bluuebunny/crossref_metadata_2025 huggingface dataset:
A Flexible Interpenetrated Zirconium‐Based Metal–Organic Framework with High Affinity toward Ammonia
Authors: Zhang Yuanyuan , Zhang Xuan , Chen Zhijie , Otake Ken‐ichi , Peterson Gregory W. , Chen Yongwei , Wang Xingjie , Redfern Louis R. , Goswami Subhadip , Li Peng , Islamoglu Timur , Wang Bo , Farha Omar K.
Published: February 2020

Flexible metal–organic frameworks (MOFs) are highly attractive porous crystalline materials presenting structural changes when exposed to external stimuli, the mechanism of which is often difficult to glean, owing to their complex and dynamic nature. Herein, a flexible interpenetrated Zr‐MOF, NU‐1401, composed of rare 4‐connected Zr6 nodes and tetratopic naphthalenediimide (NDI)‐based carboxylate linkers, was designed. The intra‐framework pore opening deformation and inter‐framework motions, when subjected to different solvent molecules, were investigated by single‐crystal XRD. The distance and overlap angle between the stacked NDI pairs in the entangled structure could be finely tuned, and the interactions between NDI and solvent molecules led to solvochromism. Furthermore, the presence of electron‐deficient NDI units in the linker and acid sites on the node of the interpenetrated porous structure offered high density of adsorption sites for ammonia molecules, resulting in high uptake at low pressures.
Ion acceleration from aluminium plasma generated by a femtosecond laser in different conditions
Authors: Torrisi Lorenzo , Rosinski Marcin , Terwinska Dominika , Tchorz Przemyslaw , Cutroneo Mariapompea , Torrisi Alfio
Published: February 2020

Non‐equilibrium plasma was obtained by irradiating Al foils in vacuum with a femtosecond (fs) laser at intensities of the order of 1018 W/cm2. Protons and other light ions were accelerated in the forward direction by using the target‐normal‐sheath acceleration regime. Time‐of‐flight technique was employed to measure the ions' kinetic energy using SiC detectors placed at known distances and angles. The ion acceleration was monitored under different conditions of laser focal position, laser pulse energy, and laser contrast. The target was irradiated using different thicknesses and anti‐reflecting graphene films. By optimizing the laser parameters, irradiation conditions, and target properties, it was possible to accelerate up to 2.3 MeV per charge state, as will be presented and discussed.
GWO‐C: Grey wolf optimizer‐based clustering scheme for WSNs
Authors: Agrawal Deepika , Wasim Qureshi Muhammad Huzaif , Pincha Pooja , Srivastava Prateet , Agarwal Sourabh , Tiwari Vikram , Pandey Sudhakar
Published: February 2020

A wireless sensor network (WSN) is a prominent technology that could assist in the fourth industrial revolution. Sensor nodes present in the WSNs are functioned by a battery. It is impossible to recharge or replace the battery, hence energy is the most important resource of WSNs. Many techniques have been devised and used over the years to conserve this scarce resource of WSNs. Clustering has turned out to be one of the most efficient methods for this purpose. This paper intends to propose an efficient technique for election of cluster heads in WSNs to increase the network lifespan. For the achievement of this task, grey wolf optimizer (GWO) has been employed. In this paper, the general GWO has been modified to cater to the specific purpose of cluster head selection in WSNs. The objective function for the proposed formulation considers average intra‐cluster distance, sink distance, residual energy, and CH balancing factor. The simulations are carried out in diverse conditions. On comparison of the proposed protocol, ie, GWO‐C protocol with some well‐known clustering protocols, the obtained results prove that the proposed protocol outperforms with respect to the consumption of the energy, throughput, and the lifespan of the network. The proposed protocol forms energy‐efficient and scalable clusters.
Teachers' beliefs in inclusive education and the attributional responses toward students with and without specific learning difficulties
Authors: Woodcock Stuart
Published: February 2020

Teachers' beliefs in inclusive education can be influential toward the success of inclusive practices and also students' successes and failures within the classroom. Having a clear understanding and high expectations toward students with specific learning difficulties (SpLD) is important if these students are to reach their potential. This study examined 276 British primary and secondary teachers' perceptions toward inclusive education for all, and their causal attributions toward students with and without SpLD. The results show that teachers who believe that inclusive education is an effective way to teach all students, provide greater positive feedback, feel less frustrated, and hold lower expectations for future failure, in comparison to their colleagues with more negative inclusive educational beliefs. Teachers need to believe that inclusive education is an effective way to teach all students, and that they, as teachers are capable of managing this. However, they need to be provided with relevant systemic support.
Heat knockdown resistance and chill‐coma recovery as correlated responses to selection on mating success at high temperature in Drosophila buzzatii
Authors: Stazione Leonel , Norry Fabian M. , Gomez Federico H. , Sambucetti Pablo
Published: February 2020

Reproduction and related traits such as mating success are strongly affected by thermal stress. We tested direct and correlated responses to artificial selection in replicated lines of Drosophila buzzatii that were selected for mating success at high temperature. Knockdown resistance at high temperature (KRHT) and chill‐coma recovery (CCR) were tested as correlated selection responses. Virgin flies were allowed to mate for four hours at 33°C in three replicated lines (S lines) to obtain the selected flies and then returned at 25°C to lay eggs. Other three replicated lines were maintained at 25°C without any selection as control (C lines). After 15 selection generations, KRHT and CCR were measured. Both traits were assessed in flies that did not receive any hardening pretreatments as well as in flies that were either heat or cold hardened. Thermotolerance traits showed significant correlated responses with higher KRHT in S than in C lines, both with a heat‐hardening pretreatment and without a heat‐hardening pretreatment. CCR time was longer in S than in C lines both with a cold‐hardening pretreatment and without a cold‐hardening pretreatment. Hardening treatments improved both KRHT and CCR in all cases excepting KRHT in C lines. Overall, KRHT and CCR showed an antagonistic pattern of correlated responses to our selection regime, suggesting either pleiotropy or tightly linked trait‐specific genes partially affecting KRHT and CCR.
Histological skeletochronology indicates developmental plasticity in the early Permian stem lissamphibian Doleserpeton annectens
Authors: Gee Bryan M. , Haridy Yara , Reisz Robert R.
Published: February 2020

Doleserpeton annectens is a small‐bodied early Permian amphibamiform, a clade of temnospondyl amphibians regarded by many workers to be on the lissamphibian stem. Most studies of this taxon have focused solely on its anatomy, but further exploration of other aspects of its paleobiology, such as developmental patterns, is critical for a better understanding of the early evolutionary history of lissamphibians. Here, we present a histological analysis of growth patterns in D. annectens that utilizes 60 femora, the largest sample size for any Paleozoic tetrapod. We identified pervasive pairs of closely spaced lines of arrested growth (LAGs), a pattern that indicates a marked degree of climatic harshness and that would result in two cessations of growth within a presumed single year. We documented a wide degree of variation compared to previous temnospondyl skeletochronological studies, reflected in the poor correlation between size and inferred age, but this observation aligns closely with patterns observed in extant lissamphibians. Furthermore, sensitivity analyses conducted by subsampling our dataset at more typical sample sizes for paleontological studies produced a wide range of results. This includes biologically improbable results and exceptionally well‐fit curves that demonstrate that low sample size can produce potentially misleading artifacts. We propose that the weak correlation between age and size represents developmental plasticity in D. annectens that typifies extant lissamphibians. Detection of these patterns is likely only possible with large sample sizes in extinct taxa, and low sample sizes can produce false, misleading results that warrant caution in drawing paleobiological interpretations from such samples.
Critical transitions in rainfall manipulation experiments on grasslands
Authors: Matos Ilaíne S. , Flores Bernardo M. , Hirota Marina , Rosado Bruno H. P.
Published: February 2020

As a result of climate and land‐use changes, grasslands have been subjected to intensifying drought regimes. Extreme droughts could interfere in the positive feedbacks between grasses and soil water content, pushing grasslands across critical thresholds of productivity and leading them to collapse. If this happens, systems may show hysteresis and costly management interventions might be necessary to restore predrought productivity. Thus, neglecting critical transitions may lead to mismanagement of grasslands and to irreversible loss of ecosystem services. Rainfall manipulation experiments constitute a powerful approach to investigate the risk of such critical transitions. However, experiments performed to date have rarely applied extreme droughts and have used resilience indices that disregard the existence of hysteresis. Here, we suggest how to incorporate critical transitions when designing rainfall manipulation experiments on grasslands and when measuring their resilience to drought. The ideas presented here have the potential to trigger a perspective shift among experimental researchers, into a new state where the existence of critical transitions will be discussed, experimentally tested, and largely considered when assessing and managing vegetation resilience to global changes.
Quantitative analysis of human NK cell reactivity using latex beads coated with defined amounts of antibodies
Authors: Dorsch Madeleine , Urlaub Doris , Bönnemann Vivian , Bröde Peter , Sandusky Mina , Watzl Carsten
Published: February 2020

Natural Killer (NK) cell responses are regulated by a variety of different surface receptors. While we can determine the overall positive or negative effect of a given receptor on NK cell functions, investigating NK cell regulation in a quantitative way is challenging. To quantitatively investigate individual receptors for their effect on NK cell activation, we chose to functionalize latex beads that have approximately the same size as lymphocytes with defined amounts of specific antibodies directed against distinct activating receptors. This enabled us to investigate NK cell reactivity in a defined, clean, and controllable system. Only CD16 and NKp30 could activate the degranulation of resting human NK cells. CD16, NKG2D, NKp30, NKp44, and NKp46 were able to activate cultured NK cells. NK cell activation resulted in the induction of polyfunctional cells that degranulated and produced IFN‐γ and MIP‐1β. Interestingly, polyfunctional NK cells were only induced by triggering ITAM‐coupled receptors. NKp44 showed a very sensitive response pattern, where a small increase in receptor stimulation caused maximal NK cell activity. In contrast, stimulation of 2B4 induced very little NK cell degranulation, while providing sufficient signal for NK cell adhesion. Our data demonstrate that activating receptors differ in their effectiveness to stimulate NK cells.
Antibody, but not B‐cell–dependent antigen presentation, plays an essential role in preventing Chlamydia systemic dissemination in mice
Authors: Malaviarachchi Priyangi A. , Mercado Miguel A.B. , McSorley Stephen J. , Li Lin‐Xi
Published: February 2020

The obligate intracellular bacterium Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. CD4 T cells play a central role in the protective immunity against Chlamydia female reproductive tract (FRT) infection, while B cells are thought to be dispensable for resolution of primary Chlamydia infection in mouse models. We recently reported an unexpected requirement of B cells in local Chlamydia‐specific CD4 T‐cell priming and bacterial containment within the FRT. Here, we sought to tackle the precise effector function of B cells during Chlamydia primary infection. Using mixed bone marrow chimeras that lack B‐cell–dependent Ag presentation () or devoid of circulating antibodies (AID−/− × μS−/−), we show that Chlamydia‐specific CD4 T‐cell expansion does not rely on Ag presentation by B cells. Importantly, we demonstrate that antibody, but not B‐cell–dependent Ag presentation, is required for preventing systemic bacterial dissemination following Chlamydia FRT infection.
Fluorescent Dyes with Large Stokes Shifts Based on Benzo[1,2‐d:4,5‐d']bis([1,3]dithiole) (“S4‐DBD Dyes”)
Authors: Wessig Pablo , Freyse Daniel , Schuster David , Kelling Alexandra
Published: February 2020

We report on a further development of [1,3]‐dioxolo[4.5‐f]benzodioxole (DBD) fluorescent dyes by replacement of the four oxygen atoms of the heterocyclic core by sulfur atoms. This variation causes striking changes of the photophysical properties. Whereas absorption and emission significantly shifted to longer wavelength, the fluorescence lifetimes and quantum yields are diminished compared to DBD dyes. The latter effect is presumably caused by an enhanced intersystem crossing to the triplet state due to the sulfur atoms. The very large Stokes shifts of the S4‐DBD dyes ranging from 3000 cm–1 to 7400 cm–1 (67 nm to 191 nm) should be especially emphasized. By analogy with DBD dyes a broad variation of absorption and emission wavelength is possible by introducing different electron withdrawing substituents. Moreover, some derivatives for coupling with biomolecules were developed.
Geological characteristics and abnormal pore pressure prediction in shale oil formations of the Dongying depression, China
Authors: Zhang Yushuai , Lv Dawei , Wang Yong , Liu Haiyan , Song Guangzeng , Gao Jie
Published: February 2020

Pore pressures in shale oil formations in the Dongying depression of the Bohai Bay Basin are highly overpressured. Understanding overpressure principles not only can reveal the mechanism of shale oil generation to provide prospects for shale oil exploration and production, but also can reduce potential drilling risks and provide insights for sweet spot identification. Overpressure generation mechanisms are analyzed based on petrophysical data, core analysis, sedimentation rate, oil saturation, and smectite and illite data. We find that undercompaction, oil generation, and smectite and illite transformation are primary causes of overpressures. Undercompaction is the major cause of overpressures in the Es3 formations because of their rapid deposition rate of 300‐700 m/m.y. For the overpressures primarily generated by undercompaction, sonic transit time can be used to predict shale pore pressure with correctly selected depth‐dependent normal compaction trend. In the Es3 and Es4 formations, overpressure data are consistent with the increase of vitrinite reflectance and oil saturation, indicators of oil generation. Additionally, in shallow formations, starting at about 2000 m, the smectite to illite transformation occurs, which makes rock property changes with depth. A composite normal compaction trendline is proposed to account for the smectite to illite transformation. Using well log data, the shale oil formations can be identified and there are two shale oil formations in the studied area, and a shale oil geo‐marker is found. At this geo‐marker, the pore pressure gradient reaches the highest value. This high pore pressure behavior is beneficial for shale oil production because of a higher pore pressure corresponds to a higher production.
High‐latitude dust deposition in snow on the glaciers of James Ross Island, Antarctica
Authors: Kavan Jan , Nývlt Daniel , Láska Kamil , Engel Zbyněk , Kňažková Michaela
Published: February 2020

High‐latitude dust (HLD) depositions on four glaciers of James Ross Island (the Ulu Peninsula) were analysed. The deposition rate on the selected glaciers varies from 11.8 to 64.0 g m−2, which is one order of magnitude higher compared to the glaciers in Antarctica or elsewhere in the world. A strong negative relationship between the sediment amount and altitude of a sampling site was found. This is most likely caused by the higher availability of aeolian material in the atmospheric boundary layer. General southerly and south‐westerly wind directions over the Ulu Peninsula – with exceptions based on local terrain configuration – help to explain the significantly lower level of sediment deposition on San Jose Glacier and the high level on Triangular Glacier. X‐ray fluorescence (XRF) spectrophotometry was used to estimate the relative proportions of the main and trace (lithophile) elements in the sediment samples. Both the sediment amount and the XRF results are analysed in a depth profile at each locality and compared among the glaciers, suggesting long‐range transport of fine mineral material from outside James Ross Island. The distribution of aeolian sediment among the glaciers corresponds well with the prevailing wind direction on the Ulu Peninsula. © 2020 John Wiley & Sons, Ltd.
Capacity driven small cell deployment in heterogeneous cellular networks: Outage probability and rate coverage analysis
Authors: Ullah Arif , Haq Abbas Ziaul , Muhammad Fazal , Abbas Ghulam , Jiao Lei
Published: February 2020

Heterogeneous cellular networks (HCNets) are one of the key enabling technologies to improve performance gain of future cellular networks. Stochastic geometry is considered a promising tool to model and analyze HCNets. Users and base stations (BSs) are generally distributed uniformly using a homogeneous Poisson point process (HPPP). The assumption of uniformly distributed users is not suitable in HCNets because of the existence of clustered users in hotspots. To consider the correlation between the users and BSs, deployment of small base stations in these areas are of great concern to increase the performance of HCNets. In this article, we assume the notion of mixed user distribution, wherein the network users are the superposition of clustered and uniform users, modeled through HPPP and Poisson cluster process, respectively. We evaluate outage probability and rate coverage of the proposed HCNet model. We compare the network performance of the proposed mixed user distribution model with the conventional uniformly distributed user model. The analytical results are validated using Monte‐Carlo simulations. Our results show that the proposed HCNet model of mixed user distribution outperforms the uniformly distributed user model in terms of outage probability and rate coverage.
The influence of individual impairments in crowd dynamics
Authors: Geoerg Paul , Schumann Jette , Holl Stefan , Boltes Maik , Hofmann Anja
Published: February 2020

The importance of empirical relations to quantify the movement of pedestrians through a facility has increased during the last decades since performance‐based design methods became more common. Bottlenecks are of special interest because of their importance for egress routes and as they result in a reduced capacity. The empirical relations as the density‐dependent movement speed or flow rate were derived by studies under laboratory conditions, which were usually conducted with populations of homogeneous characteristics for better control of influencing variables. If individual characteristics of a crowd become more heterogeneous, individuals were forced to adapt their individual movement and control individual manoeuvring. These unintended interactions lead to a different shape of the fundamental empirical relations. Here, we present results from a movement study under well‐controlled boundary conditions in which participants with and without different characteristics of disabilities participated. To consider the effect of different heterogeneities on the capacity of a facility, fundamental diagrams are generated using the Voronoi method. If participants with visible disabilities (such as using assistive devices) are part of a crowd, significant differences relating to the shape of the empirical relations and the capacities are found. This indicates that the heterogeneity of a population leads to an increased interpersonal interaction which results in influenced movement characteristics.
New synchronicity indices between real and financial cycles: Is there any link to structural characteristics and recessions in European Union countries?
Authors: Comunale Mariarosaria
Published: February 2020

In this paper, we examine the comovements and relationships between real, credit, house, and equity price cycles in European Union countries looking at their link to structural characteristics and their predictive power for future recessions. We make use of new within country synchronicity indices, finding that among the different credit cycles and between the house price cycle and the real cycle, there is a relatively high level of synchronicity. Credit and gross domestic product (GDP) fluctuations seem to be less synchronised, mostly because credit volumes tend to lag the real cycle by several quarters. The high rates of private homeownership tend to be associated with larger cycles in GDP, credit, and house prices. Higher loan‐to‐value ratios, seen as a proxy of borrowing constraints, and a higher percentage of flexible‐rate mortgages, could also indicate that a country is more sensitive to shocks and possibly increase procyclicality and increase cycle volatility. Finally, the procyclicality of the credit and housing market to the GDP cycle can be linked to the fluctuation in current accounts and their misalignments with respect to the theoretical equilibrium value. Some synchronicity measures and, above all, the credit cycles may also be considered for signalling future recessions.
The sodium channel NaX: Possible player in excitation–contraction coupling
Authors: Bogdanovic Elena , Potet Franck , Marszalec William , Iyer Hari , Galiano Robert , Hong Seok J. , Leung Kai P. , Wasserstrom John Andrew , George Alfred L. , Mustoe Thomas A.
Published: February 2020

The sodium channel NaX (encoded by the SCN7A gene) was originally identified in the heart and skeletal muscle and is structurally similar to the other voltage‐gated sodium channels but does not appear to be voltage gated. Although NaX is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of NaX in these tissues. Transcriptional profiling of ion channels in the heart in a subset of patients with Brugada syndrome revealed an inverse relationship between the expression of NaX and NaV1.5 suggesting that, in cardiac myocytes, the expression of these channels may be linked. We propose that NaX plays a role in excitation–contraction coupling based on our experimental observations. Here we show that in cardiac myocytes, NaX is expressed in a striated pattern on the sarcolemma in regions corresponding to the sarcomeric M‐line. Knocking down NaX expression decreased NaV1.5 mRNA and protein and reduced the inward sodium current (INa+) following cell depolarization. When the expression of NaV1.5 was knocked down, ~85% of the INa+ was reduced consistent with the observations that NaV1.5 is the main voltage‐gated sodium channel in cardiac muscle and that NaX likely does not directly participate in mediating the INa+ following depolarization. Silencing NaV1.5 expression led to significant upregulation of NaX mRNA. Similar to NaV1.5, NaX protein levels were rapidly downregulated when the intracellular [Ca2+] was increased either by CaCl2 or caffeine. These data suggest that a relationship exists between NaX and NaV1.5 and that NaX may play a role in excitation–contraction coupling.
The miR-143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin-1
Authors: Urdinez Joaquin , Boro Aleksandar , Mazumdar Alekhya , Arlt Matthias JE , Muff Roman , Botter Sander M , Bode-Lesniewska Beata , Fuchs Bruno , Snedeker Jess G , Gvozdenovic Ana
Published: February 2020

Chondrosarcoma is the second most frequent bone sarcoma. Due to the inherent chemotherapy and radiotherapy resistance and absence of known therapeutic targets, clinical management is limited to surgical resection. Consequently, patients with advanced disease face a poor prognosis. Hence, elucidating regulatory networks governing chondrosarcoma pathogenesis is vital for development of effective therapeutic strategies. Here, miRNA and mRNA next generation sequencing of different subtypes of human chondrogenic tumors in combination with in silico bioinformatics tools were performed with the aim to identify key molecular factors. We identified miR-143/145 cluster levels to inversely correlate with tumor grade. This deregulation was echoed in the miRNA plasma levels of patients and we provided the first evidence that circulating miR-145 is a potential noninvasive diagnostic biomarker and can be valuable as an indicator to improve the currently challenging diagnosis of cartilaginous bone tumors. Additionally, artificial upregulation of both miRNAs impelled a potent tumor suppressor effect in vitro and in vivo in an orthotopic xenograft mouse model. A combined in silico/sequencing approach revealed FSCN1 as a direct target of miR-143/145, and its depletion phenotypically resembled miR-143/145 upregulation in vitro. Last, FSCN1 is a malignancy-promoting factor associated with aggressive chondrosarcoma progression. Our findings underscore miR-143/145/FSCN1 as important players in chondrosarcoma and may potentially open new avenues for specific therapeutic intervention options. © 2020 American Society for Bone and Mineral Research.
circ‐CEP85L suppresses the proliferation and invasion of gastric cancer by regulating NFKBIA expression via miR‐942‐5p
Authors: Lu Jun , Wang Yao‐hui , Huang Xiao‐yan , Xie Jian‐wei , Wang Jia‐bin , Lin Jian‐xian , Chen Qi‐yue , Cao Long‐long , Huang Chang‐ming , Zheng Chao‐hui , Li Ping
Published: February 2020

The expression pattern and role of circular RNAs (circRNAs) in the pathogenesis of gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we identified differentially expressed circRNAs by a circRNA microarray and verified the results by quantitative reverse transcription‐polymerase chain reaction using 117 clinical samples. Cell Counting Kit‐8, wound healing, Transwell, and tumorsphere formation assays were conducted to assess the effects of circ‐CEP85L on cell proliferation and invasion in vitro. Mouse intraperitoneal injection models were used to assess the functions of circ‐CEP85L in vivo. Luciferase reporter assays, fluorescence in situ hybridization, and rescue experiments were performed to elucidate the underlying mechanism of circ‐CEP85L. We found that circ‐CEP85L, which has not been studied in GC, was significantly downregulated in GC tissues and that decreased circ‐CEP85L expression correlated significantly with a worse prognosis. The knockdown of circ‐CEP85L promoted the proliferation and invasion of GC cells, which was reversed by overexpression of circ‐CEP85L. Furthermore, inhibition of circ‐CEP85L promoted tumor growth in vivo. Mechanistically, circ‐CEP85L was confirmed to be a direct target of miR‐942‐5p. In addition, rescue experiments indicated that circ‐CEP85L is able to inhibit the proliferation and invasion of GC cells by sponging miR‐942‐5p. Finally, western blot assays verified that the downregulation of miR‐942‐5p efficiently reversed the inhibition of NFKBIA induced by circ‐CEP85L overexpression. Therefore, we conclude that circ‐CEP85L promotes NFKBIA expression by acting as a sponge of miR‐942‐5p; thus, inhibiting GC proliferation and invasion. circ‐CEP85L is a potential target in the treatment of GC.
Exosome‐mediated transfer of miR‐1260b promotes cell invasion through Wnt/β–catenin signaling pathway in lung adenocarcinoma
Authors: Xia Yang , Wei Ke , Hu Liu‐Qing , Zhou Cun‐Rong , Lu Zhi‐Bin , Zhan Gen‐Sheng , Pan Xiang‐Long , Pan Chun‐Feng , Wang Jun , Wen Wei , Xu Jing , He Zhi‐Cheng , Huang Chen‐Jun , Chen Liang
Published: February 2020

Increasing evidence confirms that exosome‐mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell–cell communication. However, the potential role of exosomal‐miR‐1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal‐miR‐1260b on cell invasion. Exosomal‐miR‐1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real‐time polymerase chain reaction assay. The sensitivity and specificity of exosomal‐miR‐1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772–0.922). Elevated expression of miR‐1260b in LAC tissues was positively correlated with exosomal‐miR‐1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal‐miR‐1260b secretion. Exosome‐mediated transfer of miR‐1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal‐miR‐1260b regulated Wnt/β–catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome‐mediated tumor‐cell‐to‐tumor‐cell communication. Targeting exosome‐microRNAs may provide new insights into the diagnosis and treatment of LAC.
Resveratrol suppresses interleukin‐6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts
Authors: Akhondzadeh Fariba , Astani Akram , Najjari Razieh , Samadi Morteza , Rezvani Mohammad Ebrahim , Zare Fatemeh , Ranjbar Ali Mohammad , Safari Fatemeh
Published: February 2020

Inflammatory cytokine, interleukin‐6 (IL‐6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL‐6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 μM) of resveratrol (R). Cell viability was measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real‐time polymerase chain reaction technique. Enzyme‐linked immunosorbent assay was used to measure IL‐6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 μM of resveratrol were used to to evaluate its anti‐inflammatory effects. The results revealed that Ang II upregulated IL‐6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 μM) decreased IL‐6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX‐527, the response of resveratrol was partially reversed. Transcription levels of IL‐6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II‐induced hypertrophy by suppression of IL‐6 through SIRT1 activation.
A Drug‐Drug Interaction Study to Evaluate the Effect of TAS‐303 on CYP3A Activity in the Small Intestine and Liver
Authors: Kumagai Yuji , Fujita Tomoe , Maeda Mika , Sasaki Yoshinobu , Nagaoka Makoto , Huang Jinhong , Takenaka Toru , Kawai Masaki
Published: February 2020

TAS‐303 (4‐piperidinyl 2,2‐diphenyl‐2‐[propoxy‐1,1,2,2,3,3,3‐d7] acetate hydrochloride) is a novel selective noradrenaline reuptake inhibitor being developed for the treatment of stress urinary incontinence. An in vitro study and a physiologically based pharmacokinetic model simulation showed that TAS‐303 had inhibitory potential against cytochrome P450 (CYP) 3A. This open‐label, single‐group study investigated the effect of TAS‐303 on CYP3A activity by evaluating the pharmacokinetics (PK) of single‐dose oral simvastatin 5 mg or intravenous midazolam 1 mg after repeated oral administration of TAS‐303 3 mg in 12 healthy participants. TAS‐303 plus simvastatin resulted in a 1.326‐fold and a 1.420‐fold increase of simvastatin in peak plasma concentration and area under the plasma concentration‐time curve from time zero to time t, where t is the final time of detection (AUC0‐t), respectively. The addition of midazolam resulted in a 1.090‐fold increase in the midazolam AUC0‐t. TAS‐303 had a weak PK interaction with simvastatin but no apparent interaction with midazolam. TAS‐303 at 3 mg/day is a weak inhibitor of intestinal but not hepatic CYP3A activity. No clinically important safety concerns related to TAS‐303 were raised.
Contrast‐enhanced ultrasonography of intraluminal inferior vena cava leiomyosarcoma: A case report
Authors: Wu Xiaobei , Zhou Pingping , Li Kaiyan
Published: February 2020

Primary leiomyosarcoma of the inferior vena cava (IVC) is a rare and fatal disease. Imaging is the main diagnostic method. CT and MRI images of IVC leiomyosarcoma have been published, but ultrasonographic features have been scarcely described, especially with contrast‐enhancement. We report the case of a patient in whom ultrasonography incidentally revealed a mass in the IVC. Contrast‐enhanced ultrasonography showed heterogeneous enhancement in the arterial phase with some irregular non‐enhanced areas, and mild clearance in the venous phase. The location and nature of the lesion as shown by ultrasonography were confirmed by CT and MRI.
Water quality performance of wetlands receiving nonpoint‐source nitrogen loads: Nitrate and total nitrogen removal efficiency and controlling factors
Authors: Crumpton William G. , Stenback Greg A. , Fisher Stephen W. , Stenback Jana Z. , Green David I. S.
Published: February 2020

Nonpoint‐source nitrogen (N) loads in the U.S. Corn Belt are a major concern both for local impacts on receiving waters and for contributing to hypoxia in the Gulf of Mexico. Nonpoint‐source nutrient loads can be ameliorated by a combination of in‐field and offsite practices, and wetland restoration is a particularly promising approach for reducing N loads from agricultural drainage. However, there is considerable variability among wetlands, and adequate performance data are available for relatively few systems receiving unregulated nonpoint‐source loads. We measured N mass balances of 26 restored wetlands receiving a wide range of unregulated, naturally varying hydraulic and nutrient loads to evaluate the N removal performance of these systems and the effects of major factors controlling their performance. Nitrogen loads were primarily in the form of nitrate, and all of the wetlands were effective in reducing both nitrate and total N loads. Nitrate N and total N removal rates averaged 1,500 and 1,440 kg N ha−1 yr−1, respectively, with the slightly lower total N removal rates reflecting a small net export of reduced N (averaging 66 kg N ha−1 yr−1). Average nitrate and total N removal rates were substantially higher than typically reported for Corn Belt wetlands but comparable with highly loaded systems elsewhere. Nitrate removal efficiency ranged from 9 to 92% and was strongly related to hydraulic loading rate and temperature. Results demonstrate the substantial capacity of wetlands to reduce unregulated and highly variable nonpoint‐source N loads over a broad range of weather and loading conditions and provide a reasonable basis for predicting average wetland performance based on hydraulic loading rate, temperature, and nitrate concentration.
Outcomes in patients with acute upper gastrointestinal bleeding following changes to management protocols at an Australian hospital
Authors: Papadinas Adrianna , Butt Joshua
Published: February 2020

Background and Aim

Upper gastrointestinal bleeding (UGIB) has a high mortality rate and requires efficient and directed acute management. This project aimed to assess patient outcomes following changes to UGIB management protocols at Northern Hospital, Victoria, Australia. Changes involved streamlining management under a single inpatient unit, earlier endoscopy, blood transfusion thresholds, and risk stratification.

Methods

This was a cohort study of 400 patients aged ≥18 years admitted to Northern Hospital who underwent endoscopy for acute UGIB. Data of preprotocol changes (Group 1) and prospectively postprotocol changes (Group 2) were collected retrospectively. Primary outcomes were inpatient mortality, rebleeding, radiologic or surgical intervention, and endoscopic reintervention. Secondary outcomes included length of stay (LOS) ≥4 days and blood units transfused. Univariate analyses were conducted comparing groups and associations between variables and outcomes, followed by multivariate analyses for each outcome.

Results

There was no difference in mortality on multivariate analysis (P = 0.95). Rebleeding reduced by 4% (adjusted odds ratio [AOR] 0.48; P = 0.03), LOS ≥4 days reduced by 15.1% (AOR 0.46; P < 0.00) and median blood units transfused decreased with adjusted incidence rate ratio of 0.81 (P = 0.00). Early endoscopy (i.e. ≤12 h) for all patients increased by 15% (P < 0.00) and there were 12% more high‐risk patients (i.e. Glasgow–Blatchford score ≥ 12) in Group 2 (P = 0.01).

Conclusion

Following changes to UGIB protocols at this Australian hospital, endoscopic times decreased with reductions in rebleeding, LOS ≥4 days, and blood transfusion rates. These findings demonstrate improved outcomes after the implementation of new treatment targets focusing on streamlined care of patients presenting with UGIB.
Repertoire analysis of memory T‐cell receptors in Japanese patients with inflammatory bowel disease
Authors: Kakuta Yoichi , Nakano Takeru , Naito Takeo , Watanabe Kazuhiro , Izumiyama Yasuhiro , Okamoto Daisuke , Ichikawa Ryo , Moroi Rintaro , Kuroha Masatake , Kanazawa Yoshitake , Kimura Tomoya , Shiga Hisashi , Naitoh Takeshi , Kinouchi Yoshitaka , Unno Michiaki , Masamune Atsushi
Published: February 2020

Background and Aim

The T‐cell receptor (TCR) repertoire was assessed in response to various antigens and was considered to be associated with the pathogenesis of inflammatory bowel disease (IBD). Thus, we performed TCR repertoire analysis to examine the pathology of IBD from changes in the TCR repertoire of memory T cells in the intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs) of patients with IBD.

Methods

LPMCs in the surgical specimens and PBMCs were isolated from 12 patients with IBD (5 patients with ulcerative colitis [UC] and 7 patients with Crohn's disease [CD]). PBMCs were collected from 10 healthy individuals as controls. Comprehensive TCR sequence analyses of adaptor‐ligation polymerase chain reaction (PCR) products were performed using MiSeq.

Results

The diversity of TCR‐α and TCR‐β in PBMCs was significantly lower in patients with IBD than that in controls (P = 0.00084 and 0.0013, respectively). Comparisons of TCR diversity in LPMCs and PBMCs between CD and UC showed that the diversity in LPMC was not affected by diseases, whereas that in PBMCs was significantly lower in CD than in UC (P = 0.045 and 0.049, respectively). Some TCR clones may have shown a specific increase or decrease in CD and UC, and many clones were common to both LPMCs and PBMCs in the same patients.

Conclusion

The diversity of TCR clones in LPMCs and PBMCs in patients with IBD was significantly lower than that of PBMCs in controls. TCR diversity in PBMCs was particularly low in patients with CD.
Synthesis of novel quinoline‐thiosemicarbazide hybrids and evaluation of their biological activities, molecular docking, molecular dynamics, pharmacophore model studies, and ADME‐Tox properties
Authors: Patel Dhaval B. , Darji Drashti G. , Patel Krupa R. , Rajani Dhanji P. , Rajani Smita D. , Patel Hitesh D.
Published: February 2020

In the present study, a novel series of N‐((substituted)carbamothioyl)‐2,4‐dimethylquinoline‐3‐carboxamide (7a‐7s) was synthesized by microwave‐assisted method. Structure of these derivatives was examined by spectroscopic techniques such as 1H NMR, 13C NMR, FT‐IR, and ESI‐MS. Further, the novel synthesized compounds were evaluated for their in‐vitro biological activities against antibacterial, antifungal, antimalarial, and antituberculosis activity as well as for in‐silico study. The antimalarial results demonstrated that compounds 7c and 7q (0.02 μg/mL) have notable potency against Plasmodium falciparum compared with chloroquine (0.02 μg/mL); compounds 7l (0.10 μg/mL), 7e, 7s (0.19 μg/mL), 7b, 7p (0.15 μg/mL), 7a, 7f, and 7f (0.25 μg/mL) also exhibited good activity against P. falciparum compared with quinine (0.26 μg/mL) as standard drug. Docking was performed on PFDHFR‐TS, given the effect of compounds against the P. falciparum strain was excellent in comparison with standard drug. Molecular docking suggested that compounds 7b, 7i and 7c, 7e, and 7l closely bind with the active site of protein 3JSU and 4DP3, respectively, and compared with biological activity. We have also carried out molecular dynamics simulation on the best dock compound 7e complex with PDB: 3JSU to check the stability of docked complex and their molecular interaction. The calculated ADME‐Tox descriptors for the synthesized compounds validated good pharmacokinetics properties, suggesting that these compounds could be used as hit for the development of the new active agents.
Automated radiosynthesis of [11C]UCB‐J for imaging synaptic density by positron emission tomography
Authors: Milicevic Sephton Selena , Miklovicz Tunde , Russell Joseph J. , Doke Aniruddha , Li Lei , Boros Istvan , Aigbirhio Franklin I.
Published: February 2020

An automated radiosynthesis of carbon‐11 positron emission tomography radiotracer [11C]UCB‐J for imaging the synaptic density biomarker synaptic vesicle glycoprotein SV2A was established using Synthra RNPlus synthesizer. Commercially available trifluoroborate UCB‐J analogue was used as a radiolabelling precursor, and the desired radiolabelled product was isolated in 11 ± 2% (n = 7) nondecay corrected radiochemical yield and formulated as a 10% EtOH solution in saline with molar activities of 20 to 100 GBq/μmol. The method was based upon the palladium(0)‐mediated Suzuki cross‐coupling reaction and [11C]CH3I as a radiolabelling synthon. The isolated product was cGMP compliant as demonstrated by the results of quality control analysis.
Relational Leadership Reconsidered: The Mentor–Protégé Connection
Authors: Early Sherry Lynn
Published: February 2020

The elements of relational leadership include “being purposeful, inclusive, ethical, and empowering” (Komives, Lucas, & McMahon, 2007, p. 3). Relational leadership is very process‐oriented, as opposed to viewing leadership as positional. A very powerful example of relational leadership in action is through engaging in mentoring relationships. The word mentor can be traced back to Homer's myth of Odysseus. Odysseus was the king of Ithaca who left his son, Telemachus in the care of Mentor, who guided and educated him for 10 years while his father was at war with the Trojans (Campbell, Smith, Dugan, & Komives, 2012; Swap, Leonard, Shields, & Abrahams, 2001). “Good developmental relationships (mentorships) promote socialization, learning, career advancement, psychological adjustment, and preparation for leadership,” noted Johnson (2007, p. 4). Those who have studied mentoring argue that in order to understand the nature and impact of mentoring relationships, it is necessary to examine its evolution (Kram, 1985). Mentoring has evolved from a formal expert–apprentice relationship like that of Mentor and Telemachus to include informal encounters and the expertise of peers. Juxtaposing this more inclusive mentor–protégé dynamic with the relationship leadership model's core elements is integral for aspiring leaders who want to build and sustain relationships in the future.
Cavitating and tigroid‐like leukoencephalopathy in a case of NDUFA2‐related disorder
Authors: Alagia Marianna , Cappuccio Gerarda , Torella Annalaura , D'Amico Alessandra , Mazio Federica , Romano Alfonso , Fecarotta Simona , Casari Giorgio , Nigro Vincenzo ,   TUDP, Brunetti‐Pierri Nicola
Published: February 2020

Biallelic variants in nuclear gene NDUFA2 have been reported so far in only three children with variable presentations including Leigh syndrome or leukoencephalopathy. Herein, we report a further female child affected by NDUFA2‐related disorder presenting with cavitating and tigroid‐like pattern of leukodystrophy and without systemic biochemical abnormalities of mitochondrial disorders.
Genomic variance of the 2019‐nCoV coronavirus
Authors: Ceraolo Carmine , Giorgi Federico M.
Published: February 2020

There is a rising global concern for the recently emerged novel coronavirus (2019‐nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019‐nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019‐nCoV. Despite the low heterogeneity of the 2019‐nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8‐encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti‐coronavirus approaches.