bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiproliferative activities of the second-generation antipsychotic drug sertindole against breast cancers with a potential application for treatment of breast-to-brain metastases
Authors: Zhang Wei , Zhang Cunlong , Liu Feng , Mao Yu , Xu Wei , Fan Tingting , Sun Qinsheng , He Shengnan , Chen Yuzong , Guo Wei , Tan Ying , Jiang Yuyang 
Published: October 2018

AbstractEpidemiological observations have shown that schizophrenia patients after long-term drug treatment exhibited reduced tumor incidences. The potential anticancer effects of antipsychotic drugs are subsequently demonstrated. These drugs are of great interest as agents against untreatable brain metastases because of their ability to traverse the blood-brain barrier (BBB). Most drugs tested thus far are the first-generation antipsychotics (FGAs). But their clinical application may be limited due to high risks of deaths in elderly patients. There is an urgent need to find additional BBB-traversing anticancer agents with lower risks of deaths. In this work, we investigated antitumor activities of eight second-generation-antipsychotic (SGA) drugs, since they exhibit lower mortality rates than FGAs. We discovered that sertindole showed broad antiproliferative activities against seven cancer types including 29 cell-lines and exhibited potent effects toward breast cancer cell-lines, with half maximal concentration to inhibit proliferation by 50% (IC50) as low as 800 nM. We further found that sertindole caused cell death through autophagy-associated apoptosis and its directly-binding inhibition of 5-HT6 involved in this process. In xenotransplant mice, sertindole administration approaching maximal therapeutic dose attenuated breast-tumor growth by 22.7%. Therefore, our study reveals promising anticancer potentials of sertindole against breast cancers, with probable applications for breast-to-brain metastases.
Dynamic volume magnetic domain wall imaging in grain oriented electrical steel at power frequencies with accumulative high-frame rate neutron dark-field imaging
Authors: Harti Ralph P. , Strobl Markus , Schäfer Rudolf , Kardjilov Nikolay , Tremsin Anton S. , Grünzweig Christian 
Published: October 2018

AbstractThe mobility of magnetic domains forms the link between the basic physical properties of a magnetic material and its global characteristics such as permeability and saturation field. Most commonly, surface domain structure are studied using magneto-optical Kerr microscopy. The limited information depth of approx. 20 nanometers, however, allows only for an indirect interpretation of the internal volume domain structures. Here we show how accumulative high-frame rate dynamic neutron dark-field imaging is able for the first time to visualize the dynamic of the volume magnetic domain structures in grain oriented electrical steel laminations at power frequencies. In particular we studied the volume domain structures with a spatial resolution of ∼100 μm and successfully quantified domain sizes, wall velocities, domain annihilation and its duration and domain wall multiplication in real time recordings at power frequencies of 10, 25 and 50 Hz with ±262.5 A/m and ±525 A/m (peak to peak) applied field.
Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration
Authors: Sato Yoshiki , Yamamoto Kenta , Horiguchi Satoshi , Tahara Yoshiro , Nakai Kei , Kotani Shin-ichiro , Oseko Fumishige , Pezzotti Giuseppe , Yamamoto Toshiro , Kishida Tsunao , Kanamura Narisato , Akiyoshi Kazunari , Mazda Osam 
Published: October 2018

AbstractTransplantation of engineered three-dimensional (3D) bone tissue may provide therapeutic benefits to patients with various bone diseases. To achieve this goal, appropriate 3D scaffolds and cells are required. In the present study, we devised a novel nanogel tectonic material for artificial 3D scaffold, namely the nanogel-cross-linked porous (NanoCliP)-freeze-dried (FD) gel, and estimated its potential as a 3D scaffold for bone tissue engineering. As the osteoblasts, directly converted osteoblasts (dOBs) were used, because a large number of highly functional osteoblasts could be induced from fibroblasts that can be collected from patients with a minimally invasive procedure. The NanoCliP-FD gel was highly porous, and fibronectin coating of the gel allowed efficient adhesion of the dOBs, so that the cells occupied the almost entire surface of the walls of the pores after culturing for 7 days. The dOBs massively produced calcified bone matrix, and the culture could be continued for at least 28 days. The NanoCliP-FD gel with dOBs remarkably promoted bone regeneration in vivo after having been grafted to bone defect lesions that were artificially created in mice. The present findings suggest that the combination of the NanoCliP-FD gel and dOBs may provide a feasible therapeutic modality for bone diseases.
The mesophilic archaeon Methanosarcina acetivorans counteracts uracil in DNA with multiple enzymes: EndoQ, ExoIII, and UDG
Authors: Shiraishi Miyako , Ishino Sonoko , Heffernan Matthew , Cann Isaac , Ishino Yoshizumi 
Published: October 2018

AbstractCytosine deamination into uracil is one of the most prevalent and pro-mutagenic forms of damage to DNA. Base excision repair is a well-known process of uracil removal in DNA, which is achieved by uracil DNA glycosylase (UDG) that is found in all three domains of life. However, other strategies for uracil removal seem to have been evolved in Archaea. Exonuclease III (ExoIII) from the euryarchaeon Methanothermobacter thermautotrophicus has been described to exhibit endonuclease activity toward uracil-containing DNA. Another uracil-acting protein, endonuclease Q (EndoQ), was recently identified from the euryarchaeon Pyrococcus furiosus. Here, we describe the uracil-counteracting system in the mesophilic euryarchaeon Methanosarcina acetivorans through genomic sequence analyses and biochemical characterizations. Three enzymes, UDG, ExoIII, and EndoQ, from M. acetivorans exhibited uracil cleavage activities in DNA with a distinct range of substrate specificities in vitro, and the transcripts for these three enzymes were detected in the M. acetivorans cells. Thus, this organism appears to conduct uracil repair using at least three distinct pathways. Distribution of the homologs of these uracil-targeting proteins in Archaea showed that this tendency is not restricted to M. acetivorans, but is prevalent and diverse in most Archaea. This work further underscores the importance of uracil-removal systems to maintain genome integrity in Archaea, including ‘UDG lacking’ organisms.
Cell Transport Prompts the Performance of Low-Voltage Electroporation for Cell Inactivation
Authors: Huo Zheng-Yang , Li Guo-Qiang , Yu Tong , Feng Chao , Lu Yun , Wu Yin-Hu , Yu Cecilia , Xie Xing , Hu Hong-Ying 
Published: October 2018

AbstractThe inactivation of pathogens in liquids has broad applications, ranging from water disinfection to food pasteurization. However, common cell inactivation methods (e.g., chlorination, ultraviolet radiation and thermal treatment) have significant drawbacks such as carcinogenic byproduct formation, energy intensiveness and/or nutrient structure destruction. Here, we fabricated a new approach to address these challenges by applying a low-voltage electroporation disinfection cell (EDC) and investigate the critical mechanisms of cell transport to allow high inactivation performance. The EDC prototypes were equipped with two one-dimensional (1D) nanostructure-assisted electrodes that enabled high electric field strength (>107 V m−1) near the electrode surface with a low applied voltage (1 V). We have identified that during electroporation disinfection, electrophoresis, dielectrophoresis and hydraulic flow are the three major mechanisms which transport cells into the vicinity of the electrode surface to achieve superior disinfection performance. The EDC treated 70 ml of bacteria sample with an initial cell concentration of 107CFU ml−1and achieved complete bacteria inactivation (survival rate <0.00001%; no live bacteria detected). Our findings will help to establish a foundation for the future development and implementation of low-voltage electroporation for cell inactivation.
Utility of the Tympanic Membrane Pressure Waveform for Non-invasive Estimation of The Intracranial Pressure Waveform
Authors: Evensen Karen Brastad , Paulat Klaus , Prieur Fabrice , Holm Sverre , Eide Per Kristian 
Published: October 2018

AbstractTime domain analysis of the intracranial pressure (ICP) waveform provides important information about the intracranial pressure-volume reserve capacity. The aim here was to explore whether the tympanic membrane pressure (TMP) waveform can be used to non-invasively estimate the ICP waveform. Simultaneous invasive ICP and non-invasive TMP signals were measured in a total of 28 individuals who underwent invasive ICP measurements as a part of their clinical work up (surveillance after subarachnoid hemorrhage in 9 individuals and diagnostic for CSF circulation disorders in 19 individuals). For each individual, a transfer function estimate between the invasive ICP and non-invasive TMP signals was established in order to explore the potential of the method. To validate the results, ICP waveform parameters including the mean wave amplitude (MWA) were computed in the time domain for both the ICP estimates and the invasively measured ICP. The patient-specific non-invasive ICP signals predicted MWA rather satisfactorily in 4/28 individuals (14%). In these four patients the differences between original and estimated MWA were <1.0 mmHg in more than 50% of observations, and <0.5 mmHg in more than 20% of observations. The study further disclosed that the cochlear aqueduct worked as a physical lowpass filter.
Characterization of transgenic rice expressing fusion protein Cry1Ab/Vip3A for insect resistance
Authors: Xu Chao , Cheng Jiahui , Lin Haiyan , Lin Chaoyang , Gao Jianhua , Shen Zhicheng 
Published: October 2018

AbstractManagement of resistance development of insect pests is of great importance for continued utilization of Bt crop. The high-dose/refuge and pyramid (gene stacking) strategy are commonly employed to delay the evolution of insect resistance. Due to the anticipated difficulty for deployment of mandatory refuge for transgenic crops in China, where the size of farmer is quite small, stacking of genes with different modes of action is a more feasible strategy. Here we report the development of transgenic rice expressing a fusion protein of Cry1Ab and Vip3A toxin. Analysis of trypsin proteolysis suggested that the fusion protein is equivalent to the combination of Cry1Ab and Vip3A protein. The transgenic plants expressing the fusion protein were found to be highly resistant to two major rice pests, Asiatic rice borer Chilo suppressalis (Lepidoptera: Crambidae) and rice leaf folder Cnaphalocrocis medinalis (Lepidoptera: Crambidae), while their agronomic performances showed no significant difference compared to the non-transgenic recipient rice. Therefore, the transgenic rice may be utilized for rice pest control in China.
A Network Model of Resilience Factors for Adolescents with and without Exposure to Childhood Adversity
Authors: Fritz J. , Fried E. I. , Goodyer I. M. , Wilkinson P. O. , van Harmelen A.-L. 
Published: October 2018

AbstractResilience factors (RFs) help prevent mental health problems after childhood adversity (CA). RFs are known to be related, but it is currently unknown how their interrelations facilitate mental health. Here, we used network analysis to examine the interrelations between ten RFs in 14-year-old adolescents exposed (‘CA’; n = 638) and not exposed to CA (‘no-CA’; n = 501). We found that the degree to which RFs are assumed to enhance each other is higher in the no-CA compared to the CA group. Upon correction for general distress levels, the global RF connectivity also differed between the two groups. More specifically, in the no-CA network almost all RFs were positively interrelated and thus may enhance each other, whereas in the CA network some RFs were negatively interrelated and thus may hamper each other. Moreover, the CA group showed more direct connections between the RFs and current distress. Therefore, CA seems to influence how RFs relate to each other and to current distress, potentially leading to a dysfunctional RF system. Translational research could explore whether intervening on negative RF interrelations so that they turn positive and RFs can enhance each other, may alter ‘RF-mental distress’ relations, resulting in a lower risk for subsequent mental health problems.
Selection, hybridization, and the evolution of morphology in the Lake Malaŵi endemic cichlids of the genus Labeotropheus
Authors: Pauers Michael J. , Fox Kelsey R. , Hall Robert A. , Patel Kesha 
Published: October 2018

AbstractThe cichlid fishes of Lake Malaŵi are the paramount example of adaptive radiation in vertebrates. Evidence of their astounding diversity is perhaps most visible in their adaptations for obtaining food; the genus Labeotropheus, due to their prominent snouts, are an interesting example of an extreme adaptation for feeding. Two different body types are found in this genus: a deep-bodied form (e.g., L. fuelleborni) found most often in turbulent shallow water; and a slender bodied form (e.g., L. trewavasae) found in structurally-complex deep water habitats. Here we test the hypothesis that L. trewavasae should suffer a loss in fitness, measured as growth rate, if raised in turbulence; additionally, we examined growth and morphology of L. fuelleborni and L. fuelleborni x L. trewavasae hybrids under these conditions. We did find the predicted loss of fitness in turbulent-raised L. trewavasae, but found no loss of fitness for L. fuelleborni in either condition; hybrids, due to an unusual morphology, performed better in turbulent as opposed to control conditions. Fitness in turbulent conditions was dependent upon morphology, with deeper bodies and upturned neurocrania allowing a greater growth rate under these conditions. Directional selection on morphology was crucial in the evolution of morphology in the Labeotropheus.
Milk Metabolomics Data Reveal the Energy Balance of Individual Dairy Cows in Early Lactation
Authors: Xu Wei , Vervoort Jacques , Saccenti Edoardo , van Hoeij Renny , Kemp Bas , van Knegsel Ariette 
Published: October 2018

AbstractIn early lactation, dairy cows typically have a negative energy balance which has been related to metabolic disorders, compromised health and fertility, and reduced productive lifespan. Assessment of the energy balance, however, is not easy on the farm. Our aims were to investigate the milk metabolic profiles of dairy cows in early lactation, and to obtain models to estimate energy balance from milk metabolomics data and milk production traits. Milk samples were collected in week 2 and 7 after calving from 31 dairy cows. For each cow, the energy balance was calculated from energy intake, milk production traits and body weight. A total of 52 milk metabolites were detected using LC-QQQ-MS. Data from different lactation weeks was analysed by partial least squares analysis, the top 15 most relevant variables from the metabolomics data related to energy balance were used to develop reduced linear models to estimate energy balance by forward selection regression. Milk fat yield, glycine, choline and carnitine were important variables to estimate energy balance (adjusted R2: 0.53 to 0.87, depending on the model). The relationship of these milk metabolites with energy balance is proposed to be related to their roles in cell renewal.
Machine learning assisted optimization of electrochemical properties for Ni-rich cathode materials
Authors: Min Kyoungmin , Choi Byungjin , Park Kwangjin , Cho Eunseog 
Published: October 2018

AbstractOptimizing synthesis parameters is the key to successfully design ideal Ni-rich cathode materials that satisfy principal electrochemical specifications. We herein implement machine learning algorithms using 330 experimental datasets, obtained from a controlled environment for reliability, to construct a predictive model. First, correlation values showed that the calcination temperature and the size of the particles are determining factors for achieving a long cycle life. Then, we compared the accuracy of seven different machine learning algorithms for predicting the initial capacity, capacity retention rate, and amount of residual Li. Remarkable predictive capability was obtained with the average value of coefficient of determinant, R2 = 0.833, from the extremely randomized tree with adaptive boosting algorithm. Furthermore, we propose a reverse engineering framework to search for experimental parameters that satisfy the target electrochemical specification. The proposed results were validated by experiments. The current results demonstrate that machine learning has great potential to accelerate the optimization process for the commercialization of cathode materials.
Development and single dose clinical pharmacokinetics investigation of novel zein assisted- alpha lipoic acid nanoencapsulation of vardenafil
Authors: Ahmed Osama A. A. 
Published: October 2018

AbstractThe aim of this study was to utilize the biocompatibility of the natural ingredients zein and alpha lipoic acid (ALA) as a novel nanosphere matrix formulation that encapsulates vardenafil (VRD) for improved drug delivery and bioavailability. Three formulations were prepared using zein: ALA ratio of 1:1, 2:1 and 3:1 by liquid–liquid phase separation method. Physicochemical characterization andin vitrodiffusion evaluation were carried out for the prepared formulations. A single dose clinical pharmacokinetic study was carried out for the selected formulation. Results revealed VRD formulations showed particle size of 836.7 ± 191.3, 179.8 ± 18.4 and 147.3 ± 18.1 nm and encapsulation efficiency of 55.72 ± 4.36, 65.33 ± 7.82 and 69.38 ± 6.83% for F1, F2 and F3, respectively. Single dose clinical pharmacokinetic results, in healthy human volunteers, showed improved VRD bioavailability by 2.5 folds from nanosphere formula (F3) compared with the marketed tablets. The formulation of novel zein-ALA nanospheres offers the possibility for application of a biocompatible nano-carrier system in drug delivery for improved drug delivery and efficacy.
Relationships between circulating branched chain amino acid concentrations and risk of adverse cardiovascular events in patients with STEMI treated with PCI
Authors: Du Xiaoyu , You Hongzhao , Li Yulin , Wang Yuan , Hui Peng , Qiao Bokang , Lu Jie , Zhang Weihua , Zhou Shanshan , Zheng Yang , Du Jie 
Published: October 2018

AbstractThe incidence of in-hospital cardiovascular adverse events (AEs) in patients with ST-segment elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI) is relatively high. Identification of metabolic markers could improve our understanding of the underlying pathological changes in these patients. We aimed to identify associations between concentrations of plasma metabolites on admission and development of in-hospital AEs in post-PCI patients with STEMI. We used targeted mass spectrometry to measure plasma concentrations of 26 amino acid metabolites on admission in 96 patients with STEMI who subsequently developed post-PCI AEs and in 96 age- and sex-matched patients without post-PCI cardiovascular AEs. Principal component analysis (PCA) revealed that PCA-derived factors, including branched chain amino acids (BCAAs), were associated with increased risks of all three pre-specified outcomes: cardiovascular mortality/acute heart failure (AHF), cardiovascular mortality, and AHF. Addition of BCAA to the Global Registry of Acute Coronary Events risk score increased the concordance C statistic from 0.702 to 0.814 (p < 0.001), and had a net reclassification index of 0.729 (95% confidence interval, 0.466–0.992, p < 0.001). These findings demonstrate that high circulating BCAA concentrations on admission are associated with subsequent in-hospital AEs after revascularization in patients with STEMI.
Osteogenic protein-1 inhibits nucleus pulposus cell apoptosis through regulating the NF-κB/ROS pathway in an inflammation environment
Authors: Yu Wei , Fu Jiabin , Liu Yan , Wu Yuchi , Jiang Dianming 
Published: October 2018

Background: Intervertebral disc degeneration is a pathological process that involves an inflammation response. As a classical cellular feature, several studies have demonstrated that inflammation can promote nucleus pulposus (NP) cell apoptosis. Therefore, attenuation of NP cell apoptosis may be a potential way to retard disc degeneration.
Objective: The present study was aimed to investigate the protective effects of osteogenic protein-1 (OP-1) against NP cell apoptosis in an inflammation environment, and the potential signaling transduction pathway.
Methods: Rat NP cells were cultured in medium with or without inflammatory cytokine tumor necrosis factor (TNF)-α for 6 days. The exogenous TNF-α was added into the medium to investigate its protective effects. NP cell apoptosis was evaluated by cell apoptosis ratio, caspase-3 activity, gene/protein expression of apoptosis-related molecules (Bcl-2, Bax, and caspase-3). Additionally, the intracellular reactive oxygen species (ROS) content and activity of the NF-κB pathway were also analyzed.
Results: Compared with the control NP cells, TNF-α significantly increased cell apoptosis ratio, caspase-3 activity, gene/protein expression of Bcl-2, Bax and caspase-3, ROS content, and activity of the NF-κB pathway. However, OP-1 partly attenuated these effects in NP cells treated with TNF-α.
Conclusion: OP-1 is effective in attenuating TNF-α-caused NP cell apoptosis, and the ROS/NF-κB pathway may be the potential signaling transduction pathway. The present study indicates that OP-1 may be helpful to inhibit inflammation-mediated disc degeneration.
A Phenomenological Analysis of the Experience of Stuttering
Authors: Tichenor Seth , Yaruss J. Scott 
Published: October 2018

PurposeStuttering behaviors and moments of stuttering are typically defined by what a listener perceives. This study evaluated participants' perceptions of their own experience of moments of stuttering.MethodThirteen adults who stutter participated in a phenomenological qualitative study examining their experience of moments of stuttering. Analysis yielded several common themes and subthemes culminating in an essential structure describing the shared experience.ResultsSpeakers experience anticipation and react in action and nonaction ways. Many speakers experience a loss of control that relates to a lack of a well-formed speech plan or agency. The experience of moments of stuttering changes through therapy, over time, with self-help, and across situations. Many speakers experience so-called typical stuttering behaviors as reactions rather than direct consequences of trying to speak. Interactions with listeners can affect the experience of stuttering.ConclusionAlthough research recognizes that the experience of the stuttering disorder involves more than just speech behaviors, people who stutter experience stuttering behaviors in time as involving more than just the disruption in speech. This finding has implications for both the theoretical understanding of stuttering and the clinical evaluation and treatment of the stuttering disorder.