bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer’s disease
Authors: Muenchhoff Julia , Poljak Anne , Thalamuthu Anbupalam , Gupta Veer B. , Chatterjee Pratishtha , Raftery Mark , Masters Colin L. , Morris John C. , Bateman Randall J. , Fagan Anne M. , Martins Ralph N. , Sachdev Perminder S. 
Published: July 2016

AbstractThe autosomal dominant form of Alzheimer’s disease (ADAD) is far less prevalent than late onset Alzheimer’s disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose metabolism. Fewer changes were observed at the asymptomatic than symptomatic stage with seven and 16 proteins altered significantly in aMC and sMC, respectively. This included complement components C3, C5, C6, apolipoproteins A-I, A-IV, C-I and M, histidine-rich glycoprotein, heparin cofactor II and attractin, which are involved in inflammation, lipid metabolism and vascular health. Proteins involved in lipid metabolism differed only at the symptomatic stage, whereas changes in inflammation and vascular health were evident at asymptomatic and symptomatic stages. Due to increasing evidence supporting the usefulness of ADAD as a model for LOAD, these proteins warrant further investigation into their potential association with early stages of LOAD.
Fully integrated multi-optoelectronic synthesizer for THz pumping source in wireless communications with rich backup redundancy and wide tuning range
Authors: Xu Junjie , Hou Lianping , Deng Qiufang , Han Liangshun , Liang Song , Marsh John H. , Zhu Hongliang 
Published: July 2016

AbstractWe report a monolithic photonic integrated circuit (PIC) for THz communication applications. The PIC generates up to 4 optical frequency lines which can be mixed in a separate device to generate THz radiation, and each of the optical lines can be modulated individually to encode data. Physically, the PIC comprises an array of wavelength tunable distributed feedback lasers each with its own electro-absorption modulator. The lasers are designed with a long cavity to operate with a narrow linewidth, typically <4 MHz. The light from the lasers is coupled via an multimode interference (MMI) coupler into a semiconductor optical amplifier (SOA). By appropriate selection and biasing of pairs of lasers, the optical beat signal can be tuned continuously over the range from 0.254 THz to 2.723 THz. The EAM of each channel enables signal leveling balanced between the lasers and realizing data encoding, currently at data rates up to 6.5 Gb/s. The PIC is fabricated using regrowth-free techniques, making it economic for volume applications, such for use in data centers. The PIC also has a degree of redundancy, making it suitable for applications, such as inter-satellite communications, where high reliability is mandatory.
Numerical indices based on circulating tumor DNA for the evaluation of therapeutic response and disease progression in lung cancer patients
Authors: Kato Kikuya , Uchida Junji , Kukita Yoji , Kumagai Toru , Nishino Kazumi , Inoue Takako , Kimura Madoka , Oba Shigeyuki , Imamura Fumio 
Published: July 2016

AbstractMonitoring of disease/therapeutic conditions is an important application of circulating tumor DNA (ctDNA). We devised numerical indices, based on ctDNA dynamics, for therapeutic response and disease progression. 52 lung cancer patients subjected to the EGFR-TKI treatment were prospectively collected and ctDNA levels represented by the activating and T790M mutations were measured using deep sequencing. Typically, ctDNA levels decreased sharply upon initiation of EGFR-TKI, however this did not occur in progressive disease (PD) cases. All 3 PD cases at initiation of EGFR-TKI were separated from other 27 cases in a two-dimensional space generated by the ratio of the ctDNA levels before and after therapy initiation (mutation allele ratio in therapy, MART) and the average ctDNA level. For responses to various agents after disease progression, PD/stable disease cases were separated from partial response cases using MART (accuracy, 94.7%; 95% CI, 73.5–100). For disease progression, the initiation of ctDNA elevation (initial positive point) was compared with the onset of objective disease progression. In 11 out of 28 eligible patients, both occurred within ±100 day range, suggesting a detection of the same change in disease condition. Our numerical indices have potential applicability in clinical practice, pending confirmation with designed prospective studies.
Neural substrates predicting short-term improvement of tinnitus loudness and distress after modified tinnitus retraining therapy
Authors: Kim Shin Hye , Jang Ji Hye , Lee Sang-Yeon , Han Jae Joon , Koo Ja-Won , Vanneste Sven , De Ridder Dirk , Song Jae-Jin 
Published: July 2016

AbstractAlthough tinnitus retraining therapy (TRT) is efficacious in most patients, the exact mechanism is unclear and no predictor of improvement is available. We correlated the extent of improvement with pre-TRT quantitative electroencephalography (qEEG) findings to identify neural predictors of improvement after TRT. Thirty-two patients with debilitating tinnitus were prospectively enrolled, and qEEG data were recorded before their initial TRT sessions. Three months later, these qEEG findings were correlated with the percentage improvements in the Tinnitus Handicap Inventory (THI) scores, and numeric rating scale (NRS) scores of tinnitus loudness and tinnitus perception. The THI score improvement was positively correlated with the pre-treatment activities of the left insula and the left rostral and pregenual anterior cingulate cortices (rACC/pgACC), which control parasympathetic activity. Additionally, the activities of the right auditory cortices and the parahippocampus, areas that generate tinnitus, negatively correlated with improvements in loudness. Improvements in the NRS scores of tinnitus perception correlated positively with the pre-TRT activities of the bilateral rACC/pgACC, areas suggested to form the core of the noise-canceling system. The current study supports both the classical neurophysiological and integrative models of tinnitus; our results serve as a milestone in the development of precision medicine in the context of TRT.
Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters
Authors: Wang Hai-yi , Su Zi-hua , Xu Xiao , Sun Zhi-peng , Duan Fei-xue , Song Yuan-yuan , Li Lu , Wang Ying-wei , Ma Xin , Guo Ai-tao , Ma Lin , Ye Hui-yi 
Published: July 2016

AbstractPharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan–rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (Ktrans & Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters.
Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection
Authors: Stevens Natalie E. , Hatjopolous Antoinette , Fraser Cara K. , Alsharifi Mohammed , Diener Kerrilyn R. , Hayball John D. 
Published: July 2016

AbstractPassive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus.
Phase diagram of quantum critical system via local convertibility of ground state
Authors: Liu Si-Yuan , Quan Quan , Chen Jin-Jun , Zhang Yu-Ran , Yang Wen-Li , Fan Heng 
Published: July 2016

AbstractWe investigate the relationship between two kinds of ground-state local convertibility and quantum phase transitions in XY model. The local operations and classical communications (LOCC) convertibility is examined by the majorization relations and the entanglement-assisted local operations and classical communications (ELOCC) via Rényi entropy interception. In the phase diagram of XY model, LOCC convertibility and ELOCC convertibility of ground-states are presented and compared. It is shown that different phases in the phase diagram of XY model can have different LOCC or ELOCC convertibility, which can be used to detect the quantum phase transition. This study will enlighten extensive studies of quantum phase transitions from the perspective of local convertibility, e.g., finite-temperature phase transitions and other quantum many-body models.
Inhibitory effect of 2-methyl-naphtho[1,2,3-de]quinolin-8-one on melanosome transport and skin pigmentation
Authors: Park Jong il , Lee Ha Yeon , Lee Ji Eun , Myung Cheol hwan , Hwang Jae Sung 
Published: July 2016

AbstractMelanosomes are lysosome-related organelles with specialized capabilities of melanin synthesis and movement mediated by the Rab27a-Melanophilin-MyosinVa protein complex. In this study, we found that 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO) induced melanosome aggregation around the nucleus in melan-a melanocytes and in melan-a melanocytes/SP-1 keratinocyte co-cultures without inducing toxicity or changing the melanin content. Western blot and real-time PCR analyses showed that MNQO decreased expression of the Rab27a, Melanophilin and MyosinVa proteins and mRNAs, respectively, in melan-a melanocytes. In a reconstituted human epidermis model, treatment with 0.001% MNQO reduced skin pigmentation. Also, MNQO reduced skin pigmentation in brown guinea pigs induced by UVB irradiation. These results indicated that regulation of melanosome transport may serve as a good target for new skin depigmenting agents and MNQO itself could be a candidate.
Thioredoxin interacting protein (TXNIP) regulates tubular autophagy and mitophagy in diabetic nephropathy through the mTOR signaling pathway
Authors: Huang Chunling , Zhang Yuan , Kelly Darren J. , Tan Christina Y. R. , Gill Anthony , Cheng Delfine , Braet Filip , Park Jin-Sung , Sue Carolyn M. , Pollock Carol A. , Chen Xin-Ming 
Published: July 2016

AbstractHyperglycemia upregulates thioredoxin interacting protein (TXNIP) expression, which in turn induces ROS production, inflammatory and fibrotic responses in the diabetic kidney. Dysregulation of autophagy contributes to the development of diabetic nephropathy. However, the interaction of TXNIP with autophagy/mitophagy in diabetic nephropathy is unknown. In this study, streptozotocin-induced diabetic rats were given TXNIP DNAzyme or scrambled DNAzyme for 12 weeks respectively. Fibrotic markers, mitochondrial function and mitochondrial reactive oxygen species (mtROS) were assessed in kidneys. Tubular autophagy and mitophagy were determined in kidneys from both human and rats with diabetic nephropathy. TXNIP and autophagic signaling molecules were examined. TXNIP DNAzyme dramatically attenuated extracellular matrix deposition in the diabetic kidneys compared to the control DNAzyme. Accumulation of autophagosomes and reduced autophagic clearance were shown in tubular cells of human diabetic compared to non-diabetic kidneys, which was reversed by TXNIP DNAzyme. High glucose induced mitochondrial dysfunction and mtROS production and inhibited mitophagy in proximal tubular cells, which was reversed by TXNIP siRNA. TXNIP inhibition suppressed diabetes-induced BNIP3 expression and activation of the mTOR signaling pathway. Collectively, hyperglycemia-induced TXNIP contributes to the dysregulation of tubular autophagy and mitophagy in diabetic nephropathy through activation of the mTOR signaling pathway.
Associations of self-reported height loss and kyphosis with vertebral fractures in Japanese women 60 years and older: a cross-sectional survey
Authors: Kamimura Mikio , Nakamura Yukio , Sugino Noriyuki , Uchiyama Shigeharu , Komatsu Masatoshi , Ikegami Shota , Kato Hiroyuki , Taguchi Akira 
Published: July 2016

AbstractSome vertebral fractures come to clinical attention but most do not. This cross-sectional survey aimed to clarify the associations of self-reported height loss and kyphosis with vertebral fractures. We enrolled 407 women aged 60–92 years who visited our orthopaedic clinic between June and August 2014 in our study. Inclusion criteria were lateral radiography followed by completion of a structured questionnaire in this study. The primary outcome was vertebral fracture diagnosed on lateral radiography and graded using a semiquantitative grading method, from SQ0 (normal) to SQ3 (severe). Self-reported kyphosis was defined as none, mild to moderate, severe. Self-reported height loss was defined as <4 cm or ≥4 cm. Number of SQ1 fracture was associated only with kyphosis. Self-reported severe kyphosis was significantly associated with increased numbers of ≥SQ2 vertebral fractures (p = 0.007). Height loss ≥4 cm was significantly associated with increased ≥SQ2 grade fractures (p < 0.001). Odds ratios (ORs) for fractures associated with mild-to-moderate and severe kyphosis were 2.1 [95% confidence interval 1.4 to 3.3) and 4.2 (1.8 to 9.5), respectively. OR for fractures associated with height loss ≥4 cm was 2.3 (1.4 to 3.7). Self-reported kyphosis may be useful for identifying Japanese women aged ≥60 years who have undetected vertebral fractures.
Penternary chalcogenides nanocrystals as catalytic materials for efficient counter electrodes in dye-synthesized solar cells
Authors: Özel Faruk , Sarılmaz Adem , İstanbullu Bilal , Aljabour Abdalaziz , Kuş Mahmut , Sönmezoğlu Savaş 
Published: July 2016

AbstractThe penternary chalcogenides Cu2CoSn(SeS)4 and Cu2ZnSn(SeS)4 were successfully synthesized by hot-injection method and employed as a catalytic materials for efficient counter electrodes in dye-synthesized solar cells (DSSCs). The structural, compositional, morphological and optical properties of these pentenary semiconductors were characterized by X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), energy-dispersive spectrometer (EDS) and ultraviolet-visible (UV–Vis) spectroscopy. The Cu2CoSn(SeS)4 and Cu2ZnSn(SeS)4 nanocrystals had a single crystalline, kesterite phase, adequate stoichiometric ratio, 18–25 nm particle sizes which are forming nanospheres and band gap energy of 1.18 and 1.45 eV, respectively. Furthermore, the electrochemical impedance spectroscopy and cyclic voltammograms indicated that Cu2CoSn(SeS)4 nanocrystals as counter electrodes exhibited better electrocatalytic activity for the reduction of iodine/iodide electrolyte than that of Cu2ZnSn(SeS)4 nanocrystals and conventional platinum (Pt). The photovoltaic results demonstrated that DSSC with a Cu2CoSn(SeS)4 nanocrystals-based counter electrode achieved the best efficiency of 6.47%, which is higher than the same photoanode employing a Cu2ZnSn(SeS)4 nanocrystals (3.18%) and Pt (5.41%) counter electrodes. These promising results highlight the potential application of penternary chalcogen Cu2CoSn(SeS)4 nanocrystals in low-cost, high-efficiency, Pt-free DSSCs.
Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique
Authors: Sun Di , Wei Cong , Shen E. , Ying Tao , Hu Bing 
Published: July 2016

AbstractAcoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results.
Proteome-wide analysis of lysine acetylation in the plant pathogen Botrytis cinerea
Authors: Lv Binna , Yang Qianqian , Li Delong , Liang Wenxing , Song Limin 
Published: July 2016

AbstractLysine acetylation is a dynamic and reversible post-translational modification that plays an important role in diverse cellular processes. Botrytis cinerea is the most thoroughly studied necrotrophic species due to its broad host range and huge economic impact. However, to date, little is known about the functions of lysine acetylation in this plant pathogen. In this study, we determined the lysine acetylome of B. cinerea through the combination of affinity enrichment and high-resolution LC-MS/MS analysis. Overall, 1582 lysine acetylation sites in 954 proteins were identified. Bioinformatics analysis shows that the acetylated proteins are involved in diverse biological functions and show multiple cellular localizations. Several particular amino acids preferred near acetylation sites, including KacY, KacH, Kac***R, KacF, FKac and Kac***K, were identified in this organism. Protein interaction network analysis demonstrates that a variety of interactions are modulated by protein acetylation. Interestingly, 6 proteins involved in virulence of B. cinerea, including 3 key components of the high-osmolarity glycerol pathway, were found to be acetylated, suggesting that lysine acetylation plays regulatory roles in pathogenesis. These data provides the first comprehensive view of the acetylome of B. cinerea and serves as a rich resource for functional analysis of lysine acetylation in this plant pathogen.
Navigation in bile acid chemical space: discovery of novel FXR and GPBAR1 ligands
Authors: Finamore Claudia , Festa Carmen , Renga Barbara , Sepe Valentina , Carino Adriana , Masullo Dario , Biagioli Michele , Marchianò Silvia , Capolupo Angela , Monti Maria Chiara , Fiorucci Stefano , Zampella Angela 
Published: July 2016

AbstractBile acids are signaling molecules interacting with nuclear receptors and membrane G-protein-coupled receptors. Among these receptors, the farnesoid X receptor (FXR) and the membrane G-coupled receptor (GPBAR1) have gained increasing consideration as druggable receptors and their exogenous dual regulation represents an attractive strategy in the treatment of enterohepatic and metabolic disorders. However, the therapeutic use of dual modulators could be associated to severe side effects and therefore the discovery of selective GPBAR1 and FXR agonists is an essential step in the medicinal chemistry optimization of bile acid scaffold. In this study, a new series of 6-ethylcholane derivatives modified on the tetracyclic core and on the side chain has been designed and synthesized and their in vitro activities on FXR and GPBAR1 were assayed. This speculation resulted in the identification of compound 7 as a potent and selective GPBAR1 agonist and of several derivatives showing potent dual agonistic activity.
Improved antifouling properties and selective biofunctionalization of stainless steel by employing heterobifunctional silane-polyethylene glycol overlayers and avidin-biotin technology
Authors: Hynninen Ville , Vuori Leena , Hannula Markku , Tapio Kosti , Lahtonen Kimmo , Isoniemi Tommi , Lehtonen Elina , Hirsimäki Mika , Toppari J. Jussi , Valden Mika , Hytönen Vesa P. 
Published: July 2016

AbstractA straightforward solution-based method to modify the biofunctionality of stainless steel (SS) using heterobifunctional silane-polyethylene glycol (silane-PEG) overlayers is reported. Reduced nonspecific biofouling of both proteins and bacteria onto SS and further selective biofunctionalization of the modified surface were achieved. According to photoelectron spectroscopy analyses, the silane-PEGs formed less than 10 Å thick overlayers with close to 90% surface coverage and reproducible chemical compositions. Consequently, the surfaces also became more hydrophilic, and the observed non-specific biofouling of proteins was reduced by approximately 70%. In addition, the attachment of E. coli was reduced by more than 65%. Moreover, the potential of the overlayer to be further modified was demonstrated by successfully coupling biotinylated alkaline phosphatase (bAP) to a silane-PEG-biotin overlayer via avidin-biotin bridges. The activity of the immobilized enzyme was shown to be well preserved without compromising the achieved antifouling properties. Overall, the simple solution-based approach enables the tailoring of SS to enhance its activity for biomedical and biotechnological applications.