bluuebunny/crossref_metadata_2025 huggingface dataset:
Graphene Oxide Quantum Dots Reduce Oxidative Stress and Inhibit Neurotoxicity In Vitro and In Vivo through Catalase‐Like Activity and Metabolic Regulation
Authors: Ren Chaoxiu , Hu Xiangang , Zhou Qixing
Published: March 2018

Both oxidative stress and neurotoxicity are huge challenges to human health, and effective methods and agents for resisting these adverse effects are limited, especially in vivo. It is shown here that, compared to large graphene oxide (GO) nanosheets, GO quantum dots (GOQDs), as nanozymes, efficiently reduce reactive oxygen species (ROS) and H2O2 in 1‐methyl‐4‐phenyl‐pyridinium ion (MPP+)‐induced PC12 cells. In addition, GOQDs exert neuroprotective effects in a neuronal cell model by decreasing apoptosis and α‐synuclein. GOQDs also efficiently diminish ROS, apoptosis, and mitochondrial damage in zebrafish treated with MPP+. Furthermore, GOQDs‐pretreated zebrafish shows increased locomotive activity and Nissl bodies in the brain, confirming that GOQDs ameliorate MPP+‐induced neurotoxicity, in contrast to GO nanosheets. GOQDs contribute to neurotoxic amelioration by increasing amino acid metabolism, decreasing tricarboxylic acid cycle activity, and reducing steroid biosynthesis, fatty acid biosynthesis, and galactose metabolic pathway activity, which are related to antioxidation and neurotransmission. Meanwhile, H2O2 decomposition and Fenton reactions suggest the catalase‐like activity of GOQDs. GOQDs can translocate into zebrafish brains and exert catalase‐mimicking activity to resist oxidation in the intracellular environment. Unlike general nanomaterials, biocompatible GOQDs demonstrate their high potential for human health by reducing oxidative stress and inhibiting neurotoxicity.
The dawn of consumer‐directed testing
Authors: Ramos Erica , Weissman Scott M.
Published: March 2018

As the public's interest in genetics and genomics has increased, there has been corresponding and unprecedented growth in direct‐to‐consumer genetic testing (DTC‐GT). Although regulatory concerns have limited true DTC‐GT available without a physician order, the paradigm has shifted to a model of consumer‐directed genetic testing (CD‐GT) in which patients are researching testing options and requesting specific genetic testing from their health‐care providers. However, many nongenetics health‐care providers do not have the background, education, interest, or time to order and/or interpret typical clinical genetic testing, let alone DTC‐GT. The lines between CD‐GT, DTC‐GT, and traditional clinical genetic testing are also blurring with the same types of tests available in different settings (e.g., carrier screening) and tests merging medical and nonmedical results, increasing the complexity for consumer decision‐making and clinician management. The genetics community has the training to work with CD‐GT, but there has been a hesitancy to commit to working with these results and questions about what to do when consumers have more complicated asks, like interpretation of raw data. Additionally, at the rate with which CD‐GT is growing, there are questions about having sufficient genetics professionals to meet the potential genetic counseling demand. While there are many complex questions and challenges, this market represents a chance for the genetics community to address and unmet need. We will review the history of the CD‐GT/DTC‐GT market and outline the issues and opportunities our profession is facing.
Reduced contrast sensitivity among older women is associated with increased risk of cognitive impairment
Authors: Ward Michael E. , Gelfand Jeffrey M. , Lui Li‐Yung , Ou Yvonne , Green Ari J. , Stone Katie , Pedula Kathryn L. , Cummings Steven R. , Yaffe Kristine
Published: March 2018

Objective

Several cross‐sectional studies have reported an association between visual contrast sensitivity (a functional measure of low contrast vision) and poor cognitive performance or dementia, but no studies have investigated this association prospectively in a population‐based cohort with final adjudication of mild cognitive impairment (MCI)/dementia.

Methods

In a prospective, community‐based study of aging women (Study of Osteoporotic Fractures), we analyzed whether visual contrast sensitivity was associated with increased risk of MCI or dementia and/or worse performance on various cognitive tests assessed 10 years later. Contrast sensitivity was assessed at baseline in each eye using a VISTECH VCTS 6500 wall chart. MCI/dementia was adjudicated by an expert panel. Multivariate logistic and linear regression models were analyzed.

Results

Of 1,352 white (88.2%) and African American (11.8%) women with a mean age of 77.7 years (standard deviation = 3.3), 536 (39.6%) went on to develop MCI/dementia over 10 years. MCI/dementia risk was more than doubled (odds ratio = 2.16, 95% confidence interval = 1.58–2.96) in women with the lowest quartile of contrast sensitivity compared to the highest (p < 0.0001 for the linear trend). Reduced baseline contrast sensitivity was also associated with lower performance on several cognitive measures assessed 10 years later.

Interpretation

Among older women, reduced contrast sensitivity is associated with a greater risk of MCI/dementia. These findings suggest that visual system neurodegeneration or dysfunction may parallel or precede dementia‐related cortical or subcortical degeneration, and that contrast sensitivity testing may be useful in identifying aging adults at high risk for dementia. Ann Neurol 2018;83:730–738
Inflammatory intrathecal profiles and cortical damage in multiple sclerosis
Authors: Magliozzi Roberta , Howell Owain W. , Nicholas Richard , Cruciani Carolina , Castellaro Marco , Romualdi Chiara , Rossi Stefania , Pitteri Marco , Benedetti Maria Donata , Gajofatto Alberto , Pizzini Francesca B. , Montemezzi Stefania , Rasia Sarah , Capra Ruggero , Bertoldo Alessandra , Facchiano Francesco , Monaco Salvatore , Reynolds Richard , Calabrese Massimiliano
Published: March 2018

Objective

Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course?

Methods

To identify possible biomarkers linking meningeal inflammation, GM damage, and disease severity, gene and protein expression were analyzed in meninges and cerebrospinal fluid (CSF) from 27 postmortem secondary progressive MS and 14 control cases. Combined cytokine/chemokine CSF profiling and 3T magnetic resonance imaging (MRI) were performed at diagnosis in 2 independent cohorts of MS patients (35 and 38 subjects) and in 26 non‐MS patients.

Results

Increased expression of proinflammatory cytokines (IFNγ, TNF, IL2, and IL22) and molecules related to sustained B‐cell activity and lymphoid‐neogenesis (CXCL13, CXCL10, LTα, IL6, and IL10) was detected in the meninges and CSF of postmortem MS cases with high levels of meningeal inflammation and GM demyelination. Similar proinflammatory patterns, including increased levels of CXCL13, TNF, IFNγ, CXCL12, IL6, IL8, and IL10, together with high levels of BAFF, APRIL, LIGHT, TWEAK, sTNFR1, sCD163, MMP2, and pentraxin III, were detected in the CSF of MS patients with higher levels of GM damage at diagnosis.

Interpretation

A common pattern of intrathecal (meninges and CSF) inflammatory profile strongly correlates with increased cortical pathology, both at the time of diagnosis and at death. These results suggest a role for detailed CSF analysis combined with MRI as a prognostic marker for more aggressive MS. Ann Neurol 2018 Ann Neurol 2018;83:739–755
Effective Equations for Repulsive Quasi‐One Dimensional Bose–Einstein Condensates Trapped with Anharmonic Transverse Potentials
Authors: Couto Hugo L. C. , Avelar Ardiley T. , Cardoso Wesley B.
Published: March 2018

One‐dimensional nonlinear Schrödinger equations are derived to describe the axial effective dynamics of cigar‐shaped atomic repulsive Bose‐Einstein condensates trapped with anharmonic transverse potentials. The accuracy of these equations in the perturbative, Thomas‐Fermi, and crossover regimes were verified numerically by comparing the ground‐state profiles, transverse chemical potentials and oscillation patterns with those results obtained for the full three‐dimensional Gross‐Pitaevskii equation. This procedure allows us to derive different patterns of 1D nonlinear models by the control of the transverse confinement even in the presence of an axial vorticity.
Controlled Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides
Authors: Lu Weigang , Zong Chengli , Chopra Pradeep , Pepi Lauren E. , Xu Yongmei , Amster I. Jonathan , Liu Jian , Boons Geert‐Jan
Published: March 2018

A chemoenzymatic approach has been developed for the preparation of diverse libraries of heparan sulfate (HS) oligosaccharides. It employs chemically synthesized oligosaccharides having a chemical entity at a GlcN residue, which in unanticipated manners influences the site of modification by NST, C5‐Epi/2‐OST and 6‐OST1/6‐OST3, thus resulting in oligosaccharides differing in N/O‐sulfation and epimerization pattern. The enzymatic transformations defined fine substrate requirements of NST, C5‐Epi, 2‐OST, and 6‐OST.
Solvent‐Dependent Asymmetric Synthesis of Alkynyl and Monofluoroalkenyl Isoindolinones by CpRhIII‐Catalyzed C−H Activation
Authors: Li Teng , Zhou Chao , Yan Xiaoqiang , Wang Jun
Published: March 2018

The asymmetric synthesis of alkynyl and monofluoroalkenyl isoindolinones from N‐methoxy benzamides and α,α‐difluoromethylene alkynes is enabled by C−H activation with a chiral CpRhIII catalyst. Remarkably, product formation is solvent‐dependent; alkynyl isoindolinones are afforded in MeOH (up to 86 % yield, 99.6 % ee) whereas monofluoroalkenyl isoindolinones are generated in iPrCN (up to 98:2 Z/E, 93 % yield, 86 % ee). Mechanistic studies revealed chiral allene and E‐configured alkenyl rhodium species as reaction intermediates. The latter is transformed into the corresponding Z‐configured monofluoroalkene upon protonation in the iPrCN system and into an alkyne by an unusual anti β‐F elimination in the MeOH system. Notably, kinetic resolution processes occur in this reaction. Despite the moderate enantiocontrol for the formation of the chiral allene, the Z‐monofluoroalkenyl isoindolinones and alkynyl isoindolinones were obtained in good enantiopurities by one or two sequential kinetic resolution processes.
Co‐Evolutionary Fitness Landscapes for Sequence Design
Authors: Tian Pengfei , Louis John M. , Baber James L. , Aniana Annie , Best Robert B.
Published: March 2018

Efficient and accurate models to predict the fitness of a sequence would be extremely valuable in protein design. We have explored the use of statistical potentials for the coevolutionary fitness landscape, extracted from known protein sequences, in conjunction with Monte Carlo simulations, as a tool for design. As proof of principle, we created a series of predicted high‐fitness sequences for three different protein folds, representative of different structural classes: the GA (all‐α) and GB (α/β) binding domains of streptococcal protein G, and an SH3 (all‐β) domain. We found that most of the designed proteins can fold stably to the target structure, and a structure for a representative of each for GA, GB and SH3 was determined. Several of our designed proteins were also able to bind to native ligands, in some cases with higher affinity than wild‐type. Thus, a search using a statistical fitness landscape is a remarkably effective tool for finding novel stable protein sequences.
Efficient Light‐Induced pKa Modulation Coupled to Base‐Catalyzed Photochromism
Authors: Gurke Johannes , Budzák Šimon , Schmidt Bernd M. , Jacquemin Denis , Hecht Stefan
Published: March 2018

Photoswitchable acid–base pairs, whose pKa values can be reversibly altered, are attractive molecular tools to control chemical and biological processes with light. A significant, light‐induced pKa change of three units in aqueous medium has been realized for two thermally stable states, which can be interconverted using UV and green light. The light‐induced pKa modulation is based on incorporating a 3‐H‐thiazol‐2‐one moiety into the framework of a diarylethene photoswitch, which loses the heteroaromatic stabilization of the negatively charged conjugate base upon photochemical ring closure, and hence becomes significantly less acidic. In addition, the efficiency of the photoreactions is drastically increased in the deprotonated state, giving rise to catalytically enhanced photochromism. It appears that protonation has a significant influence on the shape of the ground‐ and excited‐state potential energy surfaces, as indicated by quantum‐chemical calculations.
Synthesis of highly branched polyethylene using para‐phenyl‐substituted α‐diimine nickel catalysts
Authors: Wang Fuzhou , Li Ruiping , Tian Susu , Lian Kunbo , Guo Dengfeng , Li Weimin
Published: March 2018

A series of para‐phenyl‐substituted α‐diimine nickel complexes, [(2,6‐R2‐4‐PhC6H2N═C(Me))2]NiBr2 (R = iPr (1); R = Et (2); R = Me (3); R = H (4)), were synthesized and characterized. These complexes with systematically varied ligand sterics were used as precatalysts for ethylene polymerization in combination with methylaluminoxane. The results indicated the possibility of catalytic activity, molecular weight and polymer microstructure control through catalyst structures and polymerization temperature. Interestingly, it is possible to tune the catalytic activities ((0.30–2.56) × 106 g (mol Ni·h)−1), polymer molecular weights (Mn = (2.1–28.6) × 104 g mol−1) and branching densities (71–143/1000 C) over a very wide range. The polyethylene branching densities decreased with increasing bulkiness of ligand and decreasing polymerization temperature. Specifically, methyl‐substituted complex 3 showed high activities and produced highly branched amorphous polyethylene (up to 143 branches per 1000 C).
Comparison of graphene oxide and graphitic carbon nitride filled carbon–phenolic composites: Thermomechanical properties and role of the strong electronegativity of nanofillers
Authors: Ma Yuanyuan , Yang Yu , Lu Chunxiang , Lu Kuan , Wu Shijie , Liu Xingchen , Wen Xiaodong
Published: March 2018

Carbon–phenolic (CF–PR) composites with 0.1 wt % graphene oxide (GO) and acidified graphitic carbon nitride (ag‐C3N4) were synthesized and characterized to understand their thermal properties. The thermal conductivity, coefficient thermal expansion, dynamic mechanical analysis, and scanning electron microscopy were used in our experimental efforts. The results demonstrate that the ag‐C3N4‐filled composite had 17.17% and 54% reductions in the thermal conductivity and coefficient thermal expansion, respectively, when compared with the neat composite, although the GO‐filled showed a 8.54% decrease and a 30% increase, respectively. Furthermore, reactive molecular dynamics simulation was used to investigate the mechanisms at the atomistic level when the composites are subjected to thermal behavior. The simulated results show that the influence of GO and ag‐C3N4 on the thermal conductivities of the composites was different. Lowly loaded GO favored the more interfacial thermal resistance. However, the stronger electronegativity in ag‐C3N4 favored the formation of a vacuum zone in the matrix; this contributed to increasing the interfacial boundaries and defect scattering. The simulation results are expected to be of great help to serve as a guide for further experiments concerning the thermal properties. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46242.
Chromatic detection of glucose using polymerization of diacetylene vesicle
Authors: Kim Minhee , Shin Young Jae , Hwang Seung Won , Shin Min Jae , Shin Jae Sup
Published: March 2018

A polydiacetylene vesicle was used to fabricate glucose sensor, allowing feasible colorimetric detection. The vesicle was formed by sonication of 10,12‐pentacosadiynoic acid (PCDA). H2O2 formed by the reaction between glucose and glucose oxidase functioned as the initiator for the polymerization of PCDA in the presence of horseradish peroxidase. The solution turned blue after the polymerization of PCDA vesicle. Thus, the glucose concentration could be detected to the concentration level that turns the solution to blue. The ultraviolet absorbance of glucose solution was proportional to glucose concentration. The results of this study indicate that glucose concentration upto 1 mM can be detected by change in blue color by eyes. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46394.
Female Reproductive and Hormonal Factors and Incidence of Primary Total Knee Arthroplasty Due to Osteoarthritis
Authors: Hussain Sultana Monira , Wang Yuanyuan , Giles Graham G. , Graves Stephen , Wluka Anita E. , Cicuttini Flavia M.
Published: March 2018

Objective

To examine the associations of female reproductive and hormonal factors with incidence of total knee arthroplasty (TKA) for osteoarthritis (OA), and to determine whether the associations differ according to overweight/obesity status.

Methods

This study included 22,289 women in the Melbourne Collaborative Cohort Study. Data on age at menarche, pregnancy, parity, years of menstruation, oral contraceptive (OC) use, menopausal status, and hormone replacement therapy (HRT) were collected in 1990–1994. Incidence of TKA during 2001–2013 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. All analyses were adjusted for age, body mass index (BMI) at midlife, change in BMI (from early reproductive age to midlife), country of birth, physical activity, smoking, and education level.

Results

Over the course of 12.7 years, 1,208 TKAs for OA were identified. Ever being pregnant was associated with increased risk of TKA (hazard ratio [HR] 1.32 [95% confidence interval (95% CI) 1.06–1.63]). Parity was positively associated with risk of TKA (P for trend = 0.003). OC users had increased risk of TKA compared with non‐users (for OC use of <5 years, HR 1.25 [95% CI 1.08–1.45]; for OC use of ≥5 years, HR 1.17 [95% CI 1.00–1.37]). A 1‐year increase in menstruation was associated with a 1% decrease in risk of TKA (HR 0.99 [95% CI 0.97–0.99]). These associations remained significant only in women of normal weight at early reproductive age. Current HRT users had increased risk of TKA compared with non‐users (HR 1.37 [95% CI 1.14–1.64]); the association was significant only in non‐obese women at midlife.

Conclusion

Reproductive and hormonal factors were associated with risk of knee OA. These associations remained significant in women of normal weight at early reproductive age and in non‐obese women at midlife. Further work is needed to understand the complex effect of these factors on knee OA.
Virtualization for computer networking skills development in a distance learning environment
Authors: Donelan Helen , Smith Andrew , Wong Patrick
Published: March 2018

Virtualization is a core technology for teaching networking and operating system skills. In a distance learning, or e‐learning, environment, the use of virtualization presents different challenges—both technical and pedagogical. In the initiative presented here, distance learning students studying a module on computer networking and server technologies were required to install virtual machines on their own computers in order to carry out practical labs originally designed for a classroom environment. This research explores and evaluates the strategies developed to support students via a survey of students completing the module. The findings show that the majority of students found it a valuable learning experience and developed practical skills relevant to computer networking careers. Recommendations are made to inform the future development of courses considering the use of virtual machines installed on students’ machines to enable practical labs to be undertaken at a distance.
Rigid Peptide Macrocycles from On‐Resin Glaser Stapling
Authors: Cistrone Philip A. , Silvestri Anthony P. , Hintzen Jordi C. J. , Dawson Philip E.
Published: March 2018

Peptide macrocycles are widely utilized in the development of high affinity ligands, including stapled α‐helices. The linear rigidity of a 1,3‐diynyl linkage provides an optimal distance (7 Å) between β‐carbons of the i,i+4 amino acid side chains, thus suggesting its utility in stabilizing α‐helical structures. Here, we report the development of an on‐resin strategy for an intramolecular Glaser reaction between two alkyne‐terminated side chains by using copper chloride, an essential bpy‐diol ligand, and diisopropylethylamine at room temperature. The efficiency of this ligation was illustrated by the synthesis of (i,i+4)‐, (i,i+5)‐, (i,i+6)‐, and (i,i+7)‐stapled BCL‐9 α‐helical peptides using the unnatural amino acid propargyl serine. Overall, this procedurally simple method relies on inexpensive and widely available reagents to generate low molecular weight 23‐, 26‐, 29‐, and 32‐membered peptide macrocycles.
Observational study of laryngoscopy plus flow‐volume loops during exercise
Authors: Pianosi Paolo T. , Orbelo Diana M. , Cofer Shelagh A.
Published: March 2018

Key Clinical Message

Laryngoscopy is the gold standard to diagnose exercise‐induced laryngeal obstruction, though inspiratory flow‐volume loop may provide a clue. We combined tidal flow‐volume loop analysis plus laryngoscopy during exercise and found that cigar‐shaped – not flattened – inspiratory loops are associated with obstruction. Pursed‐lip breathing slows inhalation thereby reducing vocal fold adduction.
The Dynamics of Chemical Reactions: Atomistic Visualizations of Organic Reactions, and Homage to van ’t Hoff
Authors: Yang Zhongyue , Houk K. N.
Published: March 2018

Jacobus Henricus van ’t Hoff was the first Nobel Laureate in Chemistry. He pioneered in the study of chemical dynamics, which referred at that time to chemical kinetics and thermodynamics. The term has evolved in modern times to refer to the exploration of chemical transformations in a time‐resolved fashion. Chemical dynamics has been driven by the development of molecular dynamics trajectory simulations, which provide atomic visualization of chemical processes and illuminate how dynamic effects influence chemical reactivity and selectivity. In homage to the legend of van ’t Hoff, we review the development of the chemical dynamics of organic reactions, our area of research. We then discuss our trajectory simulations of pericyclic reactions, and our development of dynamic criteria for concerted and stepwise reaction mechanisms. We also describe a method that we call environment‐perturbed transition state sampling, which enables trajectory simulations in condensed‐media using quantum mechanics and molecular mechanics (QM/MM). We apply the method to reactions in solvent and in enzyme. Jacobus Henricus van ’t Hoff (1852, Rotterdam–1911, Berlin) received the Nobel Prize for Chemistry in 1901 “in recognition of the extraordinary services he has rendered by the discovery of the laws of chemical dynamics and osmotic pressure in solutions”. van ’t Hoff was born the Netherlands, and earned his doctorate in Utrecht in 1874. In 1896 he moved to Berlin, where he was offered a position with more research and less teaching. van ’t Hoff is considered one of the founders of physical chemistry. A key step in establishing this new field was the start of Zeitschrift für Physikalische Chemie in 1887.
Improvement of Photodynamic Activity of Lipid–Membrane‐Incorporated Fullerene Derivative by Combination with a Photo‐Antenna Molecule
Authors: Antoku Daiki , Satake Shuhei , Mae Tomoya , Sugikawa Kouta , Funabashi Hisakage , Kuroda Akio , Ikeda Atsushi
Published: March 2018

The weak absorbance of pristine C60, C70, and fullerene derivatives at wavelengths over 600 nm hampers the use of these molecules as photosensitizers (PSs) for photodynamic therapy (PDT). The coexistence of light‐harvesting antenna molecules with a fullerene derivative in lipid membrane bilayers solved this issue. By controlling the location of the C60 derivative in the lipid membrane, the liposomal dyad system for PDT improved the photodynamic activity via an efficient photoenergy transfer from antenna molecules to the fullerene derivative. The photodynamic activity was found to be much higher than those of dyad systems using pristine C60 and C70.
An Alumino‐Mannich Reaction of Organoaluminum Reagents, Silylated Amines, and Aldehydes
Authors: Tarasewicz Anika , Ensan Deeba , Batey Robert A.
Published: March 2018

A multi‐component coupling using organoaluminum reagents, silylated amines, and aldehydes results in the formation of tertiary amines. Both alkenyl‐ and alkylaluminum reagents undergo reaction with iminium ion substrates for which the corresponding Petasis borono‐Mannich reactions are unsuccessful.
Characterization of metastatic urothelial carcinoma via comprehensive genomic profiling of circulating tumor DNA
Authors: Agarwal Neeraj , Pal Sumanta K. , Hahn Andrew W. , Nussenzveig Roberto H. , Pond Gregory R. , Gupta Sumati V. , Wang Jue , Bilen Mehmet A. , Naik Gurudatta , Ghatalia Pooja , Hoimes Christopher J. , Gopalakrishnan Dharmesh , Barata Pedro C. , Drakaki Alexandra , Faltas Bishoy M. , Kiedrowski Lesli A. , Lanman Richard B. , Nagy Rebecca J. , Vogelzang Nicholas J. , Boucher Kenneth M. , Vaishampayan Ulka N. , Sonpavde Guru , Grivas Petros
Published: March 2018

BACKGROUND

Biomarker‐guided clinical trials are increasingly common in metastatic urothelial carcinoma (mUC), yet patients for whom contemporary tumor tissue is not available are not eligible. Technological advancements in sequencing have made cell‐free circulating DNA (cfDNA) next‐generation sequencing (NGS) readily available in the clinic. The objective of the current study was to determine whether the genomic profile of mUC detected by NGS of cfDNA is similar to historical tumor tissue NGS studies. A secondary objective was to determine whether the frequency of genomic alterations (GAs) differed between lower tract mUC (mLTUC) and upper tract mUC (mUTUC).

METHODS

Patients from 13 academic medical centers in the United States who had a diagnosis of mUC between 2014 and 2017 and for whom cfDNA NGS results were available were included. cfDNA profiling was performed using a commercially available platform (Guardant360) targeting 73 genes.

RESULTS

Of 369 patients with mUC, 294 were diagnosed with mLTUC and 75 with mUTUC. A total of 2130 GAs were identified in the overall mUC cohort: 1610 and 520, respectively, in the mLTUC and mUTUC cohorts. In the mLTUC cohort, frequently observed GAs were similar between cfDNA NGS and historical tumor tissue studies, including tumor protein p53 (TP53) (P = 1.000 and .115, respectively), AT‐rich interaction domain 1A (ARID1A) (P = .058 and .058, respectively), phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) (P = .058 and .067, respectively), erb‐b2 receptor tyrosine kinase 2 (ERBB2) (P = .565 and .074, respectively), and fibroblast growth factor receptor 3 (FGFR3) (P = .164 and .014, respectively). No significant difference was observed with regard to the frequency of GAs between patients with mLTUC and mUTUC.

CONCLUSIONS

Among patients with mUC for whom no tumor tissue was available, cfDNA NGS was able to identify a similar profile of GAs for biomarker‐driven clinical trials compared with tumor tissue. Despite the more aggressive clinical course, cases of mUTUC demonstrated a circulating tumor DNA genomic landscape that was similar to that of mLTUC. Cancer 2018;124:2115‐24. © 2018 American Cancer Society.
Understanding the Effect of Solvent on the Growth and Crystal Morphology of MTNP/CL‐20 Cocrystal Explosive: Experimental and Theoretical Studies
Authors: Zhu Shuang‐fei , Zhang Shu‐hai , Gou Rui‐jun , Wu Chun‐lei , Han Gang , Jia Hong‐yun
Published: March 2018

The cocrystal of 1‐methyl‐3,4,5‐trinitro‐1H‐pyrazole (MTNP) and 2,4,6,8,10,12‐hexanitrohexaazaisowurtzitane (CL‐20) is prepared in ethanol and investigated through molecular dynamic and quantum chemistry methods. In order to study the solvent effect on the growth and crystal morphology of the cocrystal, MTNP/CL‐20‐solvent and MTNP/CL‐20‐solution interfacial models are constructed and simulated at temperatures ranging from 293 to 323 K. The analyses of polarity and absorption energy show that ethanol molecules have a larger influence on (0 ‐2 0) and (0 2 0) growth surfaces than other faces at each temperature and the predicting and experimental crystal morphologies are similar. By analyzing the binding energy of MTNP/CL‐20‐solution models, it is clear that MTNP and CL‐20 molecules are easier to be adsorbed on the growth surfaces than ethanol in the solution, and the results of cooperativity effect show that the MTNP binding to CL‐20 is tighter in the presence of ethanol. Those are perhaps the reasons why crystals with good quality were obtained from the ethanol solvent.
A fault‐tolerant modular multilevel inverter topology
Authors: Santosh Kumar Maddugari , Borghate Vijay B. , Karasani Raghavendra Reddy , Sabyasachi Sidharth , Suryawanshi Hiralal M.
Published: March 2018

Multilevel inverter topologies have received an increasing importance for their modular structures with better integration of renewable energy sources and reduced filtering requirements. But reliability is compromised in the process of decreasing the number of switches to produce the maximum number of voltage levels. This paper elevates a single‐phase fault‐tolerant inverter topology, which is modular in structure. The proposed inverter is analyzed for open‐ or short‐circuit faults in sources and open‐circuit faults in switches. Sine Pulse Width Modulation with multicarriers technique is used to control the circuit. The carrier signals are reconfigured under fault conditions based on levels to be generated by bypassing the faulted switch or source. The circuit is simulated in MATLAB/SIMULINK, and experimental setup is developed to claim the fault tolerance of proposed inverter.
Cancer risk and clinicopathological characteristics of thyroid nodules harboring thyroid‐stimulating hormone receptor gene mutations
Authors: Mon Sann Y. , Riedlinger Gregory , Abbott Collette E. , Seethala Raja , Ohori N. Paul , Nikiforova Marina N. , Nikiforov Yuri E. , Hodak Steven P.
Published: March 2018

Background

Thyroid‐stimulating hormone receptor (TSHR) gene mutations play a critical role in thyroid cell proliferation and function. They are found in 20%‐82% of hyperfunctioning nodules, hyperfunctioning follicular thyroid cancers (FTC), and papillary thyroid cancers (PTC). The diagnostic importance of TSHR mutation testing in fine needle aspiration (FNA) specimens remains unstudied.

Methods

To examine the association of TSHR mutations with the functional status and surgical outcomes of thyroid nodules, we evaluated 703 consecutive thyroid FNA samples with indeterminate cytology for TSHR mutations using next‐generation sequencing. Testing for EZH1 mutations was performed in selected cases. The molecular diagnostic testing was done as part of standard of care treatment, and did not require informed consent.

Results

TSHR mutations were detected in 31 (4.4%) nodules and were located in exons 281‐640, with codon 486 being the most common. Allelic frequency ranged from 3% to 45%. Of 16 cases (12 benign, 3 FTC, 1 PTC) with surgical correlation, 15 had solitary TSHR mutations and 1 PTC had comutation with BRAF V600E. Hyperthyroidism was confirmed in all 3 FTC (2 overt, 1 subclinical). Of 5 nodules with solitary TSHR mutations detected at high allelic frequency, 3 (60%) were FTC. Those at low allelic frequency (3%‐22%) were benign. EZH1 mutations were detected in 2 of 4 TSHR‐mutant malignant nodules and neither of 2 benign nodules.

Conclusion

We report that TSHR mutations occur in ∼5% thyroid nodules in a large consecutive series with indeterminate cytology. TSHR mutations may be associated with an increased cancer risk when present at high allelic frequency, even when the nodule is hyperfunctioning. Benign nodules were however most strongly correlated with TSHR mutations at low allelic frequency.
The description and number of undiscovered mammal species
Authors: Fisher Molly A. , Vinson John E. , Gittleman John L. , Drake John M.
Published: March 2018

Global species counts are a key measure of biodiversity and associated metrics of conservation. It is both scientifically and practically important to know how many species exist, how many undescribed species remain, and where they are found. We modify a model for the number of undescribed species using species description data and incorporating taxonomic information. We assume a Poisson distribution for the number of species described in an interval and use maximum likelihood to estimate parameter values of an unknown intensity function. To test the model's performance, we performed a simulation study comparing our method to a previous model under conditions qualitatively similar to those related to mammal species description over the last two centuries. Because our model more accurately estimates the total number of species, we predict that 5% of mammals remain undescribed. We applied our model to determine the biogeographic realms which hold these undescribed species.
Advances in the Synthesis and Application of Tetrafluoroethylene‐ and 1,1,2,2‐Tetrafluoroethyl‐Containing Compounds
Authors: Václavík Jiří , Klimánková Iveta , Budinská Alena , Beier Petr
Published: March 2018

In this review, we provide a comprehensive and critical perspective on the synthesis and application of 1,1,2,2‐tetrafluoroethyl‐ and tetrafluoroethylene‐containing compounds. These structures have been the focus of increasing attention as witnessed by a spectrum of new synthetic approaches, which have recently appeared in the literature. Likewise, applications of molecules containing the CF2CF2 fragment as pharmaceuticals, agrochemicals, pesticides, and advanced materials are described. It is expected that the number of successful applications of these compounds will increase in the future as a result of availability of the synthetic methods outlined here.
Enantioselective Fluorescent Recognition of Amino Acids in Aqueous Solution by Using a Chiral Aldehyde Probe
Authors: Zhao Feng , Du Yi , Tian Jun , Shi Dan , Wang Yachen , Hu Lingling , Yu Shanshan , Yu Xiaoqi , Pu Lin
Published: March 2018

A BINOL‐based chiral aldehyde containing hydrophilic PEG groups was synthesized. It was found that in HEPES buffer solution at neutral pH this compound in combination with Zn2+ ions shows a highly enantioselective fluorescent response toward various amino acids and can be used to determine their enantiomeric composition. The 1H NMR and mass spectroscopic analyses have shown that the BINOL‐based chiral aldehyde can react with one enantiomer of an amino acid and Zn2+ to form the corresponding imine‐zinc complex more than the other enantiomer, giving the observed highly enantioselective fluorescence enhancement.
In‐plane quasi‐static cyclic tests of nonstructural lightweight steel drywall partitions for seismic performance evaluation
Authors: Pali Tatiana , Macillo Vincenzo , Terracciano Maria Teresa , Bucciero Bianca , Fiorino Luigi , Landolfo Raffaele
Published: March 2018

An experimental program was performed for evaluating the seismic response and fragilities of nonstructural lightweight steel drywall partitions, also considering the interaction with structural elements and other nonstructural building components, ie, outdoor façade walls. Therefore, in‐plane quasi‐static reversed cyclic tests were carried out on 8 specimens of indoor partition walls infilled in a frame and on 4 specimens of indoor partition walls connected at its ends with transversal outdoor façade walls. Constructive parameters under investigation include type of connections used for connecting the indoor partition walls to the surrounding elements, stud spacing, type of sheathing panels, and type of jointing finishing. The effect of the constructive parameters on the lateral response in secant stiffness and strength is examined. Furthermore, the main damage phenomena observed during the tests are reported and associated to 3 damage limit states distinguished for the required repair level for the tested partition walls. Fragility curves are used for the experimental assessment of seismic fragility of the tested specimens, in accordance with the interstorey drift limits required by the European code. Finally, the quantitative estimation of the repair action costs starting from the damage observation is also developed. The obtained results could be considered a starting point for developing the in‐plane seismic design assisted by testing of lightweight steel drywall partition walls.
Investigating piwi‐interacting RNA regulome in human neuroblastoma
Authors: Roy Jyoti , Mallick Bibekanand
Published: March 2018

Remarkable attempts have been exercised in recent years using high‐throughput technologies to identify and decipher the functions of piRNAs in various abnormalities like cancer. However, piRNAs in the oncogenesis of neuroblastoma (NB) has not been reported yet even after their illustrated roles in neurological processes. Therefore, we investigated the piRNA transcriptome in IMR‐32 and SH‐SY‐5Y NB cell lines by employing high‐throughput next‐generation sequencing after confirming the expression of three associated PIWILs both at mRNAs and protein level by qRT‐PCR and immunofluroscence, respectively. We identified a common pool of 525 piRNAs of 26–32 nts long expressed in both the cell lines. The possible functions of these piRNAs were charted by predicting their targeting on retrotransposon‐containing 1769 mRNAs differentially expressed in 39 NB cell lines followed by network and pathway analysis. The analysis revealed that majority of the target binding sites in NB fall within retrotransposons residing within the 3′UTR of target mRNA transcripts like miRNA‐targets. Further, we validated the expression of key piRNAs and their target genes enriched in cancer‐related networks, pathways and biological processes which are hypothesized to play crucial roles in neoplastic events of NB. We believe that the evidence of piRNAs in human NB and their possible contribution to its pathogenesis reported in this work will open up new exciting possibilities for piRNA‐mediated therapeutics for this malignancy.
Losing the battle: Perceived status loss and contemplated or attempted suicide in older adults
Authors: Dombrovski Alexandre Y. , Aslinger Elizabeth , Wright Aidan G.C. , Szanto Katalin
Published: March 2018

Objective

While loss of socioeconomic status (SES) has been linked to suicidal behavior, it is unclear whether this experience is merely a downstream effect of psychopathology (“downward drift”), a sign of hardship, or an independent psychological contributor to suicide risk. We examined the association between the subjective experience of status loss and suicidal behavior and ideation in old age, while accounting for potential confounders. We were also interested in whether status loss was associated with mere thoughts of suicide vs. suicidal behavior.

Methods

Fifty older (55+) depressed suicide attempters, 29 depressed suicide ideators with no history of attempted suicide, 38 nonsuicidal depressed participants, and 45 nonpsychiatric controls underwent detailed clinical characterization and reported their current and highest lifetime SES.

Results

Suicide attempters were more likely to report a decline in their SES compared to healthy controls and nonsuicidal depressed older adults, while not differing from suicide ideators. This difference was not explained by objective predictors of SES, including education, financial difficulties, and the presence of addiction. Interestingly, while the current SES of suicide attempters was much lower than that of comparison groups, their reported highest lifetime SES was just as high, despite the differences in education.

Conclusion

In older adults, the experience of status loss is associated with contemplated and attempted suicide even after accounting for objective indicators of social status and psychopathology. It is possible that suicidal individuals retrospectively inflate their previous status, making their current standing appear even worse by comparison.
TNF alpha inhibitors in Alzheimer's disease: A systematic review
Authors: Ekert Justyna O. , Gould Rebecca L. , Reynolds Gemma , Howard Robert J.
Published: March 2018

Objectives

The objective of this study was to evaluate the effect of tumour necrosis factor‐alpha inhibitors (TNF‐αI) on Alzheimer's disease‐associated pathology.

Design

A literature search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library databases for human and animal studies that evaluated the use of TNF‐αI was performed on 26 October 2016.

Results

The main outcomes assessed were cognition and behaviour, reduction in brain tissue mass, presence of plaques and tangles, and synaptic function. Risk of bias was assessed regarding blinding, statistical model, outcome reporting, and other biases. Sixteen studies were included, 13 of which were animal studies and 3 of which were human. All animal studies found that treatment with TNF‐αI leads to an improvement in cognition and behaviour. None of the studies measured change in brain tissue mass. The majority of studies documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The amount of data from human studies was limited. Two out of 3 studies concluded that TNF‐αI are beneficial in Alzheimer's disease patients, with one being an observational study and the latter being a small pilot study, with a high risk of bias.

Conclusion

It was concluded that a large‐scale randomized controlled trial assessing the effectiveness of TNF‐αI on humans is warranted.
Diminution of context association memory structure in subjects with subjective cognitive decline
Authors: Fan Ling‐Yun , Lai Ya‐Mei , Chen Ta‐Fu , Hsu Yung‐Chin , Chen Pin‐Yu , Huang Kuo‐Zhou , Cheng Ting‐Wen , Tseng Wen‐Yi Isaac , Hua Mau‐Sun , Chen Ya‐Fang , Chiu Ming‐Jang
Published: March 2018

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale‐III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content‐related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage.
Anatomy‐guided joint tissue segmentation and topological correction for 6‐month infant brain MRI with risk of autism
Authors: Wang Li , Li Gang , Adeli Ehsan , Liu Mingxia , Wu Zhengwang , Meng Yu , Lin Weili , Shen Dinggang
Published: March 2018

Tissue segmentation of infant brain MRIs with risk of autism is critically important for characterizing early brain development and identifying biomarkers. However, it is challenging due to low tissue contrast caused by inherent ongoing myelination and maturation. In particular, at around 6 months of age, the voxel intensities in both gray matter and white matter are within similar ranges, thus leading to the lowest image contrast in the first postnatal year. Previous studies typically employed intensity images and tentatively estimated tissue probabilities to train a sequence of classifiers for tissue segmentation. However, the important prior knowledge of brain anatomy is largely ignored during the segmentation. Consequently, the segmentation accuracy is still limited and topological errors frequently exist, which will significantly degrade the performance of subsequent analyses. Although topological errors could be partially handled by retrospective topological correction methods, their results may still be anatomically incorrect. To address these challenges, in this article, we propose an anatomy‐guided joint tissue segmentation and topological correction framework for isointense infant MRI. Particularly, we adopt a signed distance map with respect to the outer cortical surface as anatomical prior knowledge, and incorporate such prior information into the proposed framework to guide segmentation in ambiguous regions. Experimental results on the subjects acquired from National Database for Autism Research demonstrate the effectiveness to topological errors and also some levels of robustness to motion. Comparisons with the state‐of‐the‐art methods further demonstrate the advantages of the proposed method in terms of both segmentation accuracy and topological correctness.
Hydrograph separation using tracers and digital filters to quantify runoff components in a semi‐arid mesoscale catchment
Authors: Saraiva Okello Aline Maraci Lopes , Uhlenbrook Stefan , Jewitt Graham P.W. , Masih Ilyas , Riddell Edward Sebastian , Van der Zaag Pieter
Published: March 2018

Chemical hydrograph separation using electrical conductivity and digital filters is applied to quantify runoff components in the 1,640 km2 semi‐arid Kaap River catchment and its subcatchments in South Africa. A rich data set of weekly to monthly water quality data ranging from 1978 to 2012 (450 to 940 samples per site) was analysed at 4 sampling locations in the catchment. The data were routinely collected by South Africa's national Department of Water and Sanitation, using standard sampling procedures. Chemical hydrograph separation using electrical conductivity (EC) as a tracer was used as reference and a recursive digital filter was then calibrated for the catchment. Results of the two‐component hydrograph separation indicate the dominance of baseflow in the low flow regime, with a contribution of about 90% of total flow; however, during the wet season, baseflow accounts for 50% of total flow. The digital filter parameters were very sensitive and required calibration, using chemical hydrograph separation as a reference. Calibrated baseflow estimates ranged from 40% of total flow at the catchment outlet to 70% in the tributaries. The study demonstrates that routinely monitored water quality data, especially EC, can be used as a meaningful tracer, which could also aid in the calibration of a digital filter method and reduce uncertainty of estimated flow components. This information enhances our understanding of how baseflow is generated and contributed to streamflow throughout the year, which can aid in quantification of environmental flows, as well as to better parameterize hydrological models used for water resources planning and management. Baseflow estimates can also be useful for groundwater and water quality management.