bluuebunny/crossref_metadata_2025 huggingface dataset:
Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature
Authors: Cleaver Ruth , Berg Jonathan , Craft Emily , Foster Alison , Gibbons Richard J. , Hobson Emma , Lachlan Katherine , Naik Swati , Sampson Julian R. , Sharif Saba , Smithson Sarah ,   Deciphering Developmental Disorders Study, Parker Michael J. , Tatton‐Brown Katrina
Published: January 2019

Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype‐up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.
The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy
Authors: Samango‐Sprouse Carole , Lasutschinkow Patricia , Powell Sherida , Sadeghin Teresa , Gropman Andrea
Published: January 2019

47,XXY (Klinefelter syndrome) is the most common X and Y chromosomal variation (1:660 males). The incidence of anxiety disorders and the impact of hormonal replacement therapy (HRT) is not well understood. Child Behavior Checklist and Screen for Childhood Anxiety Related Emotional Disorders were completed by parents of 80 boys with 47,XXY. Forty received HRT prior to 10 years of age while 40 did not. HRT (22.5%) received early hormonal treatment prior to 18 months. About 32.5% received hormone booster treatment between 5 and 10 years. The remaining 42.5% received both. There were fewer reported social (p = .015), thought (p = .012), and affective problems (p = .048) in treated boys when compared to untreated. Boys with both treatments demonstrated fewer symptoms on anxious/depressed scale (p = .001) compared to those with early treatment only. Within the treated group, prenatally diagnosed showed fewer indications of anxiety problems (p = .02) than their postnatal counterparts. This comparative, cross‐sectional study expands previous findings on the possible positive effect of HRT in boys with 47,XXY. Anxiety disorders appear to be a penetrant aspect of the 47,XXY phenotype. Further investigation is warranted to explore the relationship between biological treatment and individual responses to HRT to develop more personalized and precise medicine.
ADHD risk genes involved in dopamine signaling and metabolism are associated with reduced estimated life expectancy at young adult follow‐up in hyperactive and control children
Authors: Barkley Russell A. , Smith Karen Müller , Fischer Mariellen
Published: January 2019

ADHD is associated with an elevated risk of mortality and reduced estimated life expectancy (ELE) by adulthood. Reduced life expectancy is substantially related to the trait of behavioral disinhibition; a correlate of both ADHD and of several dopamine genes related to dopamine signaling and metabolism. We therefore hypothesized that several ADHD risk genes related to dopamine might also be predictive of reduced ELE. Using a longitudinal study of 131 hyperactive children and 71 control cases followed to young adulthood, we examined whether several polymorphisms involving DRD4, DAT1, and DBH were related to ELE. The homozygous 9/9 allele of DAT1 and the heterozygous allele of DBH TaqI were associated with 5‐ and 2‐year reductions, respectively, in total ELE. They did not operate on ELE through any relationships to ADHD specifically or behavioral disinhibition more generally. Instead, they showed links to alcohol use (DBH), reduced education, smoking, and reduced exercise (DAT1) employed in the computation of ELE. We conclude that polymorphisms of two dopamine genes are linked to reductions in ELE independently of their association with ADHD.
Synthesis of Cobalt Sulfide Multi‐shelled Nanoboxes with Precisely Controlled Two to Five Shells for Sodium‐Ion Batteries
Authors: Wang Xiao , Chen Ye , Fang Yongjin , Zhang Jintao , Gao Shuyan , Lou Xiong Wen (David)
Published: January 2019

We report the synthesis of cobalt sulfide multi‐shelled nanoboxes through metal–organic framework (MOF)‐based complex anion conversion and exchange processes. The polyvanadate ions react with cobalt‐based zeolitic imidazolate framework‐67 (ZIF‐67) nanocubes to form ZIF‐67/cobalt polyvanadate yolk‐shelled particles. The as‐formed yolk‐shelled particles are gradually converted into cobalt divanadate multi‐shelled nanoboxes by solvothermal treatment. The number of shells can be easily controlled from 2 to 5 by varying the temperature. Finally, cobalt sulfide multi‐shelled nanoboxes are produced through ion‐exchange with S2− ions and subsequent annealing. The as‐obtained cobalt sulfide multi‐shelled nanoboxes exhibit enhanced sodium‐storage properties when evaluated as anodes for sodium‐ion batteries. For example, a high specific capacity of 438 mAh g−1 can be retained after 100 cycles at the current density of 500 mA g−1.
Ethanol‐Precipitable, Silica‐Passivated Perovskite Nanocrystals Incorporated into Polystyrene Microspheres for Long‐Term Storage and Reusage
Authors: Liang Xiao , Chen Mei , Wang Qian , Guo Shaojun , Yang Huai
Published: January 2019

Perovskite nanocrystals (PNCs) are emerging luminescent materials due to their fascinating physic‐optical properties. However, their sensitive surface chemistry with organic polar solvents, oxygen, and moisture greatly hinders their developments towards practical applications. Herein we promote silica‐passivated PNCs (SP‐PNCs) by in situ hydrolyzing the surface ligands of (3‐aminopropyl) triethoxysilane. The resultant SP‐PNCs possesses a high quantum yield (QY) of 80 % and are precipitable by polar solvents, such as ethanol and acetone, without destroying their surface chemistry or losing QY, which offers an eco‐friendly and efficient method for separation, purification, and phase transfer of PNCs. Moreover, we further promoted a swelling–deswelling encapsulation process to incorporate the as‐made SP‐PNCs into non‐crosslinked polystyrene microspheres (PMs), which can largely increase the stability of the SP‐PNCs against moisture for long‐term storage.
Iron‐containing ionic liquid as an efficient and recyclable catalyst for the synthesis of C3‐substituted indole derivatives
Authors: Gu Ying‐Chun , Hu Ren‐Ming , Li Ming‐Ming , Xu Da‐Zhen
Published: January 2019

A facile and efficient protocol for the synthesis of C3‐substituted indole derivatives has been developed under mild condition. The iron‐containing ionic liquid, 1‐(2‐hydroxyethyl)‐1,4‐diazabicyclo[2.2.2] octanylium tetrachloroferrate ([Dabco‐C2OH][FeCl4]) as a recyclable catalyst has been successfully used in the synthesis of trisindolines, bis(3‐indolyl) methanes and β‐indolyl alcohols for the first time. The products of trisindolines and bis(3‐indolyl) methanes are easily separated and purified without chromatographic technique. The catalyst was recycled six times without significant activity loss.
Sensitive spectrofluorometric method for the determination of ascorbic acid in pharmaceutical nutritional supplements using acriflavine as a fluorescence reagent
Authors: Abd Ali Layth I. , Qader Aryan F. , Salih Musher I. , Aboul‐Enein Hassan Y.
Published: January 2019

An easily performed, specific, sensitive, rapid, reliable and inexpensive procedure for the spectrofluorometric quantitation of ascorbic acid was proposed using acriflavine as a fluorescence quenching reagent. The procedure was based on the determined quenching effect of ascorbic acid on the natural fluorescence signal of acriflavine and the reaction between ascorbic acid and acriflavine in Britton–Robinson buffer solution (pH 6) to produce an ion‐associated complex. The reduction in acriflavine fluorescence intensity was detected at 505 nm, while excitation occurred at 265 nm. The relationship between quenching fluorescence intensity (∆F) and concentration of ascorbic acid was linear (R2 = 0.9967) within the range 2–10 μg/ml and with a detection limit of 0.08 μg/ml. No significant interference was detected from other materials often found in pharmaceutical nutritional tablets. The obtained results were compared with those from high‐performance liquid chromatography and appeared in good agreement, with no important differences in precision or accuracy. The proposed spectrofluorimetric method was used to determine the amount of ascorbic acid in a number of commercial pharmaceutical nutritional supplement tablets with a 95% confidence performance.
Utility of the fluorogenic characters of benzofurazan for analysis of tigecycline using spectrometric technique; application to pharmacokinetic study, urine and pharmaceutical formulations
Authors: Salman Baher I. , Ali Marwa F.B. , Marzouq Mostafa A. , Hussein Samiha A.
Published: January 2019

Tigecycline (TIGE) is the newest tetracycline derivative antibiotic with low toxicity, it is used for management of infectious diseases caused by Gram‐positive and Gram‐negative bacteria. Hence, an efficient, selective and sensitive method was developed for analysis of TIGE in commercial formulations, human plasma and urine. The spectrofluorimetric technique based on the reaction of secondary amine moiety in TIGE with 4‐chloro‐7‐nitrobenzofurazan (NBD‐Cl) in slightly alkaline medium producing a highly fluorescent product measured at 540 nm (λex at 470 nm) after heating for 15 min at 75°C. The proposed strategy was upgraded and approved by ICH rules and bio‐analytical validated using US‐FDA recommendations. A linear relationship between fluorescence intensity and TIGE concentration was observed over the concentration range 40–500 ng mL−1 with limit of quantification (LOQ) 21.09 ng mL−1 and limit of detection (LOD) 6.96 ng mL−1.The ultra‐affectability and high selectivity of the proposed strategy permits analysis of TIGE in dosage form, human plasma and urine samples with good recovery ranged from 97.23% to 98.72% and from 99.36% to 99.80% respectively, without any interfering from matrix components. Also, the developed strategy was used to examine the stability of TIGE in human plasma and applied for pharmacokinetic investigation of TIGE.
MiR‐9 promotes multiple myeloma progression by regulating TRIM56/NF‐κB pathway
Authors: Huang Guoqiang , Liu Xiaopeng , Zhao Xiaoying , Zhao Jing , Hao Jinxia , Ren Juan , Chen Ying
Published: January 2019

miR‐9 has been reported to play a pivotal role in multiple human cancers by acting as an oncogene or tumor suppressor. In this study, we explored the possible role and molecular mechanism of miR‐9 in multiple myeloma (MM). The miR‐9 expression was examined by quantitative real‐time polymerase chain reaction assay. Transfection with miR‐9‐mimics, miR‐9‐inhibitor, pcDNA‐TRIM56, or si‐TRIM56 into cells was used to change the expression levels of miR‐9 and TRIM56. Western blot analysis was used to detect the expression of TRIM56, p65, p‐p65, IκBα, and p‐IκBα. The potential target of miR‐9 was confirmed by luciferase reporter assay. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium (MTT) assay, colony formation assay, and flow cytometry were used to assess the abilities of cell proliferation and apoptosis. miR‐9 was upregulated in MM patients and cell lines, and miR‐9 overexpression promoted proliferation and repressed apoptosis in MM cell lines. TRIM56 was confirmed as a target of miR‐9. Moreover, TRIM56 reversed miR‐9‐mediated pro‐proliferation and anti‐apoptosis effect on MM cell lines. Furthermore, nuclear factor‐κB (NF‐κB) pathway was involved in miR‐9/TRIM56‐mediated regulation on MM cell lines. miR‐9 promoted the development and progression of MM by regulating TRIM56/NF‐κB pathway, thereby providing a potential microRNA‐based target for MM therapy.
Impact of baseline estimated glomerular filtration rate on inhospital outcomes of patients with ST‐elevation myocardial infarction undergoing primary percutaneous coronary intervention: A China acute myocardial infarction registry study
Authors: Jia Sida , Zhao Yanyan , Yang Jingang , Zhao Xueyan , Xu Haiyan , Gao Runlin , Wang Qingsheng , Li Junnong , Yuan Jinqing , Yang Yuejin
Published: January 2019

Objective

To explore the relationship between inhospital outcomes and different estimated glomerular filtration rates (eGFRs) and determine an optimal eGFR cutoff value for predicting risk in patients with renal insufficiency (RI).

Background

RI is a predictor of poor prognosis in patients with myocardial infarction undergoing primary percutaneous coronary intervention (PCI). However, the cutoff value of the eGFR is questionable.

Methods

We included 10,240 patients with ST segment elevation myocardial infarction (STEMI) undergoing primary PCI from January 2013 to January 2016 who participated in the China Acute Myocardial Infarction registry. RI was defined as eGFR <60 mL/min/1.73 m2. Patients were stratified into five eGFR groups to determine the optimal cutoff value: <30, 30–45, 45–60, 60–90, and > 90 mL/min/1.73 m2.

Results

Overall, 1,112 (10.9%) patients had eGFR <60 mL/min/1.73 m2. Patients with eGFR<60 mL/min/1.73 m2 had a significantly higher incidence of all‐cause death and major adverse cardiovascular and cerebrovascular events (MACCEs) than those with eGFR >60 mL/min/1.73 m2. Occurrence trend test analysis revealed that the incidence of inhospital all‐cause death and MACCEs increased as the eGFR decreased. In logistic multivariate‐adjusted analysis, eGFR <45 mL/min/1.73 m2 was associated with a higher incidence of all‐cause death and MACCEs than eGFR >90 mL/min/1.73 m2.

Conclusions

RI is common among patients with STEMI undergoing primary PCI. A low eGFR is an indicator of worse inhospital prognosis. We suggest an eGFR cutoff value of 45 mL/min/1.73 m2 to predict inhospital deaths and MACCEs.
Cytotoxicity of Shear Exfoliated Pnictogen (As, Sb, Bi) Nanosheets
Authors: Chia Hui Ling , Latiff Naziah Mohamad , Gusmão Rui , Sofer Zdeněk , Pumera Martin
Published: January 2019

The experimental achievement of phosphorene, which exhibits superior electronic, physical, and optical properties has spurred recent interest in other Group 15 elemental 2D nanomaterials such as arsenene, antimonene, and bismuthene. These unique and superior properties of the pnictogen nanosheets have spurred intensive research efforts and led to the discovery of their diversified potential applications; for instance, optical Kerr material, photonic devices, pnictogen‐decorated microfibers, high‐speed transistors, and flexible 2D electronics. Previous studies have mainly been dedicated to study the synthesis, properties, and applications of the heavy pnictogens nanosheets; however, the toxicological behaviour of these nanosheets has yet to be established. Herein, the cytotoxicity study of pnictogen nanosheets (As, Sb, and Bi) was conducted over 24 h of incubation with various concentrations of test materials and adenocarcinoma human lung epithelial A549 cells. After the treatment period, the remaining cell viabilities were obtained through absorbance measurements with WST‐8 and MTT assays. These findings demonstrate that the toxicity of pnictogen nanosheets decreases down Group 15, whereby arsenic nanosheets are considered to be the most toxic, whereas bismuth nanosheets induce low cytotoxicity. The findings of this study constitute an important initial step towards enhancing our understanding of the toxicological effects of pnictogen nanosheets in light of their prospective commercial applications.
Infrared Spectra of the HAnX and H2AnX2 Molecules (An=Th and U, X=Cl and Br) in Argon Matrices Supported by Electronic Structure Calculations
Authors: Li Lin , Stüker Tony , Andrews Lester , Beckers Helmut , Riedel Sebastian
Published: January 2019

Uranium and thorium hydrides are known as functional groups for ligand stabilized complexes and as isolated molecules under matrix isolation conditions. Here, the new molecular products of the reactions of laser‐ablated U and Th atoms with HCl and with HBr, namely HUCl, HUBr and HThCl, HThBr, based on their mid and far infrared spectra in solid argon, are reported. The assignment of these species is based on the close agreement between observed and calculated vibrational frequencies. The H−U and U−35Cl stretching modes of HUCl were observed at 1404.6 and 323.8 cm−1, respectively. Using DCl instead to form DUCl gives absorption bands at 1003.1 and 314.7 cm−1. The corresponding bands of HThCl are 1483.8 (H−Th) and 1058.0 (D−Th), as well as 340.3 and 335.8 cm−1 (Th−35Cl), respectively. HUBr is observed at 1410.6 cm−1 and the BP86 computed shift from HUCl is 6.2 cm−1 in excellent agreement. The U−H stretching frequency increases from 1383.1 (HUF), 1404.6 (HUCl), 1410.6 (HUBr) to 1423.6 cm−1 (UH) as less electronic charge is removed from the U−H bond by the less electronegative substituent. These U−H stretching frequencies follow the Mayer bond orders calculated for the three HUX molecules. A similar trend is found for the Th counterparts. Additional absorptions are assigned to the H2AnX2 molecules (An=U, Th, X=Cl, Br) formed by the exothermic reaction of a second HX molecule with the above primary products.
Deactivation study of Ru‐Sn‐B/Al2O3 catalysts during selective hydrogenation of methyl oleate to fatty alcohol
Authors: Sánchez María A. , Vicerich María A. , Mazzieri Vanina A. , Gioria Esteban , Gutierrez Laura B. , Pieck Carlos L.
Published: January 2019

In this work, the deactivation of the Ru‐Sn‐B/Al2O3 catalyst prepared by the incipient wetness method in the selective hydrogenation reaction of methyl oleate to fatty alcohol was studied. There was a decrease in both the activity and selectivity of fatty alcohol during successive reaction experiments. The fresh and deactivated catalysts were evaluated by different techniques such as TPR, XPS, TGA, Raman, and FTIR to determine the deactivation causes. Lower Ru and Sn content were found in the deactivated catalyst due to the loss of the active material during hydrogenation reaction. As the metal loss was more important for Ru than for Sn, the Ru/Sn ratio was changed, leading to a decrease of the selectivity. Moreover, the analysis of the XPS peak by the deconvolution of Sn species suggests the more active (SnOx) species for selective hydrogenation are more affected than the less selective (SnOy). Coke deposition was not observed by Raman and FTIR.
Chloroform aerobic cometabolic biodegradation in a continuous‐flow reactor: Model calibration by means of the gauss‐newton method
Authors: Frascari Dario , Pinelli Davide , Ciavarelli Roberta , Nocentini Massimo , Zama Fabiana
Published: January 2019

Chlorinated solvents are toxic and poorly biodegradable pollutants frequently found in contaminated aquifers. Experimental data of chloroform (CF) aerobic cometabolic biodegradation in a sand column with butane as growth substrate were simulated with a system of non‐stationary second‐order partial differential equations with non‐linear kinetic terms. A MATLAB optimization code based on the Gauss‐Newton method and coupled with the Comsol Multiphysics finite elements solver was developed to calibrate the model. For each experimental phase, the best‐fit quality was evaluated by an innovative multi‐variable model adequacy test. The proposed code solved systems of up to 5 partial differential equations and optimized up to 6 unknown parameters, leading to statistically acceptable best‐fits. The optimization of the butane/oxygen pulsed feed led to an 82 % CF biodegradation and to a 0.27 gCF/gbutane transformation yield. When the substrate/pollutant ratio was minimized, the standard model of aerobic cometabolism initially tested required additional terms aimed at taking into account the depletion of reducing energy, in order to attain a statistically acceptable best‐fit. This is the first work in which a model of aerobic cometabolism taking into account reducing energy availability was applied to a continuous‐flow process. The proposed optimization code can be used for model calibration in a wide range of physical problems described by non‐stationary, non‐linear partial differential equations, a task that no commercial software can perform. The developed code is made available in the Supplementary Material.
Enhancement of low‐temperature lignite pyrolysis by recycled carbocoal for high‐quality tar in fixed‐bed reactor
Authors: Liu Tao , Guo Qingjie , Chang Guozhang
Published: January 2019

Lignite could be converted to high value‐added char and tar through a pyrolysis process. To improve the tar yield as well as the quality of tar/char during a low temperature (550 °C) lignite pyrolysis (LT‐LP) process, the influence of mixing inexpensive and accessible recycled carbocoal with three kinds of lignite was investigated in a fixed‐bed reactor. The LT‐LP processes with and without recycled carbocoal were investigated using a TGA and were compared in detail. The results indicated that the addition of the recycled carbocoal into the three lignite optimized the light tar yield from 4.63, 3.33, and 2.09 g/g to 10.50, 6.10, and 5.01 g/g, and improved the gasification reactivity of the chars up to 2.88, 2.58, and 2.88 h−1, respectively. To identify the role of recycled carbocoal during the LT‐LP process, the obtained products, such as tar and char, were characterized by chromatography, thermal gravimetric analyzer, chromatograph‐mass spectrometer, elemental analyzer, Fourier transform infrared spectroscopy, and scanning electron microscope. It was demonstrated that the existence of the recycled carbocoal could impede the self‐polymerization of small molecule hydrogen‐containing (SM‐HC) free radicals and cut down the reactions between SM‐HC and hydroxyl radicals at the weak‐bonds breaking zone (300–450 °C), thereby supplying sufficient free radical stabilizers for the tar intermediates at the molecular skeleton region (450–550 °C). The high‐valued tar and char were obtained. In summary, the employment of recycled carbocoal during the LT‐LP process could not only promote the economic benefit of LT‐LP products but also reduce the cost of lignite value‐added utilization.
Experimental and kinetics study on oxidation of three‐component in supercritical water
Authors: Zhang Jie , Lu Jinling , Chen Senlin , He Denghui , Huang Rui , Luo XingQi
Published: January 2019

The supercritical water oxidation of a methanol, acetic acid, and phenol mixture was investigated in this study. The experimental design was accomplished by means of response surface methodology. 16 experimental runs were performed in a continuous tubular reactor. Quadratic polynomial equations with a satisfactory data fit and accuracy were established on the basis of the experimental results. The calculation results demonstrate the promotion behaviour of methanol, the inhibition behaviour of acetic acid, and the positive effect of phenol on the supercritical water oxidation of the ternary mixture. The interactive effect of the mechanism was characterized by means of the computational simulation with the mechanism‐based kinetic model. It seems that the positive influence of methanol was derived from the co‐oxidation effect of the methanol in the destruction of both acetic acid and phenol. The oxidation of acetic acid was restrained in the mixture system, which is attributed to the more favourable radical capture for phenol, and, thus, the overall disappearance kinetics was retarded with the addition of acetic acid. Finally, the co‐oxidation enhancement of both methanol and acetic acid related to phenol oxidation in supercritical water contributed to the positive effect of phenol on mixture oxidation efficiencies.
Prevalence of familial hypercholesterolemia in patients with premature myocardial infarction
Authors: Cui Yuxia , Li Sufang , Zhang Feng , Song Junxian , Lee Chongyou , Wu Manyan , Chen Hong
Published: January 2019

Background

Familial hypercholesterolemia (FH) is a genetic cause of premature myocardial infarction (PMI). Early diagnosis of FH is critical for prognosis.

Hypothesis

To investigate the prevalence of FH among a cohort of Chinese patients with PMI using genetic testing, and to evaluate different diagnostic criteria.

Methods

A total of 225 consecutive PMI patients were recruited. Low‐density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin‐kexin type 9 (PCSK9) and low‐density lipoprotein receptor adaptor protein 1 (LDLRAP1) genes were detected by Sanger sequencing. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria and modified DLCN criteria, respectively. The prevalence and clinical features of FH were analyzed.

Results

In all PMI patients, pathogenic mutations of LDLR, APOB, PCSK9 and LDLRAP1 genes were found in 10 of 225 patients. Among all mutations, four mutations (LDLR c.129G>C, LDLR c.1867A>T, LDLRAP1 c.65G>C, and LDLRAP1 c.274G>A) were newly discovered. The prevalence of FH diagnosed by genetic testing was 4.4%. The prevalence of definite/probable FH diagnosed by DLCN and modified DLCN criteria reached 8.0% and 23.6%, respectively, and the mutation rates were 33.3% and 12.2%, respectively. The low‐density lipo‐protein cholesterol (LDL‐C) levels in PMI patients with FH were far from goal attainment. Only one of the FH patients had LDL‐C <2.5 mmol/L, and none of them had LDL‐C <1.8 mmol/L.

Conclusions

The prevalence of FH among Chinese patients with PMI appeared relatively common. Underdiagnosis and undertreatment of FH are still a big problem, which should arouse a widespread concern.
Synthesis and Immunomodulatory Activity of Fluorine‐Containing Bisphosphonates
Authors: Mizuta Satoshi , Tagod Mohammed S. O. , Iwasaki Masashi , Nakamura Yoichi , Senju Hiroaki , Mukae Hiroshi , Morita Craig T. , Tanaka Yoshimasa
Published: January 2019

Immune checkpoint blockade using anti‐PD‐1/PD‐L1 or anti‐CTLA‐4 monoclonal antibodies (mAbs) has revolutionized cancer treatment. However, many types of cancer do not respond and for those that do, only a minority of patients achieve durable remissions. Therefore, oncoimmunologists are working to develop adoptive cell therapies for non‐hematopoietic tumors by harnessing immune effector cells such as αβ T cells and γδ T cells. In contrast to conventional αβ T cells that recognize peptides in the context of MHC class I or II molecules, γδ T cells expressing Vγ2Vδ2 T cell receptors (also termed Vγ9Vδ2) are stimulated by isoprenoid metabolites (phosphoantigens) such as isopentenyl diphosphate in a butyrophilin‐3A1‐dependent manner. Vγ2Vδ2 T cells kill almost all types of tumor cells that have been treated with bisphosphonates. In this study, we synthesized a series of fluorine‐containing bisphosphonates based on current drugs and found that they stimulated Vγ2Vδ2 T cell killing of tumor cells. A fluorine‐containing prodrug analogue of zoledronate where phosphonate moieties were masked with pivaloyloxymethyl groups markedly enhanced Vγ2Vδ2 T‐cell‐mediated cytotoxicity, and also promoted the expansion of peripheral blood Vγ2Vδ2 T cells. These results demonstrate that a prodrug of a fluorine‐containing zoledronate analogue can sensitize tumor cells for killing as well as expand Vγ2Vδ2 T cells for adoptive cell therapy.
Atomic Layer Deposition of NiOOH/Ni(OH)2 on PIM‐1‐Based N‐Doped Carbon Nanofibers for Electrochemical Water Splitting in Alkaline Medium
Authors: Patil Bhushan , Satilmis Bekir , Khalily Mohammad Aref , Uyar Tamer
Published: January 2019

Portable and flexible energy devices demand lightweight and highly efficient catalytic materials for use in energy devices. An efficient water splitting electrocatalyst is considered an ideal future energy source. Well‐aligned high‐surface‐area electrospun polymers of intrinsic microporosity (PIM‐1)‐based nitrogen‐doped carbon nanofibers were prepared as a free‐standing flexible electrode. A non‐noble‐metal catalyst NiOOH/Ni(OH)2 was precisely deposited over flexible free‐standing carbon nanofibers by using atomic layer deposition (ALD). The morphology, high surface area, nitrogen doping, and Ni states synergistically showed a low onset potential (ηHER=−40 and ηOER=290 mV vs. reversible hydrogen electrode), small overpotential at η10 [oxygen evolution reaction (OER)=390.5 mV and hydrogen evolution reaction (HER)=−147 mV], excellent kinetics (Tafel slopes for OER=50 mV dec−1 and HER=41 mV dec−1), and high stability (>16 h) towards water splitting in an alkaline medium (0.1 m KOH). The performance was comparable with that of state‐of‐the‐art noble‐metal catalysts (e.g., Ir/C, Ru/C for OER, and Pt/C for HER). Post‐catalytic characterization with X‐ray photoelectron spectroscopy (XPS) and Raman spectroscopy further proved the durability of the electrode. This study provides insight into the design of 1D‐aligned N‐doped PIM‐1 electrospun carbon nanofibers as a flexible and free‐standing NiOOH/Ni(OH)2 decorated electrode as a highly stable nanocatalyst for water splitting in an alkaline medium.
Regioselective Hydrogenation of Itaconic Acid to γ‐Isovalerolactone by Transition‐Metal Nanoparticle Catalysts
Authors: Gowda Ravikumar R. , Chen Eugene Y.‐X.
Published: January 2019

Current methods for hydrogenation of bio‐derived itaconic acid (IA) lead to a mixture of isomeric lactone products. Transition‐metal nanoparticles (TM‐NPs), in situ‐generated through thermolysis of TM(0) (Ru, Fe, W, Cr) carbonyls, in particular Ru‐NPs, were found to catalyze regioselective hydrogenation of IA by syngas (2 H2/CO) into γ‐isovalerolactone (GiVL) in approximately 70 % isolated yield. Key sustainability features of this new route include: a one‐pot direct transformation of bio‐renewable IA into value‐added GiVL selectively, use of inexpensive and renewable syngas in aqueous solution, and development of a supported recyclable NP catalyst system, Al2O3‐Ru‐NPs.
Application of intense ion beams to planetary physics research at the Facility for Antiprotons and Ion Research facility
Authors: Tahir Naeem A. , Shutov Alexander , Piriz Antonio R. , Neumayer Paul , Lomonosov Igor V. , Bagnoud Vincent , Piriz Sofia A.
Published: January 2019

This paper presents detailed 2D hydrodynamic simulations of implosion of a multi‐layered cylindrical target that is driven by an intense uranium beam. The target is comprised of a thick, high‐Z, high‐ρ cylindrical shell that encloses a sample material (Fe in the present case). Two options have been used for the focal spot geometry: an annular form and a circular form. The purpose of this work is to show that an intense heavy‐ion beam can induce the extreme physical conditions in the sample material similar to those that exist in the planetary cores. In this study, we use parameters of the beam that will be generated at the Facility for Antiprotons and Ion Research (FAIR), Darmstadt, in a few years' time. Production of these high‐energy‐density (HED) samples will allow us to study planetary physics in the laboratory. It is to be noted that planetary physics research is an important part of the FAIR HED physics program. A dedicated experiment named LAboratory PLAnetary Sciences (LAPLAS) has been proposed for this purpose. These simulations show that in such experiments an Fe sample can be imploded to the Earth's core conditions and to those in more massive rocky planets called Super‐Earths. Similarly, implosion of hydrogen and water samples will generate the core conditions of solar and extrasolar hydrogen‐rich gas giants and water‐rich icy planets, respectively. The LAPLAS experiments will thus provide very valuable information on the equation of state and transport properties of matter under extreme physical conditions, which will help scientists understand the structure and evolution of the planets in our solar system as well as of the extrasolar planets.
Nature‐inspired meta‐heuristic algorithms for solving the load balancing problem in the software‐defined network
Authors: Akbar Neghabi Ali , Jafari Navimipour Nima , Hosseinzadeh Mehdi , Rezaee Ali
Published: January 2019

The growth of the networks has difficult network management. Recently, a concept called software‐defined network (SDN) has been proposed to address this issue, which makes network management more adaptable. Control and forwarding planes are separated in SDN. The control plane is a centralized logical controller that controls the network. The forwarding plane that consists of transfer devices is responsible for transmitting packets. Because the network resources are limited, optimizing the use of resources in the networks is an important issue. Load balancing improves the balanced distribution of loads across multiple resources in order to maximize the reliability and network resources efficiency. SDN controllers can create an optimal load balancing compared to traditional networks because they have a network global view. The load‐balancing problem can be solved using many different nature‐inspired meta‐heuristic techniques because it has the NP‐complete nature. Hence, for solving load balancing problem in SDN, nature‐inspired meta‐heuristic techniques are important methods. However, to the best of our knowledge, there is not a survey or systematic review on studying these matters. Accordingly, in the area of the load balancing in the SDN, this paper reviews systematically the nature‐inspired meta‐heuristic techniques. Also, this study demonstrates advantages and disadvantages regarded of the chosen nature‐inspired meta‐heuristic techniques and considers their algorithms metrics. Moreover, to apply better load balancing techniques in the future, the important challenges of these techniques have been investigated.
Oncocytic poorly differentiated (insular) thyroid carcinoma mimicking metastatic adenocarcinoma. A case report and review of the literature
Authors: Laforga Juan B. , Cortés Virginia A.
Published: January 2019

We report the cytohistologic and immunohistochemical findings of an oncocytic variant of poorly differentiated thyroid carcinoma in a 76‐year old man with a prior history of prostatic adenocarcinoma. The man complained of a palpable nodule in the right thyroid lobe and cervical lymph node. Fine‐needle aspiration (FNA) in both cases yielded solid clusters of cells/insulae, microfollicles, and isolated atypical cells. Considering the patient's past history, an initial diagnosis of metastasis from prostate adenocarcinoma was considered. However, immunohistochemical staining of liquid‐based cytology specimens (Thin‐Prep) showed diffuse positive results for TTF‐1 and thyroglobulin. The patient underwent total thyroidectomy with bilateral neck dissection. Histologic and immunohistochemical evaluation showed a poorly differentiated oncocytic thyroid carcinoma with lymphovascular invasion and lymph node metastases. To our knowledge, this is the first description of the immunocytochemical evaluation of this rare variant of poorly differentiated thyroid carcinoma using FNA and liquid based cytology.
The microbiota–gut–brain axis: A promising avenue to foster healthy developmental outcomes
Authors: Brett Bonnie E. , de Weerth Carolina
Published: January 2019

Fostering healthy developmental growth in the first years of life is associated with numerous favorable cognitive, social, and economic outcomes. Funding and promoting research aimed at identifying potential targets for early intervention should be a top priority for lawmakers and funders. One promising avenue of research and potential early intervention is the microbiota–gut–brain axis. In this report, we briefly examine the role of the gut microbiota in human life, focusing on links with health, cognition, and behavior. We then discuss the development of the gut microbiota and the critical early window in which colonization occurs. Then, we review current nonnutritive means of influencing the gut microbiota in early life. Finally, we discuss the implications this work has for early intervention in low‐income communities and end with recommendations regarding further research and research funding priorities.
Characterizing bumble bee (Bombus) communities in the United States and assessing a conservation monitoring method
Authors: Strange James P. , Tripodi Amber D.
Published: January 2019

Aim

Bumble bees (Hymenoptera: Apidae: Bombus) are economically and ecologically important pollinators in agroecosystems and wildland habitats. In the Nearctic region, there are approximately 41 species, of which the IUCN lists twelve species as vulnerable, endangered, or critically endangered. We conducted a standardized faunal survey to inform ongoing conservation efforts including petitions under review for the Endangered Species Act. Furthermore, we test the appropriateness of a methodology for accurately sampling bumble bee communities.

Location

The United States of America, including 31 sites in 15 states.

Methods

We surveyed 15 states in the summer of 2015 to assess community composition and relative species abundance at agricultural and seminatural sites throughout the United States. We collected approximately 100 bees, using aerial nets, from each of 31 sites and identified specimens to species, totaling 3,252 bees. We assessed our survey methodology to understand whether it accurately sampled the potential community of bumble bees at each site for utility in future monitoring efforts.

Results

Average site species richness was 5.1 ± 2.05, and we detected 30 of the 41 species documented historically within the contiguous United States. Sampling a site beyond 100 bees rarely added additional species detections, whereas adding additional sampling sites within an ecoregion frequently increased the species richness for the ecoregion. Thirteen of the 30 species we detected each accounted for <1% of the total fauna, and two species accounted for 49.02% of all bees captured. Species richness and evenness increased with increasing latitude across communities.

Main Conclusions

Species diversity and evenness in bumble bees increases in northern latitudes and increasing elevation in the United States; however, a few common species tend to dominate communities while many species occur only in low numbers. The results of this survey effort can inform current conservation evaluations and planning.
Plasma mammalian leptin analogue predicts reproductive phenology, but not reproductive output in a capital‐income breeding seaduck
Authors: Hennin Holly L. , Legagneux Pierre , Gilchrist H. Grant , Bêty Joël , McMurtry John P. , Love Oliver P.
Published: January 2019

To invest in energetically demanding life history stages, individuals require a substantial amount of resources. Physiological traits, particularly those related to energetics, can be useful for examining variation in life history decisions and trade‐offs because they result from individual responses to environmental variation. Leptin is a protein hormone found in mammals that is proportional to the amount of endogenous fat stores within an individual. Recently, researchers have confirmed that a mammalian leptin analogue (MLA), based on the mammalian sequence of leptin, is present with associated receptors and proteins in avian species, with an inhibitory effect on foraging and body mass gain at high circulating levels. While MLA has been both quantified and manipulated in avian species, little is currently known regarding whether plasma MLA in wild‐living species and individuals is associated with key reproductive decisions. We quantified plasma MLA in wild, Arctic‐nesting female common eiders (Somateria mollissima) at arrival on the breeding grounds and followed them to determine subsequent breeding propensity, and reproductive phenology, investment, and success. Common eiders are capital‐income breeding birds that require the accumulation of substantial fat stores to initiate laying and successfully complete incubation. We found that females with lower plasma MLA initiated breeding earlier and in a shorter period of time. However, we found no links between plasma MLA levels and breeding propensity, clutch size, or reproductive success. Although little is still known about plasma MLA, based on these results and its role in influencing foraging behaviors and condition gain, plasma MLA appears to be closely linked to reproductive timing and is therefore likely to underlie trade‐offs surrounding life history decisions.
Blockchain technology outline and its application to field of power and energy system
Authors: Sawa Toshiyuki
Published: January 2019

Blockchains were developed as a technology used for transactions of Bitcoins (cryptocurrency). Blockchains have several features such as decentralized transaction without third parties, tolerance network, prevention of data manipulation, and operational cost reduction. This technology is gaining attention in the world, and by adding extensions, improvements, or new technologies, it is expected to be used not only in cryptocurrency and fintech but also in the power and energy system field. This technical note explains the outline of the blockchain technology and its application to the field of power and energy system.
Methanation of CO2 Over Bimetallic Ni–5f Block Element (Th, U) Oxides
Authors: Branco Joaquim B. , Ferreira Ana C.
Published: January 2019

THe methanation of carbon dioxide was studied over bimetallic nickel‐5f block element oxides, 2NiO·ThO2 and 2NiO·UO3. The catalysts were prepared by two approaches: controlled oxidation under dry air using intermetallic binary compounds (AnNi2; An=Th, U) as precursors and by a modified sol‐gel method. The best results were those obtained using the thorium‐based catalysts that present activities and selectivities higher than those measured over two reference catalysts. To the best of our knowledge, this is one of the few times that bimetallic nickel‐5f block element oxides were tested for the methanation of carbon dioxide and their behaviour was a complete, or not, surprise. The catalysts present also unusual and long stability in the gaseous stream and with activities 10–30 times superior to that measured over a commercial 5wt.‐%Rh catalyst supported on alumina, they clearly merit an opportunity and further studies.
UVCB substances II: Development of an endpoint-nonspecific procedure for selection of computationally generated representative constituents
Authors: Kutsarova Stela S. , Yordanova Darina G. , Karakolev Yordan H. , Stoeva Stoyanka , Comber Mike , Hughes Christopher B. , Vaiopoulou Eleni , Dimitrov Sabcho D. , Mekenyan Ovanes G.
Published: January 2019

Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) comprise approximately 40% of all registered substances submitted to the European Chemicals Agency. One of the main characteristics of UVCBs is that they have no unique representation. Industry scientists who are part of the scientific community have been working with academics and consultants to address the problem of a lack of a defined structural description. It has been acknowledged that one of the obstacles is the large number of possible structural isomers. We have recently proposed and published a methodology, based on the generic substance identifiers, to address this issue. The methodology allows for the coding of constituents, their generation, calculation of important characteristics of UVCB constituents, and selection of representative constituents. In the present study we introduce a statistical selection of the minimum number of generated constituents representing a UVCB. This representative sample was selected in such a way that the structural variability and the properties of concern of the UVCB were approximated within a predefined tolerable error. The aim of the statistical selection was to enable the assessment of UVCB substances by decreasing the number of constituents that need to be evaluated. The procedure, which was shown to be endpoint-independent, was validated theoretically and on real case studies. Environ Toxicol Chem 2019;38:682–694. © 2019 SETAC
Lysophosphatidic acid activates satellite glia cells and Schwann cells
Authors: Robering Jan W. , Gebhardt Lisa , Wolf Katharina , Kühn Helen , Kremer Andreas E. , Fischer Michael J. M.
Published: January 2019

Pruritus is a common and disabling symptom in patients with hepatobiliary disorders, particularly in those with cholestatic features. Serum levels of lysophosphatidic acid (LPA) and its forming enzyme autotaxin were increased in patients suffering from hepatic pruritus, correlated with itch severity and response to treatment. Here we show that in a culture of dorsal root ganglia LPA 18:1 surprisingly activated a large fraction of satellite glia cells, and responses to LPA 18:1 correlated inversely with responses to neuronal expressed transient receptor potential channels. LPA 18:1 caused only a marginal activation of heterologously expressed TRPV1, and responses in dorsal root ganglion cultures from TRPV1‐deficient mice were similar to controls. LPA 18:1 desensitized subsequent responsiveness to chloroquine and TGR5 agonist INT‐777. The LPA 18:1‐induced increase in cytoplasmatic calcium stems from the endoplasmatic reticulum. LPA receptor expression in dorsal root ganglia and Schwann cells, LPAR1 immunohistochemistry, and pharmacological results indicate a signaling pathway through LPA receptor 1. Peripheral rat Schwann cells, which are of glial lineage as the satellite glia cells, were also responsive to LPA 18:1. Summarizing, LPA 18:1 primarily activates rather glial cells than neurons, which may subsequently modulate neuronal responsiveness and sensory sensations such as itch and pain.
Identifying the neural correlates of doorway freezing in Parkinson's disease
Authors: Matar Elie , Shine James M. , Gilat Moran , Ehgoetz Martens Kaylena A. , Ward Philip B. , Frank Michael J. , Moustafa Ahmed A. , Naismith Sharon L. , Lewis Simon J. G.
Published: January 2019

Freezing of gait (FOG) in Parkinson's disease (PD) is frequently triggered upon passing through narrow spaces such as doorways. However, despite being common the neural mechanisms underlying this phenomenon are poorly understood. In our study, 19 patients who routinely experience FOG performed a previously validated virtual reality (VR) gait paradigm where they used foot‐pedals to navigate a series of doorways. Patients underwent testing randomised between both their “ON” and “OFF” medication states. Task performance in conjunction with blood oxygenation level dependent (BOLD) signal changes between “ON” and “OFF” states were compared within each patient. Specifically, as they passed through a doorway in the VR environment patients demonstrated significantly longer “footstep” latencies in the OFF state compared to the ON state. As seen clinically in FOG this locomotive delay was primarily triggered by narrow doorways rather than wide doorways. Functional magnetic resonance imaging revealed that footstep prolongation on passing through doorways was associated with selective hypoactivation in the presupplementary motor area (pSMA) bilaterally. Task‐based functional connectivity analyses revealed that increased latency in response to doorways was inversely correlated with the degree of functional connectivity between the pSMA and the subthalamic nucleus (STN) across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associated with increased connectivity between the bilateral STN. These findings suggest that the effect of environmental cues on triggering FOG reflects a degree of impaired processing within the pSMA and disrupted signalling between the pSMA and STN, thus implicating the “hyperdirect” pathway in the generation of this phenomenon.