , Broda Daniel , Gonchar Mykhailo V.
Published: February 2020

Laccases are enzymes belonging to the family of blue copper oxidases. Due to their broad substrate specificity, they are widely used in many industrial processes and environmental bioremediations for removal of a large number of pollutants. During last decades, laccases attracted scientific interest also as highly promising enzymes to be used in bioanalytics. The aim of this study is to obtain a highly purified laccase from an efficient fungal producer and to demonstrate the applicability of this enzyme for analytics and bioremediation. To select the best microbial source of laccase, a screening of fungal strains was carried out and the fungus Monilinia fructicola was chosen as a producer of an extracellular enzyme. Optimal cultivation conditions for the highest yield of laccase were established; the enzyme was purified by a column chromatography and partially characterized. Molecular mass of the laccase subunit was determined to be near 35 kDa; the optimal pH ranges for the highest activity and stability are 4.5–5.0 and 3.0–5.0, respectively; the optimal temperature for laccase activity is 30°C. Laccase preparation was successfully used as a biocatalyst in the amperometric biosensor for bisphenol A assay and in the bioreactor for bioremediation of some xenobiotics.
Sweet syndrome in a patient with Hidradenitis Suppurativa
Authors: Jain Lakshay , Meegada Sreenath
Published: February 2020

Neutrophilic Dermatoses should be considered in the differential diagnosis, if a patient with abrupt onset of painful erythematous plaques/nodules and elevated erythrocyte sedimentation rate is not responding to antibiotics.
Design and synthesis of chiral spirobifluorenes
Authors: Ozcelik Ani , Peña‐Gallego María de los Ángeles , Pereira‐Cameselle Raquel , Alonso‐Gómez J. Lorenzo
Published: February 2020

Chiroptical spectroscopic methods serve as a practical tool for the structural characterization of chiral systems based on the interaction with polarized light. The higher sensitivity of these methods, compared with their achiral counterparts, not only enables the determination of absolute configuration and conformational preferences, but also supramolecular interactions may be monitored. In order to expand the applicability of chiroptical systems, the development of functional materials exhibiting intense chiroptical responses is essential. As a proof of principle, we previously constructed chiroptical interfaces via thioacetate‐derivatized allenes. Because of the photoisomerization issues associated with allenes, we have recently proposed their replacement by spirobifluorenes to achieve robust chiroptical systems. Thus, we hereby present the design and synthesis of chiral spirobifluorenes bearing thioacetates suitable for suface functionalization.
Alkali and Alkaline Earth Metal Ions Complexes with a Partial Peptide of the Selectivity Filter in K+ Channels Studied by a Cold Ion Trap Infrared Spectroscopy
Authors: Otsuka Remina , Hirata Keisuke , Sasaki Yuta , Lisy James M. , Ishiuchi Shun‐ichi , Fujii Masaaki
Published: February 2020

The infrared (IR) spectra of alkali and alkaline earth metal ion complexes with the Ac‐Tyr‐NHMe (GYG) peptide have been measured by laser photodissociation in a cold ion trap coupled with an electrospray mass spectrometer. The GYG peptide corresponds to a portion of the ion selectivity filter in the KcsA K+ channel that allows K+ to pass, but blocks Na+ even though it has a smaller ionic radius than K+. This current study extends a previous investigation on Na+ and K+ to the entire set of alkali metaI ions and alkaline earth dications. IR‐IR hole‐burning (IR2 dip) spectroscopy has established the coexistence of several conformers of the GYG‐metal ion complexes. The structures of the conformers were assigned by comparison between the isomer‐selected IR spectra and theoretical IR spectra obtained from quantum chemical calculations. It was found that the structure of the dominant conformer correlates with the ability of the ion to permeate through the K+ channel.
Inter‐individual variation of the urinary steroid profiles in Swedish and Norwegian athletes
Authors: Mullen Jenny , Bækken Lasse Vestli , Törmäkangas Timo , Ekström Lena , Ericsson Magnus , Hullstein Ingunn R. , Schulze Jenny J.
Published: February 2020

The steroidal module of the Athlete Biological Passport (ABP) aims to detect doping with endogenous steroids, e.g. testosterone (T), by longitudinally monitoring several biomarkers. These biomarkers are ratios combined into urinary concentrations of testosterone and metabolically related steroids. However, it is evident after 5 years of monitoring steroid passports that there are large variations in the steroid ratios complicating its interpretation. In this study, we used over 11000 urinary steroid profiles from Swedish and Norwegian athletes to determine both the inter‐ and intra‐individual variations of all steroids and ratios in the steroidal passport. Furthermore, we investigated if the inter‐individual variations could be associated with factors such as gender, type of sport, age, time of day, time of year, and if the urine was collected in or out of competition. We show that there are factors reported in today's doping tests that significantly affect the steroid profiles. The factors with the largest influence on the steroid profile were the type of sport classification that the athlete belonged to as well as whether the urine was collected in or out of competition. There were also significant differences based on what time of day and time of year the urine sample was collected. Whether these significant changes are relevant when longitudinally monitoring athletes in the steroidal module of the ABP should be evaluated further.
Temporal variation in the roles of exotic and native plant species in plant–pollinator networks
Authors: Vitt Pati , Havens Kayri , Jolls Claudia L. , Knight Tiffany M.
Published: February 2020

The role of individual plant species, including those that are rare or invasive, in the structure of plant–pollinator networks will depend on how connected the plants are to pollinator species and when they flower. Plant species visited by a high diversity of pollinators that visit few other species during a particular time period are thought to provide high value to the insect community. Here, we examined the role of plant species in a plant–pollinator network across the entire flowering season and across dune and adjacent woodland habitats in Wisconsin,USA. We found strong turnover of plants, pollinators, and their interactions in time and space. Both native and exotic species play important structural roles in plant–pollinator networks. Simulations reveal that the loss of the early‐flowering rare plant,Cirsium pitcheri, would result in a disproportionate loss of pollinator species. Furthermore, the critical role that this species plays in the network is not replaced by its exotic relative,Centaurea stoebe. Our research demonstrates that consideration of temporal and spatial variability in networks allows for critical plant species to be identified within a plant–pollinator network that might otherwise be overlooked.
Niche change analysis as a tool to inform management of two invasive species in Eastern Africa
Authors: Eckert Sandra , Hamad Amina , Kilawe Charles Joseph , Linders Theo E. W. , Ng Wai‐Tim , Mbaabu Purity Rima , Shiferaw Hailu , Witt Arne , Schaffner Urs
Published: February 2020

Significant progress has been made in providing guidelines and recommendations for assessing the ecological niche, stage of invasion, and probability of invasive alien plant species (IAPS) potential distribution in space and time. We followed these recommendations by developing and comparing ordination and species distribution models (SDMs) of two important woody IAPS in Eastern Africa,Prosopis julifloraandLantana camara, and interpreting the results to inform IAPS management. The two species differ in their invasion history in Eastern Africa; whileL. camarawas widely introduced there in the 19th century,P. juliflorawas only planted at selected locations in the 1970s and 1980s. For the SDMs, machine learning algorithms were used to generate one ensemble model each forP. julifloraandL. camara. For ordination, we used bioclimatic variables, performed a principal component analysis, and compared the native and global niches of the species with the Eastern African niche. Niches varied substantially depending on the percentage of marginal climates excluded from the models. Additional analysis of the local niches surrounding the originalP. julifloraplantations showed that they are complementary, which may have led to an overestimation of regional niche filling. While niche expansion was absent or small depending on the percentage of marginal climates excluded, analysis of the stages of invasion suggested thatP. julifloramay have started to adapt to novel climatic conditions and thatL. camarais approaching a pseudo‐stable equilibrium in Eastern Africa. The SDMs showed that large areas in Eastern Africa that have not yet been invaded byP. julifloraare suitable or will become suitable with climate change. ForL. camara, the global SDM predicted a considerably larger suitable area than the Eastern African one, raising uncertainty about the areas to be included in a regional management strategy. Thus, combining ordination and SDMs and integrating a geographic component into ordination is useful in assessing IAPS invasion stages and potential niche shifts, and the results help inform IAPS policy and management. The combined approach can also serve to guide experimental studies addressing divergences between results generated with the different approaches.
Loss of NKG2D in murine NK cells leads to increased perforin production upon long‐term stimulation with IL‐2
Authors: Prinz Daniela , Klein Klara , List Julia , Knab Vanessa M. , Menzl Ingeborg , Leidenfrost Nicoletta , Heller Gerwin , Polić Bojan , Putz Eva Maria , Witalisz‐Siepracka Agnieszka , Sexl Veronika , Gotthardt Dagmar
Published: February 2020

NK cells are innate lymphocytes responsible for lysis of pathogen‐infected and transformed cells. One of the major activating receptors required for target cell recognition is the NK group 2D (NKG2D) receptor. Numerous reports show the necessity of NKG2D for effective tumor immune surveillance. Further studies identified NKG2D as a key element allowing tumor immune escape. We here use a mouse model with restricted deletion of NKG2D in mature NKp46+ cells (NKG2DΔNK). NKG2DΔNK NK cells develop normally, have an unaltered IFN‐γ production but kill tumor cell lines expressing NKG2D ligands (NKG2DLs) less efficiently. However, upon long‐term stimulation with IL‐2, NKG2D‐deficient NK cells show increased levels of the lytic molecule perforin. Thus, our findings demonstrate a dual function of NKG2D for NK cell cytotoxicity; while NKG2D is a crucial trigger for cytotoxicity of tumor cells expressing activating ligands it is also capable to limit perforin production in IL‐2 activated NK cells.
Integrated approach of lithofacies and granulometric analysis of the sediments of the Proterozoic Upper Kaimur Group of Vindhyan Supergroup, Son Valley, India: Palaeo‐environmental implications
Authors: Quasim Mohammad A. , Ghosh Sumit K. , Ahmad Abul Hasnat Masood , Srivastava Vineet Kumar , Albaroot Mohammed
Published: February 2020

Two major facies associations are identified in the Upper Kaimur Group of the Son Valley, namely, tidally influenced fluvial channel facies association and tidal sand flat association. Lithofacies supports the Dhandraul Sandstone as the product of a tidally‐influenced fluvial channel and the underlying Scarp Sandstone as a tidal sand flat, which endorse a tide‐dominated estuarine setting. Grain size analysis shows that most of the sandstone samples are medium‐ to coarse‐grained and only small fractions are of fine‐ and very fine‐grained categories. In general, sediments are moderately well sorted, near‐symmetrical to fine‐skewed and leptokurtic to mesokurtic in nature, suggesting deposition under fluctuating energy conditions in different geomorphic domains from a tidally‐influenced fluvial channel to beach settings. Bivariant plots combining the textural parameters imply that marine processes dominate over fluvial processes in the Upper Kaimur Group sediments. Cumulative curves and C–M plot suggest sediment transport mainly by saltation and bottom suspension processes under varying energy conditions.
New Drugs for NASH and HIV Infection: Great Expectations for a Great Need
Authors: Guaraldi Giovanni , Maurice James B. , Marzolini Catia , Monteith Kenneth , Milic Jovana , Tsochatzis Emmanuel , Bhagani Sanjay , Morse Caryn G. , Price Jennifer C. , Ingiliz Patrick , Lemoine Maud , Sebastiani Giada ,   on behalf of the SHIVER Network
Published: February 2020

In recent years, there has been an increasing number of clinical trials for the treatment of nonalcoholic steatohepatitis (NASH). People living with human immunodeficiency virus (PLWH) are commonly excluded from these studies, usually due to concerns over drug–drug interactions associated with antiretroviral therapy. The Steatohepatitis in HIV Emerging Research Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between human immunodeficiency virus and NASH, and the issues related to the inclusion of PLWH in NASH clinical trials. Recent trials addressing NASH treatment in PLWH are discussed. The risk of drug–drug interactions between antiretroviral therapy and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGL‐3196), which are currently in phase 3 trials for the treatment of NASH, are reviewed. A model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a subpopulation within studies.
Retracted: Circular RNA ciRS‐7 promotes tube formation in microvascular endothelial cells through downregulation of miR‐26a‐5p
Authors: Cui Ming , Shen Wenjia , Qin Weiwei , Wang Xu , Li Yanhua , Xu Fei , Xin Zhenlei
Published: February 2020

Atherosclerosis is one of the most common and crucial heart diseases involving the heart and brain. At present, atherosclerosis and its major complications comprise the leading causes of death worldwide. Our purpose was to identify the role of ciRS‐7 in atherosclerosis. Tubulogenesis of HMEC‐1 cell was evaluated utilizing tube formation assay. Cell Counting Kit‐8 assay and flow cytometry were utilized to test viability and apoptosis. Migration assay was utilized to determine the migration capacity of experimental cells. Western blot was applied to examine apoptosis and tube formation‐associated protein expression. In addition, the above experiments were repeated when silencing ciRS‐7, overexpressing ciRS‐7, and upregulating miR‐26a‐5p. HMEC‐1 cells formed tube‐like structures over time. Silencing ciRS‐7 suppressed viability, migration, and tube formation but promoted apoptosis. Oppositely, overexpressing ciRS‐7 reversed the effect in HMEC‐1 cells. miR‐26a‐5p expression was elevated by silencing ciRS‐7 and reduced by overexpressing ciRS‐7. Moreover, overexpressing ciRS‐7 facilitated viability, migration, and tube formation via upregulating miR‐26a‐5p. Conclusively, overexpressing ciRS‐7 mobilized phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway and suppressed c‐Jun N‐terminal kinase (JNK)/p38 pathway. ciRS‐7 exerted influence on apoptosis, viability, migration, and tube formation through mediating PI3K/AKT and JNK/p38 pathways by miR‐26a‐5p downregulation in HMEC‐1 cells.
T‐cell blast crisis of chronic myelogenous leukemia presented with coexisting p210 and p190 BCR‐ABL transcripts and t(10;11)(q11;p15)
Authors: Xia Ting , Yang Yuchao , Li Guoxia , Chang Jianmei , Li Jianlan , Ren Fanggang , Ren Weixiao , Wang Hongwei , Xu Zhifang
Published: February 2020

Background

Blast transformation of chronic myelogenous leukemia (CML) to T lymphoblastic lymphoma/acute lymphoblastic leukemia (T‐LBL/ALL) is rare, and the molecular mechanism is still unclear.

Case report

A 28‐year‐old woman who developed T‐ALL with coexpressing both p210 and p190 BCR‐ABL transcripts five years after the initial diagnosis of CML in chronic phase. The proliferation of bone marrow was extremely active with blast cells over 20%. Chromosome analysis revealed t(9;22)(q34;q11) and t(10;11)(q25;p15). Flow immunophenotyping showed that blasts expressed CD4, CD7, CD11b, CD38, CD34, CD33, and cCD3.

Conclusion

It is the first T‐cell blast of CML case with coexisting p210 and p190 as well as additional chromosome translocations. Through review this case and previous reports, we will reveal that CML patients with T‐lymphocyte transformation depend on potential molecular and pathological mechanism.
The relevance of soluble CD137 in the regulation of immune responses and for immunotherapeutic intervention
Authors: Luu Khang , Shao Zhe , Schwarz Herbert
Published: February 2020

CD137 is a potent costimulatory receptor. Several agonistic anti-CD137 antibodies are currently in clinical trials for tumor immunotherapy. Soluble forms of CD137 (sCD137) are generated by differential splicing and antagonize the activities of membrane-bound CD137 (mCD137) and of therapeutic CD137 agonists. sCD137 is found in sera of patients suffering from autoimmune diseases where it is a natural regulator of immune responses, and which has therapeutic potential for immune-mediated diseases. This review summarizes the current knowledge on sCD137, highlights its potential role in immunotherapy against cancer and in autoimmune diseases, and presents important issues to be addressed by future research.
Multivariate image analysis–quantitative structure‐retention relationship study of polychlorinated biphenyls using partial least squares and radial basis function neural networks
Authors: Jalili‐Jahani Nasser , Fatehi Azadeh
Published: February 2020

Polychlorinated biphenyls belong to a class of hazardous and environmental pollutants. Gas chromatography separation and experimental relative retention time evaluation of these compounds on a poly (94% methyl/5% phenyl) silicone‐based capillary non‐bonded and cross‐linked column are time consuming and expensive. In this study, relative retention times were estimated using two‐dimensional images of molecules based on a newly implemented rapid and simple quantitative structure retention relationship methodology. The resulting descriptors were subjected to partial least square and principal component‐radial basis function neural networks as linear and nonlinear models, respectively, to attain a statistical explanation of the retention behavior of the molecules. The high numerical values of correlation coefficients and low root mean square errors in the case of the partial least square model, confirm the supremacy of this model as well as the linear dependency of images of molecules to their relative retention times. Evaluation of the best correlation model performed using internal and external tests and its good applicability domain was checked using a distance to the model in the X‐Space plot. This study provides a practical and effective method for analytical chemists working with chromatographic platforms to improve predictive confidence of studies that seek to identify unknown molecules or impurities.
An Insight into Phenomenology of Polytrimethylene Terephthalate Fibrillation
Authors: Hajiraissi Roozbeh
Published: February 2020

The objective of this work is to analyze the effect of the processing temperature on fibrillation of the dispersed phase and to correlate melt viscoelastic responses to formed morphologies. A blend system of polypropylene (PP)/polytrimethylene terephthalate (PTT) with varying ratios (PP/PTT: 99/1, 94/6, 90/10, and 80/20) is prepared on a co‐rotating twin screw extruder, and then pelletized blend samples are fed into a laboratory mixing extruder to spin monofilaments at three different orifice temperatures of 180, 195, and 240 °C. As revealed by scanning electron microscopy, a nano‐fibrillar morphology forms after employing spinning. Rheological approach performed in the linear region shows a transition from terminal trend into non‐terminal trend in the low‐frequency region when the fibrillar morphology forms, the magnitude and width of which are reflective of the fibril growth. Transient stress measurements prove its capability to enable the blend system to show potentials of morphology development during dynamic tests. Startup of steady shear flow shows that after reaching the percolation concentration of dispersed phase, fibril–fibril coalescence leads to the formation of long fibrils whose contribution to the blend system increases the elasticity of the blend fibers.
Electrical impedance myography: MRI‐like data without the need for MRI
Authors: Rutkove Seward B.
Published: February 2020

See article on pages 644–649 in this issue.
Registration of two confection sunflower germplasms, HA‐DM5 and HA‐DM6, resistant to sunflower downy mildew
Authors: Qi L. L. , Ma G. J. , Seiler G. J.
Published: February 2020

Downy mildew (DM) is a primary biotic threat to sunflower (Helianthus annuus L.) production worldwide, negatively impacting yield. Germplasms HA‐DM5 (Reg. no. GP‐367, PI 687025) and HA‐DM6 (Reg. no. GP‐368, PI 691507) were developed and released through the collaboration of the USDA‐ARS and the North Dakota State University as new sources of resistance to downy mildew for confection sunflower. The backcross breeding method and DNA marker‐assisted selection were used to develop HA‐DM5 and HA‐DM6. HA‐DM5 is a BC2F3‐derived BC2F4 maintainer selection from the cross of CONFSCLB1*2//CMS CONFSCLB1/ PI 435414 with the DM resistance transferred from a wild H. annuus PI 435414. Phenotypic/molecular characterizations confirmed the presence of the DM resistance gene Pl19 located on sunflower chromosome 4 derived from PI 435414 in HA‐DM5. HA‐DM6 is a composite of seed from individual BC2F4 plants from the cross of CONFSCLB1*2//CMS CONFSCLB1/ PI 494576. The DM resistance in HA‐DM6 is controlled by a single dominant gene Pl35 located on chromosome 1 derived from wild H. argophyllus PI 494576. Both HA‐DM5 and HA‐DM6 confer resistance to several modern P. halstedii races currently identified in the United States and Europe. They provide new genetic diversity in addition to the few currently used DM‐resistant inbred lines in confection sunflower ensuring protection from yield loss.
Random graphs with given vertex degrees and switchings
Authors: Janson Svante
Published: February 2020

Random graphs with a given degree sequence are often constructed using the configuration model, which yields a random multigraph. We may adjust this multigraph by a sequence of switchings, eventually yielding a simple graph. We show that, assuming essentially a bounded second moment of the degree distribution, this construction with the simplest types of switchings yields a simple random graph with an almost uniform distribution, in the sense that the total variation distance iso(1). This construction can be used to transfer results on distributional convergence from the configuration model multigraph to the uniform random simple graph with the given vertex degrees. As examples, we give a few applications to asymptotic normality. We show also a weaker result yielding contiguity when the maximum degree is too large for the main theorem to hold.
A roadmap for neurodevelopmental disease modeling for non-stem cell biologists
Authors: Ernst Carl
Published: February 2020

Stem and derivative cells induced from somatic tissues are a critical tool for disease modeling but significant technical hurdles hamper their use. The purpose of this review is to provide an overview of pitfalls and mitigation strategies for the nonstem cell biologist using induced pluripotent stem cells and investigating neurodevelopmental disorders. What sample sizes are reasonable? What derivation and purification protocols should be used to make human neurons? In what way should gene editing technologies be used to support discoveries? What kinds of preclinical studies are the most feasible? It is hoped that this roadmap will provide the necessary details for experimental planning and execution for those less familiar in the area of stem cell disease modeling. High-quality human preclinical models will allow for the discovery of molecular and cellular phenotypes specific to different neurodevelopmental disorders, and may provide the assays to advance translational medicine for unmet medical needs.
Functionalized Alpha‐lactalbumin Conjugated with Gold Nanoparticle for Targeted Drug Delivery
Authors: Waghmare Manik N. , Qureshi Tazeen S. , Shaikh Afrin N. , Khade Bipin S. , Murali Krishna C. , Dongre Prabhakar M.
Published: February 2020

The protein‐nanoparticles conjugate has been developed as a targeted drug delivery system which selectively and preferentially delivers the therapeutic agents. Here, the alpha‐lactalbumin (ALA) was purified by size exclusion chromatography and confirmed by gel electrophoresis and mass spectrometry (MS). Functionalization of gold nanoparticles (AuNP, ∼29 nm) with ALA was optimized by light scattering and zeta potential measurements. The nanoconjugates (AuNP‐ALA) and ALA showed strong binding and affinity with curcumin and gemcitabine studied using biophysical analysis. The presence of native form of curcumin with ALA was investigated by MS. 8‐anilino‐1‐naphthalenesulfonic acid binding assay showed 95 % surface hydrophilicity of ALA. Circular dichroism and Fourier transform infrared spectroscopy analysis shows increased alpha‐helicity due to the binding of drugs, revealed large increase in non‐covalent interaction. Vesicular membrane interaction with ALA and nanoconjugate exhibited strong interaction at the vesicles surface. The alpha‐lactalbumin‐nanoparticle conjugate in combination with drugs, could be exploited to establish a targeted drug delivery system.
Co–Catalyzed Oxidative Alkylation between Styrenes and Cyclic Ethers via sp3 C−H Functionalization
Authors: Chen Rongxiang , Wang Kai‐Kai , Wang Zhan‐Yong , Ma Xueji , Wang Doudou , Zhang An‐an , Liu Lantao
Published: February 2020

A new cobalt‐catalyzed oxidative alkylation from readily available styrenes and ethers has been disclosed for a rapid and highly efficient construction of C−C bond via sp3 C−H bond functionalization. Various substituted styrenes and cyclic ethers are well investigated and give satisfactory results. Preliminary mechanism studies suggested that this transformation may involve a radical process. This methodology was demonstrated by good yields and functional group compatibility with simple operation, easily available starting materials and low catalyst loadings.
Synthesis, Biological Activity, and Molecular Docking Studies of Novel 5‐Substituted‐1,2,4‐Triazole‐3‐thione Derivatives
Authors: Qi Le , Wu Shao‐Jie , Li Mou‐Cui , Bai Jia‐Chao , Ma Hai‐Xia , Ren Ying‐Hui
Published: February 2020

Seven Schiff base compounds were synthesized via the nucleophilic condensation of 5‐substituted‐3‐thione‐1,2,4‐triazole and 2,4,6‐trimethyl benzaldehyde. All of the synthesized compounds (A1–A3 and B1–B4) were thoroughly characterized by using spectroscopic and physical analytical methods. The in vitro antifungal activities of the prepared compounds were studied, and results showed that A2, B1, B2, and B3 have good biological activity. Molecular docking was used to predict the binding modes of the ligands to 6CR2 protein, and the reasons behind the excellent activities of A2 and B2 were explored. Finally,the highest occupied molecular orbital, lowest unoccupied molecular orbital, and natural bonding orbital of the compounds were calculated by using density functional theory at the B3LYP/6‐31G level.
A multicriteria optimization model for cloud service provider selection in multicloud environments
Authors: Mohamed Amany M. , Abdelsalam Hisham M.
Published: February 2020

Multicloud computing is a strategy that helps customers to reduce reliance on any single cloud provider (known as the vendor lock‐in problem). The value of such strategy increases with proper selection of qualified service providers. In this paper, a constrained multicriteria multicloud provider selection mathematical model is proposed. Three metaheuristics algorithms (simulated annealing [SA], genetic algorithm [GA], and particle swarm optimization algorithm [PSO]) were implemented to solve the model, and their performance was studied and compared using a hypothetical case study. For the sake of comparison, Taguchi's robust design method was used to select the algorithms' parameters values, an initial feasible solution was generated using analytic hierarchy process (AHP)—as the most used method to solve the cloud provider selection problem in the literature, all three algorithms used that solution and, in order to avoid AHP limitations, another initial solution was generated randomly and used by the three algorithm in a second set of performance experiments. Results showed that SA, GA, PSO improved the AHP solution by 53.75%, 60.41%, and 60.02%, respectively, SA and PSO are robust because of reaching the same best solution in spite of the initial solution.
Photosensitizing proteins for antibacterial photodynamic inactivation
Authors: Hally Cormac , Delcanale Pietro , Nonell Santi , Viappiani Cristiano , Abbruzzetti Stefania
Published: February 2020

We review recent applications of water‐soluble proteins as carriers for photosensitizing molecules in antimicrobial photodynamic therapy (aPDT). The low water solubility of photosensitizers and their tendency to aggregate often impair their photophysics, thus resulting in lower bioavailability of the compounds. Taking advantage of the spontaneous interaction between water soluble proteins endowed with hydrophobic cavities and the otherwise insoluble photosensitizing compounds, it is possible to obtain efficient delivery systems to be applied inaPDT. These self‐assembled structures are endowed with good photosensitizing and fluorescence emission properties (comparable to those of monomerized photosensitizers) with high biocompatibility and warrant good bioavailability of the photoactive drug. The proteins used so far comprise serum albumins, β‐lactoglobulin, and apomyoglobin, while photosensitizers considered up to now have been hypericin, curcumin, Zn‐protoporphyrin IX, and Zn‐phthalocyanine. Furthermore, mutants of fluorescent proteins derived from GFP‐like systems or from flavin binding proteins complete the array of available photosensitizing proteins for aPDT.
Spin Interactions and Magnetic Anisotropy in a Triangular Nickel(II) Complex with Triaminoguanidine Ligand Framework
Authors: Böhme Michael , Schuch Dirk , Buchholz Axel , Görls Helmar , Plass Winfried
Published: February 2020

The trinuclear nickel(II) complex [Ni3(saltagtBu)(bpy)3(H2O)3]Cl (H5saltagtBu = 1,2,3‐tris[(5‐tert‐butylsalicylidene)amino]guanidine) was synthesized and characterized by experimental as well as theoretical methods. The complex salt crystallizes with three molecules of dimethylformamide (dmf) and water as [Ni3(saltagtBu)(bpy)3(H2O)3]Cl·3dmf·3H2O (1) in the trigonal space group P3, with the complex located on a threefold rotation axis, which is consistent with the molecular C3 symmetry of the complex cation. Magnetic measurements reveal an antiferromagnetic coupling (J = –35.9 cm–1) between the nickel(II) ions leading to a diamagnetic ground state for the trinuclear complex cation. Theoretical investigations based on broken‐symmetry DFT confirm the antiferromagnetic exchange within the complex cation of 1. Additional single‐ion CASSCF ab initio studies reveal that magnetic anisotropy is present in the system. The experimental and theoretical results for 1 are compared with those of a structurally similar nickel(II) complex that is based on the bromo‐substituted derivative of the triaminoguanidine ligand. The differences in their magnetic properties can be attributed to the stronger elongation of the pseudo‐octahedral coordination sphere at the nickel(II) centers in case of 1. The analysis of the magnetic properties of 1 clearly shows that for such exchange coupled systems reliable parameters for the magnetic anisotropy cannot be extracted from experimental data alone.
The soft drop groomed jet radius at NLL
Authors: Kang Zhong-Bo , Lee Kyle , Liu Xiaohui , Neill Duff , Ringer Felix
Published: February 2020

Abstract

We present results for the soft drop groomed jet radius Rg at next-to-leading logarithmic accuracy. The radius of a groomed jet which corresponds to the angle between the two branches passing the soft drop criterion is one of the characteristic observables relevant for the precise understanding of groomed jet substructure. We establish a factorization formalism that allows for the resummation of all relevant large logarithms, which is based on demonstrating the all order equivalence to a jet veto in the region between the boundaries of the groomed and ungroomed jet. Non-global logarithms including clustering effects due to the Cambridge/Aachen algorithm are resummed to all orders using a suitable Monte Carlo algorithm. We perform numerical calculations and find a very good agreement with Pythia 8 simulations. We provide theoretical predictions for the LHC and RHIC.