bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical focusing inside scattering media with time-reversed ultrasound microbubble encoded light
Authors: Ruan Haowen , Jang Mooseok , Yang Changhuei 
Published: November 2015

AbstractFocusing light inside scattering media in a freely addressable fashion is challenging, as the wavefront of the scattered light is highly disordered. Recently developed ultrasound-guided wavefront shaping methods are addressing this challenge, albeit with relatively low modulation efficiency and resolution limitations. In this paper, we present a new technique, time-reversed ultrasound microbubble encoded (TRUME) optical focusing, which can focus light with improved efficiency and sub-ultrasound wavelength resolution. This method ultrasonically destroys microbubbles, and measures the wavefront change to compute and render a suitable time-reversed wavefront solution for focusing. We demonstrate that the TRUME technique can create an optical focus at the site of bubble destruction with a size of ∼2 μm. We further demonstrate a twofold enhancement in addressable focus resolution in a microbubble aggregate target by exploiting the nonlinear pressure-to-destruction response of the microbubbles. The reported technique provides a deep tissue-focusing solution with high efficiency, resolution, and specificity.
Loss of Polo ameliorates APP-induced Alzheimer’s disease-like symptoms in Drosophila
Authors: Peng Fei , Zhao Yu , Huang Xirui , Chen Changyan , Sun Lili , Zhuang Luming , Xue Lei 
Published: November 2015

AbstractThe amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Despite extensive studies, little is known about the regulation of APP’s functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP and provide insight into the role of cell cycle re-entry in AD pathogenesis.
Classification of Parkinson’s Disease Genotypes in Drosophila Using Spatiotemporal Profiling of Vision
Authors: West Ryan J.H. , Elliott Christopher J.H. , Wade Alex R. 
Published: November 2015

AbstractElectrophysiological studies indicate altered contrast processing in some Parkinson’s Disease (PD) patients. We recently demonstrated that vision is altered in Drosophila PD models and hypothesised that different types of genetic and idiopathic PD may affect dopaminergic visual signalling pathways differently. Here we asked whether visual responses in Drosophila could be used to identify PD mutations. To mimic a clinical setting a range of flies was used. Young flies from four control lines were compared to three early-onset PD mutations (PINK1, DJ-1α and DJ-1β) and to two other neurodegenerative mutations, one in the fly LRRK2 orthologue (dLRRK) the other in eggroll, a model of general neurodegeneration in Drosophila. Stimuli were contrast reversing gratings spanning 64 spatiotemporal frequency combinations. We recorded the steady-state visually-evoked response amplitude across all combinations. We found that the pattern of neuronal responses differed between genotypes. Wild-type and early-onset PD flies formed separate clusters; the late-onset mutation is an outlier. Neuronal responses in early-onset PD flies were stronger than in wild-types. Multivariate pattern analysis grouped flies by PD/non-PD genotype with an accuracy >85%. We propose that machine learning algorithms may be useful in increasing the diagnostic specificity of human electrophysiological measurements in both animal models and PD patients.
“Thermal Stabilization Effect” of Al2O3 nano-dopants improves the high-temperature dielectric performance of polyimide
Authors: Yang Yang , He Jinliang , Wu Guangning , Hu Jun 
Published: November 2015

AbstractInsulation performance of the dielectrics under extreme conditions always attracts widespread attention in electrical and electronic field. How to improve the high-temperature dielectric properties of insulation materials is one of the key issues in insulation system design of electrical devices. This paper studies the temperature-dependent corona resistance of polyimide (PI)/Al2O3 nanocomposite films under high-frequency square-wave pulse conditions. Extended corona resistant lifetime under high-temperature conditions is experimentally observed in the 2 wt% nanocomposite samples. The “thermal stabilization effect” is proposed to explain this phenomenon which attributes to a new kind of trap band caused by nanoparticles. This effect brings about superior space charge characteristics and corona resistance under high temperature with certain nano-doping concentration. The proposed theory is experimentally demonstrated by space charge analysis and thermally stimulated current (TSC) tests. This discovered effect is of profound significance on improving high-temperature dielectric properties of nanocomposites towards various applications.
Kill-painting of hypoxic tumours in charged particle therapy
Authors: Tinganelli Walter , Durante Marco , Hirayama Ryoichi , Krämer Michael , Maier Andreas , Kraft-Weyrather Wilma , Furusawa Yoshiya , Friedrich Thomas , Scifoni Emanuele 
Published: November 2015

AbstractSolid tumours often present regions with severe oxygen deprivation (hypoxia), which are resistant to both chemotherapy and radiotherapy. Increased radiosensitivity as a function of the oxygen concentration is well described for X-rays. It has also been demonstrated that radioresistance in anoxia is reduced using high-LET radiation rather than conventional X-rays. However, the dependence of the oxygen enhancement ratio (OER) on radiation quality in the regions of intermediate oxygen concentrations, those normally found in tumours, had never been measured and biophysical models were based on extrapolations. Here we present a complete survival dataset of mammalian cells exposed to different ions in oxygen concentration ranging from normoxia (21%) to anoxia (0%). The data were used to generate a model of the dependence of the OER on oxygen concentration and particle energy. The model was implemented in the ion beam treatment planning system to prescribe uniform cell killing across volumes with heterogeneous radiosensitivity. The adaptive treatment plans have been validated in two different accelerator facilities, using a biological phantom where cells can be irradiated simultaneously at three different oxygen concentrations. We thus realized a hypoxia-adapted treatment plan, which will be used for painting by voxel of hypoxic tumours visualized by functional imaging.
Vibration mechanosignals superimposed to resistive exercise result in baseline skeletal muscle transcriptome profiles following chronic disuse in bed rest
Authors: Salanova Michele , Gambara Guido , Moriggi Manuela , Vasso Michele , Ungethuem Ute , Belavý Daniel L. , Felsenberg Dieter , Cerretelli Paolo , Gelfi Cecilia , Blottner Dieter 
Published: November 2015

AbstractDisuse-induced muscle atrophy is a major concern in aging, in neuromuscular diseases, post-traumatic injury and in microgravity life sciences affecting health and fitness also of crew members in spaceflight. By using a laboratory analogue to body unloading we perform for the first time global gene expression profiling joined to specific proteomic analysis to map molecular adaptations in disused (60 days of bed rest) human soleus muscle (CTR) and in response to a resistive exercise (RE) countermeasure protocol without and with superimposed vibration mechanosignals (RVE). Adopting Affymetrix GeneChip technology we identified 235 differently transcribed genes in the CTR group (end- vs. pre-bed rest). RE comprised 206 differentially expressed genes, whereas only 51 changed gene transcripts were found in RVE. Most gene transcription and proteomic changes were linked to various key metabolic pathways (glycolysis, oxidative phosphorylation, tricarboxylic acid (TCA) cycle, lipid metabolism) and to functional contractile structures. Gene expression profiling in bed rest identified a novel set of genes explicitly responsive to vibration mechanosignals in human soleus. This new finding highlights the efficacy of RVE protocol in reducing key signs of disuse maladaptation and atrophy and to maintain a close-to-normal skeletal muscle quality outcome following chronic disuse in bed rest.
PRL-3 activates mTORC1 in Cancer Progression
Authors: Ye Zu , Al-aidaroos Abdul Qader Omer , Park Jung Eun , Yuen Hiu Fung , Zhang Shu Dong , Gupta Abhishek , Lin Youbin , Shen Han-Ming , Zeng Qi 
Published: November 2015

AbstractPRL-3, a metastasis-associated phosphatase, is known to exert its oncogenic functions through activation of PI3K/Akt, which is a key regulator of the rapamycin-sensitive mTOR complex 1 (mTORC1), but a coherent link between PRL-3 and activation of mTOR has not yet been formally demonstrated. We report a positive correlation between PRL-3 expression and mTOR phospho-activation in clinical tumour samples and mouse models of cancer and demonstrate that PRL-3 increased downstream signalling to the mTOR substrates, p70S6K and 4E-BP1, by increasing PI3K/Akt-mediated activation of Rheb-GTP via TSC2 suppression. We also show that PRL-3 increases mTOR translocation to lysosomes via increased mTOR binding affinity to Rag GTPases in an Akt-independent manner, demonstrating a previously undescribed mechanism of action for PRL-3. PRL-3 also enhanced matrix metalloproteinase-2 secretion and cellular invasiveness via activation of mTOR, attributes which were sensitive to rapamycin treatment. The downstream effects of PRL-3 were maintained even under conditions of environmental stress, suggesting that PRL-3 provides a strategic survival advantage to tumour cells via its effects on mTOR.
Processing of frequency and location in human subcortical auditory structures
Authors: Moerel Michelle , De Martino Federico , Uğurbil Kâmil , Yacoub Essa , Formisano Elia 
Published: November 2015

AbstractTo date it remains largely unknown how fundamental aspects of natural sounds, such as their spectral content and location in space, are processed in human subcortical structures. Here we exploited the high sensitivity and specificity of high field fMRI (7 Tesla) to examine the human inferior colliculus (IC) and medial geniculate body (MGB). Subcortical responses to natural sounds were well explained by an encoding model of sound processing that represented frequency and location jointly. Frequency tuning was organized in one tonotopic gradient in the IC, whereas two tonotopic maps characterized the MGB reflecting two MGB subdivisions. In contrast, no topographic pattern of preferred location was detected, beyond an overall preference for peripheral (as opposed to central) and contralateral locations. Our findings suggest the functional organization of frequency and location processing in human subcortical auditory structures and pave the way for studying the subcortical to cortical interaction required to create coherent auditory percepts.
Effect of Diabetes Mellitus on Survival in Patients with Pancreatic Cancer: A Systematic Review and Meta-analysis
Authors: Mao Yixiang , Tao Min , Jia Xiaoyan , Xu Hong , Chen Kai , Tang Hongwei , Li Donghui 
Published: November 2015

AbstractConcurrent diabetes has been linked with an increased risk of death in many cancers, but findings in pancreatic cancer have been inconsistent. We performed a systematic review and meta-analysis to assess the effect of diabetes on survival in patients with pancreatic cancer. Of 4, 463 original articles, 41 were included in the review; 29 studies with 33 risk estimates were included in the meta-analysis. In the overall comparison of patients with pancreatic cancer and diabetes with their nondiabetic counterparts, the former had significantly higher all-cause mortality (pooled HR: 1.13; 95% CI: 1.04–1.22). Subgroup analyses showed that diabetes was associated with poor survival in patients with resectable disease (HR: 1.37; 95% CI: 1.15–1.63) but not in those with unresectable disease (HR: 1.07; 95% CI: 0.89–1.29). The HR (95% CI) was 1.52 (1.20–1.93) for patients with new-onset diabetes (≤2 years of diabetes duration) and 1.22 (0.83–1.80) for those with longstanding diabetes (>2 years). Diabetes was associated with higher mortality overall in patients with pancreatic cancer. The effect of diabetes on overall survival was associated with the stages of tumor and the duration of diabetes.
Spatial working memory is enhanced in children by differential outcomes
Authors: Esteban Laura , Vivas Ana B. , Fuentes Luis J. , Estévez Angeles F. 
Published: November 2015

AbstractWorking memory (WM) is essential to academic achievement. Any enhancement of WM abilities may improve children’s school performance. We tested the usefulness of the differential outcomes procedure (DOP) to enhance typically developing children’s performance on a spatial WM task. The DOP involves a conditional discriminative learning task in which a correct choice response to a specific stimulus-stimulus association is reinforced with a particular reinforcer (outcome). We adapted a spatial memory task to be used with the DOP. Participants had to learn and retain in their WM four target locations of eight possible locations where a shape could be presented. Two groups of 5- and 7-year-old children performed the low-attentional version of the spatial task and an additional group of 7-year-old children performed the high-attentional version. The results showed that compared with the standard non-differential outcomes procedure (NOP), the DOP produced better memory-based performance in 5-year-old children with the low-attentional task and in 7-year-old children with the high-attentional task. Additionally, delay intervals impaired performance in the NOP but not in the DOP. These findings suggest that the DOP may be a useful complement to other WM intervention programs targeted to improve children´s academic performance at school.
Amelanism in the corn snake is associated with the insertion of an LTR-retrotransposon in the OCA2 gene
Authors: Saenko Suzanne V. , Lamichhaney Sangeet , Barrio Alvaro Martinez , Rafati Nima , Andersson Leif , Milinkovitch Michel C. 
Published: November 2015

AbstractThe corn snake (Pantherophis guttatus) is a new model species particularly appropriate for investigating the processes generating colours in reptiles because numerous colour and pattern mutants have been isolated in the last five decades. Using our captive-bred colony of corn snakes, transcriptomic and genomic next-generation sequencing, exome assembly and genotyping of SNPs in multiple families, we delimit the genomic interval bearing the causal mutation of amelanism, the oldest colour variant observed in that species. Proceeding with sequencing the candidate gene OCA2 in the uncovered genomic interval, we identify that the insertion of an LTR-retrotransposon in its 11th intron results in a considerable truncation of the p protein and likely constitutes the causal mutation of amelanism in corn snakes. As amelanistic snakes exhibit white, instead of black, borders around an otherwise normal pattern of dorsal orange saddles and lateral blotches, our results indicate that melanocytes lacking melanin are able to participate to the normal patterning of other colours in the skin. In combination with research in the zebrafish, this work opens the perspective of using corn snake colour and pattern variants to investigate the generative processes of skin colour patterning shared among major vertebrate lineages.
Small Sample Sizes Yield Biased Allometric Equations in Temperate Forests
Authors: Duncanson L. , Rourke O. , Dubayah R. 
Published: November 2015

AbstractAccurate quantification of forest carbon stocks is required for constraining the global carbon cycle and its impacts on climate. The accuracies of forest biomass maps are inherently dependent on the accuracy of the field biomass estimates used to calibrate models, which are generated with allometric equations. Here, we provide a quantitative assessment of the sensitivity of allometric parameters to sample size in temperate forests, focusing on the allometric relationship between tree height and crown radius. We use LiDAR remote sensing to isolate between 10,000 to more than 1,000,000 tree height and crown radius measurements per site in six U.S. forests. We find that fitted allometric parameters are highly sensitive to sample size, producing systematic overestimates of height. We extend our analysis to biomass through the application of empirical relationships from the literature and show that given the small sample sizes used in common allometric equations for biomass, the average site-level biomass bias is ~+70% with a standard deviation of 71%, ranging from −4% to +193%. These findings underscore the importance of increasing the sample sizes used for allometric equation generation.
Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia
Authors: Royer-Bertrand Beryl , Castillo-Taucher Silvia , Moreno-Salinas Rodrigo , Cho Tae-Joon , Chae Jong-Hee , Choi Murim , Kim Ok-Hwa , Dikoglu Esra , Campos-Xavier Belinda , Girardi Enrico , Superti-Furga Giulio , Bonafé Luisa , Rivolta Carlo , Unger Sheila , Superti-Furga Andrea 
Published: November 2015

AbstractWe and others have reported mutations inLONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia and other malformations and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation inLONP1was found; instead, we found biallelic mutations inHSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of “mitochondrial chaperonopathies” and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis.
Copy number variations play important roles in heredity of common diseases: a novel method to calculate heritability of a polymorphism
Authors: Nagao Yoshiro 
Published: November 2015

Abstract“Missing heritability” in genome wide association studies, the failure to account for a considerable fraction of heritability by the variants detected, is a current puzzle in human genetics. For solving this puzzle the involvement of genetic variants like rare single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) has been proposed. Many papers have published estimating the heritability of sets of polymorphisms, however, there has been no paper discussing the estimation of a heritability of a single polymorphism. Here I show a simple but rational method to calculate heritability of an individual polymorphism, hp2. Using this method, I carried out a trial calculation of hp2 of CNVs and SNPs using published data. It turned out that hp2 of some CNVs is quite large. Noteworthy examples were that about 25% of the heritability of type 2 diabetes mellitus and about 15% of the heritability of schizophrenia could be accounted for by one CNV and by four CNVs, respectively. The results suggest that a large part of missing heritability could be accounted for by re-evaluating the CNVs which have been already found and by searching novel CNVs with large hp2.
Global Prioritization of Disease Candidate Metabolites Based on a Multi-omics Composite Network
Authors: Yao Qianlan , Xu Yanjun , Yang Haixiu , Shang Desi , Zhang Chunlong , Zhang Yunpeng , Sun Zeguo , Shi Xinrui , Feng Li , Han Junwei , Su Fei , Li Chunquan , Li Xia 
Published: November 2015

AbstractThe identification of disease-related metabolites is important for a better understanding of metabolite pathological processes in order to improve human medicine. Metabolites, which are the terminal products of cellular regulatory process, can be affected by multi-omic processes. In this work, we propose a powerful method, MetPriCNet, to predict and prioritize disease candidate metabolites based on integrated multi-omics information. MetPriCNet prioritized candidate metabolites based on their global distance similarity with seed nodes in a composite network, which integrated multi-omics information from the genome, phenome, metabolome and interactome. After performing cross-validation on 87 phenotypes with a total of 602 metabolites, MetPriCNet achieved a high AUC value of up to 0.918. We also assessed the performance of MetPriCNet on 18 disease classes and found that 4 disease classes achieved an AUC value over 0.95. Notably, MetPriCNet can also predict disease metabolites without known disease metabolite knowledge. Some new high-risk metabolites of breast cancer were predicted, although there is a lack of known disease metabolite information. A predicted disease metabolic landscape was constructed and analyzed based on the results of MetPriCNet for 87 phenotypes to help us understand the genetic and metabolic mechanism of disease from a global view.
Proline biosynthesis augments tumor cell growth and aerobic glycolysis: involvement of pyridine nucleotides
Authors: Liu Wei , Hancock Chad N. , Fischer Joseph W. , Harman Meredith , Phang James M. 
Published: November 2015

AbstractThe metabolism of the nonessential amino acid proline contributes to tumor metabolic reprogramming. Previously we showed that MYC increases proline biosynthesis (PB) from glutamine. Here we show MYC increases the expression of the enzymes in PB at both protein and mRNA levels. Blockade of PB decreases tumor cell growth and energy production. Addition of Δ1-pyrroline-5-carboxylate (P5C) or proline reverses the effects of P5C synthase knockdown but not P5C reductases knockdown. Importantly, the reversal effect of proline was blocked by concomitant proline dehydrogenase/oxidase (PRODH/POX) knockdown. These findings suggest that the important regulatory contribution of PB to tumor growth derives from metabolic cycling between proline and P5C rather than product proline or intermediate P5C. We further document the critical role of PB in maintaining pyridine nucleotide levels by connecting the proline cycle to glycolysis and to the oxidative arm of the pentose phosphate pathway. These findings establish a novel function of PB in tumorigenesis, linking the reprogramming of glucose, glutamine and pyridine nucleotides and may provide a novel target for antitumor therapy.