bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the Performance of Inverted Organic Photovoltaics Using Cathode Interlayers Based on Solution‐Processable Tetrabutylammonium Halides
Authors: Hyun Gyeongho , Shin Dongguen , Lee Hyunbok , Yi Yeonjin
Published: September 2017

High‐performance inverted organic photovoltaics (OPVs) require the work function of transparent bottom cathodes to be low, which can be efficiently achieved by inserting an ultrathin interlayer to form an interface dipole. Herein, solution‐processable tetrabutylammonium halides (TBAXs, X = Cl, Br, and I) are employed as a cathode interlayer in inverted OPVs, leading to the disappearance of an S‐shaped kink in their current density–voltage curves and increasing their open‐circuit voltages and fill factors, which resulted in significantly enhanced power conversion efficiencies. Ultraviolet photoelectron spectroscopy measurements revealed that the work function of indium tin oxide (ITO) was considerably lowered in the presence of TBAX interlayers, resulting in efficient electron extraction from the C60 acceptor to the ITO bottom cathode and increasing the built‐in potential across devices. Thus, TBAXs are demonstrated to be promising materials for efficient cathode interlayer formation in inverted OPVs.
The Use of Traditional Herbal Medicines Amongst South Asian Diasporic Communities in the UK
Authors: Bhamra Sukvinder K. , Slater Adrian , Howard Caroline , Johnson Mark , Heinrich Michael
Published: September 2017

Migrant South Asian communities in the UK have brought with them their own traditional forms of medicine, yet little is known about their current use of herbal medicines (HMs) in the UK. The aim of the study was to explore the origins, use and transmission of knowledge of traditional HMs used by diasporic South Asian communities in the UK. A researcher‐administered questionnaire was used for data collection (n = 192). An opportunity sampling technique was used to recruit participants across several locations in Birmingham and Leicester. Two thirds of participants (n = 126) stated they used HMs to maintain their health and to treat various health conditions such as digestive problems, skin conditions and diabetes. Almost 2000 actively used HMs were documented including 123 plant species that were identified. Participants imported HMs from abroad as well as sourcing them locally and even growing some of their own plants. Up to 82% (n = 87) of participants who took prescription medicines did not tell their healthcare professionals about any HMs they consumed; this raises concerns about people's knowledge of herb–drug interactions, compliance and effect on prescribed medicine regimens. Similar studies to explore the use of HMs by other ethnic groups are imperative to help optimise pharmaceutical care of patients. Copyright © 2017 John Wiley & Sons, Ltd.
QFT bounds for robust stability specifications defined on the open‐loop function
Authors: Rico‐Azagra J. , Gil‐Martínez M. , Rico R. , Maisterra P.
Published: September 2017

In the framework of quantitative feedback theory, this paper develops a new method to compute robust stability bounds. This is of special interest when stability is defined directly on the open‐loop function. Thus, ignorance of the plant gain and phase shift can be specifically and independently considered. Furthermore, upper and lower stability margins for both gain and phase can be chosen. However, classical quantitative feedback theory stability specifications are defined as constraining the peak magnitude of closed‐loop functions, which lack the said flexibility. Once the upper tolerance has been defined, all stability margins are determined. Moreover, confining the most restrictive stability margin may result in other excessive margins. However, the stability bounds of the new approach guard just the required distance from the open‐loop frequency response to the critical point. This allows maximization of the available feedback in the functional bandwidth and minimization of the cost of feedback beyond the crossover frequency, provided that the open‐loop frequency response is shaped to closely follow the stability bounds. It should be noted that the new bound computation algorithm performs few and simple arithmetic operations. This makes it far more efficient than traditional methods. The flight altitude control of an unmanned aerial vehicle is proposed as a practical example to show the new method's potential benefits.
Tuning of CO2 Reduction Selectivity on Metal Electrocatalysts
Authors: Wang Yuhang , Liu Junlang , Wang Yifei , Al‐Enizi Abdullah M. , Zheng Gengfeng
Published: September 2017

Climate change, caused by heavy CO2 emissions, is driving new demands to alleviate the rising concentration of atmospheric CO2 levels. Enlightened by the photosynthesis of green plants, photo(electro)chemical catalysis of CO2 reduction, also known as artificial photosynthesis, is emerged as a promising candidate to address these demands and is widely investigated during the past decade. Among various artificial photosynthetic systems, solar‐driven electrochemical CO2 reduction is widely recognized to possess high efficiencies and potentials for practical application. The efficient and selective electroreduction of CO2 is the key to the overall solar‐to‐chemical efficiency of artificial photosynthesis. Recent studies show that various metallic materials possess the capability to play as electrocatalysts for CO2 reduction. In order to achieve high selectivity for CO2 reduction products, various efforts are made including studies on electrolytes, crystal facets, oxide‐derived catalysts, electronic and geometric structures, nanostructures, and mesoscale phenomena. In this Review, these methods for tuning the selectivity of CO2 electrochemical reduction of metallic catalysts are summarized. The challenges and perspectives in this field are also discussed.
Myeloid Zinc Finger 1 and GA Binding Protein Co-Operate with Sox2 in Regulating the Expression of Yes-Associated Protein 1 in Cancer Cells
Authors: Verma Narendra Kumar , Gadi Abhilash , Maurizi Giulia , Roy Upal Basu , Mansukhani Alka , Basilico Claudio
Published: September 2017

The transcription factor (TF) yes-associated protein 1 (YAP1) is a major effector of the tumor suppressive Hippo signaling pathway and is also necessary to maintain pluripotency in embryonic stem cells. Elevated levels of YAP1 expression antagonize the tumor suppressive effects of the Hippo pathway that normally represses YAP1 function. High YAP1 expression is observed in several types of human cancers and is particularly prominent in cancer stem cells (CSCs). The stem cell TF Sox2, which marks and maintains CSCs in osteosarcomas (OSs), promotes YAP1 expression by binding to an intronic enhancer element and YAP1 expression is also crucial for the maintainance of OS stem cells. To further understand the regulation of YAP1 expression in OSs, we subjected the YAP1 intronic enhancer to scanning mutagenesis to identify all DNA cis-elements critical for enhancer function. Through this approach, we identified two novel TFs, GA binding protein (GABP) and myeloid zinc finger 1 (MZF1), which are essential for basal YAP1 transcription. These factors are highly expressed in OSs and bind to distinct sites in the YAP1 enhancer. Depletion of either factor leads to drastically reduced YAP1 expression and thus a reversal of stem cell properties. We also found that YAP1 can regulate the expression of Sox2 by binding to two distinct DNA binding sites upstream and downstream of the Sox2 gene. Thus, Sox2 and YAP1 reinforce each others expression to maintain stemness and tumorigenicity in OSs, but the activity of MZF1 and GABP is essential for YAP1 transcription.
Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development
Authors: Kim Yong Kyun , Refaeli Ido , Brooks Craig R. , Jing Peifeng , Gulieva Ramila E. , Hughes Michael R. , Cruz Nelly M. , Liu Yannan , Churchill Angela J. , Wang Yuliang , Fu Hongxia , Pippin Jeffrey W. , Lin Lih Y. , Shankland Stuart J. , Vogl A. Wayne , McNagny Kelly M. , Freedman Benjamin S.
Published: September 2017

A critical event during kidney organogenesis is the differentiation of podocytes, specialized epithelial cells that filter blood plasma to form urine. Podocytes derived from human pluripotent stem cells (hPSC-podocytes) have recently been generated in nephron-like kidney organoids, but the developmental stage of these cells and their capacity to reveal disease mechanisms remains unclear. Here, we show that hPSC-podocytes phenocopy mammalian podocytes at the capillary loop stage (CLS), recapitulating key features of ultrastructure, gene expression, and mutant phenotype. hPSC-podocytes in vitro progressively establish junction-rich basal membranes (nephrin+podocin+ZO-1+) and microvillus-rich apical membranes (podocalyxin+), similar to CLS podocytes in vivo. Ultrastructural, biophysical, and transcriptomic analysis of podocalyxin-knockout hPSCs and derived podocytes, generated using CRISPR/Cas9, reveals defects in the assembly of microvilli and lateral spaces between developing podocytes, resulting in failed junctional migration. These defects are phenocopied in CLS glomeruli of podocalyxin-deficient mice, which cannot produce urine, thereby demonstrating that podocalyxin has a conserved and essential role in mammalian podocyte maturation. Defining the maturity of hPSC-podocytes and their capacity to reveal and recapitulate pathophysiological mechanisms establishes a powerful framework for studying human kidney disease and regeneration.
A review on statistical postprocessing methods for hydrometeorological ensemble forecasting
Authors: Li Wentao , Duan Qingyun , Miao Chiyuan , Ye Aizhong , Gong Wei , Di Zhenhua
Published: September 2017

Computer simulation models have been widely used to generate hydrometeorological forecasts. As the raw forecasts contain uncertainties arising from various sources, including model inputs and outputs, model initial and boundary conditions, model structure, and model parameters, it is necessary to apply statistical postprocessing methods to quantify and reduce those uncertainties. Different postprocessing methods have been developed for meteorological forecasts (e.g., precipitation) and for hydrological forecasts (e.g., streamflow) due to their different statistical properties. In this paper, we conduct a comprehensive review of the commonly used statistical postprocessing methods for both meteorological and hydrological forecasts. Moreover, methods to generate ensemble members that maintain the observed spatiotemporal and intervariable dependency are reviewed. Finally, some perspectives on the further development of statistical postprocessing methods for hydrometeorological ensemble forecasting are provided.WIREs Water2017, 4:e1246. doi: 10.1002/wat2.1246

This article is categorized under:

Science of Water > Methods

Science of Water > Water Extremes
Models of convergent extension during morphogenesis
Authors: Shindo Asako
Published: September 2017

Convergent extension (CE) is a fundamental and conserved collective cell movement that forms elongated tissues during embryonic development. Thus far, studies have demonstrated two different mechanistic models of collective cell movements during CE. The first, termed the crawling mode, was discovered in the process of notochord formation in Xenopus laevis embryos, and has been the established model of CE for decades. The second model, known as the contraction mode, was originally reported in studies of germband extension in Drosophila melanogaster embryos and was recently demonstrated to be a conserved mechanism of CE among tissues and stages of development across species. This review summarizes the two modes of CE by focusing on the differences in cytoskeletal behaviors and relative expression of cell adhesion molecules. The upstream molecules regulating these machineries are also discussed. There are abundant studies of notochord formation in X. laevis embryos, as this was one of the pioneering model systems in this field. Therefore, the present review discusses these findings as an approach to the fundamental biological question of collective cell regulation. WIREs Dev Biol 2018, 7:e293. doi: 10.1002/wdev.293

This article is categorized under:

Early Embryonic Development > Gastrulation and Neurulation

Comparative Development and Evolution > Model Systems
Lead Carbodiimides Related to the Mineral Bideauxite
Authors: Dolabdjian Konstantin , Meyer Hans‐Jürgen
Published: September 2017

Solid state metathesis reactions of PbCl2 with metal carbodiimides yielded multinary lead carbodiimide chlorides APb2Cl3(CN2) (A = Li, Na, Ag). Their crystal structures strongly relate to the mineral Bideauxite [AgPb2Cl3(OH,F)2], all crystallizing in the space group Fd3m. The same crystal structure exists not only with chloride but also with bromide. Another compound obtained in this system is LiPbCl(CN2) with a crystal structure that can be considered as the result of an intercalation of LiCl into the layered structure of Pb(CN2).
Improvised Hand Injury Treatment Using Traditional Veterinary Medicine in Ethiopia
Authors: Aerts Raf , November Eva J.J. , Rayyan Maissa
Published: September 2017

In remote wilderness environments, local people with traditional knowledge of medicinal plants are potentially important first-line health care providers. We present a case of a 31-year-old man who fell off a horse while trekking through a remote mountain landscape in Ethiopia and sustained blunt force trauma to the hand. A local mountain hut keeper examined the patient’s hand and used heated leaves of the succulent plant Kalanchoe petitiana to treat a suspected metacarpal fracture. As first responder in a low-resource setting, the hut keeper relied on his traditional knowledge of ethnoveterinary medicine to improvise a treatment for a human injury in a remote mountain environment. Although in this case the outcome of the traditional intervention was positive, our analysis shows that the massage component of the intervention could have led to complications. Conversely, reports from the use of related Kalanchoe species suggest that heated Kalanchoe leaves could be useful in the compression component of traditional care for hand injuries. Validation of traditional remedies and their therapeutic potential are needed if they are to complement wilderness wound care safely and reliably. The documentation and validation of these remedies are urgently needed, as many medicinal plants and indigenous knowledge of how to use these valuable natural resources are being lost.
Algebraic disturbance growth by interaction of Orr and lift-up mechanisms
Authors: Hack M. J. Philipp , Moin Parviz
Published: September 2017

Algebraic disturbance growth in spatially developing boundary-layer flows is investigated using an optimization approach. The methodology builds on the framework of the parabolized stability equations and avoids some of the limitations associated with adjoint-based schemes. In the Blasius boundary layer, non-parallel effects are shown to significantly enhance the energy gain due to algebraic growth mechanisms. In contrast to parallel flow, the most energetic perturbations have finite frequency and are generated by the simultaneous activity of the Orr and lift-up mechanisms. The highest amplification occurs in a limited region of the parameter space that is characterized by a linear relation between the wavenumber and frequency of the disturbances. The frequency of the most highly amplified perturbations decreases with Reynolds number. Adverse streamwise pressure gradient further enhances the amplification of disturbances while preserving the linear trend between the wavenumber and frequency of the most energetic perturbations.
SIMPLE GROUPS, PRODUCT ACTIONS, AND GENERALIZED QUADRANGLES
Authors: BAMBERG JOHN , POPIEL TOMASZ , PRAEGER CHERYL E.
Published: September 2017

The classification of flag-transitive generalized quadrangles is a long-standing open problem at the interface of finite geometry and permutation group theory. Given that all known flag-transitive generalized quadrangles are also point-primitive (up to point–line duality), it is likewise natural to seek a classification of the point-primitive examples. Working toward this aim, we are led to investigate generalized quadrangles that admit a collineation group$G$preserving a Cartesian product decomposition of the set of points. It is shown that, under a generic assumption on$G$, the number of factors of such a Cartesian product can be at most four. This result is then used to treat various types of primitive and quasiprimitive point actions. In particular, it is shown that$G$cannot haveholomorph compoundO’Nan–Scott type. Our arguments also pose purely group-theoretic questions about conjugacy classes in nonabelian finite simple groups and fixities of primitive permutation groups.
‘Pathways to choice’ of care setting
Authors: HILLCOAT-NALLÉTAMBY SARAH
Published: September 2017

This article aims to encourage critical reflection about the limitations of the rational choice approach as an explanatory insight to understanding older people's choice-making about their health or social care requirements. It develops an interpretive framework examining how older people engage in the process of choice-making when selecting a care option. Choice-making is conceptualised as a temporal, processual phenomenon, influenced by others, and characterised by an individual's behavioural responses to changing circumstance and lifecourse events. Data are from qualitative interviews with 29 older adults whose choice of care option involved moving to an extra-care setting in Wales (United Kingdom). Transcripts were coded using in-case and constant-comparison approaches, and analysis was undertaken using concepts ofengagementandtemporalityas elements of the choice-making process. Using an inductive approach, a typology of six different ‘pathways to choice’ of care setting was identified; these findings suggest that choosing a care option in later life is a diverse, interactive and time-bound social phenomenon, inadequately captured by the rational choice approach where it is understood more as an individualised, linear and logical process. Recognising that choice-making evolves through time as part of a process shaped by others means service providers will be better positioned to offer opportunities for more preventative-focused interventions which empower older consumers to make planned and informed choices about care options.
Analysis of Ship Accidents in the Istanbul Strait Using Neuro-Fuzzy and Genetically Optimised Fuzzy Classifiers
Authors: Erol Sercan , Demir Mengü , Çetişli Bayram , Eyüboğlu Ekrem
Published: September 2017

Marine accident analysis is important for ships passing through narrow, shallow and busy waterways. This study analyses the accidents which have occurred in the Istanbul Strait and proposes both quantitative and qualitative assessments of marine accidents. Marine accidents occurring in the Istanbul Strait are analysed by using a method based on neuro-fuzzy and genetically optimised fuzzy classifiers. It can be concluded that accident severity increases when poor weather conditions prevail in the Strait regardless of ship size. Therefore, solutions to reduce unwanted events should be prioritised by accounting for weather conditions and the capacity of the vessels. This analysis indicates that the safety level would be significantly improved if all the vessels follow the passage guidelines.
A bridge to systems thinking in engineering design: An examination of students’ ability to identify functions at varying levels of abstraction
Authors: Tomko Megan , Nelson Jacob , Nagel Robert L. , Bohm Matthew , Linsey Julie
Published: September 2017

This paper aims to situate functional abstraction in light of systems thinking. While function does not extensively appear in systems thinking literature, the literature does identify function as part of systems thinking that enables us to recognize and connect that function has a role in building a systems thinking approach for students. A systems thinking approach is valuable for students since it helps them view a system holistically. In this research, we measure how well students are able to abstract function. We asked students to generate functions for two different products and examined how students taught functional modeling and function enumeration compare to students who are only taught function enumeration. The student responses were examined using a rubric that we developed and validated for assessing function. This rubric may be used to classify functions by correctness (correct, partially correct, and incorrect) and categories (high level, interface, low level, and ambiguous). On questions where students were not explicitly asked to write a high-level function or low-level function, and so on, students who were taught functional modeling were able to better demonstrate systems thinking in their responses (low-level and interface functions) than those students who were only taught function enumeration.
Outbreaks attributed to pork in the United States, 1998–2015
Authors: SELF J. L. , LUNA-GIERKE R. E. , FOTHERGILL A. , HOLT K. G. , VIEIRA A. R.
Published: September 2017

Each year in the United States, an estimated 525 000 infections, 2900 hospitalizations, and 82 deaths are attributed to consumption of pork. We analyzed the epidemiology of outbreaks attributed to pork in the United States reported to the Centers for Disease Control and Prevention (CDC) 1998–2015. During that period, 288 outbreaks were attributed to pork, resulting in 6372 illnesses, 443 hospitalizations, and four deaths. The frequency of outbreaks attributed to pork decreased by 37% during this period, consistent with a decline in total foodborne outbreaks. However, outbreaks attributed to pork increased by 73% in 2015 (19 outbreaks) compared with the previous 3 years (average of 11 outbreaks per year), without a similar increase in total foodborne outbreaks. Most (>99%) of these outbreaks occurred among people exposed in the same state. The most frequent etiology shifted fromStaphylococcus aureustoxin during 1998–2001 (19%) toSalmonelladuring 2012–2015 (46%). Outbreaks associated with ham decreased from eight outbreaks per year during 1998–2001, to one per year during 2012–2015 (P< 0·01). Additional efforts are necessary to reduce outbreaks and sporadic illnesses associated with pork products.
Food insecurity and emotional health in the USA: a systematic narrative review of longitudinal research
Authors: Bruening Meg , Dinour Lauren M , Chavez Jose B Rosales
Published: September 2017

Objective

To examine the causal directionality in the relationship between food insecurity and emotional well-being among US-based populations.

Design

Systematic literature review from January 2006 to July 2016 using MEDLINE (PubMed), PsychInfo, Web of Science and CINHAL. Inclusion criteria were: written in English; examined a longitudinal association between food insecurity and emotional well-being.

Setting

The USA.

Subjects

Children and adults.

Results

Twelve out of 4161 peer-reviewed articles met inclusion criteria. Three articles examined the effect of emotional well-being on food insecurity, five studies examined the effect of food insecurity on emotional well-being, and four studies examined a bidirectional relationship. Most studies (83 %) reported a positive relationship between negative emotional well-being and food insecurity over time.

Conclusions

Findings suggest a bidirectional association whereby food insecurity increases the risk of poor emotional health, and poor emotional health increases the risk of food insecurity. Better-constructed studies are needed to follow cohorts at risk for both food insecurity and poor emotional health to further understand the mediators and moderators of the relationships. Intervention studies designed to mitigate or reverse risks are also needed to determine best evidence for practice and policy.
Beyond the dinner table: who’s having breakfast, lunch and dinner family meals and which meals are associated with better diet quality and BMI in pre-school children?
Authors: Berge Jerica M , Truesdale Kimberly P , Sherwood Nancy E , Mitchell Nathan , Heerman William J , Barkin Shari , Matheson Donna , Levers-Landis Carolyn E , French Simone A
Published: September 2017

Objective

Having frequent family dinners is associated with better diet quality in children; however, it is unknown whether the frequency of certain family meal types (i.e. dinner) is more strongly associated with better child weight and diet quality compared with other meal types (i.e. breakfast, lunch). Thus, the current study examined the frequency of eating breakfast, lunch or dinner family meals and associations with pre-school children’s overall diet quality (HEI-2010) and BMI percentile.

Design

Cross-sectional baseline data (2012–2014) from two randomized controlled childhood obesity prevention trials, NET-Works and GROW, were analysed together.

Setting

Studies were carried out in community and in-home settings in urban areas of Minnesota and Tennessee, USA.

Subjects

Parent–child (ages 2–5 years) pairs from Minnesota (n 222 non-Hispanics; n 312 Hispanics) and Tennessee (n 545 Hispanics; n 55 non-Hispanics) participated in the study.

Results

Over 80 % of families ate breakfast or lunch family meals at least once per week. Over 65 % of families ate dinner family meals ≥5 times/week. Frequency of breakfast family meals and total weekly family meals were significantly associated with healthier diet quality for non-Hispanic pre-school children (P<0·05), but not for Hispanic children. Family meal frequency by meal type was not associated with BMI percentile for non-Hispanic or Hispanic pre-school children.

Conclusions

Breakfast family meal frequency and total weekly family meal frequency were associated with healthier diet quality in non-Hispanic pre-school children but not in Hispanic children. Longitudinal research is needed to clarify the association between family meal type and child diet quality and BMI percentile.
We Spend How Much? Misperceptions, Innumeracy, and Support for the Foreign Aid in the United States and Great Britain
Authors: Scotto Thomas J. , Reifler Jason , Hudson David , vanHeerde-Hudson Jennifer
Published: September 2017

Majorities of citizens in high-income countries often oppose foreign aid spending. One popular explanation is that the public overestimates the percentage and amount of taxpayer funds that goes toward overseas aid. Does expressing aid flows in dollar and/or percentage terms shift public opinion toward aid? We report the results of an experiment examining differences in support for aid spending as a function of the information American and British respondents receive about foreign aid spending. In both nations, providing respondents with information about foreign aid spending as a percentage of the national budget significantly reduces support for cuts. The findings suggest that support for aid can be increased, but significant opposition to aid spending remains.
Novel chimeric transcript RRM2-c2orf48 promotes metastasis in nasopharyngeal carcinoma
Authors: Han Ping , Chen Ren-Hui , Wang Fang , Zeng Jia-Yi , Yu Shi-Tong , Xu Li-Hua , Cai Qian , Liang Fa-Ya , Xia Tian-Liang , Lin Zhi-Rui , Zhong Qian , Huang Xiao-Ming
Published: September 2017

Recently, chimeric transcripts have been found to be associated with the pathogenesis and poor prognosis of malignant tumors. Through our preliminary experiment, a novel chimeric transcript called chimeric transcript RRM2-c2orf48 was detected in C666-1, a classical cell line of human nasopharyngeal carcinoma (NPC). Therefore, the objective of this study was to demonstrate the existence and expression of novel chimeric transcript RRM2-c2orf48 and to explore the main functions and mechanisms of RRM2-c2orf48 in NPC. In this study, the expression of RRM2-c2orf48 was evaluated in NPC cells and specimens. Effects of RRM2-c2orf48 on migration and invasive capacities were detected invivo and vitro. Moreover, ways in which RRM2-c2orf48 increases the invasive capacities of NPC were explored. As a result, the presence of novel chimeric transcript RRM2-c2orf48 was confirmed in C666-1 by RT-PCR and sequencing, and it was a read-through between RRM2 and c2orf48 through the transcription of interchromosome. Higher expressions of novel RRM2-c2orf48 were detected in NPC cell lines and NPC tissue specimens relative to the controls and its expression was be statistically relevant to TNM staging. High level of RRM2-c2orf48 could increase the migration and invasive capacities of NPC cells, potentially as a result of NPC cell epithelial–mesenchymal transition. RRM2-c2orf48 could also enhance resistance of chemotherapy. In vivo, RRM2-c2orf48 could enhance lung and lymph node metastasis in nude mice. These results demonstrate that high levels of RRM2-c2orf48 expression may be a useful predictor of NPC patients of metastatic potency, presenting potential implications for NPC diagnosis and therapy.
Small-molecule RL71-triggered excessive autophagic cell death as a potential therapeutic strategy in triple-negative breast cancer
Authors: Gao Jian , Fan Minmin , Peng Shuang , Zhang Minxia , Xiang Gang , Li Xin , Guo Wenjie , Sun Yang , Wu Xuefeng , Wu Xudong , Liang Guang , Shen Yan , Xu Qiang
Published: September 2017

Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca2+ from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity. The disruption of calcium homeostasis induced ER stress, leading to apoptosis. More importantly, the elevated intracellular calcium signals induced autophagy through the activation of the CaMKK-AMPK-mTOR pathway and mitochondrial damage. In two TNBC xenograft mouse models, RL71 also displayed strong efficacy including the inhibition of tumor growth, the reduction of metastasis, as well as the prolongation of survival time. These findings suggest SERCA2 as a previous unknown target candidate for TNBC treatment and support the idea that autophagy inducers could be useful as new therapeutics in TNBC treatment.
Ti(Oi-Pr)4-promoted photoenolization Diels–Alder reaction to construct polycyclic rings and its synthetic applications
Authors: Yang Baochao , Lin Kuaikuai , Shi Yingbo , Gao Shuanhu
Published: September 2017

Stereoselective construction of polycyclic rings with all-carbon quaternary centers, and vicinal all-carbon quaternary stereocenters, remains a significant challenge in organic synthesis. These structures can be found in a wide range of polycyclic natural products and drug molecules. Here we report a Ti(Oi-Pr)4-promoted photoenolization/Diels–Alder (PEDA) reaction to construct hydroanthracenol and related polycyclic rings bearing all-carbon quaternary centers. This photolysis proceeds under mild conditions and generates a variety of photo-cycloaddition products in good reaction efficiency and stereoselectivity (48 examples), and has been successfully used in the construction of core skeleton of oncocalyxones, tetracycline and pleurotin. It also provides a reliable method for the late-stage modification of natural products bearing enone groups, such as steroids. The total synthesis of oncocalyxone B was successfully achieved using this PEDA approach.
Silicate dissolution boosts the CO2 concentrations in subduction fluids
Authors: Tumiati S. , Tiraboschi C. , Sverjensky D. A. , Pettke T. , Recchia S. , Ulmer P. , Miozzi F. , Poli S.
Published: September 2017

Estimates of dissolved CO2 in subduction-zone fluids are based on thermodynamic models, relying on a very sparse experimental data base. Here, we present experimental data at 1–3 GPa, 800 °C, and ∆FMQ ≈ −0.5 for the volatiles and solute contents of graphite-saturated fluids in the systems COH, SiO2–COH ( + quartz/coesite) and MgO–SiO2–COH ( + forsterite and enstatite). The CO2 content of fluids interacting with silicates exceeds the amounts measured in the pure COH system by up to 30 mol%, as a consequence of a decrease in water activity probably associated with the formation of organic complexes containing Si–O–C and Si–O–Mg bonds. The interaction of deep aqueous fluids with silicates is a novel mechanism for controlling the composition of subduction COH fluids, promoting the deep CO2 transfer from the slab–mantle interface to the overlying mantle wedge, in particular where fluids are stable over melts.
Measuring the effects of particle orientation to improve the efficiency of electron cryomicroscopy
Authors: Naydenova Katerina , Russo Christopher J.
Published: September 2017

The orientation distribution of a single-particle electron cryomicroscopy specimen limits the resolution of the reconstructed density map. Here we define a statistical quantity, the efficiency, Eod, which characterises the orientation distribution via its corresponding point spread function. The efficiency measures the ability of the distribution to provide uniform information and resolution in all directions of the reconstruction, independent of other factors. This metric allows rapid and rigorous evaluation of specimen preparation methods, assisting structure determination to high resolution with minimal data.
Inhibition of PDE2 reverses beta amyloid induced memory impairment through regulation of PKA/PKG-dependent neuro-inflammatory and apoptotic pathways
Authors: Wang Li , Xiaokaiti Yilixiati , Wang Gang , Xu Xiaoxiao , Chen Ling , Huang Xianfeng , Liu Li , Pan Jianchun , Hu Shuqun , Chen Zhuoyou , Xu Ying
Published: September 2017

Beta amyloid peptides (Aβ) are known risk factors involved in cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer’s disease (AD). Phosphodiesterase 2 (PDE2) inhibitors increase the intracellular cAMP and/or cGMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE2 mediated neuroapoptotic and neuroinflammatory events, as well as cognitive performance in AD are related to cAMP/cGMP-dependent pathways. The present study investigated how the selective PDE2 inhibitor BAY60-7550 (BAY) affected Aβ-induced learning and memory impairment in two classic rodent models. IL-22 and IL-17, Bax and Bcl-2, PKA/PKG and the brain derived neurotropic factor (BDNF) levels in hippocampus and cortex were detected with immunoblotting assay. The results showed that BAY reversed Aβ-induced cognitive impairment as shown in the water maze test and step-down test. Moreover, BAY treatment reversed the Aβ-induced changes in IL-22 and IL-17 and the ratio of Bax/Bcl-2. Changes in cAMP/cGMP levels, PKA/PKG and BDNF expression were also prevented by BAY. These effects of BAY on memory performance and related neurochemical changes were partially blocked by the PKG inhibitor KT 5823. These findings indicated that the protective effects of BAY against Aβ-induced memory deficits might involve the regulation of neuroinflammation and neuronal apoptotic events.
Unveiling the signals from extremely noisy microseismic data for high-resolution hydraulic fracturing monitoring
Authors: Huang Weilin , Wang Runqiu , Li Huijian , Chen Yangkang
Published: September 2017

Microseismic method is an essential technique for monitoring the dynamic status of hydraulic fracturing during the development of unconventional reservoirs. However, one of the challenges in microseismic monitoring is that those seismic signals generated from micro seismicity have extremely low amplitude. We develop a methodology to unveil the signals that are smeared in the strong ambient noise and thus facilitate a more accurate arrival-time picking that will ultimately improve the localization accuracy. In the proposed technique, we decompose the recorded data into several morphological multi-scale components. In order to unveil weak signal, we propose an orthogonalization operator which acts as a time-varying weighting in the morphological reconstruction. The orthogonalization operator is obtained using an inversion process. This orthogonalized morphological reconstruction can be interpreted as a projection of the higher-dimensional vector. We first test the proposed technique using a synthetic dataset. Then the proposed technique is applied to a field dataset recorded in a project in China, in which the signals induced from hydraulic fracturing are recorded by twelve three-component (3-C) geophones in a monitoring well. The result demonstrates that the orthogonalized morphological reconstruction can make the extremely weak microseismic signals detectable.
Boosted Regeneration and Reduced Denervated Muscle Atrophy by NeuroHeal in a Pre-clinical Model of Lumbar Root Avulsion with Delayed Reimplantation
Authors: Romeo-Guitart David , Forés Joaquim , Navarro Xavier , Casas Caty
Published: September 2017

The “gold standard” treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.
Cerebellar anatomical alterations and attention to eyes in autism
Authors: Laidi Charles , Boisgontier Jennifer , Chakravarty M. Mallar , Hotier Sevan , d’Albis Marc-Antoine , Mangin Jean-François , Devenyi Gabriel A. , Delorme Richard , Bolognani Federico , Czech Christian , Bouquet Céline , Toledano Elie , Bouvard Manuel , Gras Doriane , Petit Julie , Mishchenko Marina , Gaman Alexandru , Scheid Isabelle , Leboyer Marion , Zalla Tiziana , Houenou Josselin
Published: September 2017

The cerebellum is implicated in social cognition and is likely to be involved in the pathophysiology of autism spectrum disorder (ASD). The goal of our study was to explore cerebellar morphology in adults with ASD and its relationship to eye contact, as measured by fixation time allocated on the eye region using an eye-tracking device. Two-hundred ninety-four subjects with ASD and controls were included in our study and underwent a structural magnetic resonance imaging scan. Global segmentation and cortical parcellation of the cerebellum were performed. A sub-sample of 59 subjects underwent an eye tracking protocol in order to measure the fixation time allocated to the eye region. We did not observe any difference in global cerebellar volumes between ASD patients and controls; however, regional analyses found a decrease of the volume of the right anterior cerebellum in subjects with ASD compared to controls. There were significant correlations between fixation time on eyes and the volumes of the vermis and Crus I. Our results suggest that cerebellar morphology may be related to eye avoidance and reduced social attention. Eye tracking may be a promising neuro-anatomically based stratifying biomarker of ASD.
Identification and correction of spatial bias are essential for obtaining quality data in high-throughput screening technologies
Authors: Mazoure Bogdan , Nadon Robert , Makarenkov Vladimir
Published: September 2017

Spatial bias continues to be a major challenge in high-throughput screening technologies. Its successful detection and elimination are critical for identifying the most promising drug candidates. Here, we examine experimental small molecule assays from the popular ChemBank database and show that screening data are widely affected by both assay-specific and plate-specific spatial biases. Importantly, the bias affecting screening data can fit an additive or multiplicative model. We show that the use of appropriate statistical methods is essential for improving the quality of experimental screening data. The presented methodology can be recommended for the analysis of current and next-generation screening data.
Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis
Authors: Chun Haarin , Catterton Tracy , Kim Heejeong , Lee Jaekwon , Kim Byung-Eun
Published: September 2017

Copper (Cu) is an essential cofactor for various enzymatic activities including mitochondrial electron transport, iron mobilization, and peptide hormone maturation. Consequently, Cu dysregulation is associated with fatal neonatal disease, liver and cardiac dysfunction, and anemia. While the Cu transporter ATP7A plays a major role in both intestinal Cu mobilization to the periphery and prevention of Cu over-accumulation, it is unclear how regulation of ATP7A contributes to Cu homeostasis in response to systemic Cu fluctuation. Here we show, using Cu-deficient mouse models, that steady-state levels of ATP7A are lower in peripheral tissues (including the heart, spleen, and liver) under Cu deficiency and that subcutaneous administration of Cu to these animals restore normal ATP7A levels in these tissues. Strikingly, ATP7A in the intestine is regulated in the opposite manner - low systemic Cu increases ATP7A while subcutaneous Cu administration decreases ATP7A suggesting that intestine-specific non-autonomous regulation of ATP7A abundance may serve as a key homeostatic control for Cu export into the circulation. Our results support a systemic model for how a single transporter can be inversely regulated in a tissue-specific manner to maintain organismal Cu homeostasis.
Bite force in the horned frog (Ceratophrys cranwelli) with implications for extinct giant frogs
Authors: Lappin A. Kristopher , Wilcox Sean C. , Moriarty David J. , Stoeppler Stephanie A. R. , Evans Susan E. , Jones Marc E. H.
Published: September 2017

Of the nearly 6,800 extant frog species, most have weak jaws that play only a minor role in prey capture. South American horned frogs (Ceratophrys) are a notable exception. Aggressive and able to consume vertebrates their own size, these “hopping heads” use a vice-like grip of their jaws to restrain and immobilize prey. Using a longitudinal experimental design, we quantified the ontogenetic profile of bite-force performance in post-metamorphic Ceratophrys cranwelli. Regression slopes indicate positive allometric scaling of bite force with reference to head and body size, results that concur with scaling patterns across a diversity of taxa, including fish and amniotes (lizards, tuatara, turtles, crocodylians, rodents). Our recovered scaling relationship suggests that exceptionally large individuals of a congener (C. aurita) and extinct giant frogs (Beelzebufo ampinga, Late Cretaceous of Madagascar) probably could bite with forces of 500 to 2200 N, comparable to medium to large-sized mammalian carnivores.
Matching DMFT calculations with photoemission spectra of heavy fermion insulators: universal properties of the near-gap spectra of SmB6
Authors: Min Chul-Hee , Goth F. , Lutz P. , Bentmann H. , Kang B. Y. , Cho B. K. , Werner J. , Chen K.-S. , Assaad F. , Reinert F.
Published: September 2017

Paramagnetic heavy fermion insulators consist of fully occupied quasiparticle bands inherent to Fermi liquid theory. The gap emergence below a characteristic temperature is the ultimate sign of coherence for a many-body system, which in addition can induce a non-trivial band topology. Here, we demonstrate a simple and efficient method to compare a model study and an experimental result for heavy fermion insulators. The temperature dependence of the gap formation in both local moment and mixed valence regimes is captured within the dynamical mean field (DMFT) approximation to the periodic Anderson model (PAM). Using the topological coherence temperature as the scaling factor and choosing the input parameter set within the mixed valence regime, we can unambiguously link the theoretical energy scales to the experimental ones. As a particularly important result, we find improved consistency between the scaled DMFT density of states and the photoemission near-gap spectra of samarium hexaboride (SmB6).
Secular trends in overweight and obesity among urban children and adolescents, 2003–2012: A serial cross-sectional study in Guangzhou, China
Authors: Zong Yinan , Xie Runsheng , Deng Nali , Liu Li , Tan Weiqing , Gao Yanhui , Yang Jiewen , Yang Yi
Published: September 2017

Childhood and adolescent overweight and obesity are increasing in China, but limited information is available on its secular trends in Guangzhou. In this cross-sectional study, ten-wave successive data were obtained from the physical fitness surveillance for students in Guangzhou from 2003 to 2012. A total of 2,619,154 urban students aged 7–18 years were included. The age-standardized prevalence of overweight and obesity increased significantly over the period: overweight rose from 10.15% to 14.07% in boys and 6.39% to 8.11% in girls, while obesity increased from 5.65% to 8.31% for boys and 3.43% to 4.12% for girls, respectively (P < 0.05). The increasing trend was significant across almost all age-sex-specific groups (P < 0.05), especially in the last five years. The prevalence of overweight and obesity grew continuously in both sexes, but the pace of change for boys were faster than that for girls. The highest prevalence of overweight was found among 10- to 12-year-old boys, that of obesity among 7- to 9-year-old boys and girls. In conclusion, overweight and obesity have increased significantly among urban children and adolescents in Guangzhou during 2003–2012. Further analysis of influencing factors and comprehensive interventions are urgently needed to combat the obesity epidemic among urban children and adolescents in Guangzhou.
Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
Authors: Huang Lizhen , Zhang Kailiang , Guo Yingying , Huang Fengyuan , Yang Kevin , Chen Long , Huang Kai , Zhang Fengxue , Long Qinqiang , Yang Qinglin
Published: September 2017

Honokiol is a key component of a medicinal herb, Magnolia bark. Honokiol possesses potential pharmacological benefits for many disease conditions, especially cancer. Recent studies demonstrate that Honokiol exerts beneficial effects on cardiac hypertrophy and doxorubicin (Dox)-cardiotoxicity via deacetylation of mitochondrial proteins. However, the effects and mechanisms of Honokiol on cardiac mitochondrial respiration remain unclear. In the present study, we investigate the effect of Honokiol on cardiac mitochondrial respiration in mice subjected to Dox treatment. Oxygen consumption in freshly isolated mitochondria from mice treated with Honokiol showed enhanced mitochondrial respiration. The Dox-induced impairment of mitochondrial respiration was less pronounced in honokiol-treated than control mice. Furthermore, Luciferase reporter assay reveals that Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat cardiomyocytes (H9c2). Honokiol upregulated the expression of PPARγ in the mouse heart. Honokiol repressed cardiac inflammatory responses and oxidative stress in mice subjected to Dox treatment. As a result, Honokiol alleviated Dox-cardiotoxicity with improved cardiac function and reduced cardiomyocyte apoptosis. We conclude that Honokiol protects the heart from Dox-cardiotoxicity via improving mitochondrial function by not only repressing mitochondrial protein acetylation but also enhancing PPARγ activity in the heart. This study further supports Honokiol as a promising therapy for cancer patients receiving Dox treatment.