bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of User Emotions for Content Personalization in e-Commerce: Literature Review
Authors: Bielozorov Artem , Bezbradica Marija , Helfert Markus
Published: July 2019

Purchasing decisions do not always come from the rational mental processes but are often being driven by emotions. This insight made researchers think of emotions as of an essential contextual variable capable of enhancing personalized services and providing more precise recommendations within e-Commerce. In this paper we explore the studies made to discover why emotions are an important research domain necessary to understand purchasing behavior of online shoppers. We also explore how user emotions can be captured and recognized by existing technologies to provide enhanced personalization. Specifically, we apply Webster and Watson (2002) literature review approach to create a sample of studies published in scientific journals and conference proceedings. We synthesize the extant studies on the role of user emotions for personalized services within e-Commerce. We also provide a comprehensive concept-matrix which aggregates the range of existing emotions recognition technologies and highlights which specific emotions these technologies are able to recognize as well as in which domains these solutions are applied. Our study extends prior reviews and provides insights into open research areas which will benefit Human-Computer Interactions (HCI) practitioners and researchers in academia and industry.
Alzheimer's disease drug development pipeline: 2019
Authors: Cummings Jeffrey , Lee Garam , Ritter Aaron , Sabbagh Marwan , Zhong Kate
Published: July 2019

Introduction

Alzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD drug development programs. Study of the AD drug development pipeline can provide insight into the evolution of drug development and how best to optimize development practices.

Methods

We reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD.

Results

There are 132 agents in clinical trials for the treatment of AD. Twenty‐eight agents are in 42 phase 3 trials; 74 agents are in 83 phase 2 trials; and 30 agents are in 31 phase 1 trials. There is an increase in the number of agents in each phase compared with that in the 2018 pipeline. Nineteen agents in trials target cognitive enhancement, and 14 are intended to treat neuropsychiatric and behavioral symptoms. There are 96 agents in disease modification trials; of these, 38 (40%) have amyloid as the primary target or as one of several effects. Eighteen of the antiamyloid agents are small molecules, and 20 are monoclonal antibodies or biological therapies. Seven small molecules and ten biologics have tau as a primary or combination target (18%). Amyloid is the most common specific target in phase 3 and phase 2 disease modification trials. Novel biomarkers (e.g., neurofilament light), new outcomes (e.g., AD Composite Score [ADCOMS]), enrollment of earlier populations, and innovative trial designs (e.g., Bayesian adaptive designs) are new features in recent clinical trials.

Discussion

Drug development continues robustly at all phases despite setbacks in several programs in the recent past. Continuing unmet needs require a commitment to growing and accelerating the pipeline.
Going along with the default does not mean going on with it: attrition in a charitable giving experiment
Authors: GAUDEUL ALEXIA , KACZMAREK MAGDALENA C.
Published: July 2019

Defaults may not directly get people to behave as intended, such as saving more, eating healthy food or donating to charity. Rather, defaults often only put people on the ‘right’ path, such as joining a savings plan, buying healthy food or pledging money to charity. This an issue because getting more people to take those first steps does not necessarily motivate them to go on with further steps. Indeed, the default does little to help them understand the benefit of doing so. This can greatly reduce the impact of the default. We test this idea in a charitable giving experiment where people first can promise to give to charity (‘pledge’) and then can go on to donate. We find that participants pledge more often when that is the default, but those who pledge in that case are less likely to take further steps to donate than those who pledge when pledging is against the default. We interpret this in terms of motivation and transaction costs. Some people pledge only to avoid the psychological costs of going against the default. Those people are closest to indifference between donating or not and are therefore less motivated to go on to donate. We also show that the intrinsic motivation of pledgers is lower when pledging is the default and that making pledges the default does not change attitudes to charities.
Closure of tracheocutaneous fistula using prefabricated conchal bowl cartilage and a supraclavicular flap
Authors: Mundi N , Patel K B , Yeh D H , Nichols A C
Published: July 2019

Background

Tracheocutaneous fistula represents one of the most troublesome complications of prolonged tracheostomy. Simple closure of a fistula can be ineffective, particularly in the context of prior surgery and adjuvant radiation. As such, modes of repair have expanded to include locoregional flaps and even free tissue transfers.

Objective

This paper describes a case of persistent tracheocutaneous fistula in an irradiated patient who had undergone previous unsuccessful attempts at repair.

Method and results

The use of regional fasciocutaneous supraclavicular flap with prefabricated conchal bowl cartilage resulted in successful closure of the tracheocutaneous fistula.

Conclusion

This represents a novel technique for closure of such fistulas in patients for whom previous attempts have failed. This mode of repair should be added to the surgeon's repertoire of reparative techniques.
Using the Bioelectric Signals to Control of Wearable Orthosis of the Elbow Joint with Bi-Muscular Pneumatic Servo-Drive
Authors: Dindorf Ryszard , Wos Piotr
Published: July 2019

This study presents a new design of a wearable orthosis of elbow joint with a bimuscular pneumatic servo-drive (PSD) with control based on the recording of bioelectric signals (BESs). The authors analyzed the impact of the induced brain activity and the muscular tension within the head of the participant on the BESs that can be used to control the PSD of the elbow joint orthosis. To control the elbow joint orthosis, a distributed control system (DCS) was developed, which contains two control layers: a master layer connected to the device for recording the BES and a direct layer contained in a wireless manner with the controller of the PSD. A kinematic-dynamic model of the elbow joint orthosis, patterned after the biological model of human biceps–triceps, was used in the programming of the PSD controller. A biomimetic dynamic model of the pneumatic muscle actuator (PMA) was used, in which the contraction force results from the adopted exponential static model of the pneumatic muscle (PM). The use of direct visual feedback (DVF) makes it possible for the participant to focus on the movement of the orthosis taking into account the motoric functions of the elbow.
A “Struggle of Life or Death”: Han and Uyghur Insecurities on China's North-West Frontier
Authors: Tobin David
Published: July 2019

In July 2009, nearly 200 people were killed in ethnically targeted mass violence between Turkic-speaking Muslim Uyghurs and Han Chinese in Urumqi, overshadowing the 60th anniversary of the founding of the People's Republic of China (PRC). How have ethnic relations between Han and Uyghurs descended into mass violence among ordinary people? This paper argues that the party-state exacerbates ethnic tensions between Han and Uyghurs through ethnocentric security narratives. These narratives frame China's identity as being under threat from Turkic enemies within who are supported by Islamic terrorists and Western “enemies of China” from outside. Discourse analysis of official texts, participant-observation of security practices, and interviews with Han and Uyghurs reveal the interplay between official identity discourses and everyday security practices before, during and after the violence. Since July 2009, one official solution to ethnic violence has been the construction of a shared multi-ethnic identity, officially described as a “zero-sum political struggle of life or death.” However, Han-centric conceptualizations of ethnic unity promote Han chauvinism and portray the Uyghur as a security threat. The party-state thus creates hierarchical ethnic relations that exacerbate both Han and Uyghur insecurities and contribute to spirals of violence. China's extra-judicial internment camps in Xinjiang are the logical conclusions of the ethnocentric insecurity cycles analysed in this article.
Global Evaluation of Proxy System Models for Stable Water Isotopes With Realistic Atmospheric Forcing
Authors: Okazaki Atsushi , Yoshimura Kei
Published: July 2019

Proxy system models (PSMs) are an important bridge between climate simulations and climate records prior to the period where instrumental observations are available. PSMs help to interpret what proxies show and how they record climate. Although previous studies have evaluated PSMs for individual sites, their systematic evaluation on a global scale has not yet been conducted. This study evaluated the performance of PSMs for stable water isotopes in ice cores, corals, and tree‐ring cellulose for the period 1950–2007. Spatial distributions of the mean state were well simulated for all proxy types, albeit with a bias for tree‐ring cellulose. Interannual variability was well simulated for corals and tree‐ring cellulose. These results indicate that the models represent key mechanisms for the proxies. In contrast, the reproducibility of interannual variability in ice cores was markedly lower than that for the other proxies. Although the reproducibility was limited by the atmospheric forcing used to drive the model, the results suggest that the PSM may be missing postdepositional processes, such as sublimation for ice cores on the interannual time scale.
Lightning Location, NOx Production, and Transport by Anomalous and Normal Polarity Thunderstorms
Authors: Davis Trenton C. , Rutledge Steven A. , Fuchs Brody R.
Published: July 2019

Production and transport of NOx by convection is critical as it serves as a precursor to tropospheric ozone, an important greenhouse gas. Lightning serves as the largest source of nitrogen oxides (NOx = NO + NO2) to the upper troposphere (UT) and is one of the largest natural sources of NOx. Interest is placed on the vertical advection of NOx because its lifetime increases to several days in the UT compared to roughly 3 hr in the lower troposphere and boundary layer. Thus, lightning can play an important role in ozone production within the UT. However, the amount of NOx produced per flash and NOx advection in storms remain uncertain. This study investigates lightning NOx (LNOx) production and transport processes in anomalous (midlevel positive charge) and normal polarity (midlevel negative charge) thunderstorms by advecting parcels containing LNOx from the flash channels of over 5,600 lightning flashes observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. Results reveal that most flash channels occur near 6‐8 km in the normal polarity thunderstorms and 5‐6 km within anomalous polarity thunderstorms. Larger flash rates and stronger updrafts in anomalous storms result in considerably larger LNOx mixing ratios (peaks of 0.75‐1.75 ppb) in the UT compared to normal polarity storms (peaks < 0.5 ppb). A slightly lower mean flash LNOx production was also found among all five storms in this study (storm mean values of 72‐158 moles per flash) compared to previous estimates, which generally parameterize LNOx by flash rate rather than flash count.
Bainaimiao Arc as an Exotic Terrane Along the Northern Margin of the North China Craton: Evidences From Petrography, Zircon U‐Pb Dating, and Geochemistry of the Early Devonian Deposits
Authors: Ma Shouxian , Wang Zongqi , Zhang Yingli , Sun Jianxun
Published: July 2019

As one of the most important Early Paleozoic arc systems in the Central Asian Orogenic Belt, the tectonic affinity of the Bainaimiao arc belt is highly controversial. This study performed paleocurrent, petrography, trace elements of the whole rocks and U‐Pb geochronology of tuff and detrital zircons of the Early Devonian deposits, to constrain the tectonic affinity of the Bainaimiao arc belt. New zircon U‐Pb age constrains the Xibiehe Formation to the Early Devonian. Both the Xibiehe and Qiankuntougou formations show similar framework mineral and trace element components, suggesting a dissected ensialic island arc source. However, the U‐Pb age spectra of detrital zircons for the two formations are totally different. The Xibiehe Formation reflects continuous ages ranging 1977–597 Ma, indicating the Bainaimiao arc origin. The Qiankuntougou Formation has a mixed source displaying the North China Craton‐derived ages (~1.85 and ~2.52 Ga) and Bainaimiao arc ages (~1.4, ~1.2, ~0.97, 0.55, and 0.5–0.43 Ga). The comparable age components indicate that the Bainaimiao arc is an exotic terrane accreted to the North China Craton in an arc‐continent collision way at ca. 430–410 Ma. The arc‐continent collision and the following postorogenic magmatism (410–360 Ma), sedimentation during extensional collapse and south dipping subduction complex evolution imply a subduction polarity flip from the northward subduction to the southward subduction.
An Overview of the Atmospheric Component of the Energy Exascale Earth System Model
Authors: Rasch P. J. , Xie S. , Ma P.‐L. , Lin W. , Wang H. , Tang Q. , Burrows S. M. , Caldwell P. , Zhang K. , Easter R. C. , Cameron‐Smith P. , Singh B. , Wan H. , Golaz J.‐C. , Harrop B. E. , Roesler E. , Bacmeister J. , Larson V. E. , Evans K. J. , Qian Y. , Taylor M. , Leung L. R. , Zhang Y. , Brent L. , Branstetter M. , Hannay C. , Mahajan S. , Mametjanov A. , Neale R. , Richter J. H. , Yoon J.‐H. , Zender C. S. , Bader D. , Flanner M. , Foucar J. G. , Jacob R. , Keen N. , Klein S. A. , Liu X. , Salinger A.G. , Shrivastava M. , Yang Y.
Published: July 2019

The Energy Exascale Earth System Model Atmosphere Model version 1, the atmospheric component of the Department of Energy's Energy Exascale Earth System Model is described. The model began as a fork of the well‐known Community Atmosphere Model, but it has evolved in new ways, and coding, performance, resolution, physical processes (primarily cloud and aerosols formulations), testing and development procedures now differ significantly. Vertical resolution was increased (from 30 to 72 layers), and the model top extended to 60 km (~0.1 hPa). A simple ozone photochemistry predicts stratospheric ozone, and the model now supports increased and more realistic variability in the upper troposphere and stratosphere. An optional improved treatment of light‐absorbing particle deposition to snowpack and ice is available, and stronger connections with Earth system biogeochemistry can be used for some science problems. Satellite and ground‐based cloud and aerosol simulators were implemented to facilitate evaluation of clouds, aerosols, and aerosol‐cloud interactions. Higher horizontal and vertical resolution, increased complexity, and more predicted and transported variables have increased the model computational cost and changed the simulations considerably. These changes required development of alternate strategies for tuning and evaluation as it was not feasible to “brute force” tune the high‐resolution configurations, so short‐term hindcasts, perturbed parameter ensemble simulations, and regionally refined simulations provided guidance on tuning and parameterization sensitivity to higher resolution. A brief overview of the model and model climate is provided. Model fidelity has generally improved compared to its predecessors and the CMIP5 generation of climate models.
Constrictional Strain and Linear Fabrics as a Result of Deformation Partitioning: A Multiscale Modeling Investigation and Tectonic Significance
Authors: Yang Rui , Jiang Dazhi , Lu Lucy X.
Published: July 2019

Rocks with a well‐developed lineation but weak or no foliation (L‐tectonites) commonly occur as isolated volumes dispersed in other tectonites. We consider L‐tectonites that reflect constrictional finite strains here and use a multiscale approach to investigate the conditions for constrictional strain fields. The approach combines the strength of kinematic and mechanical analyses in large strain three‐dimensional deformations. Our modeling shows that, in simple shearing and thinning zone progressive deformations, constrictional strains develop only in rheological heterogeneities that are moderately stronger than the bulk material as a whole. Stronger elements never accumulate enough internal strains for any fabric to develop. Inclusions weaker than the bulk material will develop flattening strains. L‐tectonites are most likely developed in macroscale simple shearing, simple‐shearing‐dominated plane‐strain general shearing, or simple‐shearing‐dominated Sanderson and Marchini transpression. The lineations of the L‐tectonites are always nearly parallel to the lineations in the bulk material. Where the lineations are nearly 90° from the vorticity axis, the macroscale flow is close to a plane‐strain general shearing. Where the lineations are oblique to the vorticity axis or more variable, a simple‐shearing‐dominated triclinic thinning zone with mainly uniaxial boundary stretching is likely. The concept of homogeneous transtension deformation, combining a homogeneous pure shearing and a transcurrent simple shearing, is unsupported by fabric evidence and is likely unrealistic. Under an oblique divergence boundary condition, the upper lithosphere deforms by folding and fracturing and the ductile lithosphere develops simple‐shearing‐dominated detachment shear zones. Constrictional strains (hence L‐tectonites) can develop in these detachment zones due to flow partitioning.
A novel method to test non-exclusive hypotheses applied to Arctic ice projections from dependent models
Authors: Olson R. , An S.-I. , Fan Y. , Chang W. , Evans J. P. , Lee J.-Y.
Published: July 2019

A major conundrum in climate science is how to account for dependence between climate models. This complicates interpretation of probabilistic projections derived from such models. Here we show that this problem can be addressed using a novel method to test multiple non-exclusive hypotheses, and to make predictions under such hypotheses. We apply the method to probabilistically estimate the level of global warming needed for a September ice-free Arctic, using an ensemble of historical and representative concentration pathway 8.5 emissions scenario climate model runs. We show that not accounting for model dependence can lead to biased projections. Incorporating more constraints on models may minimize the impact of neglecting model non-exclusivity. Most likely, September Arctic sea ice will effectively disappear at between approximately 2 and 2.5 K of global warming. Yet, limiting the warming to 1.5 K under the Paris agreement may not be sufficient to prevent the ice-free Arctic.
Mapping the drivers of within-host pathogen evolution using massive data sets
Authors: Palmer Duncan S. , Turner Isaac , Fidler Sarah , Frater John , Goedhals Dominique , Goulder Philip , Huang Kuan-Hsiang Gary , Oxenius Annette , Phillips Rodney , Shapiro Roger , Vuuren Cloete van , McLean Angela R. , McVean Gil
Published: July 2019

Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.
Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor
Authors: Liu Xiaoyang , Palaniyandi Senthilkumar , Zhu Iowis , Tang Jin , Li Weizhong , Wu Xiaoling , Ochsner Susan Park , Pauza C. David , Cohen Jeffrey I. , Zhu Xiaoping
Published: July 2019

Human cytomegalovirus (HCMV) can persistently infect humans, but how HCMV avoids humoral immunity is not clear. The neonatal Fc receptor (FcRn) controls IgG transport from the mother to the fetus and prolongs IgG half-life. Here we show that US11 inhibits the assembly of FcRn with β2m and retains FcRn in the endoplasmic reticulum (ER), consequently blocking FcRn trafficking to the endosome. Furthermore, US11 recruits the ubiquitin enzymes Derlin-1, TMEM129 and UbE2J2 to engage FcRn, consequently initiating the dislocation of FcRn from the ER to the cytosol and facilitating its degradation. Importantly, US11 inhibits IgG-FcRn binding, resulting in a reduction of IgG transcytosis across intestinal or placental epithelial cells and IgG degradation in endothelial cells. Hence, these results identify the mechanism by which HCMV infection exploits an ER-associated degradation pathway through US11 to disable FcRn functions. These results have implications for vaccine development and immune surveillance.
Future nitrogen availability and its effect on carbon sequestration in Northern Eurasia
Authors: Kicklighter David W. , Melillo Jerry M. , Monier Erwan , Sokolov Andrei P. , Zhuang Qianlai
Published: July 2019

Nitrogen (N) availability exerts strong control on carbon storage in the forests of Northern Eurasia. Here, using a process-based model, we explore how three factors that alter N availability—permafrost degradation, atmospheric N deposition, and the abandonment of agricultural land to forest regrowth (land-use legacy)—affect carbon storage in the region’s forest vegetation over the 21st century within the context of two IPCC global-change scenarios (RCPs 4.5 and 8.5). For RCP4.5, enhanced N availability results in increased tree carbon storage of 27.8 Pg C, with land-use legacy being the most important factor. For RCP8.5, enhanced N availability results in increased carbon storage in trees of 13.4 Pg C, with permafrost degradation being the most important factor. Our analysis reveals complex spatial and temporal patterns of regional carbon storage. This study underscores the importance of considering carbon-nitrogen interactions when assessing regional and sub-regional impacts of global change policies.
Author Correction: Engineering Auger recombination in colloidal quantum dots via dielectric screening
Authors: Hou Xiaoqi , Kang Jun , Qin Haiyan , Chen Xuewen , Ma Junliang , Zhou Jianhai , Chen Liping , Wang Linjun , Wang Lin-Wang , Peng Xiaogang
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Discovery of novel hit compounds with broad activity against visceral and cutaneous Leishmania species by comparative phenotypic screening
Authors: Lamotte S. , Aulner N. , Späth G. F. , Prina E.
Published: July 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Prevalence and antimicrobial susceptibilities of bacterial pathogens in Chinese pig farms from 2013 to 2017
Authors: Zhang Bingzhou , Ku Xugang , Yu Xuexiang , Sun Qi , Wu Hao , Chen Fangzhou , Zhang Xiaoqian , Guo Long , Tang Xibiao , He Qigai
Published: July 2019

Bacterial diseases of swine are a kind of multifactorial and uncontrollable diseases that commonly exist in pig farms all over the world and will lead to huge economic losses every year. In this study, a detailed and overall survey was carried out to better understand the prevalence and antimicrobial susceptibilities of bacterial diseases from 2013 to 2017 in China. A total of 19673 bacterial strains were isolated from 44175 samples collected from 9661 pig farms that distributed in 16 Chinese major pig breeding provinces. The results showed that the average isolation rates of Streptococcus suis (SS), Haemophilus parasuis (HPS), Escherichia coli (E. coli), Pasteurella multocida (Pm), Actinobacillus pleuropneumoniae (APP), Brodetella bronchiseptica (Bb), Salmonella enteria (SE), Erysipelothrix rhusiopathiae (E. rhusiopathiae) were 16.9%, 9.7%, 6.3%, 3.4%, 0.3%, 1.5%, 2.3% and 0.9%, respectively. The isolate rates of E. coli, APP and SE showed an increasing trend from 2013 to 2017. The seasonal prevalence characteristics of SS, HPS and Pm were obviously higher from April to August for first two bacteria and higher at February, March, April, and October for Pm. The dominant serotypes for SS, HPS were serotype 2 and serotype 5 (changed from serotype 4), respectively. The SS, HPS, and Pm showed very high antibiotic resistance rates to almost 8 common antibiotics (β-lactam, aminoglycoside, macrolides, lincomycin, tetracycline, quinolone, polymyxin, and sulfonamide) and an obvious increasing trend of antibiotic resistance rates from 2013 to 2017. In conclusion, the study provides detailed information on the prevalence and antimicrobial susceptibilities of different bacterial pathogens of swine from 2013 to 2017 in China. These data can provide a foundation for monitoring epidemiological patterns of bacterial diseases in the Chinese swine herds, as well as provide insight into potential antibiotic resistance profiles in these pathogens.
Identification and characterisation of the novel endogenous promoter HASP1 and its signal peptide from Phaeodactylum tricornutum
Authors: Erdene-Ochir Erdenedolgor , Shin Bok-Kyu , Kwon Byeori , Jung Choonkyun , Pan Cheol-Ho
Published: July 2019

Although diatoms have been extensively studied as bioreactors, only a limited number of efficient gene promoters are available. Therefore, the development of new endogenous promoters is important for the heterologous production of a variety of recombinant proteins. Herein, we identified the most abundant secreted protein inPhaeodactylum tricornutum, designated ‘highly abundant secreted protein 1’ (HASP1), and characterised the activities of its promoter and signal peptide using green fluorescent protein (GFP) as a reporter. TheHASP1promoter strongly drove GFP expression during all growth phases ofP.tricornutumin culture, in contrast to the commonly usedfcpApromoter, which is less active during the stationary phase. The HASP1 signal peptide was also sufficient for facilitating efficient secretion of GFP byP.tricornutum. Our findings suggest that both the promoter and the signal peptide of HASP1 can be utilized as novel tools for the overexpression and secretion of recombinant proteins inP.tricornutum.
CRISPR/Cas9 mediated generation of an ovine model for infantile neuronal ceroid lipofuscinosis (CLN1 disease)
Authors: Eaton S. L. , Proudfoot C. , Lillico S. G. , Skehel P. , Kline R. A. , Hamer K. , Rzechorzek N. M. , Clutton E. , Gregson R. , King T. , O’Neill C. A. , Cooper J. D. , Thompson G. , Whitelaw C. B. , Wishart T. M.
Published: July 2019

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating monogenetic lysosomal disorders that affect children and young adults with no cure or effective treatment currently available. One of the more severe infantile forms of the disease (INCL or CLN1 disease) is due to mutations in the palmitoyl-protein thioesterase 1 (PPT1) gene and severely reduces the child’s lifespan to approximately 9 years of age. In order to better translate the human condition than is possible in mice, we sought to produce a large animal model employing CRISPR/Cas9 gene editing technology. Three PPT1 homozygote sheep were generated by insertion of a disease-causing PPT1 (R151X) human mutation into the orthologous sheep locus. This resulted in a morphological, anatomical and biochemical disease phenotype that closely resembles the human condition. The homozygous sheep were found to have significantly reduced PPT1 enzyme activity and accumulate autofluorescent storage material, as is observed in CLN1 patients. Clinical signs included pronounced behavioral deficits as well as motor deficits and complete loss of vision, with a reduced lifespan of 17 ± 1 months at a humanely defined terminal endpoint. Magnetic resonance imaging (MRI) confirmed a significant decrease in motor cortical volume as well as increased ventricular volume corresponding with observed brain atrophy and a profound reduction in brain mass of 30% at necropsy, similar to alterations observed in human patients. In summary, we have generated the first CRISPR/Cas9 gene edited NCL model. This novel sheep model of CLN1 disease develops biochemical, gross morphological and in vivo brain alterations confirming the efficacy of the targeted modification and potential relevance to the human condition.
Peat substrate amended with chitin modulates the N-cycle, siderophore and chitinase responses in the lettuce rhizobiome
Authors: De Tender C. , Mesuere B. , Van der Jeugt F. , Haegeman A. , Ruttink T. , Vandecasteele B. , Dawyndt P. , Debode J. , Kuramae E. E.
Published: July 2019

Chitin is a valuable peat substrate amendment by increasing lettuce growth and reducing the survival of the zoonotic pathogenSalmonella entericaon lettuce leaves. The production of chitin-catabolic enzymes (chitinases) play a crucial role and are mediated through the microbial community. A higher abundance of plant-growth promoting microorganisms and genera involved in N and chitin metabolism are present in a chitin-enriched substrate. In this study, we hypothesize that chitin addition to peat substrate stimulates the microbial chitinase production. The degradation of chitin leads to nutrient release and the production of small chitin oligomers that are related to plant growth promotion and activation of the plant’s defense response. First a shotgun metagenomics approach was used to decipher the potential rhizosphere microbial functions then the nutritional content of the peat substrate was measured. Our results show that chitin addition increases chitin-catabolic enzymes, bacterial ammonium oxidizing and siderophore genes. Lettuce growth promotion can be explained by a cascade degradation of chitin to N-acetylglucosamine and eventually ammonium. The occurrence of increased ammonium oxidizing bacteria,Nitrosospira, andamoAgenes results in an elevated concentration of plant-available nitrate. In addition, the increase in chitinase and siderophore genes may have stimulated the plant’s systemic resistance.
Antitumor effects of the GM3(Neu5Gc) ganglioside-specific humanized antibody 14F7hT against Cmah-transfected cancer cells
Authors: Dorvignit Denise , Boligan Kayluz F. , Relova-Hernández Ernesto , Clavell Marilyn , López Armando , Labrada Mayrel , Simon Hans-Uwe , López-Requena Alejandro , Mesa Circe , von Gunten Stephan
Published: July 2019

The GM3(Neu5Gc) ganglioside represents a tumor-specific antigen that is considered a promising target for cancer immunotherapy. We previously demonstrated that the humanized antibody 14F7hT, specific for this ganglioside, exhibited significant antitumor effects in preclinical hematological tumor models. As this antibody recognizes human tumor tissues from several origins, we addressed its potential effect on different tumor types. The use of cell lines for testing GM3(Neu5Gc)-targeting strategies, in particular for human malignancies, is complicated by the absence in humans of functional cytidine monophospho-N-acetyl-neuraminic acid hydroxylase (CMAH), the enzyme required for Neu5Gc sialic acid biosynthesis. Quantitative flow cytometry revealed the absence of surface GM3(Neu5Gc) in several human but also mouse cell lines, in the last case due to low expression of the enzyme. Hypoxia-induced expression of this ganglioside on human SKOV3 cells was observed upon culture in Neu5Gc-containing medium without evidence for CMAH-independent biosynthesis. However, only transfection of the mouse Cmah gene into human SKOV3 and mouse 3LL cells induced a stable expression of GM3(Neu5Gc) on the cancer cell surface, resulting in effective models to evaluate the antitumor responses by 14F7hT in vitro and in vivo. This antibody exerted antibody-dependent cell-mediated cytotoxicity (ADCC) and in vivo antitumor effects on these Cmah-transfected non-hematological tumors from both mouse and human origin. These results contribute to validate GM3(Neu5Gc) as a relevant target for cancer immunotherapy and reinforces the value of 14F7hT as a novel anti-cancer drug.
Ki-67, p53 and BCL-2 Expressions and their Association with Clinical Histopathology of Breast Cancer among Women in Tanzania
Authors: Mansouri Hidaya , Mnango Leah F. , Magorosa Erick P. , Sauli Elingarami , Mpolya Emmanuel A.
Published: July 2019

This study associated Ki-67, p53, and BCL-2 markers with clinical histopathological (CH) features using currently available limited data on these markers in Tanzania. Retrospective chart review study was conducted among females with confirmed breast cancer (BC) at Muhimbili National Hospital in Tanzania between 2016 and 2017. Inclusion criteria were met by 76 patients with a mean age of 51.32 ± 14.28 years. Of these, 86.4% were stage III and IV, whereas 83.5% cases had grade 2 and grade 3. Upon immunostaining, 85.5% and 57.9% were Ki-67 and BCL-2 positive respectively. Log-linear analysis showed no statistically significant association among biomarkers expression and CH features. However, multinomial linear regression showed higher possibility for association between high expression of Ki-67, low expression of p53 and high expression of BCL-2 with age, grade, stage and tumor (T) stage. BCL-2 was positively correlated with Ki-67 expression contrary to p53, which was negatively correlated with BCL-2. Conclusively, there is evidence of correlation between the studied markers with CH features. However, studies with larger sample sizes will likely reveal significant associations that will validate the role of these markers as tools for evaluating treatment response in individualized therapeutic schemes in Tanzania.
Premedication with a cathepsin C inhibitor alleviates early primary graft dysfunction in mouse recipients after lung transplantation
Authors: Rehm Salome R. T. , Smirnova Natalia F. , Morrone Carmela , Götzfried Jessica , Feuchtinger Annette , Pedersen John , Korkmaz Brice , Yildirim Ali Önder , Jenne Dieter E.
Published: July 2019

Neutrophil serine proteases (NSPs), like proteinase 3 (PR3) and neutrophil elastase (NE) are implicated in ischemia-reperfusion responses after lung transplantation (LTx). Cathepsin C (CatC) acts as the key regulator of NSP maturation during biosynthesis. We hypothesized that CatC inhibitors would reduce vascular breakdown and inflammation during reperfusion in pretreated lung transplant recipients by blocking NSP maturation in the bone marrow. An orthotopic LTx model in mice was used to mimic the induction of an ischemia-reperfusion response after 18 h cold storage of the graft and LTx. Recipient mice were treated subcutaneously with a chemical CatC inhibitor (ICatC) for 10 days prior to LTx. We examined the effect of the ICatC treatment by measuring the gas exchange function of the left lung graft, protein content, neutrophil numbers and NSP activities in the bone marrow 4 h after reperfusion. Pre-operative ICatC treatment of the recipient mice improved early graft function and lead to the disappearance of active NSP protein in the transplanted lung. NSP activities were also substantially reduced in bone marrow neutrophils. Preemptive NSP reduction by CatC inhibition may prove to be a viable and effective approach to reduce immediate ischemia reperfusion responses after LTx.
Microcrystalline array structures induced by heat treatment of friction-transferred organic semiconductor films
Authors: Inada Yuhi , Koda Masashi , Urabe Yuji , Katagiri Toshifumi , Yamao Takeshi , Yoshida Yuji , Hotta Shu
Published: July 2019

The correlation between molecular orientation and optoelectrical properties is most critical to the future design of molecular materials. We made highly-anisotropic microcrystalline array structures with an organic semiconductor, a methoxy-substituted thiophene/phenylene co-oligomer (TPCO), by depositing it on friction-transferred poly(tetrafluoroethylene) (PTFE) layers fabricated on substrates with several heat treatments. Polarising microscope observation, polarised emission and absorption spectra measurements indicated that the TPCO molecules aligned along the drawing direction of PTFE. Using these films, we fabricated two types of field-effect transistors (FETs) and compared them with those using non-heated TPCO films which provide aligned pleats structures. Ones had the channel length direction parallel to the drawing direction of PTFE and the others had the channel length direction perpendicular to that drawing direction. As for the microcrystalline array films, the mobility ratio of the former FET to that of the latter device was about 27 in the saturation region, while the emission polarisation ratio was 4.5. The heat treatment promoted the crystal growth to enhance the mobility while retaining the high anisotropy. The results demonstrate that the heat treatments of the TPCO films on the friction-transferred layers were useful for controlling crystallinity and orientation of the molecules.
Highly Sensitive NH3 Wireless Sensor Based on Ag-RGO Composite Operated at Room-temperature
Authors: Zhang Lei , Tan Qiulin , Kou Hairong , Wu Dezhi , Zhang Wendong , Xiong Jijun
Published: July 2019

The detection of ammonia (NH3) in low concentrations is very important in the chemical industry and for human health. In this paper, we present reduced graphene oxide (RGO) decorated with silver nanoparticles (AgNPs) as a sensing material for NH3. A simple, environmentally friendly, and cost-efficient green approach for the preparation of the sensing material is proposed. X-ray diffraction (XRD), Raman spectroscopy, and field emission scanning electron microscopy (FE-SEM) were used to analyze the crystalline structure, material composition, and surface appearance characteristics of the sensing material. By combining the material with a commercial near-field communication (NFC) tag, a wireless gas sensor was built. The enhanced NH3-sensing performance is mainly due to the synergistic effect between Ag and RGO. More specifically, AgNPs enhanced the adsorption capacity of RGO for NH3 electrons. The excellent performance of the sensor shows that it has potential for applications in food safety, environment, and human health monitoring.
Integrin α7 expression is increased in asthmatic patients and its inhibition reduces Kras protein abundance in airway smooth muscle cells
Authors: Teoh Chun Ming , Tan Sheryl S. L. , Langenbach Shenna Y. , Wong Amanda H. , Cheong Dorothy H. J. , Tam John K. C. , New Chih Sheng , Tran Thai
Published: July 2019

Airway smooth muscle (ASM) cells exhibit plastic phenotypic behavior marked by reversible modulation and maturation between contractile and proliferative phenotypic states. Integrins are a class of transmembrane proteins that have been implicated as novel therapeutic targets for asthma treatment. We previously showed that integrin α7 is a novel marker of the contractile ASM phenotype suggesting that targeting this protein may offer new avenues to counter the increase in ASM cell mass that underlies airways hyperresponsiveness (AHR) in asthma. We now determine whether inhibition of integrin α7 expression would revert ASM cells back to a proliferative phenotype to cause an increase in ASM cell mass. This would be detrimental to asthmatic patients who already exhibit increased ASM mass in their airways. Using immunohistochemical analysis of the Melbourne Epidemiological Study of Childhood Asthma (MESCA) cohort, we show for the first time that integrin α7 expression in patients with severe asthma is increased, supporting a clinically relevant role for this protein in asthma pathophysiology. Moreover, inhibition of the laminin-integrin α7 signaling axis results in a reduction in smooth muscle-alpha actin abundance and does not revert ASM cells back to a proliferative phenotype. We determined that integrin α7-induced Kras isoform of p21 Ras acts as a point of convergence between contractile and proliferative ASM phenotypic states. Our study provides further support for targeting integrin α7 for the development of novel anti-asthma therapies.
A Fairy Chemical, Imidazole-4-carboxamide, is Produced on a Novel Purine Metabolic Pathway in Rice
Authors: Takemura Hirohide , Choi Jae-Hoon , Matsuzaki Nobuo , Taniguchi Yuki , Wu Jing , Hirai Hirofumi , Motohashi Reiko , Asakawa Tomohiro , Ikeuchi Kazutada , Inai Makoto , Kan Toshiyuki , Kawagishi Hirokazu
Published: July 2019

Rings or arcs of fungus-regulated plant growth occurring on the floor of woodlands and grasslands are commonly called “fairy rings”. Fairy chemicals, 2-azahypoxanthine (AHX), imidazole-4-carboxamide (ICA), and 2-aza-8-oxohypoxanthine (AOH), are plant growth regulators involved in the phenomenon. The endogeny and biosynthetic pathways of AHX and AOH in plants have already been proven, however, those of ICA have remained unclear. We developed a high-sensitivity detection method for FCs including ICA and the endogenous ICA was detected in some plants for the first time. The quantitative analysis of the endogenous level of ICA in rice and Arabidopsis were performed using 13C-double labeled ICA. In addition, the incorporation experiment and enzyme assay using the labeled compound into rice and partially purified fraction of rice indicated that ICA is biosynthesized from 5-aminoimidazole-4-carboxamide (AICA), a metabolite on the purine metabolic pathway. The relationship between ICA and AHX was also discussed based on quantitative analysis and gene expression analysis.
Poleward-propagating near-inertial waves enabled by the western boundary current
Authors: Jeon Chanhyung , Park Jae-Hun , Nakamura Hirohiko , Nishina Ayako , Zhu Xiao-Hua , Kim Dong Guk , Min Hong Sik , Kang Sok Kuh , Na Hanna , Hirose Naoki
Published: July 2019

Near-inertial waves (NIWs), which have clockwise (anticlockwise) rotational motion in the Northern (Southern) Hemisphere, exist everywhere in the ocean except at the equator; their frequencies are largely determined by the local inertial frequency, f. It is thought that they supply about 25% of the energy for global ocean mixing through turbulence resulting from their strong current shear and breaking; this contributes mainly to upper-ocean mixing which is related to air-sea interaction, typhoon genesis, marine ecosystem, carbon cycle, and climate change. Observations and numerical simulations have shown that the low-mode NIWs can travel many hundreds of kilometres from a source region toward the equator because the lower inertial frequency at lower latitudes allows their free propagation. Here, using observations and a numerical simulation, we demonstrate poleward propagation of typhoon-induced NIWs by a western boundary current, the Kuroshio. Negative relative vorticity, meaning anticyclonic rotational tendency opposite to the Earth’s spin, existing along the right-hand side of the Kuroshio path, makes the local inertial frequency shift to a lower value, thereby trapping the waves. This negative vorticity region works like a waveguide for NIW propagation, and the strong Kuroshio current advects the waves poleward with a speed ~85% of the local current. This finding emphasizes that background currents such as the Kuroshio and the Gulf Stream play a significant role in redistribution of the NIW energy available for global ocean mixing.
Transcription Factors Regulation in Human Peripheral White Blood Cells during Hypobaric Hypoxia Exposure: an in-vivo experimental study
Authors: Malacrida Sandro , Giannella Alessandra , Ceolotto Giulio , Reggiani Carlo , Vezzoli Alessandra , Mrakic-Sposta Simona , Moretti Sarah , Turner Rachel , Falla Marika , Brugger Hermann , Strapazzon Giacomo
Published: July 2019

High altitude is a natural laboratory, within which the clinical study of human physiological response to hypobaric hypoxia (HH) is possible. Failure in the response results in progressive hypoxemia, inflammation and increased tissue oxidative stress (OxS). Thus, investigating temporal changes in key transcription factors (TFs)HIF-1α,HIF-2α,NF-κB and NRF2mRNA levels, relative to OxS and inflammatory markers, may reveal molecular targets which contrast deleterious effects of hypoxia. Biological samples and clinical data from 15 healthy participants were collected at baseline and after rapid, passive ascent to 3830 m (24 h and 72 h). Gene expression was assessed by qPCR and ROS generation was determined by EPR spectroscopy. Oxidative damage and cytokine levels were estimated by immuno or enzymatic methods. Hypoxia transiently enhancedHIF-1αmRNA levels over time reaching a peak after 24 h. Whereas,HIF-2αandNRF2mRNA levels increased over time. In contrast, theNF-κBmRNA levels remained unchanged. Plasma levels of IL-1β and IL-6 also remained within normal ranges. ROS production rate and markers of OxS damage were significantly increased over time. The analysis of TF-gene expression suggests that HIF-1α is a lead TF during sub-acute HH exposure. The prolongation of the HH exposure led to a switch between HIF-1α and HIF-2α/NRF2, suggesting the activation of new pathways. These results provide new insights regarding the temporal regulation of TFs, inflammatory state, and ROS homeostasis involved in human hypoxic response, potentially also relevant to the mediation of diseases that induce a hypoxic state.
Actively tunable terahertz chain-link metamaterial with bidirectional polarization-dependent characteristic
Authors: Liu Pengyu , Liang Zihao , Lin Zhicheng , Xu Zefeng , Xu Ruijia , Yao Dongyuan , Lin Yu-Sheng
Published: July 2019

A tunable terahertz (THz) chain-link metamaterial (CLM) is presented, which is composed of a tailored Au layer fabricated on Si substrate. CLM exhibits bidirectional polarization-dependent characteristic by applying a direct-current (dc) bias voltage on device. This CLM device can be heated up the surrounding temperature to tune the corresponding resonance. The tuning range is 0.027 THz from 0.318 THz to 0.291 THz on the bias of 0.60 V to 1.32 V. By reconfiguring the gap between CLM, there are single-resonance with red-shift at TE mode, and multi-resonance with blue-shift and red-shift at TM mode, respectively. These characterizations of CLM are polarization-dependence and bidirectional tunability. These results show the electromagnetic responses of proposed CLM device is suitable for the uses for resonator, filter, switch, and sensor in the THz frequency range.
Preparation and evaluation of PAMAM dendrimer-based polymer gels physically cross-linked by hydrogen bonding
Authors: Cong Hailin , Zhou Liping , Meng Qingye , Zhang Yixin , Yu Bing , Shen Youqing , Hu Hao
Published: July 2019

Dendrimer-based polymer gels with good antibacterial properties and anti-inflammatory properties were prepared without any covalent bonding cross-linking agents.
Amorphous TiO2nanostructures: synthesis, fundamental properties and photocatalytic applications
Authors: Sun Shaodong , Song Peng , Cui Jie , Liang Shuhua
Published: July 2019

In this review, we mainly highlight the advances made in the development of amorphous TiO2nanostructures for photocatalysts. Some perspectives on the challenges and new direction are also discussed.