bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient RNA drug delivery using red blood cell extracellular vesicles
Authors: Usman Waqas Muhammad , Pham Tin Chanh , Kwok Yuk Yan , Vu Luyen Tien , Ma Victor , Peng Boya , Chan Yuen San , Wei Likun , Chin Siew Mei , Azad Ajijur , He Alex Bai-Liang , Leung Anskar Y. H. , Yang Mengsu , Shyh-Chang Ng , Cho William C. , Shi Jiahai , Le Minh T. N.
Published: June 2018

Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR–Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.
Serum Proteomic Profiling to Identify Biomarkers of Premature Carotid Atherosclerosis
Authors: Bhosale Santosh D. , Moulder Robert , Venäläinen Mikko S. , Koskinen Juhani S. , Pitkänen Niina , Juonala Markus T. , Kähönen Mika A. P. , Lehtimäki Terho J. , Viikari Jorma S. A. , Elo Laura L. , Goodlett David R. , Lahesmaa Riitta , Raitakari Olli T.
Published: June 2018

To evaluate the presence of serum protein biomarkers associated with the early phases of formation of carotid atherosclerotic plaques, label-free quantitative proteomics analyses were made for serum samples collected as part of The Cardiovascular Risk in Young Finns Study. Samples from subjects who had an asymptomatic carotid artery plaque detected by ultrasound examination (N = 43, Age = 30–45 years) were compared with plaque free controls (N = 43) (matched for age, sex, body weight and systolic blood pressure). Seven proteins (p < 0.05) that have been previously linked with atherosclerotic phenotypes were differentially abundant. Fibulin 1 proteoform C (FBLN1C), Beta-ala-his-dipeptidase (CNDP1), Cadherin-13 (CDH13), Gelsolin (GSN) and 72 kDa type IV collagenase (MMP2) were less abundant in cases, whereas Apolipoproteins C-III (APOC3) and apolipoprotein E (APOE) were more abundant. Using machine learning analysis, a biomarker panel of FBLN1C, APOE and CDH13 was identified, which classified cases from controls with an area under receiver-operating characteristic curve (AUROC) value of 0.79. Furthermore, using selected reaction monitoring mass spectrometry (SRM-MS) the decreased abundance of FBLN1C was verified. In relation to previous associations of FBLN1C with atherosclerotic lesions, the observation could reflect its involvement in the initiation of the plaque formation, or represent a particular risk phenotype.
The germline mutational landscape of BRCA1 and BRCA2 in Brazil
Authors: Palmero Edenir Inêz , Carraro Dirce Maria , Alemar Barbara , Moreira Miguel Angelo Martins , Ribeiro-dos-Santos Ândrea , Abe-Sandes Kiyoko , Galvão Henrique Campos Reis , Reis Rui Manuel , de Pádua Souza Cristiano , Campacci Natalia , Achatz Maria Isabel , Brianese Rafael Canfield , da Cruz Formiga Maria Nirvana , Makdissi Fabiana Baroni , Vargas Fernando Regla , Evangelista dos Santos Anna Cláudia , Seuanez Hector N. , Lobo de Souza Kelly Rose , Netto Cristina B. O. , Santos-Silva Patrícia , da Silva Gustavo Stumpf , Burbano Rommel M. R. , Santos Sidney , Assumpção Paulo Pimentel , Bernardes Izabel Maria Monteiro , Machado-Lopes Taisa Manuela Bonfim , Bomfim Thais Ferreira , Toralles Maria Betânia Pereira , Nascimento Ivana , Garicochea Bernardo , Simon Sergio D. , Noronha Simone , de Lima Fernanda Teresa , Chami Anisse Marques , Bittar Camila Matzenbacher , Bines Jose , Artigalas Osvaldo , Esteves-Diz Maria Del Pilar , Lajus Tirzah Braz Petta , Gifoni Ana Carolina Leite Vieira Costa , Guindalini Rodrigo S. C. , Cintra Terezinha Sarquis , Schwartz Ida V. D. , Bernardi Pricila , Miguel Diego , Nogueira Sonia Tereza dos Santos , Herzog Josef , Weitzel Jeffrey N. , Ashton-Prolla Patricia
Published: June 2018

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.
Predictive Modeling of the Progression of Alzheimer’s Disease with Recurrent Neural Networks
Authors: Wang Tingyan , Qiu Robin G. , Yu Ming
Published: June 2018

The number of service visits of Alzheimer’s disease (AD) patients is different from each other and their visit time intervals are non-uniform. Although the literature has revealed many approaches in disease progression modeling, they fail to leverage these time-relevant part of patients’ medical records in predicting disease’s future status. This paper investigates how to predict the AD progression for a patient’s next medical visit through leveraging heterogeneous medical data. Data provided by the National Alzheimer’s Coordinating Center includes 5432 patients with probable AD from August 31, 2005 to May 25, 2017. Long short-term memory recurrent neural networks (RNN) are adopted. The approach relies on an enhanced “many-to-one” RNN architecture to support the shift of time steps. Hence, the approach can deal with patients’ various numbers of visits and uneven time intervals. The results show that the proposed approach can be utilized to predict patients’ AD progressions on their next visits with over 99% accuracy, significantly outperforming classic baseline methods. This study confirms that RNN can effectively solve the AD progression prediction problem by fully leveraging the inherent temporal and medical patterns derived from patients’ historical visits. More promisingly, the approach can be customarily applied to other chronic disease progression problems.
Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) gene causes spermatogenesis defects and male infertility in mice
Authors: Ali Asmaa , Mistry Bhavesh V. , Ahmed Hala A. , Abdulla Razan , Amer Hassan A. , Prince Abdelbary , Alazami Anas M. , Alkuraya Fowzan S. , Assiri Abdullah
Published: June 2018

DDB1– and CUL4–associated factor 17 (Dcaf17) is a member of DCAF family genes that encode substrate receptor proteins for Cullin-RING E3 ubiquitin ligases, which play critical roles in many cellular processes. To unravel the function of DCAF17, we performed expression profiling of Dcaf17 in different tissues of wild type mouse by qRT-PCR and generated Dcaf17 knockout mice by gene targeting. Expression profiling of Dcaf17 showed highest expression in testis. Analyses of Dcaf17 transcripts during post-natal development of testis at different ages displayed gradual increase in Dcaf17 mRNA levels with the age. Although Dcaf17 disruption did not have any effect on female fertility, Dcaf17 deletion led to male infertility due to abnormal sperm development. The Dcaf17−/− mice produced low number of sperm with abnormal shape and significantly low motility. Histological examination of the Dcaf17−/− testis revealed impaired spermatogenesis with presence of vacuoles and sloughed cells in the seminiferous tubules. Disruption of Dcaf17 caused asymmetric acrosome capping, impaired nuclear compaction and abnormal round spermatid to elongated spermatid transition. For the first time, these data indicate that DCAF17 is essential for spermiogenesis.
Duplication of a germline promoter downstream of the IgH 3′ regulatory region impairs class switch recombination
Authors: Santos Joana M. , Braikia Fatima-Zohra , Oudinet Chloé , Haddad Dania , Conte Caroline , Dauba Audrey , Khamlichi Ahmed Amine
Published: June 2018

During an adaptive immune response, B cells can change their surface immunoglobulins from IgM to IgG, IgE or IgA through a process called class switch recombination (CSR). Switching is preceded by inducible non-coding germline transcription (GLT) of the selected constant gene(s), which is largely controlled by a super-enhancer called the 3′ regulatory region (3′RR). Despite intense efforts, the precise mechanisms that regulate GLT are still elusive. In order to gain additional insights into these mechanisms, we analyzed GLT and CSR in mutant B cells carrying a duplication of the promoter of the α constant gene (Iα) downstream of 3′RR. Duplication of the Iα promoter affected differently GLT and CSR. While for most isotypes a drop in GLT was accompanied by a decrease in CSR, that was not the case for switching to IgA, which diminished despite unchanged GLT. Unexpectedly, there was no obvious effect on GLT and CSR to IgG3. Remarkably, specific stimuli that normally induce switching to IgG2b had contrasting effects in mutant B cells; Iγ2b was now preferentially responsive to the stimulus that induced Iα promoter. We propose that one mechanism underlying the induced 3′RR-mediated activation of GL promoters involves, at least in part, specific transcription factories.
Place Cell-Like Activity in the Primary Sensorimotor and Premotor Cortex During Monkey Whole-Body Navigation
Authors: Yin A. , Tseng P. H. , Rajangam S. , Lebedev M. A. , Nicolelis M. A. L.
Published: June 2018

Primary motor (M1), primary somatosensory (S1) and dorsal premotor (PMd) cortical areas of rhesus monkeys previously have been associated only with sensorimotor control of limb movements. Here we show that a significant number of neurons in these areas also represent body position and orientation in space. Two rhesus monkeys (K and M) used a wheelchair controlled by a brain-machine interface (BMI) to navigate in a room. During this whole-body navigation, the discharge rates of M1, S1, and PMd neurons correlated with the two-dimensional (2D) room position and the direction of the wheelchair and the monkey head. This place cell-like activity was observed in both monkeys, with 44.6% and 33.3% of neurons encoding room position in monkeys K and M, respectively, and the overlapping populations of 41.0% and 16.0% neurons encoding head direction. These observations suggest that primary sensorimotor and premotor cortical areas in primates are likely involved in allocentrically representing body position in space during whole-body navigation, which is an unexpected finding given the classical hierarchical model of cortical processing that attributes functional specialization for spatial processing to the hippocampal formation.
Foveal Crowding Resolved
Authors: Coates Daniel R. , Levi Dennis M. , Touch Phanith , Sabesan Ramkumar
Published: June 2018

Crowding is the substantial interference of neighboring items on target identification. Crowding with letter stimuli has been studied primarily in the visual periphery, with conflicting results for foveal stimuli. While a cortical locus for peripheral crowding is well established (with a large spatial extent up to half of the target eccentricity), disentangling the contributing factors in the fovea is more challenging due to optical limitations. Here, we used adaptive optics (AO) to overcome ocular aberrations and employed high-resolution stimuli to precisely characterize foveal lateral interactions with high-contrast letters flanked by letters. Crowding was present, with a maximal edge-to-edge interference zone of 0.75-1.3 minutes at typical unflanked performance levels. In agreement with earlier foveal contour interaction studies, performance was non-monotonic, revealing a recovery effect with proximal flankers. Modeling revealed that the deleterious effects of flankers can be described by a single function across stimulus sizes when the degradation is expressed as a reduction in sensitivity (expressed in Z-score units). The recovery, however, did not follow this pattern, likely reflecting a separate mechanism. Additional analysis reconciles multiple results from the literature, including the observed scale invariance of center-to-center spacing, as well as the size independence of edge-to-edge spacing.
Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets
Authors: Nagy Ádám , Lánczky András , Menyhárt Otília , Győrffy Balázs
Published: June 2018

Multiple studies suggested using different miRNAs as biomarkers for prognosis of hepatocellular carcinoma (HCC). We aimed to assemble a miRNA expression database from independent datasets to enable an independent validation of previously published prognostic biomarkers of HCC. A miRNA expression database was established by searching the TCGA (RNA-seq) and GEO (microarray) repositories to identify miRNA datasets with available expression and clinical data. A PubMed search was performed to identify prognostic miRNAs for HCC. We performed a uni- and multivariate Cox regression analysis to validate the prognostic significance of these miRNAs. The Limma R package was applied to compare the expression of miRNAs between tumor and normal tissues. We uncovered 214 publications containing 223 miRNAs identified as potential prognostic biomarkers for HCC. In the survival analysis, the expression levels of 55 and 84 miRNAs were significantly correlated with overall survival in RNA-seq and gene chip datasets, respectively. The most significant miRNAs were hsa-miR-149, hsa-miR-139, and hsa-miR-3677 in the RNA-seq and hsa-miR-146b-3p, hsa-miR-584, and hsa-miR-31 in the microarray dataset. Of the 223 miRNAs studied, the expression was significantly altered in 102 miRNAs in tumors compared to normal liver tissues. In summary, we set up an integrated miRNA expression database and validated prognostic miRNAs in HCC.
Bladder cancer recurrence surveillance by urine metabolomics analysis
Authors: Loras A. , Trassierra M. , Sanjuan-Herráez D. , Martínez-Bisbal M. C. , Castell J. V. , Quintás G. , Ruiz-Cerdá J. L.
Published: June 2018

Non Muscle Invasive Bladder Cancer (NMIBC) is among the most frequent malignant cancers worldwide. NMIBC is treated by transurethral resection of the bladder tumor (TURBT) and intravesical therapies, and has the highest recurrence rate among solid tumors. It requires a lifelong patient monitoring based on repeated cystoscopy and urinary cytology, both having drawbacks that include lack of sensitivity and specificity, invasiveness and care costs. We conducted an investigative clinical study to examine changes in the urinary metabolome of NMBIC patients before and after TURBT, as well during the subsequent surveillance period. Adjusting by prior probability of recurrence per risk, discriminant analysis of UPLC-MS metabolic profiles, displayed negative predictive values for low, low-intermediate, high-intermediate and high risk patient groups of 96.5%, 94.0%, 92.9% and 76.1% respectively. Detailed analysis of the metabolome revealed several candidate metabolites and perturbed phenylalanine, arginine, proline and tryptophan metabolisms as putative biomarkers. A pilot retrospective analysis of longitudinal trajectories of a BC metabolic biomarkers during post TURBT surveillance was carried out and the results give strong support for the clinical use of metabolomic profiling in assessing NMIBC recurrence.
Examining the Associations among Fibrocystic Breast Change, Total Lean Mass, and Percent Body Fat
Authors: Chen Yuan-Yuei , Fang Wen-Hui , Wang Chung-Ching , Kao Tung-Wei , Chang Yaw-Wen , Yang Hui-Fang , Wu Chen-Jung , Sun Yu-Shan , Chen Wei-Liang
Published: June 2018

Fibrocystic breast change (FBC) is extremely common and occurrs in 90% of women during their lives. The association between body composition and risk of breast cancer is well established. We hypothesized that the effect might exist during the development of FBC. Our aim was to examine the relationships of total lean mass (TLM) and percent body fat (PBF) with FBC in a general female population. In total, 8477 female subjects aged 20 years or older were enrolled in the study at the Tri-Service General Hospital in Taiwan from 2011 to 2016. Comprehensive examinations including biochemical data, measurements of body composition and breast ultrasound were performed. PBF was positively associated with the presence of FBC (OR = 1.039, 95%CI: 1.018–1.060), and TLM showed the opposite result (OR = 0.893, 95%CI: 0.861–0.926). Condition of metabolic syndrome (MetS), diabetes (DM) and fatty liver modified the association between PBF and FBC (P < 0.001, P = 0.032 and P = 0.007, respectively). Female subjects diagnosed with MetS, DM, and fatty liver had higher risk of developing FBC than control subjects (OR = 1.110, 95%CI: 1.052–1.171; OR = 1.144, 95%CI: 1.024–1.278; OR = 1.049, 95%CI: 1.019, 1.080). Those with higher PBF (for highest quartile versus lowest, OR = 2.451, 95%CI: 1.523–3.944) or lower TLM (for highest quartile versus lowest, OR = 0.279, 95%CI: 0.171–0.455) had increased risk of developing FBC. In conclusion, increased PBF and reduced TLM were likely to predict the risk of the presence of FBC in a general female population.
Reverse Transcription Polymerase Chain Reaction in Giant Unilamellar Vesicles
Authors: Tsugane Mamiko , Suzuki Hiroaki
Published: June 2018

We assessed the applicability of giant unilamellar vesicles (GUVs) for RNA detection using in vesicle reverse transcription polymerase chain reaction (RT-PCR). We prepared GUVs that encapsulated one-pot RT-PCR reaction mixture including template RNA, primers, and Taqman probe, using water-in-oil emulsion transfer method. After thermal cycling, we analysed the GUVs that exhibited intense fluorescence signals, which represented the cDNA amplification. The detailed analysis of flow cytometry data demonstrated that rRNA and mRNA in the total RNA can be amplified from 10–100 copies in the GUVs with 5–10 μm diameter, although the fraction of reactable GUV was approximately 60% at most. Moreover, we report that the target RNA, which was directly transferred into the GUV reactors via membrane fusion, can be amplified and detected using in vesicle RT-PCR. These results suggest that the GUVs can be used as biomimetic reactors capable of performing PCR and RT-PCR, which are important in analytical and diagnostic applications with additional functions.
Effects of 8-week sensory electrical stimulation combined with motor training on EEG-EMG coherence and motor function in individuals with stroke
Authors: Pan Li-Ling Hope , Yang Wen-Wen , Kao Chung-Lan , Tsai Mei-Wun , Wei Shun-Hwa , Fregni Felipe , Chen Vincent Chiun-Fan , Chou Li-Wei
Published: June 2018

The peripheral sensory system is critical to regulating motor plasticity and motor recovery. Peripheral electrical stimulation (ES) can generate constant and adequate sensory input to influence the excitability of the motor cortex. The aim of this proof of concept study was to assess whether ES prior to each hand function training session for eight weeks can better improve neuromuscular control and hand function in chronic stroke individuals and change electroencephalography-electromyography (EEG-EMG) coherence, as compared to the control (sham ES). We recruited twelve subjects and randomly assigned them into ES and control groups. Both groups received 20-minute hand function training twice a week, and the ES group received 40-minute ES on the median nerve of the affected side before each training session. The control group received sham ES. EEG, EMG and Fugl-Meyer Assessment (FMA) were collected at four different time points. The corticomuscular coherence (CMC) in the ES group at fourth weeks was significantly higher (p = 0.004) as compared to the control group. The notable increment of FMA at eight weeks and follow-up was found only in the ES group. The eight-week rehabilitation program that implemented peripheral ES sessions prior to function training has a potential to improve neuromuscular control and hand function in chronic stroke individuals.
Multiparametric magnetic resonance imaging for quantitation of liver disease: a two-centre cross-sectional observational study
Authors: McDonald Natasha , Eddowes Peter J. , Hodson James , Semple Scott I. K. , Davies Nigel P. , Kelly Catherine J. , Kin Stella , Phillips Miranda , Herlihy Amy H. , Kendall Timothy J. , Brown Rachel M. , Neil Desley A. H. , Hübscher Stefan G. , Hirschfield Gideon M. , Fallowfield Jonathan A.
Published: June 2018

LiverMultiScan is an emerging diagnostic tool using multiparametric MRI to quantify liver disease. In a two-centre prospective validation study, 161 consecutive adult patients who had clinically-indicated liver biopsies underwent contemporaneous non-contrast multiparametric MRI at 3.0 tesla (proton density fat fraction (PDFF), T1 and T2* mapping), transient elastography (TE) and Enhanced Liver Fibrosis (ELF) test. Non-invasive liver tests were correlated with gold standard histothological measures. Reproducibility of LiverMultiScan was investigated in 22 healthy volunteers. Iron-corrected T1 (cT1), TE, and ELF demonstrated a positive correlation with hepatic collagen proportionate area (all p < 0·001). TE was superior to ELF and cT1 for predicting fibrosis stage. cT1 maintained good predictive accuracy for diagnosing significant fibrosis in cases with indeterminate ELF, but not for cases with indeterminate TE values. PDFF had high predictive accuracy for individual steatosis grades, with AUROCs ranging from 0.90–0.94. T2* mapping diagnosed iron accumulation with AUROC of 0.79 (95% CI: 0.67–0.92) and negative predictive value of 96%. LiverMultiScan showed excellent test/re-test reliability (coefficients of variation ranging from 1.4% to 2.8% for cT1). Overall failure rates for LiverMultiScan, ELF and TE were 4.3%, 1.9% and 15%, respectively. LiverMultiScan is an emerging point-of-care diagnostic tool that is comparable with the established non-invasive tests for assessment of liver fibrosis, whilst at the same time offering a superior technical success rate and contemporaneous measurement of liver steatosis and iron accumulation.
Ex vivo biomechanical characterization of syringe-needle ejections for intracerebral cell delivery
Authors: Wahlberg Brendon , Ghuman Harmanvir , Liu Jessie R. , Modo Michel
Published: June 2018

Intracerebral implantation of cell suspensions is finding its clinical translation with encouraging results in patients with stroke. However, the survival of cells in the brain remains poor. Although the biological potential of neural stem cells (NSCs) is widely documented, the biomechanical effects of delivering cells through a syringe-needle remain poorly understood. We here detailed the biomechanical forces (pressure, shear stress) that cells are exposed to during ejection through different sized needles (20G, 26G, 32G) and syringes (10, 50, 250 µL) at relevant flow rates (1, 5, 10 µL/min). A comparison of 3 vehicles, Phosphate Buffered Saline (PBS), Hypothermosol (HTS), and Pluronic, indicated that less viscous vehicles are favorable for suspension with a high cell volume fraction to minimize sedimentation. Higher suspension viscosity was associated with greater shear stress. Higher flow rates with viscous vehicle, such as HTS reduced viability by ~10% and also produced more apoptotic cells (28%). At 5 µL/min ejection using a 26G needle increased neuronal differentiation for PBS and HTS suspensions. These results reveal the biological impact of biomechanical forces in the cell delivery process. Appropriate engineering strategies can be considered to mitigate these effects to ensure the efficacious translation of this promising therapy.
Musical Competence is Predicted by Music Training, Cognitive Abilities, and Personality
Authors: Swaminathan Swathi , Schellenberg E. Glenn
Published: June 2018

Individuals differ in musical competence, which we defined as the ability to perceive, remember, and discriminate sequences of tones or beats. We asked whether such differences could be explained by variables other than music training, including socioeconomic status (SES), short-term memory, general cognitive ability, and personality. In a sample of undergraduates, musical competence had positive simple associations with duration of music training, SES, short-term memory, general cognitive ability, and openness-to-experience. When these predictors were considered jointly, musical competence had positive partial associations with music training, general cognitive ability, and openness. Nevertheless, moderation analyses revealed that the partial association between musical competence and music training was evident only among participants who scored below the mean on our measure of general cognitive ability. Moreover, general cognitive ability and openness had indirect associations with musical competence by predicting music training, which in turn predicted musical competence. Musical competence appears to be the result of multiple factors, including but not limited to music training.
Investigation of return photons from sodium laser beacon excited by a 40-watt facility-class pulsed laser for adaptive optical telescope applications
Authors: Bian Qi , Bo Yong , Zuo Junwei , Li Min , Dong Ruoxi , Deng Keran , Zhang Dingwen , He Liping , Zong Qingshuang , Cui Dafu , Peng Qinjun , Chen Hongbin , Xu Zuyan
Published: June 2018

The brightness of the artificial beacon is one critical performance parameter for adaptive optics. Here, a 40-watt level narrow-linewidth microsecond pulsed yellow laser is produced at 589 nm with a high repetition frequency of 600 Hz and a pulse duration of 120 μs. An experiment to project the pulse beam up to the sky and measure the fluorescence photon returns of the Na atoms has been held on the 1.8-meter telescope in Lijiang observatory. During the sky test, a laser guide star (LGS) spot is firstly observed with Rayleigh scattering elimination by means of a gateable pulse format. And, the central wavelength of the laser could be accurately locked to be 589.1584 nm with a linewidth of ~0.34 GHz to match that of sodium-D2a line. Optical pumping with circularly polarized light has also been used to increase the brightness of sodium LGS. In order to maximize the return flux, sodium D2b repumping option is done by an electro-optic modulator with the optimum D2a-D2b frequency offset. As a result, a bright sodium LGS with the return flux of 1610 photons/cm2/s is achieved, corresponding to ~47 photons/cm2/s/W of emitted laser power, which represents a significant improvement in terms of brightness reported ever.
Nano-particle mediated inhibition of Parkinson’s disease using computational biology approach
Authors: Kaushik Aman Chandra , Bharadwaj Shiv , Kumar Sanjay , Wei Dong-Qing
Published: June 2018

Parkinson’s disease (PD) arises as neurodegenerative disorder and characterized by progressive deterioration of motor functions due to forfeiture of dopamine-releasing neurons. During PD, neurons at stake loss their functionality that results into cognition impairment and forgetfulness, commonly called as dementia. Recently, nanoparticles (NPs) have been reported for easy drug delivery through blood-brain barrier (BBB) into the central nervous system (CNS) against the conventional drug delivery systems. However, present study attempted to elucidate the α-synuclein activity, a major factor casing PD, in presence of its inhibitor cerium oxide (CeO2) nanoparticle via computational biology approach. A computational analysis was also conducted for the α-synuclein activity with biocompatible metal NPs such as GOLD NPs and SPIONs to scrutinize the efficacy and degree of inhibition induced by the CeO2 NP. The obtained results concluded that CeO2 NP fit best in the active site of α-synuclein with good contacts and interaction, and potentially inhibited the PD against L-DOPA drug selected as positive control in the designed PD biochemical pathway. Hence, CeO2 NP has been purposed as potential inhibitor of α-synuclein and can be employed as nano-drug against the PD.
Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model
Authors: Imai Kenji , Kotani Tomomi , Tsuda Hiroyuki , Nakano Tomoko , Ushida Takafumi , Iwase Akira , Nagai Taku , Toyokuni Shinya , Suzumura Akio , Kikkawa Fumitaka
Published: June 2018

The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H2) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H2attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H2administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H2on LPS-induced astrocytic activation, bothin vivoandin vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H2-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H2administration. Overall, these findings indicate that maternal H2administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life.
Similar ligand–metal bonding for transition metals and actinides? 5f1 U(C7H7)2−versus 3dn metallocenes
Authors: Sergentu Dumitru-Claudiu , Gendron Frédéric , Autschbach Jochen
Published: June 2018

A computational analysis of the electronic structure, bonding and magnetic properties in the 5f1 U(C7H7)2− complex vs. 3d metallocenes is performed. Notably, it is shown that the proton hyperfine coupling constant in U(C7H7)2− is the same in sign and magnitude to that of the 3d7 cobaltocene, but the two systems do not share a similar covalent metal–ligand bonding.
Direct-laser-writing of three-dimensional porous graphene frameworks on indium-tin oxide for sensitive electrochemical biosensing
Authors: Hong Qing , Yang Limin , Ge Lei , Liu Zhenhui , Li Feng
Published: June 2018

Direct-laser-writing of three-dimensional porous graphene frameworks on indium-tin-oxide glass towards the fabrication of a unique electrode with outstanding electrochemical performance.
Gold nanocone arrays directly grown on nickel foam for improved SERS detection of aromatic dyes
Authors: Xu Fugang , Lai Huasheng , Xu Hui
Published: June 2018

An efficient SERS substrate composed of gold nanocone arrays with abundant sharp tips directly grown on 3D porous Ni foam (AuNCA@Ni foam) was developed for sensitive detection of aromatic dyes.
Supramolecular hydrogel based on a sodium deep eutectic solvent
Authors: Florindo Catarina , Celia-Silva Lucas G. , Martins Luís F. G. , Branco Luís C. , Marrucho Isabel M.
Published: June 2018

Supramolecular hydrogel based on a metal containing deep eutectic solvent (DES) is presented here for the first time.
N2O5at water surfaces: binding forces, charge separation, energy accommodation and atmospheric implications
Authors: Hirshberg Barak , Rossich Molina Estefanía , Götz Andreas W. , Hammerich Audrey D. , Nathanson Gilbert M. , Bertram Timothy H. , Johnson Mark A. , Gerber R. Benny
Published: June 2018

Studying the interactions between N2O5and water in nano-sized clusters, in bulk and on the surface of water.
Fe2O3@SiTi core–shell catalyst for the selective catalytic reduction of NOx with NH3: activity improvement and HCl tolerance
Authors: Chang Huazhen , Zhang Tao , Dang Hao , Chen Xiaoyin , You Yanchen , Schwank Johannes W. , Li Junhua
Published: June 2018

A core–shell structured Fe2O3@SiTi catalyst with a SiTi shell and Fe2O3 core was prepared and used for the selective catalytic reduction (SCR) of NOx with NH3.
Solvent effects on the crystal structure of silver pentacyanocyclopentadienide: supramolecular isomerism and solvent coordination
Authors: Nimax P. R. , Reimann D. , Sünkel K.
Published: June 2018

Recrystallization of Silver pentacyanocyclopentadienide from methanol, ethanol or acetonitrile yields coordination polymers of different dimensionality.
Complete charge separation provoked by full cation encapsulation in the radical mono- and di-anions of 5,6:11,12-di-o-phenylene-tetracene
Authors: Wombacher Tobias , Goddard Richard , Lehmann Christian W. , Schneider Jörg J.
Published: June 2018

Full encapsulation of the K+counterions between two benzo-15-crown-5-ether (B15C5) ligands results in a (κ10O) environment which ensures a complete cation/anion separation resulting in planar bare anionic PAH species [LDOPT˙−] and [LDOPT2−].
Oxygen activation at a dicobalt centre of a dipyridylethane naphthyridine complex
Authors: Brodsky Casey N. , Passard Guillaume , Ullman Andrew M. , Jaramillo David E. , Bloch Eric D. , Huynh Michael , Gygi David , Costentin Cyrille , Nocera Daniel G.
Published: June 2018

The mechanism of oxygen activation at a dicobalt bis-μ-hydroxo core is probed by the implementation of synthetic methods to isolate reaction intermediates.
Alkali metal complexes based on bisheterocyclomethanide ligands
Authors: Kretsch Johannes , Kreyenschmidt Anne , Herbst-Irmer Regine , Stalke Dietmar
Published: June 2018

A series of new alkali metal complexes containing deprotonated bisheterocyclomethanide were synthesised and the potassium derivatives were exposed to hydrolysis.
Curation of datasets, assessment of their quality and completeness, and nanoSAR classification model development for metallic nanoparticles
Authors: Trinh Tung X. , Ha My Kieu , Choi Jang Sik , Byun Hyung Gi , Yoon Tae Hyun
Published: June 2018

Workflow for curation of datasets, assessment of their quality and completeness, and nanoSAR model development.
Triterpenoids fromZiziphus jujubainduce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production
Authors: Shin Minna , Lee Bo-Mi , Kim Okwha , Tran Huynh Nguyen Khanh , Lee Suhyun , Hwangbo Cheol , Min Byung-Sun , Lee Jeong-Hyung
Published: June 2018

Coumaroyl alphitolic acids induce apoptotic cell death in cancer cellsviamitochondrial ROS production and ER stress.
Evaluation of biological and antimicrobial properties of freeze-dried whey fermented by different strains ofLactobacillus plantarum
Authors: Luz C. , Izzo L. , Graziani G. , Gaspari A. , Ritieni A. , Mañes J. , Meca G.
Published: June 2018

The aim of this study was to evaluate the biological and antimicrobial activities of commercial freeze-dried whey fermented by lactic acid bacteria in order to valorize this high polluting liquid waste of the dairy industry.
Sensory acceptable equivalent doses of β-phenylethyl isothiocyanate (PEITC) induce cell cycle arrest and retard the growth of p53 mutated oral cancerin vitroandin vivo
Authors: Lam-ubol Aroonwan , Fitzgerald Alison Lea , Ritdej Arnat , Phonyiam Tawaree , Zhang Hui , Myers Jeffrey N. , Huang Peng , Trachootham Dunyaporn
Published: June 2018

Sensory acceptable doses of PEITC are selectively toxic to oral cancer cellsviaROS-mediated cell cycle arrest.
Green and continuous route to assemble lateral nanodimensional graphitic oxide composites without process interruption
Authors: Poudel Bijay Kumar , Doh Kyung-Oh , Byeon Jeong Hoon
Published: June 2018

Lateral nanoscaled graphitic oxide composite flakes were assembled in a single-pass configuration without process interruption, and the assembled flakes demonstrated controlled drug release having magneto- and photothermal activities as well as contrasting properties.
Parameter control for enhanced peak-to-valley current ratio in a MoS2/MoTe2 van der Waals heterostructure
Authors: Duong Ngoc Thanh , Bang Seungho , Lee Seung Mi , Dang Dang Xuan , Kuem Dong Hoon , Lee Juchan , Jeong Mun Seok , Lim Seong Chu
Published: June 2018

The parameters of the MoS2/MoTe2 van der Waals tunnel diode are optimized to obtain a peak-to-valley current ratio of 4.8.
Application of organocatalysis in bioorganometallic chemistry: asymmetric synthesis of multifunctionalized spirocyclic pyrazolone–ferrocene hybrids as novel RalA inhibitors
Authors: Zhang Yuehua , Wang Chunting , Huang Wei , Haruehanroengra Phensinee , Peng Cheng , Sheng Jia , Han Bo , He Gu
Published: June 2018

Asymmetric construction of chiral spirocyclic pyrazolone–ferrocene hybrids has been developed. The lead compound displayed potent RalA inhibition.
Template-free synthesis of monolithic carbon xerogels with hierarchical porosity from resorcinol and formaldehyde via hydrothermal reaction
Authors: Cho G. , Lee J. Y. , Yoon T. H.
Published: June 2018

Monolithic porous carbon with hierarchical porosity via a one-step template-free hydrothermal polycondensation reaction with resorcinol and formaldehyde.
A new and informative [a,b,c,d] nomenclature for one-pot multistep transformations: a simple tool to measure synthetic efficiency
Authors: Indu Satrajit , Kaliappan Krishna P.
Published: June 2018

We propose a generalized and informative [a,b,c,d] nomenclature for various types of one-pot multistep reactions, which emphasizes the fundamental parameters that define the synthetic efficiency of such transformations.
Spiropyran in nanoassemblies as a photosensitizer for photoswitchable ROS generation in living cells
Authors: Ji Jinkai , Li Xiao , Wu Tiantian , Feng Fude
Published: June 2018

The aggregation-induced enhanced photosensitization and emission (AIEPE) properties of spiropyrans in nanoassemblies enable reversibly controlled singlet oxygen generation.
Binding mode of AIF(370–394) peptide to CypA: insights from NMR, label-free and molecular docking studies
Authors: Farina Biancamaria , Sturlese Mattia , Mascanzoni Fabiola , Caporale Andrea , Monti Alessandra , Di Sorbo Gianluigi , Fattorusso Roberto , Ruvo Menotti , Doti Nunzianna
Published: June 2018

The complex formation between the proteins apoptosis-inducing factor (AIF) and cyclophilin A (CypA) following oxidative stress in neuronal cells has been suggested as a main target for reverting ischemia-stroke damage. Recently, a peptide encompassing AIF residues 370–394 has been developed to target the AIF-binding site on CypA, to prevent the association between the two proteins and suppress glutamate-induced cell death in neuronal cells. Using a combined approach based on NMR spectroscopy, synthesis and in vitro testing of all Ala-scan mutants of the peptide and molecular docking/molecular dynamics, we have generated a detailed model of the AIF (370–394)/CypA complex. The model suggests us that the central region of the peptide spanning residues V374–K384 mostly interacts with the protein and that for efficient complex inhibition and preservation of CypA activity, it is bent around amino acids F46–G75 of the protein. The model is consistent with experimental data also from previous works and supports the concept that the peptide does not interfere with other CypA activities unrelated to AIF activation; therefore, it may serve as an ideal template for generating future non-peptidic antagonists.
CTA 102 in exceptionally high state during 2016–2017
Authors: Kaur Navpreet , Baliyan Kiran S.
Published: June 2018

Blazars in outburst provide a unique opportunity to study their spectral behavior, correlated variations at different frequencies, and jet structure. An unprecedented flaring activity in FSRQ CTA 102, occuring from 2016 November to 2017 January, is used here for a detailed study to understand flaring mechanisms at short and long timescales, spectral behavior in different energy regimes, and to estimate sizes and location of the high-energy emitting region in the jet. Multiwavelength (MW) data for CTA 102 during its outburst period, were obtained from Fermi-LAT, Swift-XRT/UVOT, Steward Observatory, Mt Abu Infrared Observatory, and OVRO. These were analyzed to construct MW light curves, extract the spectral information, and to perform the correlated variability studies. Our study shows that CTA 102 attained the highest ever flux levels across the electromagnetic spectrum (EMS) while flaring and otherwise, with rapid and prolonged activities at all the frequencies. A number of short-term (three to eight days) and long-term (more than a month) variability events are noticed across the EMS. We infer a redder when brighter trend in faint state and a bluer when brighter trend during a few optical flares. Based on the flux doubling timescale, the size of γ-ray emitting region is estimated as ≈8.76 × 1015 cm, located at a distance of about 5.58 × 1016 cm from the central engine. CTA 102 was in extremely bright phase during 2016–2017, possibly due to, successive high energy particle injections into the jet, creating shocks traveling down the jet which lead to the overall flux enhancement across the EMS. Alternatively, a decreasing viewing angle could also lead to such flux enhancement. The study reveals correlated variations in all the energy bands, with lags within time bins, indicating co-spatial origin of the emissions. During the flaring event, a bluer-when-brighter color in the optical and harder when brighter trend in the X-ray and γ-ray spectra are noticed. During some flares softer γ-ray spectra are observed.
14N/15N ratio measurements in prestellar cores with N2H+: new evidence of 15N-antifractionation
Authors: Redaelli E. , Bizzocchi L. , Caselli P. , Harju J. , Chacón-Tanarro A. , Leonardo E. , Dore L.
Published: June 2018

Context. The 15N fractionation has been observed to show large variations among astrophysical sources, depending both on the type of target and on the molecular tracer used. These variations cannot be reproduced by the current chemical models.

Aims. Until now, the 14N/15N ratio in N2H+ has been accurately measured in only one prestellar source, L1544, where strong levels of fractionation, with depletion in 15N, are found (14N/15N ≈ 1000). In this paper, we extend the sample to three more bona fide prestellar cores, in order to understand if the antifractionation in N2H+ is a common feature of this kind of source.

Methods. We observed N2H+, N15NH+, and 15NNH+ in L183, L429, and L694-2 with the IRAM 30 m telescope. We modelled the emission with a non-local radiative transfer code in order to obtain accurate estimates of the molecular column densities, including the one for the optically thick N2H+. We used the most recent collisional rate coefficients available, and with these we also re-analysed the L1544 spectra previously published.

Results. The obtained isotopic ratios are in the range 580–770 and significantly differ with the value, predicted by the most recent chemical models, of ≈440, close to the protosolar value. Our prestellar core sample shows a high level of depletion of 15N in diazenylium, as previously found in L1544. A revision of the N chemical networks is needed in order to explain these results.
Study on Fatigue Life of Heat-treated Aluminium alloy coated with Castor oil.
Authors: Sivasubramanian A. , Kirubasankar T.S. , Vinoth kumar S.
Published: June 2018

This paper involves the study of fatigue life of coated aluminium alloy Al 7075-T651 that is heat-treated under 100oC soaked in castor oil for three days. The specimen after heat treatment is subjected to fatigue test using rotary bending machine for number of cycles to fail under cyclic load of 15kgf, 25Kgf, and 50kgf.The life of the specimen is found and compared with uncoated specimen and improved life in number of cycle is noticed. The crack propagation and its type is analysed using scanning electron microscope for knowing the point of fracture and its initiation to failure.
Malay Wisdom in the Motifs of Bamboo Shoots
Authors: Aqbar Zakaria Safial , Latif Ramlah , Bahauddin Azizi
Published: June 2018

The study aims to reveal Malay’s philosophical wisdom that is implied in Malay culture. Weaving is a part of Malay culture that is rich in historical and cultural value. Samples of the study are the ikat limar woven cloth, while the focus of the study is the bamboo shoots’ motif. Bamboo shoots are one of the motifs synonymous with the ikat limar weaving. The bamboo shoots’ motifs are located on the head of the sarong and on the edge of the shawl. Bamboo shoots in a tapered triangular shape is an implementation of the shape of the bamboo stems that appear from the culms. Bamboos are such a plant that brings a lot of benefits to the lives of the Malays from the shoots to the mature canes. The Malays often connect the bamboos with experiences, adulthood, beliefs, as well as pure values that shape the Malay ethos. Bamboo shoots are seen to own a broad sense of cultural philosophies that bring about the existence of sayings, expressions, poem, and figurative speeches. The objectives of the study are to explore the values of Malay wisdom in the motifs of bamboo shoots aside from introducing limar cloth as one of the heritages of Malay wisdom. The methods of the study are interviewing of the aesthetes, experts in textile field as well as those who are related to the textile and cultural field. The qualitative analysis will be used to combine the descriptions, analyses, and interpretations. Based on the outcome of the study, it will become a cultural document and source of reference for the young generations. This study also manages to attract outsiders to recognize and understand the Malay culture as well as getting to know the Malay nature realm.
Nature manifestation in philosophy, diagnosis and treatment of disease based on Ayurvedic and Malay traditional medicine: A comparative study
Authors: Wan Yusoff Wan Faizah
Published: June 2018

Man and nature is an important concept in the traditional community’s universal perspective. This concept can be seen in the universal and cosmological view which discusses questions on the origin of human and nature existence. In traditional medicine context such as Ayurvedic and Malay, this nature manifestation not only can be seen in medical philosophy but also diagnosed medically, as well as treatment given to the disease. This research paper discussion is focused on the community’s conception towards natural elements either physically or the opposite and the manifestation of understanding towards their medical philosophy. Among the concept that will be discussed are natural elements such as soil, water, fire, air and ether or better known as the space which is not only important in the context of nature composition but also in the human body based on Ayurvedic medicine. Research is done through the observation of literature and interview with Ayurvedic and Malay traditional medicine practitioners. The outcome obtained has shown that there is a difference between the diagnosis and Ayurvedic treatment which focuses on the characteristics and physical signs compared to traditional Malay medicine which also includes personality diagnostic methods as well as physical attributes and signs for the purpose of disease diagnosis.