bluuebunny/crossref_metadata_2025 huggingface dataset:
How Important Are Model Structural and Contextual Uncertainties when Estimating the Optimized Performance of Water Resource Systems?
Authors: Dobson Barnaby , Wagener Thorsten , Pianosi Francesca
Published: February 2019

Uncertainty in simulating water resource systems (WRSs) makes it difficult to assess how effective different water management decisions will be. Uncertainty in simulation models can undermine the credibility of simulation and optimization studies and the uptake of their results. We identify different sources of uncertainty in WRS models and find that structural uncertainty (i.e., around definition of interrelationships within the system) and contextual uncertainty (i.e., around definition of the system boundaries) are rarely considered when simulating and optimizing WRSs. We propose a methodology to quantify the effects of structural and contextual uncertainties on the estimated performance of optimized water management decisions and demonstrate that they have a significant impact on a real‐world case study of a pumped‐storage system in the UK. To the best of the authors' knowledge, this is the first study to consider the impact of these types of uncertainty on optimized operating policies and their simulated performances. Our main finding is that of all the considered uncertainties, the assumptions made about context—specifically around the level of cooperation between neighboring water companies—had the greatest impact on performance estimates. This is important because few WRSs exist in isolation, yet discussion of the effects that a given definition of the system boundaries have on the simulation/optimization results is uncommon. We also highlight the significance of adequately considering aleatory uncertainty when evaluating performance estimates—something that few studies do—and present a simple technique to justify the sample size used for the evaluation of optimization results.
System Modeling, Optimization, and Analysis of Recycled Water and Dynamic Storm Water Deliveries to Spreading Basins for Urban Groundwater Recharge
Authors: Bradshaw Jonathan L. , Osorio Mauricio , Schmitt Theo G. , Luthy Richard G.
Published: February 2019

To bolster freshwater supplies, water managers are increasingly interested in recharging groundwater using storm water and recycled water. However, such multisupply groundwater recharge projects are hindered by the lack of planning tools to evaluate system design costs and trade‐offs. This study presents modeling advancements that provide enhanced insights into multisupply spreading basin systems (i.e., spreading basins that accommodate both advanced treated recycled water and dynamically available storm water), a form of managed aquifer recharge. The model identifies system designs that optimize infrastructure life cycle cost and water volumes infiltrated for groundwater recharge. To illustrate the model's application under realistic conditions, we present a case study of Los Angeles, California. In this case study, we find that competition between storm water and recycled water for spreading basin use is relatively minor. Moreover, compared to systems based on existing conservative assumptions, our methods identify optimal dynamic system designs that are 5%–20% more cost‐effective, primarily resulting from higher water recycling facility utilization. Overall, this approach, which considers the dynamic nature of storm water availability and variable recycled water production, can inform water planners of the cost, water volume, and energy trade‐offs associated with different multisupply spreading basin system designs, including varying levels of centralization.
A negative feedback loop between XBP1 and Fbw7 regulates cancer development
Authors: Chae Unbin , Lee Heejin , Kim Bokyung , Jung Haiyoung , Kim Byeong Mo , Lee Ann- Hwee , Lee Dong-Seok , Min Sang-Hyun
Published: February 2019

In cancer, activation of X-box binding protein (XBP1) has a critical role in tumorigenesis and cancer progression. Transcriptional regulatory mechanism of XBP1 in cancer development has been well known, however, regulation of ubiquitination and degradation of XBP1 has not been elucidated yet. Here we show that Fbw7, a substrate recognition component of the SKP1-Cullin-F-box-type E3 ligase, interacts with XBP1 in a phosphorylation-dependent manner, and facilitates XBP1 ubiquitination and protein degradation. Moreover, Fbw7 inhibits oncogenic pathways including NF-κB, AP1, and Myc induced by XBP1. Interestingly, XBP1 negatively regulates transcription of Fbw7 via a feedback mechanism through NF-κB/E2F-1 axis signaling pathway, suggesting that overexpression of XBP1s may contribute to low level of Fbw7 expression in human cancers. Therefore, a negative feedback loop between Fbw7 and XBP1 contributes to the regulation of tumor development and can be an attractive target for novel therapy in cancers.
An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance
Authors: Li Ningning , Babaei-Jadidi Roya , Lorenzi Federica , Spencer-Dene Bradley , Clarke Philip , Domingo Enric , Tulchinsky Eugene , Vries Robert G. J. , Kerr David , Pan Yihang , He Yulong , Bates David O. , Tomlinson Ian , Clevers Hans , Nateri Abdolrahman S.
Published: February 2019

Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial–mesenchymal transition (EMT) process. Currently, it remains poorly understood how EMT programmes enable CSCs residing in the tumour microenvironment to escape the effects of chemotherapy. This study identifies a key molecular pathway that is responsible for the formation of drug-resistant CSC populations. Using a modified yeast-2-hybrid system and 2D gel-based proteomics methods, we show that the E3-ubiquitin ligase FBXW7 directly binds and degrades the EMT-inducing transcription factor ZEB2 in a phosphorylation-dependent manner. Loss of FBXW7 induces an EMT that can be effectively reversed by knockdown of ZEB2. The FBXW7-ZEB2 axis regulates such important cancer cell features, as stemness/dedifferentiation, chemoresistance and cell migration in vitro, ex vivo and in animal models of metastasis. High expression of ZEB2 in cancer tissues defines the reduced ZEB2 expression in the cancer-associated stroma in patients and in murine intestinal organoids, demonstrating a tumour-stromal crosstalk that modulates a niche and EMT activation. Our study thus uncovers a new molecular mechanism, by which the CRC cells display differences in resistance to chemotherapy and metastatic potential.
Stereoselective synthesis of sulfur-containing β-enaminonitrile derivatives through electrochemical Csp3–H bond oxidative functionalization of acetonitrile
Authors: He Tian-Jun , Ye Zongren , Ke Zhuofeng , Huang Jing-Mei
Published: February 2019

Incorporation of nitrile groups into fine chemicals is of particular interest through C(sp3)–H bonds activation of alkyl nitriles in the synthetic chemistry due to the highly efficient atom economy. However, the direct α-functionalization of alkyl nitriles is usually limited to its enolate chemistry. Here we report an electro-oxidative C(sp3)–H bond functionalization of acetonitrile with aromatic/aliphatic mercaptans for the synthesis of sulfur-containing β-enaminonitrile derivatives. These tetrasubstituted olefin products are stereoselectively synthesized and the stereoselectivity is enhanced in the presence of a phosphine oxide catalyst. With iodide as a redox catalyst, activation of C(sp3)–H bond to produce cyanomethyl radicals proceeds smoothly at a decreased anodic potential, and thus highly chemoselective formation of C–S bonds and enamines is achieved. Importantly, the process is carried out at ambient temperature and can be easily scaled up.
Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2
Authors: Dong Jiangqing , Du Ximing , Wang Huan , Wang Jue , Lu Chang , Chen Xiang , Zhu Zhiwen , Luo Zhipu , Yu Li , Brown Andrew J. , Yang Hongyuan , Wu Jia-Wei
Published: February 2019

Phosphatidylinositol phosphates (PIPs) and cholesterol are known to regulate the function of late endosomes and lysosomes (LELs), and ORP1L specifically localizes to LELs. Here, we show in vitro that ORP1 is a PI(4,5)P2- or PI(3,4)P2-dependent cholesterol transporter, but cannot transport any PIPs. In cells, both ORP1L and PI(3,4)P2are required for the efficient removal of cholesterol from LELs. Structures of the lipid-binding domain of ORP1 (ORP1-ORD) in complex with cholesterol or PI(4,5)P2display open conformations essential for ORP function. PI(4,5)P2/PI(3,4)P2can facilitate ORP1-mediated cholesterol transport by promoting membrane targeting and cholesterol extraction. Thus, our work unveils a distinct mechanism by which PIPs may allosterically enhance OSBP/ORPs-mediated transport of major lipid species such as cholesterol.
Path integration maintains spatial periodicity of grid cell firing in a 1D circular track
Authors: Jacob Pierre-Yves , Capitano Fabrizio , Poucet Bruno , Save Etienne , Sargolini Francesca
Published: February 2019

Entorhinal grid cells are thought to provide a 2D spatial metric of the environment. In this study we demonstrate that in a familiar 1D circular track (i.e., a continuous space) grid cells display a novel 1D equidistant firing pattern based on integrated distance rather than travelled distance or time. In addition, field spacing is increased compared to a 2D open field, probably due to a reduced access to the visual cue in the track. This metrical modification is accompanied by a change in LFP theta oscillations, but no change in intrinsic grid cell rhythmicity, or firing activity of entorhinal speed and head-direction cells. These results suggest that in a 1D circular space grid cell spatial selectivity is shaped by path integration processes, while grid scale relies on external information.
Decoding the 5′ nucleotide bias of PIWI-interacting RNAs
Authors: Stein Chad B. , Genzor Pavol , Mitra Sanga , Elchert Alexandra R. , Ipsaro Jonathan J. , Benner Leif , Sobti Sushil , Su Yijun , Hammell Molly , Joshua-Tor Leemor , Haase Astrid D.
Published: February 2019

PIWI-interacting RNAs (piRNAs) are at the center of a small RNA-based immune system that defends genomes against the deleterious action of mobile genetic elements (transposons). PiRNAs are highly variable in sequence with extensive targeting potential. Their diversity is restricted by their preference to start with a Uridine (U) at the 5′ most position (1U-bias), a bias that remains poorly understood. Here we uncover that the 1U-bias of Piwi-piRNAs is established by consecutive discrimination against all nucleotides but U, first during piRNA biogenesis and then upon interaction with Piwi’s specificity loop. Sequence preferences during piRNA processing also restrict U across the piRNA body with the potential to directly impact target recognition. Overall, the uncovered signatures could modulate specificity and efficacy of piRNA-mediated transposon restriction, and provide a substrate for purifying selection in the ongoing arms race between genomes and their mobile parasites.
High performance n-type Ag2Se film on nylon membrane for flexible thermoelectric power generator
Authors: Ding Yufei , Qiu Yang , Cai Kefeng , Yao Qin , Chen Song , Chen Lidong , He Jiaqing
Published: February 2019

Researches on flexible thermoelectric materials usually focus on conducting polymers and conducting polymer-based composites; however, it is a great challenge to obtain high thermoelectric properties comparable to inorganic counterparts. Here, we report an n-type Ag2Se film on flexible nylon membrane with an ultrahigh power factor ~987.4 ± 104.1 μWm−1K−2 at 300 K and an excellent flexibility (93% of the original electrical conductivity retention after 1000 bending cycles around a 8-mm diameter rod). The flexibility is attributed to a synergetic effect of the nylon membrane and the Ag2Se film intertwined with numerous high-aspect-ratio Ag2Se grains. A thermoelectric prototype composed of 4-leg of the Ag2Se film generates a voltage and a maximum power of 18 mV and 460 nW, respectively, at a temperature difference of 30 K. This work opens opportunities of searching for high performance thermoelectric film for flexible thermoelectric devices.
Publisher Correction: Online photochemical derivatization enables comprehensive mass spectrometric analysis of unsaturated phospholipid isomers
Authors: Zhang Wenpeng , Zhang Donghui , Chen Qinhua , Wu Junhan , Ouyang Zheng , Xia Yu
Published: February 2019

The original version of this Article contained an error in Fig. 2f, in which the phospholipid was incorrectly labelled ‘PE’ rather than the correct ‘PC’. This has now been corrected in the PDF and HTML versions of the Article.
Insight of Captagon Abuse by Chemogenomics Knowledgebase-guided Systems Pharmacology Target Mapping Analyses
Authors: Wu Nan , Feng Zhiwei , He Xibing , Kwon William , Wang Junmei , Xie Xiang-Qun
Published: February 2019

Captagon, known by its genetic name Fenethylline, is an addictive drug that complicates the War on Drugs. Captagon has a strong CNS stimulating effect than its primary metabolite, Amphetamine. However, multi-targets issues associated with the drug and metabolites as well as its underlying mechanisms have not been fully defined. In the present work, we applied our established drug-abuse chemogenomics-knowledgebase systems pharmacology approach to conduct targets/off-targets mapping (SP-Targets) investigation of Captagon and its metabolites for hallucination addiction, and also analyzed the cell signaling pathways for both Amphetamine and Theophylline with data mining of available literature. Of note, Amphetamine, an agonist for trace amine-associated receptor 1 (TAAR1) with enhancing dopamine signaling (increase of irritability, aggression, etc.), is the main cause of Captagon addiction; Theophylline, an antagonist that blocks adenosine receptors (e.g. A2aR) in the brain responsible for restlessness and painlessness, may attenuate the behavioral sensitization caused by Amphetamine. We uncovered that Theophylline’s metabolism and elimination could be retarded due to competition and/or blockage of the CYP2D6 enzyme by Amphetamine; We also found that the synergies between these two metabolites cause Captagon’s psychoactive effects to act faster and far more potently than those of Amphetamine alone. We carried out further molecular docking modeling and molecular dynamics simulation to explore the molecular interactions between Amphetamine and Theophylline and their important GPCRs targets, including TAAR1 and adenosine receptors. All of the systems pharmacology analyses and results will shed light insight into a better understanding of Captagon addiction and future drug abuse prevention.
The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer
Authors: Banys-Paluchowski Malgorzata , Witzel Isabell , Aktas Bahriye , Fasching Peter A. , Hartkopf Andreas , Janni Wolfgang , Kasimir-Bauer Sabine , Pantel Klaus , Schön Gerhard , Rack Brigitte , Riethdorf Sabine , Solomayer Erich-Franz , Fehm Tanja , Müller Volkmar
Published: February 2019

In breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5–10.5 months] vs. not reached, p < 0.001; PFS: 4.8 [95%-CI: 3.1–6.5] vs. 9.1 [7.4–10.8] months, p < 0.001). In multivariate analysis, elevated uPA, presence of ≥5 CTCs, elevated RAS p21, higher grading and higher line of therapy were independent predictors of shorter OS, while elevated CTC counts, higher line of therapy and negative estrogen receptor status were independent predictors of shorter PFS. In conclusion, elevated uPA levels independently predict reduced overall survival and improved prognostication in patients with known CTC status. Whether high serum uPA might identify patients most likely to benefit from therapies targeting uPA, remains to be evaluated in future trials.
Protective effects of fermented goat milk on genomic stability, oxidative stress and inflammatory signalling in testis during anaemia recovery
Authors: Moreno-Fernandez Jorge , Alférez María J. M. , López-Aliaga Inmaculada , Diaz-Castro Javier
Published: February 2019

Oxidative stress is a harmful factor for male reproductive function, and a major cause of infertility. On the other hand, fermented goat milk has positive effects on anemia recovery and mineral metabolism. This study evaluated the effect of feeding rats with fermented milks during anaemia recovery on molecular mechanisms linked to oxidative stress and inflammatory signalling in rats reproductive system. Forty male Wistar rats were placed on a pre-experimental period of 40 days (control group, receiving normal-Fe diet and Fe-deficient group, receiving low-Fe diet). Lately, rats were fed with fermented goat or cow milk-based diets during 30 days. After feeding the fermented milks, Total antioxidant status (TAS) and non-esterified fatty acids (NEFA) increased and 8-hydroxy-2’-deoxyguanosine (8-OHdG), 15-F2t-isoprostanes and thiobarbituric acid reactive substances (TBARS) decreased in testis. DNA oxidative damage in testis germ cells was lower with fermented goat milk. Fermented goat milk reduced IL-6 and TNF-α in control animals, increasing INF-γ in control and anaemic rats. NRF2 and PGC-1α protein levels increased in testis after fermented goat milk consumption in control and anaemic rats. Fermented goat milk also increased TAS and decreased oxidative damage, protecting the main testis cell bioconstituents (lipids, proteins, DNA, prostaglandins) from oxidative damage and reduced inflammatory activity, preventing injuries to testis germinal epithelium. Fermented goat milk enhanced lipolysis, fatty acids degradation and immune response, attenuating inflammatory signalling, representing a positive growth advantage for testicular cells.
Influence of rewetting on microbial communities involved in nitrification and denitrification in a grassland soil after a prolonged drought period
Authors: Hammerl Verena , Kastl Eva-Maria , Schloter Michael , Kublik Susanne , Schmidt Holger , Welzl Gerhard , Jentsch Anke , Beierkuhnlein Carl , Gschwendtner Silvia
Published: February 2019

The frequency of extreme drought and heavy rain events during the vegetation period will increase in Central Europe according to future climate change scenarios, which will affect the functioning of terrestrial ecosystems in multiple ways. In this study, we simulated an extreme drought event (40 days) at two different vegetation periods (spring and summer) to investigate season-related effects of drought and subsequent rewetting on nitrifiers and denitrifiers in a grassland soil. Abundance of the microbial groups of interest was assessed by quantification of functional genes (amoA, nirS/nirK and nosZ) via quantitative real-time PCR. Additionally, the diversity of ammonia-oxidizing archaea was determined based on fingerprinting of the archaeal amoA gene. Overall, the different time points of simulated drought and rewetting strongly influenced the obtained response pattern of microbial communities involved in N turnover as well as soil ammonium and nitrate dynamics. In spring, gene abundance of nirS was irreversible reduced after drought whereas nirK and nosZ remained unaffected. Furthermore, community composition of ammonia-oxidizing archaea was altered by subsequent rewetting although amoA gene abundance remained constant. In contrast, no drought/rewetting effects on functional gene abundance or diversity pattern of nitrifying archaea were observed in summer. Our results showed (I) high seasonal dependency of microbial community responses to extreme events, indicating a strong influence of plant-derived factors like vegetation stage and plant community composition and consequently close plant-microbe interactions and (II) remarkable resistance and/or resilience of functional microbial groups involved in nitrogen cycling to extreme weather events what might indicate that microbes in a silty soil are better adapted to stress situations as expected.
Metabolomics reveals citric acid secretion in mechanically–stimulated osteocytes is inhibited by high glucose
Authors: Villaseñor Alma , Aedo-Martín Daniel , Obeso David , Erjavec Igor , Rodríguez-Coira Juan , Buendía Irene , Ardura Juan Antonio , Barbas Coral , Gortazar Arancha R.
Published: February 2019

Osteocytes are the main cells of bone tissue and play a crucial role in bone formation and resorption. Recent studies have indicated that Diabetes Mellitus (DM) affects bone mass and potentially causes higher bone fracture risk. Previous work on osteocyte cell cultures has demonstrated that mechanotransduction is impaired after culture under diabetic pre-conditioning with high glucose (HG), specifically osteoclast recruitment and differentiation. The aim of this study was to analyze the extracellular metabolic changes of osteocytes regarding two conditions: pre-conditioning to either basal levels of glucose (B), mannitol (M) or HG cell media, and mechanical stimulation by fluid flow (FF) in contrast to static condition (SC). Secretomes were analyzed using Liquid Chromatography and Capillary Electrophoresis both coupled to Mass Spectrometry (LC-MS and CE-MS, respectively). Results showed the osteocyte profile was very similar under SC, regardless of their pre-conditioning treatment, while, after FF stimulation, secretomes followed different metabolic signatures depending on the pre-conditioning treatment. An important increment of citrate pointed out that osteocytes release citrate outside of the cell to induce osteoblast activation, while HG environment impaired FF effect. This study demonstrates for the first time that osteocytes increase citrate excretion under mechanical stimulation, and that HG environment impaired this effect.
Hyperosmotic stress induces cell-dependent aggregation of α-synuclein
Authors: Fragniere Alexandra M. C. , Stott Simon R. W. , Fazal Shaline V. , Andreasen Maria , Scott Kirsten , Barker Roger A.
Published: February 2019

The aggregation of alpha-synuclein (α-syn) is a pathological feature of a number of neurodegenerative conditions, including Parkinson’s disease. Genetic mutations, abnormal protein synthesis, environmental stress, and aging have all been implicated as causative factors in this process. The importance of water in the polymerisation of monomers, however, has largely been overlooked. In the present study, we highlight the role of hyperosmotic stress in inducing human α-syn to aggregate in cells in vitro, through rapid treatment of the cells with three different osmolytes: sugar, salt and alcohol. This effect is cell-dependent and not due to direct protein-osmolyte interaction, and is specific for α-syn when compared to other neurodegeneration-related proteins, such as Tau or Huntingtin. This new property of α-syn not only highlights a unique aspect of its behaviour which may have some relevance for disease states, but may also be useful as a screening test for compounds to inhibit the aggregation of α-syn in vitro.
Radiation Pneumonitis after Intensity-Modulated Radiotherapy for Esophageal Cancer: Institutional Data and a Systematic Review
Authors: Tonison J. J. , Fischer S. G. , Viehrig M. , Welz S. , Boeke S. , Zwirner K. , Klumpp B. , Braun L. H. , Zips D. , Gani C.
Published: February 2019

Radiation pneumonitis (RP) is a serious complication that can occur after thoracic radiotherapy. The goal of this study is to investigate the incidence of RP after radiochemotherapy with intensity modulated radiotherapy (IMRT) in patients with esophageal cancer and correlate this with dose volume histogram (DVH) related parameters. For this purpose, the clinical course of 73 patients was evaluated and irradiation doses to the lungs were extracted from radiotherapy treatment plans. Furthermore, a systematic review on this topic was conducted across PubMed. In our institutional cohort, Common Terminology Criteria for Adverse Events (CTCAE) grade II or higher RP occurred in four patients (5.5%). The systematic review identified 493 titles of which 19 studies reporting 874 patients qualified for the final analysis. No grade IV or V RP after radiochemotherapy with IMRT for esophageal cancer was reported in the screened literature. Grade II or higher RP is reported in 6.6% of the patients. A higher incidence can be seen with increasing values for lung V20. In conclusion, our institutional data and the literature consistently show a low incidence of symptomatic RP after radiochemotherapy in patients with esophageal cancer treated with IMRT. However, efforts should be made to keep the lung V20 below 23% and specific caution is warranted in patients with pre-existing lung conditions.
To jump or not to jump - The Bereitschaftspotential required to jump into 192-meter abyss
Authors: Nann M. , Cohen L. G. , Deecke L. , Soekadar S. R.
Published: February 2019

Self-initiated voluntary acts, such as pressing a button, are preceded by a surface-negative electrical brain potential, the Bereitschaftspotential (BP), that can be recorded over the human scalp using electroencephalography (EEG). While the BP’s early component (BP1, generated in the supplementary and cingulate motor area) was linked to motivational, intentional and timing properties, the BP’s late component (BP2, generated in the primary motor cortex) was found to be linked to motor execution and performance. Up to now, the BP required to initiate voluntary acts has only been recorded under well-controlled laboratory conditions, and it was unknown whether possible life-threatening decision making, e.g. required to jump into a 192-meter abyss, would impact this form of brain activity. Here we document for the first time pre-movement brain activity preceding 192-meter bungee jumping. We found that the BP’s spatiotemporal dynamics reflected by BP1 and BP2 are comparable before 192-meter bungee jumping and jumping from 1-meter. These results, possible through recent advancements in wireless and portable EEG technology, suggest that possible life-threatening decision-making has no impact on the BP’s spatiotemporal dynamics.
RETRACTED ARTICLE: Optical rectification and absorption coefficients studied by a short-range topless exponential potential well with inverse square root
Authors: Yu Qiucheng , Guo Kangxian , Hu Meilin
Published: February 2019

A topless potential energy with inverse square root is introduced to solve the energy spectrum equations and the bound state wave functions of the static Schrödinger equation by coordinate variation and combining the extraordinary coefficients of the confluent hypergeometric functions. Furthermore, the model of optical rectification (OR) and absorption coefficients (AC) with this special potential energy V(x) will appear regular changes. In this work, we explore the specific characteristics of the OR and AC with the inverse square root potential through multiple factors such as energy intervals and matrix elements.
Identification of MRP2 as a targetable factor limiting oxaliplatin accumulation and response in gastrointestinal cancer
Authors: Myint Khine , Biswas Riya , Li Yan , Jong Nancy , Jamieson Stephen , Liu Johnson , Han Catherine , Squire Christopher , Merien Fabrice , Lu Jun , Nakanishi Takeo , Tamai Ikumi , McKeage Mark
Published: February 2019

Oxaliplatin is important for the clinical treatment of colorectal cancer and other gastrointestinal malignancies, but tumour resistance is limiting. Several oxaliplatin transporters were previously identified but their relative contributions to determining oxaliplatin tumour responses and gastrointestinal tumour cell sensitivity to oxaliplatin remains unclear. We studied clinical associations between tumour expression of oxaliplatin transporter candidate genes and patient response to oxaliplatin, then experimentally verified associations found with MRP2 in models of human gastrointestinal cancer. Among 18 oxaliplatin transporter candidate genes, MRP2 was the only one to be differentially expressed in the tumours of colorectal cancer patients who did or did not respond to FOLFOX chemotherapy. Over-expression of MRP2 (endogenously in HepG2 and PANC-1 cells, or induced by stable transfection of HEK293 cells) decreased oxaliplatin accumulation and cytotoxicity but those deficits were reversed by inhibition of MRP2 with myricetin or siRNA knockdown. Mice bearing subcutaneous HepG2 tumour xenografts were sensitised to oxaliplatin antitumour activity by concurrent myricetin treatment with little or no increase in toxicity. In conclusion, MRP2 limits oxaliplatin accumulation and response in human gastrointestinal cancer. Screening tumour MRP2 expression levels, to select patients for treatment with oxaliplatin-based chemotherapy alone or in combination with a MRP2 inhibitor, could improve treatment outcomes.
Langmuir films at the oil/water interface revisited
Authors: Mottola Milagro , Caruso Benjamín , Perillo Maria A.
Published: February 2019

We studied monomolecular layers at the oil/water interface (O/Wint) in a Langmuir interfacial trough using egg-yolk phosphatidylcholine (EPC) (the model phospholipid) and Vaseline (VAS) as oil phase. The temporal dynamics in the surface pressure (π) evolution depended on the method (spreading/adsorption) used for monolayers preparation and reflected the different distribution of EPC between all the system compartments (bulk phases and interfaces). We distinguished between EPC located either stable at the interface or hopping between the interface and bulk phases. The size order of the apparent mean molecular area, at constant π, of EPC at different interfaces (EPCO/W > EPC/VAS0.02;A/W > EPCA/W), suggested that VAS molecules intercalated between the hydrocarbon chains of EPCO/W, at a molar fraction xVAS > 0.02. However, EPC/VAS0.02;A/W showed the highest compressional free energy. This leaded us to study the EPC/VAS0.02 mixture at A/W by Brewster Angle Microscopy (BAM), finding that upon compression VAS segregated over the monolayer, forming non-coalescent lenses (as predicted by the spreading coefficient S = −13 mN/m) that remained after decompression and whose height changed (increase/decrease) accompanied the compression/decompression cycle. At the O/Wint, while some VAS molecules remained at the interface up to the collapse, others squeezed out towards the VAS bulk phase with an energy requirement lower than towards the air.
Rho-kinase inhibitor coupled to peptide-modified albumin carrier reduces portal pressure and increases renal perfusion in cirrhotic rats
Authors: Klein Sabine , Frohn Franziska , Magdaleno Fernando , Reker-Smit Catharina , Schierwagen Robert , Schierwagen Irela , Uschner Frank Erhard , van Dijk Fransien , Fürst Dieter O. , Djudjaj Sonja , Boor Peter , Poelstra Klaas , Beljaars Leonie , Trebicka Jonel
Published: February 2019

Rho-kinase (ROCK) activation in hepatic stellate cells (HSC) is a key mechanism promoting liver fibrosis and portal hypertension (PTH). Specific delivery of ROCK-inhibitor Y-27632 (Y27) to HSC targeting mannose-6-phosphate-receptors reduces portal pressure and fibrogenesis. In decompensated cirrhosis, presence of ascites is associated with reduced renal perfusion. Since in cirrhosis, platelet-derived growth factor receptor beta (PDGFRβ) is upregulated in the liver as well as the kidney, this study coupled Y27 to human serum albumin (HSA) substituted with PDGFRβ-recognizing peptides (pPB), and investigated its effect on PTH in cirrhotic rats. In vitro collagen contraction assays tested biological activity on LX2 cells. Hemodynamics were analyzed in BDL and CCl4 cirrhotic rats 3 h, 6 h and 24 h after i.v. administration of Y27pPBHSA (0.5/1 mg/kg b.w). Phosphorylation of moesin and myosin light chain (MLC) assessed ROCK activity in liver, femoral muscle, mesenteric artery, kidney and heart. Three Y27 molecules were coupled to pPBHSA as confirmed by HPLC/MS, which was sufficient to relax LX2 cells. In vivo, Y27pPBHSA-treated rats exhibited lower portal pressure, hepatic vascular resistance without effect on systemic vascular resistance, but a tendency towards lower cardiac output compared to non-treated cirrhotic rats. Y27pPBHSA reduced intrahepatic resistance by reduction of phosphorylation of moesin and MLC in Y27pPBHSA-treated cirrhotic rats. Y27pPBHSA was found in the liver of rats up to 6 hours after its injection, in the HSC demonstrated by double-immunostainings. Interestingly, Y27pPBHSA increased renal arterial flow over time combined with an antifibrotic effect as shown by decreased renal acta2 and col1a1 mRNA expression. Therefore, targeting the ROCK inhibitor Y27 to PDGFRβ decreases portal pressure with potential beneficial effects in the kidney. This unique approach should be tested in human cirrhosis.
Both cold and sub-zero acclimation induce cell wall modification and changes in the extracellular proteome in Arabidopsis thaliana
Authors: Takahashi Daisuke , Gorka Michal , Erban Alexander , Graf Alexander , Kopka Joachim , Zuther Ellen , Hincha Dirk K.
Published: February 2019

Cold acclimation (CA) leads to increased plant freezing tolerance during exposure to low, non-freezing temperatures as a result of many physiological, biochemical and molecular changes that have been extensively investigated. In addition, many plant species, such asArabidopsis thaliana, respond to a subsequent exposure to mild, non-damaging freezing temperatures with an additional increase in freezing tolerance referred to as sub-zero acclimation (SZA). There is comparatively little information available about the molecular basis of SZA. However, previous transcriptomic studies indicated that cell wall modification may play an important role during SZA. Here we show that CA and SZA are accompanied by extensive changes in cell wall amount, composition and structure. While CA leads to a significant increase in cell wall amount, the relative proportions of pectin, hemicellulose and cellulose remained unaltered during both CA and SZA. However, both treatments resulted in more subtle changes in structure as determined by infrared spectroscopy and monosaccharide composition as determined by gas chromatography-mass spectrometry. These differences could be related through a proteomic approach to the accumulation of cell wall modifying enzymes such as pectin methylesterases, pectin methylesterase inhibitors and xyloglucan endotransglucosylases/hydrolases in the extracellular matrix.
Aplysinopsin-type and Bromotyrosine-derived Alkaloids from the South China Sea Sponge Fascaplysinopsis reticulata
Authors: Wang Qi , Tang Xu-Li , Luo Xiang-Chao , de Voog Nicole J. , Li Ping-Lin , Li Guo-Qiang
Published: February 2019

Seven pairs of new oxygenated aplysinopsin-type enantiomers, (+)- and (−)-oxoaplysinopsins A‒G (1‒7), two new bromotyrosine-derived alkaloids, subereamollines C and D (18 and 19), together with ten known compounds (8‒17) were isolated from the Xisha Islands sponge Fascaplysinopsis reticulata. The planar structures were determined by extensive NMR and MS spectroscopic data. Each of the optically pure enantiomers was achieved by chiral HPLC separation. The absolute configurations were assigned by the quantum chemical calculation methods. Compound 19 showed cytotoxicity against Jurkat cell lines with IC50 value of 0.88 μM. Compounds 2, 16 and 17 showed tyrosine phosphatase 1B (PTP1B) inhibition activity with IC50 value ranging from 7.67 to 26.5 μM, stronger than the positive control of acarbose and 1-deoxynojirimycin. A structural activity relationship for the aplysinopsin-type enantiomers were observed in PTP1B inhibition activity of 2 and cytotoxicity of 3 that the dextrorotary (+)-2 and (+)-3 showed stronger activity than the levorotary (−)-2 and (−)-3.
Compressing the lumbar nerve root changes the frequency-associated cerebral amplitude of fluctuations in patients with low back/leg pain
Authors: Zhou Fuqing , Zhao Yanlin , Zhu Li , Jiang Jian , Huang Muhua , Zhang Yong , Zhuang Ying , Gong Honghan
Published: February 2019

Understanding the central mechanisms responsible for lumbar nerve root compression may facilitate the development of new therapeutic strategies. In this study, our aim was to investigate the amplitude of fluctuations (AF) in five specific frequency bands and the full-frequency band realm to provide novel insight into the rhythm of the neuronal activity of low back/leg pain (LBLP) patients (n = 25). Compared with healthy controls, LBLP patients exhibited a significantly altered AF in multiple brain regions, including the right or left middle and inferior temporal gyri, bilateral precuneus, right anterior insula/frontal operculum, right or left inferior parietal lobule/postcentral gyrus, and other locations at five specific frequencies (P < 0.01, with Gaussian random field theory correction). Trends of an increase and a decrease in the AF in pain- and sensory-related regions, respectively, were also observed from low to high frequencies (Bonferroni-corrected α level of P < 0.05/84). In addition, in the bilateral rectal gyrus, a significant association was identified between the AF in the five specific frequency bands and disease status (P < 0.05). These findings suggest that in LBLP patients, intrinsic functional plasticity related to low back pain, leg pain and numbness affects the AF of the pain matrix and sensory-processing regions in both low- and high-frequency bands.
Cultivable microbial community in 2-km-deep, 20-million-year-old subseafloor coalbeds through ~1000 days anaerobic bioreactor cultivation
Authors: Imachi Hiroyuki , Tasumi Eiji , Takaki Yoshihiro , Hoshino Tatsuhiko , Schubotz Florence , Gan Shuchai , Tu Tzu-Hsuan , Saito Yumi , Yamanaka Yuko , Ijiri Akira , Matsui Yohei , Miyazaki Masayuki , Morono Yuki , Takai Ken , Hinrichs Kai-Uwe , Inagaki Fumio
Published: February 2019

Recent explorations of scientific ocean drilling have revealed the presence of microbial communities persisting in sediments down to ~2.5 km below the ocean floor. However, our knowledge of these microbial populations in the deep subseafloor sedimentary biosphere remains limited. Here, we present a cultivation experiment of 2-km-deep subseafloor microbial communities in 20-million-year-old lignite coalbeds using a continuous-flow bioreactor operating at 40 °C for 1029 days with lignite particles as the major energy source. Chemical monitoring of effluent samples via fluorescence emission-excitation matrices spectroscopy and stable isotope analyses traced the transformation of coalbed-derived organic matter in the dissolved phase. Hereby, the production of acetate and 13C-depleted methane together with the increase and transformation of high molecular weight humics point to an active lignite-degrading methanogenic community present within the bioreactor. Electron microscopy revealed abundant microbial cells growing on the surface of lignite particles. Small subunit rRNA gene sequence analysis revealed that diverse microorganisms grew in the bioreactor (e.g., phyla Proteobacteria, Firmicutes, Chloroflexi, Actinobacteria, Bacteroidetes, Spirochaetes, Tenericutes, Ignavibacteriae, and SBR1093). These results indicate that activation and adaptive growth of 2-km-deep microbes was successfully accomplished using a continuous-flow bioreactor, which lays the groundwork to explore networks of microbial communities of the deep biosphere and their physiologies.
Impact of gynecologic cancer on pelvic floor disorder symptoms and quality of life: an observational study
Authors: Neron Mathias , Bastide Sophie , Tayrac Renaud de , Masia Florent , Ferrer Catherine , Labaki Majd , Boileau Laurent , Letouzey Vincent , Huberlant Stephanie
Published: February 2019

The objective of our observational prospective study was to investigate the severity and prevalence of urinary and pelvic floor disorders in gynecologic cancer survivors. All patients surviving gynecological cancer in the region as well as women receiving invitations to attend breast-screening checkups as the control population were asked to fill-in questionnaires assessing pelvic prolapse symptoms (PFDI-20, Wexner) and associated quality of life (PFIQ-7). Eighty-nine women were included in the cancer survivor group and 1088 in the control group. Pelvic floor symptoms (PFDI-20 questionnaire) were significantly worse in cancer survivors than in control women (score: 33.3 [14.6–74.1] vs. 20 [4.2–50.0], p = 0.0003). Urge incontinence was significantly worse in cancer survivors in both univariable (ORb = 2.061 [95% CI = 1.284–3.309], p = 0.0027) and multivariable analyses (ORa = 1.672 [95% CI = 1.014–2.758], p = 0.0442), as was fecal incontinence in univariable (ORb = 3.836 [95% CI = 1.710–8.602], p = 0.0011) and in multivariable (ORa = 3.862 [95% CI = 1.657–9.001], p = 0.0018) analyses. Women with benign hysterectomies had poorer quality of life and increased pelvic floor disorders compared to women with no history of surgery. Survivors of gynecological cancer experience significantly more pelvic floor symptoms and an associated reduction in quality of life.
Transparent Display using a quasi-array of Si-SiO2 Core-Shell Nanoparticles
Authors: Dolatyari Mahboubeh , Jafari Ali , Rostami Ali , Klein Axel
Published: February 2019

A novel type of transparent monitor with high-resolution images based on Si-SiO2 core-shell nanoparticles is presented in this contribution. In this monitor, a quasi-array of nanoparticles was used to obtain a very sharp scattering profile. For this purpose, the Si-SiO2 nanoparticles were synthesized and with controlling the size of particles, the dominant emission wavelength was controlled. For the fabrication of a blue color transparent monitor the solution processed Si-SiO2 nanoparticles were dispersed in polystyrene and then coated on a transparent glass surface. After drying the film, the typical features representing a transparent monitor were studied. A video projector was used and text and pictures were sent on the monitor. This monitor reveals very attractive features such as simplicity, wide viewing angle, scalability to larger sizes and low cost. Importantly, the texts and pictures can be well presented on both sides of the fabricated monitor. The composite thin film can be also separated from the glass and can be used as a flexible display. To shed light on the impact of the structure on the optical properties Si-SiO2 and Ag nanomaterials representing perfect arrays of nanoparticles, quasi-arrays and randomly oriented nanoparticles were calculated/simulated using the finite-difference time-domain (FDTD) method. The results were compared to the experimental data and show a high accordance.
Maximizing Network Resilience against Malicious Attacks
Authors: Li Wenguo , Li Yong , Tan Yi , Cao Yijia , Chen Chun , Cai Ye , Lee Kwang Y. , Pecht Michael
Published: February 2019

The threat of a malicious attack is one of the major security problems in complex networks. Resilience is the system-level self-adjusting ability of a complex network to retain its basic functionality and recover rapidly from major disruptions. Despite numerous heuristic enhancement methods, there is a research gap in maximizing network resilience: current heuristic methods are designed to immunize vital nodes or modify a network to a specific onion-like structure and cannot maximize resilience theoretically via network structure. Here we map complex networks onto a physical elastic system to introduce indices of network resilience, and propose a unified theoretical framework and general approach, which can address the optimal problem of network resilience by slightly modifying network structures (i.e., by adding a set of structural edges). We demonstrate the high efficiency of this approach on three realistic networks as well as two artificial random networks. Case studies show that the proposed approach can maximize the resilience of complex networks while maintaining their topological functionality. This approach helps to unveil hitherto hidden functions of some inconspicuous components, which in turn, can be used to guide the design of resilient systems, offer an effective and efficient approach for mitigating malicious attacks, and furnish self-healing to reconstruct failed infrastructure systems.
Codonopsis lanceolata attenuates allergic lung inflammation by inhibiting Th2 cell activation and augmenting mitochondrial ROS dismutase (SOD2) expression
Authors: Seo Yun-Soo , Kim Hyo Seon , Lee A. Yeong , Chun Jin Mi , Kim Sung Bae , Moon Byeong Cheol , Kwon Bo-In
Published: February 2019

Allergic asthma is a chronic inflammatory disease induced by the inhalation of allergens, which trigger the activation of T helper type 2 (Th2) cells that release Th2 cytokines. Recently, herbal medicines are being considered a major source of novel agents to treat various diseases. In the present study, we evaluated the anti-asthmatic effects of aCodonopsis lanceolataextract (CLE) and the mechanisms involved in its anti-inflammatory effects. Treatment with CLE reduced infiltration of inflammatory cells, especially eosinophils, and the production of mucus in lung tissues. Levels of Th2 cytokines, such as IL-4, IL-5, and IL-13, and chemokines were also decreased following treatment with CLE. Moreover, Th2 cell proportionin vivoand differentiationin vitrowere reduced as evidenced by the decreased expression of GATA3+. Furthermore, the expression of superoxide dismutase (SOD)2, a mitochondrial ROS (mROS) scavenger, was increased, which was related to Th2 cell regulation. Interestingly, treatment with CLE increased the number of macrophages in the lungs and enhanced the immune-suppressive property of macrophages. Our findings indicate that CLE has potential as a novel therapeutic agent to inhibit Th2 cell differentiation by regulating mROS scavenging.
Myeloid-derived suppressor cells in the patients with liver resection for hepatitis B virus-related hepatocellular carcinoma
Authors: Lee Wei-Chen , Wang Yu-Chao , Cheng Chih-Hsien , Wu Tsung-Han , Lee Chen-Fang , Wu Ting-Jung , Chou Hong-Shiue , Chan Kun-Ming
Published: February 2019

Liver resection remains the popular treatment for hepatocellular carcinoma (HCC). The aim of this study was to explore the alteration of immune cells in HCC patients with liver resections. Nineteen patients were included and their peripheral blood samples were taken before and after liver resections for immune-cell analysis. The clinical characteristics showed that the median diameter of the resected tumors was 7.5 cm with a range from 1.4 to 16.5 cm. The analysis of immune cells showed that the percentage of CD4+T-cells were not altered by liver resection, but the percentage of CD8+T-cell was decreased from 31.7 ± 12.4% to 20.2 ± 10.4% at one week after liver resection (p = 0.006). For immunosuppressor cells, regulatory T-cells were not altered, but myeloid-derived suppressor cells (MDSC) were decreased from 7.75 ± 8.16% to 1.51 ± 1.32% at one month after liver resection (p = 0.022) in 10 of 19 patients with high frequency of MDSC. Furthermore, it was also found that MDSC population was linearly correlated to tumor volume. In conclusion, CD8+ T-cellsand MDSC were altered by liver resection. The percentage of CD8+ T-cellswas decreased by surgery, but the accumulation of MDSC was abrogated.