bluuebunny/crossref_metadata_2025 huggingface dataset:
Capillary hysteresis in sloshing dynamics: a weakly nonlinear analysis
Authors: Viola Francesco , Brun P.-T. , Gallaire François
Published: January 2018

The sloshing of water waves in a vertical cylindrical tank is an archetypal damped oscillator in fluid mechanics. The wave frequency is traditionally derived in the potential flow limit (Lamb, Hydrodynamics, Cambridge University Press, 1932), and the damping rate results from the combined effects of the viscous dissipation at the wall, in the bulk and at the free surface (Case & Parkinson, J. Fluid Mech., vol. 2, 1957, pp. 172–184). Still, the classic theoretical prediction accounting for these effects significantly underestimates the damping rate when compared to careful laboratory experiments (Cocciaro et al., J. Fluid Mech., vol. 246, 1993, pp. 43–66). Specifically, theory provides a unique value for the damping rate, while experiments reveal that the damping increases as the sloshing amplitude decreases. Here, we investigate theoretically the effects of capillarity at the contact line on the decay time of capillary–gravity waves. To this end, we marry a model for the inviscid waves to a nonlinear empiric law for the contact line that incorporates contact angle hysteresis. The resulting system of equations is solved by means of a weakly nonlinear analysis using the method of multiple scales. Capillary effects have a dramatic influence on the calculated damping rate, especially when the sloshing amplitude gets small: this nonlinear interfacial term increases in the limit of zero wave amplitude. In contrast to viscous damping, where the wave motion decays exponentially, the contact angle hysteresis can act as Coulomb solid friction, thus yielding the arrest of the contact line in a finite time.
Hydrodynamic dispersion in a tube with diffusive losses through its walls
Authors: Zimmerman R. A. , Severino G. , Tartakovsky D. M.
Published: January 2018

Advective–diffusive transport of passive or reactive scalars in confined environments (e.g. tubes and channels) is often accompanied by diffusive losses/gains through the confining walls. We present analytical solutions for transport of a reactive solute in a tube, whose walls are impermeable to flow but allow for solute diffusion into the surrounding medium. The solute undergoes advection, diffusion and first-order chemical reaction inside the tube, while diffusing and being consumed in the surrounding medium. These solutions represent a leading-order (in the radius-to-length ratio) approximation, which neglects the longitudinal variability of solute concentration in the surrounding medium. A numerical solution of the full problem is used to demonstrate the accuracy of this approximation for a physically relevant range of model parameters. Our analysis indicates that the solute delivery rate can be quantified by a dimensionless parameter, the ratio of a solute’s residence time in a tube to the rate of diffusive losses through the tube’s wall.
Wo sind die wissenschaftlichen Standards für hochwertige Replikationsforschung?
Authors: Fiedler Klaus
Published: January 2018

Zusammenfassung. Es gibt einen breiten Konsens, dass Replikation ein wichtiges Instrument ist, um valide Befunde und solide Forschung zu erkennen. Wenn sie aber wissenschaftlich bedeutsam ist, dann muss auch die Replikationsforschung an strengen methodischen Regeln und an klar artikulierten wissenschaftlichen Zielen gemessen werden. Eine kritische Beschäftigung mit der aktuellen Replikationsforschung – etwa im jüngst veröffentlichten Bericht der Open Science Collaboration – zeigt jedoch, dass eine strenge und forschungslogisch begründete Methodologie für Replikationsstudien bislang weder angewandt noch entwickelt wurde. Infolgedessen bleibt die Validität der Schlüsse, die aus Replikationsstudien gezogen werden dürfen, oftmals unklar. Dieses grundlegende Problem wird hier unter vier Gesichtspunkten diskutiert: Unklarheit des Gegenstandes der Replikation (Replicandum), Vernachlässigung einschlägiger methodischer Probleme (Regressivität; Reliabilität der Veränderungsmessung), einseitige Vermeidung von angeblich kostenträchtigen „Falsch-Positiven“ ohne Versuch einer systematischen Kosten-Nutzen-Messung sowie das vernachlässigte Ziel, Replikationsforschung so zu implementieren, dass sie echte Erkenntnisfortschritte bringt und als exzellente Forschung anerkannt werden kann.
Erik M. Conway Receives 2017 Athelstan Spilhaus Award
Authors:   AGU
Published: January 2018

Erik M. Conway received the Athelstan Spilhaus Award at the 2017 American Geophysical Union Fall Meeting Honors Ceremony, held on 13 December 2017 in New Orleans, La. The award honors an individual “for the enhancement of the public engagement with Earth and space sciences.”
Sea Level 2017 Conference Looks to Coastal Sea Level Rise Impact
Authors: Stammer Detlef , van de Wal Roderik , Nicholls Robert
Published: January 2018

International World Climate Research Programme/Intergovernmental Oceanographic Commission (WCRP/IOC) Open Science Conference on Regional Sea Level Rise and Its Impacts; New York, New York, 10–14 July 2017
Hubert H. G. Savenije Receives 2017 International Award
Authors:   AGU
Published: January 2018

Hubert H. G. Savenije received the 2017 International Award at the American Geophysical Union Fall Meeting Honors Ceremony, held on 13 December 2017 in New Orleans, La. The award honors “an individual scientist, group, or a small team for making an outstanding contribution to furthering the Earth and space sciences and using science for the benefit of society in developing nations.”
Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma
Authors: Redlich Nathan , Robinson Anthony M. , Nickel Kwangok P. , Stein Andrew P. , Wheeler Deric L. , Adkins Douglas R. , Uppaluri Ravindra , Kimple Randall J. , Van Tine Brian A. , Michel Loren S.
Published: January 2018

ErbB3 has been widely implicated in treatment resistance, but its role as a primary treatment target is less clear. Canonically ErbB3 requires EGFR or ErbB2 for activation, whereas these two established treatment targets are thought to signal independently of ErbB3. In this study, we show that ErbB3 is essential for tumor growth of treatment-naive HNSCC patient-derived xenografts. This ErbB3 dependency occurs via ErbB3-mediated control of EGFR activation and HIF1α stabilization, which require ErbB3 and its ligand neuregulin-1. Here, we show that ErbB3 antibody treatment selects for a population of ErbB3-persister cells that express high levels of the transmembrane protein Trop2 that we previously identified as an inhibitor of ErbB3. Co-treatment with anti-ErbB3 and anti-Trop2 antibodies is synergistic and produces a greater anti-tumor response than either antibody alone. Collectively, these data both compel a revision of ErbB-family signaling and delineate a strategy for its effective inhibition in HNSCC.
Deregulated PP1α phosphatase activity towards MAPK activation is antagonized by a tumor suppressive failsafe mechanism
Authors: Chen Ming , Wan Lixin , Zhang Jiangwen , Zhang Jinfang , Mendez Lourdes , Clohessy John G. , Berry Kelsey , Victor Joshua , Yin Qing , Zhu Yuan , Wei Wenyi , Pandolfi Pier Paolo
Published: January 2018

The mitogen-activated protein kinase (MAPK) pathway is frequently aberrantly activated in advanced cancers, including metastatic prostate cancer (CaP). However, activating mutations or gene rearrangements among MAPK signaling components, such as Ras and Raf, are not always observed in cancers with hyperactivated MAPK. The mechanisms underlying MAPK activation in these cancers remain largely elusive. Here we discover that genomic amplification of the PPP1CA gene is highly enriched in metastatic human CaP. We further identify an S6K/PP1α/B-Raf signaling pathway leading to activation of MAPK signaling that is antagonized by the PML tumor suppressor. Mechanistically, we find that PP1α acts as a B-Raf activating phosphatase and that PML suppresses MAPK activation by sequestering PP1α into PML nuclear bodies, hence repressing S6K-dependent PP1α phosphorylation, 14-3-3 binding and cytoplasmic accumulation. Our findings therefore reveal a PP1α/PML molecular network that is genetically altered in human cancer towards aberrant MAPK activation, with important therapeutic implications.
Publisher Correction: Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs
Authors: Vannini Ivan , Wise Petra M. , Challagundla Kishore B. , Plousiou Meropi , Raffini Mirco , Bandini Erika , Fanini Francesca , Paliaga Giorgia , Crawford Melissa , Ferracin Manuela , Ivan Cristina , Fabris Linda , Davuluri Ramana V. , Guo Zhiyi , Cortez Maria Angelica , Zhang Xinna , Chen Lu , Zhang Shuxing , Fernandez-Cymering Cecilia , Han Leng , Carloni Silvia , Salvi Samanta , Ling Hui , Murtadha Mariam , Neviani Paolo , Gitlitz Barbara J. , Laird-Offringa Ite A. , Nana-Sinkam Patrick , Negrini Massimo , Liang Han , Amadori Dino , Cimmino Amelia , Calin George A. , Fabbri Muller
Published: January 2018

In the originally published version of this Article, the positions of the final two authors in the author list were inadvertently inverted during the production process. This error has now been corrected in both the PDF and HTML versions of the Article.
MXene molecular sieving membranes for highly efficient gas separation
Authors: Ding Li , Wei Yanying , Li Libo , Zhang Tao , Wang Haihui , Xue Jian , Ding Liang-Xin , Wang Suqing , Caro Jürgen , Gogotsi Yury
Published: January 2018

Molecular sieving membranes with sufficient and uniform nanochannels that break the permeability-selectivity trade-off are desirable for energy-efficient gas separation, and the arising two-dimensional (2D) materials provide new routes for membrane development. However, for 2D lamellar membranes, disordered interlayer nanochannels for mass transport are usually formed between randomly stacked neighboring nanosheets, which is obstructive for highly efficient separation. Therefore, manufacturing lamellar membranes with highly ordered nanochannel structures for fast and precise molecular sieving is still challenging. Here, we report on lamellar stacked MXene membranes with aligned and regular subnanometer channels, taking advantage of the abundant surface-terminating groups on the MXene nanosheets, which exhibit excellent gas separation performance with H2 permeability >2200 Barrer and H2/CO2 selectivity >160, superior to the state-of-the-art membranes. The results of molecular dynamics simulations quantitatively support the experiments, confirming the subnanometer interlayer spacing between the neighboring MXene nanosheets as molecular sieving channels for gas separation.
Curvy surface conformal ultra-thin transfer printed Si optoelectronic penetrating microprobe arrays
Authors: Sim Kyoseung , Rao Zhoulyu , Li Yanbin , Yang Dong , Yu Cunjiang
Published: January 2018

Penetrating neural probe arrays are powerful bio-integrated devices for studying basic neuroscience and applied neurophysiology, underlying neurological disorders, and understanding and regulating animal and human behavior. This paper presents a penetrating microprobe array constructed in thin and flexible fashion, which can be seamlessly integrated with the soft curvy substances. The function of the microprobes is enabled by transfer printed ultra-thin Si optoelectronics. As a proof-of-concept device, microprobe array with Si photodetector arrays are demonstrated and their capability of mapping the photo intensity in space are illustrated. The design strategies of utilizing thin polyimide based microprobes and supporting substrate, and employing the heterogeneously integrated thin optoelectronics are keys to accomplish such a device. The experimental and theoretical investigations illustrate the materials, manufacturing, mechanical and optoelectronic aspects of the device. While this paper primarily focuses on the device platform development, the associated materials, manufacturing technologies, and device design strategy are applicable to more complex and multi-functionalities in penetrating probe array-based neural interfaces and can also find potential utilities in a wide range of bio-integrated systems.
Handling variability and incompleteness of biological data by flexible nets: a case study for Wilson disease
Authors: Júlvez Jorge , Dikicioglu Duygu , Oliver Stephen G.
Published: January 2018

Mathematical models that combine predictive accuracy with explanatory power are central to the progress of systems and synthetic biology, but the heterogeneity and incompleteness of biological data impede our ability to construct such models. Furthermore, the robustness displayed by many biological systems means that they have the flexibility to operate under a range of physiological conditions and this is difficult for many modeling formalisms to handle. Flexible nets (FNs) address these challenges and represent a paradigm shift in model-based analysis of biological systems. FNs can: (i) handle uncertainties, ranges and missing information in concentrations, stoichiometry, network topology, and transition rates without having to resort to statistical approaches; (ii) accommodate different types of data in a unified model that integrates various cellular mechanisms; and (iii) be employed for system optimization and model predictive control. We present FNs and illustrate their capabilities by modeling a well-established system, the dynamics of glucose consumption by a microbial population. We further demonstrate the ability of FNs to take control actions in response to genetic or metabolic perturbations. Having bench-marked the system, we then construct the first quantitative model for Wilson disease—a rare genetic disorder that impairs copper utilization in the liver. We used this model to investigate the feasibility of using vitamin E supplementation therapy for symptomatic improvement. Our results indicate that hepatocytic inflammation caused by copper accumulation was not aggravated by limitations on endogenous antioxidant supplies, which means that treating patients with antioxidants is unlikely to be effective.
The Endogenous GRP78 Interactome in Human Head and Neck Cancers: A Deterministic Role of Cell Surface GRP78 in Cancer Stemness
Authors: Chen Hsin-Ying , Chang Joseph Tung-Chieh , Chien Kun-Yi , Lee Yun-Shien , You Guo-Rung , Cheng Ann-Joy
Published: January 2018

Cell surface glucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone, was suggested to be a cancer stem cell marker, but the influence of this molecule on cancer stemness is poorly characterized. In this study, we developed a mass spectrometry platform to detect the endogenous interactome of GRP78 and investigated its role in cancer stemness. The interactome results showed that cell surface GRP78 associates with multiple molecules. The influence of cell population heterogeneity of head and neck cancer cell lines (OECM1, FaDu, and BM2) according to the cell surface expression levels of GRP78 and the GRP78 interactome protein, Progranulin, was investigated. The four sorted cell groups exhibited distinct cell cycle distributions, asymmetric/symmetric cell divisions, and different relative expression levels of stemness markers. Our results demonstrate that cell surface GRP78 promotes cancer stemness, whereas drives cells toward a non-stemlike phenotype when it chaperones Progranulin. We conclude that cell surface GRP78 is a chaperone exerting a deterministic influence on cancer stemness.
Evaluation of animal-to-human and human-to-human transmission of influenza A (H7N9) virus in China, 2013–15
Authors: Virlogeux Victor , Feng Luzhao , Tsang Tim K. , Jiang Hui , Fang Vicky J. , Qin Ying , Wu Peng , Wang Xiling , Zheng Jiandong , Lau Eric H. Y. , Peng Zhibin , Yang Juan , Cowling Benjamin J. , Yu Hongjie
Published: January 2018

A novel avian-origin influenza A(H7N9) virus emerged in China in March 2013 and by 27 September 2017 a total of 1533 laboratory-confirmed cases have been reported. Occurrences of animal-to-human and human-to-human transmission have been previously identified, and the force of human-to-human transmission is an important component of risk assessment. In this study, we constructed an ecological model to evaluate the animal-to-human and human-to-human transmission of H7N9 during the first three epidemic waves in spring 2013, winter/spring 2013–2014 and winter/spring 2014–2015 in China based on 149 laboratory-confirmed urban cases. Our analysis of patterns in incidence in major cities allowed us to estimate a mean incubation period in humans of 2.6 days (95% credibility interval, CrI: 1.4–3.1) and an effective reproduction number Re of 0.23 (95% CrI: 0.05–0.47) for the first wave, 0.16 (95% CrI: 0.01–0.41) for the second wave, and 0.16 (95% CrI: 0.01–0.45) for the third wave without a significant difference between waves. There was a significant decrease in the incidence of H7N9 cases after live poultry market closures in various major cities. Our analytic framework can be used for continued assessment of the risk of human to human transmission of A(H7N9) virus as human infections continue to occur in China.
Publisher Correction: A fossil species of the enigmatic early polypod fern genus Cystodium (Cystodiaceae) in Cretaceous amber from Myanmar
Authors: Regalado Ledis , Schmidt Alexander R. , Appelhans Marc S. , Ilsemann Bork , Schneider Harald , Krings Michael , Heinrichs Jochen
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Composition of salivary microbiota in elderly subjects
Authors: Ogawa Taiji , Hirose Yujiro , Honda-Ogawa Mariko , Sugimoto Minami , Sasaki Satoshi , Kibi Masahito , Kawabata Shigetada , Ikebe Kazunori , Maeda Yoshinobu
Published: January 2018

Frailty is gaining attention worldwide with the aging of society. Despite the potential lethality and multiple signs and symptoms in affected individuals, preclinical detection of early manifestations leading to frailty syndrome have not been established. We speculated that the composition of the oral microbiota is associated with general frailty, as well as a relationship between gut microbiota and general health condition. In the present study, we investigated the salivary microbiota composition in samples from healthy and frail elderly individuals using 16S rRNA sequencing analysis for characterization. We found a significant difference in diversity between elderly individuals living in a nursing home (EN) and healthy control (HC) subjects, as well as in the microbiota composition at the phyla level. A supervised orthogonal partial least squared discriminant analysis (OPLS-DA) revealed a significant difference in clear classification trend between the EN and HC groups, with all observations falling within the Hotellings T2 (0.95) ellipse, with model fitness parameters of R2(cum) = 0.937 and Q2(cum) = 0.888, respectively. In addition, the score plots by unsupervised principal component analysis (PCA) showed a clear classification trend in both groups. Our findings suggest that general frailty is associated with oral microbiota composition and formation.
Comparison Long-term Outcome of Definitive Radiotherapy plus Different Chemotherapy Schedules in Patients with Advanced Nasopharyngeal Carcinoma
Authors: Liu Yi-Chun , Wang Wen-Yi , Twu Chih-Wen , Jiang Rong-San , Liang Kai-Li , Lin Po-Ju , Lin Jing-Wei , Lin Jin-Ching
Published: January 2018

Concurrent chemoradiotherapy (CCRT) is the current standard of care for advanced nasopharyngeal carcinoma (NPC). We hypothesize that shifting CCRT to neoadjuvant chemotherapy followed by radiotherapy (NeoCT-RT) is an alternative option. From December 2004 to January 2009, 256 NPC patients with stage II-IVB were treated by either CCRT or NeoCT-RT. All patients received the same dosage and fractionation schedule of RT. After long-term follow-up, 26.8% (34/127) and 23.3% (30/129) of patients who received CCRT and NeoCT-RT respectively, developed a tumor relapse (P = 0.6134). Overall survival (HR = 1.52, 95%CI = 0.91–2.55, P = 0.1532) and progression-free survival (HR = 1.22, 95%CI = 0.75–1.99, P = 0.4215) were similar in both groups. However, acute toxicities during RT period revealed a significant reduction of grade 3/4 vomiting (23% vs. 0%, P < 0.0001), mucositis (55% vs. 16%, P < 0.0001), and neck dermatitis (31% vs. 16%, P = 0.0041) in the NeoCT-RT group, resulting in fewer emergency room visits (10.2% vs. 1.6%, P = 0.0071). Severe treatment-related late toxicity (15% vs. 14%, P = 0.9590) and the occurrence of second malignancy (3.9% vs. 5.4%, P = 0.7887) also showed no differences. We concluded that NeoCT-RT could be an attractive alternative option of CCRT for advanced NPC.
Cooperative standing-horizontal-standing reentrant transition for numerous solid particles under external vibration
Authors: Takatori Satoshi , Baba Hikari , Ichino Takatoshi , Shew Chwen-Yang , Yoshikawa Kenichi
Published: January 2018

We report the collective behavior of numerous plastic bolt-like particles exhibiting one of two distinct states, either standing stationary or horizontal accompanied by tumbling motion, when placed on a horizontal plate undergoing sinusoidal vertical vibration. Experimentally, we prepared an initial state in which all of the particles were standing except for a single particle that was placed at the center of the plate. Under continuous vertical vibration, the initially horizontal particle triggers neighboring particles to fall over into a horizontal state through tumbling-induced collision, and this effect gradually spreads to all of the particles, i.e., the number of horizontal particles is increased. Interestingly, within a certain range of vibration intensity, almost all of the horizontal particles revert back to standing in association with the formation of apparent 2D hexagonal dense-packing. Thus, phase segregation between high and low densities, or crystalline and disperse domains, of standing particles is generated as a result of the reentrant transition. The essential features of such cooperative dynamics through the reentrant transition are elucidated with a simple kinetic model. We also demonstrate that an excitable wave with the reentrant transition is observed when particles are situated in a quasi-one-dimensional confinement on a vibrating plate.
Frequent implementation of interventions may increase HIV infections among MSM in China
Authors: Sun Xiaodan , Xiao Yanni , Peng Zhihang , Wang Ning
Published: January 2018

Intervention measures among men who have sex with men (MSM) are usually designed to reduce the frequency of high risk behaviors (within-community level), but unfortunately may change the contact network and consequently increase the opportunity for them to have sex with new partners (between-community level). A multi-community periodic model on complex network is proposed to study the two-side effects of interventions on HIV transmission among MSM in China, in which the wanning process of the impacts of interventions are modelled. The basic reproduction number for the multi-community periodic system is defined and calculated numerically. Based on the number of annual reported HIV/AIDS cases among MSM in China, the unknown parameters are estimated by using MCMC method and the basic reproduction number is estimated as 3.56 (95%CI [3.556, 3.568]). Our results show that strong randomness of the community-connection networks leads to more new infections and more HIV/AIDS cases. Moreover, main conclusion indicates that implementation of interventions may induce more new infections, depending on relative level of between- and within-community impacts, and the frequency of implementation of interventions. The findings can help to guide the policy maker to choose the appropriate intervention measures, and to implement the interventions with proper frequency.
Publisher Correction: Patterns and drivers of daily bed-level dynamics on two tidal flats with contrasting wave exposure
Authors: Hu Zhan , Yao Peng , van der Wal Daphne , Bouma Tjeerd J.
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Biotransformation and tissue distribution of protopine and allocryptopine and effects of Plume Poppy Total Alkaloid on liver drug-metabolizing enzymes
Authors: Huang Ya-Jun , Cheng Pi , Zhang Zhuo-Yi , Tian Shi-Jie , Sun Zhi-Liang , Zeng Jian-Guo , Liu Zhao-Ying
Published: January 2018

In this study, the biotransformation in the plasma, urine and feces of rats following oral administration of protopine (PRO) and allocryptopine (ALL)were explored using HPLC-QqTOF MS. An HPLC-MS/MS method for the determination of tissues was developed and applied to the tissue distribution study in rats following intragastric administration of Plume Poppy Total Alkaloid for 3 weeks. A total of ten PRO metabolites and ten ALL metabolites were characterized in rats in vivo. Among these metabolites, six PRO metabolites and five ALL metabolites were reported for the first time. The predicated metabolic pathways including ring cleavage, demethylation following ring cleavage, and glucuronidation were proposed. The low-concentration residue of PRO and ALL in various tissues was detected at 24 h and 48 h after dosing, which indicated that both compounds could be widely distributed in tissues and exist as low levels of residue. The activities of erythromycin N-demethylase, aminopyrine N-demethylase and NAD (P)H quinone oxidoreductase in female rats can be induced post-dose, but these activities were inhibited in male rats. The proposed biotransformation and residues of PRO and ALL and their effects on enzymes may provide a basis for clarifying the metabolism and interpreting pharmacokinetics.
Baseline IL-2 and the AIH score can predict the response to standard therapy in paediatric autoimmune hepatitis
Authors: Diestelhorst Jana , Junge Norman , Jonigk Danny , Schlue Jerome , Falk Christine S. , Manns Michael P. , Baumann Ulrich , Jaeckel Elmar , Taubert Richard
Published: January 2018

Although autoimmune hepatitis (AIH) can be treated with corticosteroid-based first-line therapy, incomplete remission is associated with progressive liver fibrosis. So far accepted predictors of the subsequent treatment response of AIH patients are lacking. Therefore, we analysed baseline parameters, including iron homeostasis and cytokine levels, in 60 children with paediatric AIH (pAIH). In contrast to adults, elevated serum markers indicating iron overload were not commonly found in children. Therefore, ferritin was not predictive of the treatment response in pAIH. Although baseline immunoglobulins were lower in pAIH children with subsequent complete biochemical remission (BR) upon standard first-line therapy, only lower AIH scores (≤16 points) could predict BR upon standard therapy in our training and validation cohorts. Additionally, higher baseline IL-2 and MCP-1/CCL2 levels were associated with BR in a sub-cohort. A combined score of IL-2 level and a simplified AIH score predicted treatment response more precisely than both parameter alone in this sub-cohort. In conclusion, the baseline AIH score could be validated as a predictor of treatment response in pAIH. Additionally, low baseline IL-2 may help identify children who need salvage therapy. This could be important because the use of low-dose IL-2 therapies is being tested in various autoimmune diseases.
Electroporation of mice zygotes with dual guide RNA/Cas9 complexes for simple and efficient cloning-free genome editing
Authors: Teixeira Marie , Py Bénédicte F. , Bosc Christophe , Laubreton Daphné , Moutin Marie-Jo , Marvel Jacqueline , Flamant Frédéric , Markossian Suzy
Published: January 2018

In this report, we present an improved protocol for CRISPR/Cas9 genome editing in mice. The procedure consists in the electroporation of intact mouse zygotes with ribonucleoprotein complexes prepared in vitro from recombinant Cas9 nuclease and synthetic dual guide RNA. This simple cloning-free method proves to be extremely efficient for the generation of indels and small deletions by non-homologous end joining, and for the generation of specific point mutations by homology-directed repair. The procedure, which avoids DNA construction, in vitro transcription and oocyte microinjection, greatly simplifies genome editing in mice.
Characterization of a new Pm2 allele associated with broad-spectrum powdery mildew resistance in wheat line Subtil
Authors: Jin Yuli , Xu Hongxing , Ma Pengtao , Fu Xiaoyi , Song Liping , Xu Yunfeng , Zhang Xiaotian , An Diaoguo
Published: January 2018

Wheat powdery mildew is a severe disease affecting yield and quality. Host resistance was proved to be effective and environment-friendly. Wheat line Subtil is an elite germplasm resource resistant to 28 of 30 tested Bgt isolates. Genetic analysis showed that the powdery mildew resistance in Subtil was conferred by a single dominant gene, temporarily designated PmSub. Using bulked segregant analysis, PmSub was mapped to chromosome arm 5DS, and flanked by the markers Bwm16 and Cfd81/Bwm21 at 5.0 and 0.9 cM, respectively. Allelism tests further confirmed PmSub was allelic with documented Pm2 alleles. Then, homologous sequences of Pm2a related sequence was cloned from Subtil and Chinese Spring. It was completely identical to the reported Pm2a sequence, but significantly different from that of Chinese Spring. A marker SWGI067 was developed based on the sequence divergence of homologous sequence in Subtil and Chinese Spring. SWGI067 was closely linked to PmSub, indicating that the gene PmSub itself was different from the cloned Pm2a related sequence. Meanwhile, Subtil produced significantly different reaction pattern compared with other genotypes with Pm genes at or near Pm2 locus. Therefore, PmSub was most likely a new allele of Pm2. PmSub has opportunities for marker-assisted selecting for high-efficiency wheat improvement.
A set of synthetic versatile genetic control elements for the efficient expression of genes in Actinobacteria
Authors: Horbal Lilya , Siegl Theresa , Luzhetskyy Andriy
Published: January 2018

The design and engineering of secondary metabolite gene clusters that are characterized by complicated genetic organization, require the development of collections of well-characterized genetic control elements that can be reused reliably. Although a few intrinsic terminators and RBSs are used routinely, their translation and termination efficiencies have not been systematically studied in Actinobacteria. Here, we analyzed the influence of the regions surrounding RBSs on gene expression in these bacteria. We demonstrated that inappropriate RBSs can reduce the expression efficiency of a gene to zero. We developed a genetic device – an in vivo RBS-selector – that allows selection of an optimal RBS for any gene of interest, enabling rational control of the protein expression level. In addition, a genetic tool that provides the opportunity for measurement of termination efficiency was developed. Using this tool, we found strong terminators that lead to a 17–100-fold reduction in downstream expression and are characterized by sufficient sequence diversity to reduce homologous recombination when used with other elements. For the first time, a C-terminal degradation tag was employed for the control of protein stability in Streptomyces. Finally, we describe a collection of regulatory elements that can be used to control metabolic pathways in Actinobacteria.
Exploring the utility of alcohol flushing as an instrumental variable for alcohol intake in Koreans
Authors: Cho Yoonsu , Kwak Soyoung , Lewis Sarah J. , Wade Kaitlin H. , Relton Caroline L. , Smith George Davey , Shin Min-Jeong
Published: January 2018

Previous studies have indicated an association of higher alcohol intake with cardiovascular disease and related traits, but causation has not been definitively established. In this study, the causal effect of alcohol intake on hypertension in 2,011 men and women from the Ansan-Ansung cohort was estimated using an instrumental variable (IV) approach, with both a phenotypic and genotypic instrument for alcohol intake: alcohol flushing and the rs671 genotype (in the alcohol dehydrogenase 2 [ALDH2] gene), respectively. Both alcohol flushing and the rs671 genotype were associated with alcohol intake (difference in alcohol intake with alcohol flushers vs. non-flushers: −9.07 g/day; 95% confidence interval [CI]: −11.12, −7.02; P-value: 8.3 × 10−18 and with the rs671 GA + AA vs. GG genotype: −7.94 g/day; 95% CI: −10.20, −5.69; P-value: 6.1 × 10−12). An increase in alcohol intake, as predicted by both the absence of alcohol flushing and the presence of the rs671 GG genotype in the IV analyses, was associated with an increase in blood pressure in men from this Korean population. In conclusion, this study supports a causal effect of alcohol intake on hypertension and indicated that alcohol flushing may be a valid proxy for the ALDH2 rs671 polymorphism, which influences alcohol intake in this Korean population.
Microbial synthesis of a useful optically active (+)-isomer of lactone with bicyclo[4.3.0]nonane structure
Authors: Boratyński Filip , Janik-Polanowicz Agata , Szczepańska Ewa , Olejniczak Teresa
Published: January 2018

Lactone 2a of a bicyclo[4.3.0]nonane structure is a good starting material for synthesis of many attractive compounds. Enantiomerically enriched (−)-(3aR,7aS)-lactone 2a is produced by whole cells of bacteria. In order to examine the impact of the absolute configuration on biological activity we evaluated the process affording the opposite isomer. To this purpose Candida pelliculosa ZP22 characterized by high dehydrogenase activity was used. The goal of presented work was to perform bioreactor scale microbial one-pot oxidation of diol with selected yeast strain C. pelliculosa ZP22 to obtain chiral (+)-(3aS,7aR)-lactone 2a. The idea was to influence on alcohol dehydrogenase activity by increasing the activity of pro-(+)-ADH and simultanously diminishing the activity of pro-(−)-ADH. The optimization of biotransformation conditions involved the manipulation of the nutritional and physical parameters. Selection of the optimal medium in order to improve yield and process enantioselectivity was based on a two-level factorial design methodology. We have also studied the relationship between microbial growth and biosynthesis of lactone 2a. Preparative oxidation of diol 3a (400 mg/L, 2.9 mM) catalyzed by C. pelliculosa ZP22 in an optimized conditions afforded enantiomerically enriched (+)-(3aS,7aR)-isomer of lactone 2a with the isolated yield (30%).
Low amounts of dietary fibre increase in vitro production of short-chain fatty acids without changing human colonic microbiota structure
Authors: Sasaki Daisuke , Sasaki Kengo , Ikuta Naoko , Yasuda Takahiro , Fukuda Itsuko , Kondo Akihiko , Osawa Ro
Published: January 2018

This study investigated the effect of various prebiotics (indigestible dextrin, α-cyclodextrin, and dextran) on human colonic microbiota at a dosage corresponding to a daily intake of 6 g of prebiotics per person (0.2% of dietary intake). We used an in vitro human colonic microbiota model based on batch fermentation starting from a faecal inoculum. Bacterial 16S rRNA gene sequence analysis showed that addition of 0.2% prebiotics did not change the diversity and composition of colonic microbiota. This finding coincided with results from a clinical study showing that the microbiota composition of human faecal samples remained unchanged following administration of 6 g of prebiotics over seven days. However, compared to absence of prebiotics, their addition reduced the pH and increased the generation of acetate and propionate in the in vitro system. Thus, even at such relatively low amounts, prebiotics appear capable of activating the metabolism of colonic microbiota.
Neither action nor phonological video games make dyslexic children read better
Authors: Łuniewska Magdalena , Chyl Katarzyna , Dębska Agnieszka , Kacprzak Agnieszka , Plewko Joanna , Szczerbiński Marcin , Szewczyk Jakub , Grabowska Anna , Jednoróg Katarzyna
Published: January 2018

The prevalence and long-term consequences of dyslexia make it crucial to look for effective and efficient ways of its therapy. Action video games (AVG) were implied as a possible remedy for difficulties in reading in Italian and English-speaking children. However, the studies examining the effectiveness of AVG application in dyslexia suffered from significant methodological weaknesses such as small sample sizes and lack of a control group with no intervention. In our study, we tested how two forms of training: based on AVG and on phonological non-action video games (PNAVG), affect reading in a group of fifty-four Polish children with dyslexia. Both speed and accuracy of reading increased in AVG as much as in PNAVG group. Moreover, both groups improved in phonological awareness, selective attention and rapid naming. Critically, the reading progress in the two groups did not differ from a dyslexic control group which did not participate in any training. Thus, the observed improvement in reading in AVG and PNAVG can be attributed either to the normal reading development related to schooling or to test practice effect. Overall, we failed to replicate previous studies: Neither AVG nor PNAVG remedy difficulties in reading in school children.
Crystallization and Polymorphism of Organic Semiconductor in Thin Film Induced by Surface Segregated Monolayers
Authors: Izawa Seiichiro , Nakano Kyohei , Suzuki Kaori , Chen Yujiao , Kikitsu Tomoka , Hashizume Daisuke , Koganezawa Tomoyuki , Nguyen Thuc-Quyen , Tajima Keisuke
Published: January 2018

Preparation of highly crystalline organic semiconductor films is vital to achieving high performance in electronic devices. Here we report that surface segregated monolayers (SSMs) on top of phenyl-C61-butyric acid methyl ester (PCBM) thin films induce crystal growth in the bulk, resulting in a dramatic change in the structure to form a new crystal phase. Highly ordered crystalline films with large domain sizes of several hundreds of nanometers are formed with uniaxial orientation of the crystal structure perpendicular to the substrate. The molecular rearrangements in SSMs trigger the nucleation at a lower temperature than that for the spontaneous nucleation in PCBM. The vertical charge mobility in the SSM-induced crystal domains of PCBM is five times higher than in the ordinary polycrystalline domains. Using surface monolayers may be a new strategy for controlling crystal structures and obtaining high-quality organic thin films by post-deposition crystallization.
Outcomes of ureteroscopy miniaturization on tissue damage and tissue hypoxia in a pig model
Authors: Caballero-Romeu Juan P. , Galán-Llopis Juan A. , Soria Federico , Morcillo-Martín Esther , Caballero-Pérez Pablo , De La Cruz-Conty Julia E. , Romero-Maroto Jesús
Published: January 2018

Miniaturization of ureteroscopy materials is intended to decrease tissue damage. However, tissue hypoxia and the gross and microscopic effects on tissue have not been adequately assessed. We compared the gross and microscopic effects of micro-ureteroscopy (m-URS) and conventional ureteroscopy (URS) on the urinary tract. We employed 14 pigs of the Large White race. URS was performed in one of the ureters with an 8/9.8 F ureteroscope, while a 4.85 F m-URS sheath was used in the contralateral ureter. Gross assessment of ureteral wall damage and ureteral orifice damage was performed. For microscopic assessment hematoxylin-eosin staining and immunohistochemistry for detection of tissue hypoxia were conducted. Regarding the macroscopic assessment of ureteral damage, substantial and significant differences were recorded using URS (C = 0.8), but not with m-URS. Microscopic assessment after staining with hematoxylin-eosin revealed greater epithelial desquamation in the URS group (p < 0.05). Pimonidazole staining revealed greater hypoxia in the epithelial cells than in the remainder of the ureteral layers. We conclude that m-URS causes less damage to the ureteral orifice than URS. Histopathological findings show m-URS reduces ureteral epithelial damage compared with conventional ureteroscopy. Both URS and m-URS cause cellular hypoxia.
Impacts of simulated erosion and soil amendments on greenhouse gas fluxes and maize yield in Miamian soil of central Ohio
Authors: Liang Yanru , Lal Rattan , Guo Shengli , Liu Ruiqiang , Hu Yaxian
Published: January 2018

Erosion-induced topsoil loss is a threat to sustainable productivity. Topsoil removal from, or added to, the existing surface is an efficient technique to simulate on-site soil erosion and deposition. A 15-year simulated erosion was conducted at Waterman Farm of Ohio State University to assess impacts of topsoil depth on greenhouse gas (GHG) emissions and maize yield. Three topsoil treatments were investigated: 20 cm topsoil removal, 20 cm topsoil addition, and undisturbed control. Results show that the average global warming potential (GWP) (Mg CO2 Eq ha−1 growing season−1) from the topsoil removal plot (18.07) exhibited roughly the same value as that from the undisturbed control plot (18.11), but declined evidently from the topsoil addition plot (10.58). Maize yield decreased by 51% at the topsoil removal plot, while increased by 47% at the topsoil addition plot, when compared with the undisturbed control (7.45 Mg ha−1). The average GWP of erosion-deposition process was 21% lower than that of the undisturbed control, but that greenhouse gas intensity (GHGI) was 22% higher due to lower yields from the topsoil removal plot. Organic manure application enhanced GWP by 15%, and promoted maize yield by 18%, but brought a small reduction GHGI (3%) against the N-fertilizer application.
Rapid Biochemical Mixture Screening by Three-Dimensional Patterned Multifunctional Substrate with Ultra-Thin Layer Chromatography (UTLC) and Surface Enhanced Raman Scattering (SERS)
Authors: Lee Bi-Shen , Lin Pi-Chen , Lin Ding-Zheng , Yen Ta-Jen
Published: January 2018

We present a three-dimensional patterned (3DP) multifunctional substrate with the functions of ultra-thin layer chromatography (UTLC) and surface enhanced Raman scattering (SERS), which simultaneously enables mixture separation, target localization and label-free detection. This multifunctional substrate is comprised of a 3DP silicon nanowires array (3DP-SiNWA), decorated with silver nano-dendrites (AgNDs) atop. The 3DP-SiNWA is fabricated by a facile photolithographic process and low-cost metal assisted chemical etching (MaCE) process. Then, the AgNDs are decorated onto 3DP-SiNWA by a wet chemical reduction process, obtaining 3DP-AgNDs@SiNWA multifunctional substrates. With various patterns designed on the substrates, the signal intensity could be maximized by the excellent confinement and concentrated effects of patterns. By using this 3DP-AgNDs@SiNWA substrate to scrutinize the mixture of two visible dyes, the individual target could be recognized and further boosted the Raman signal of target 15.42 times comparing to the un-patterned AgNDs@SiNWA substrate. Therefore, such a three-dimensional patterned multifunctional substrate empowers rapid mixture screening, and can be readily employed in practical applications for biochemical assays, food safety and other fields.
Counting statistics of photon emissions detected in non-Markovian environment
Authors: Xu Luting , Li Xin-Qi
Published: January 2018

In this work we present a large-deviation analysis for the counting statistics of atomic spontaneous emissions continuously detected in finite-bandwidth non-Markovian environment. We show that the statistics of the spontaneous emissions depends on the time interval (τ) of successive detections, which can result in big differences such as dynamical phase transition. This feature excludes the idea of regarding the spontaneous emissions as detection-free objective events. Possible experiment is briefly discussed in connection with the state-of-the-art optical cavity set-up.
Splicing of platelet resident pre-mRNAs upon activation by physiological stimuli results in functionally relevant proteome modifications
Authors: Nassa Giovanni , Giurato Giorgio , Cimmino Giovanni , Rizzo Francesca , Ravo Maria , Salvati Annamaria , Nyman Tuula A. , Zhu Yafeng , Vesterlund Mattias , Lehtiö Janne , Golino Paolo , Weisz Alessandro , Tarallo Roberta
Published: January 2018

Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide. Combining proteomics and transcriptomics allowed in depth platelet proteome characterization, revealing a significant effect of either stimulus on proteome composition. In silico analysis revealed the presence of resident immature RNAs in resting platelets, characterized by retained introns, while unbiased proteogenomics correlated intron removal by RNA splicing with changes on proteome composition upon activation. This allowed identification of a set of transcripts undergoing maturation by intron removal during activation and resulting in accumulation of the corresponding peptides at exon-exon junctions. These results indicate that RNA splicing events occur in platelets during activation and that maturation of specific pre-mRNAs is part of the activation cascade, contributing to a dynamic fine-tuning of the transcriptome.
Chemotherapy plus Panitumumab Versus Chemotherapy plus Bevacizumab in Metastatic Colorectal Cancer: A Meta-analysis
Authors: Li Zhigui , Huang Yuqian , Zhao Rui , Cui Yaping , Zhou Yong , Wu Xiaoting
Published: January 2018

Panitumumab and bevacizumab have been widely used in combination with chemotherapy for patients with wild type RAS metastatic colorectal cancer (mCRC). Whether panitumumab or bevacizumab was the optimal option remained controversial. Thus, we conducted a meta-anaylsis to evaluate chemotherapy plus panitumumab (C + P) versus chemotherapy plus bevacizumab (C + B) in wild type RAS mCRC. Electronic databases including PubMed, Embase, and Web of Science, Cochrane Library, ClinicalTrials.gov, were searched. This meta-analysis estimated the progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and adverse events (AEs). Three randomized controlled trials with a total number of 577 patients were included. In wild type RAS population, PFS [hazard ratio (HR) = 0.96; 95% confidence interval (CI), 0.76 to 1.15] and OS (HR = 0.90; 95% CI, 0.54 to 1.27) and ORR [relative ratio (RR) = 2.06; 95% CI, 0.86 to 4.90] appeared similar between the two treatments, the incidence of AEs slightly increased (RR = 1.16; 95% CI 1.08 to 1.26). In conclusion, there was insufficient evidence to precisely conclude that combination treatment of C + P had an improved efficacy compared with C + B. Further large-scale and better-designed clinical trials are still needed to evaluate the combination treatment of C + P in patients with wild type RAS mCRC.