bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Piperazinylbenzenesulfonamides as New Inhibitors of Claudin-1 Trafficking and Hepatitis C Virus Entry
Authors: Riva Laura , Song Ok-ryul , Prentoe Jannick , Helle François , L'homme Laurent , Gattolliat Charles-Henry , Vandeputte Alexandre , Fénéant Lucie , Belouzard Sandrine , Baumert Thomas F. , Asselah Tarik , Bukh Jens , Brodin Priscille , Cocquerel Laurence , Rouillé Yves , Dubuisson Jean
Published: February 2018

Hepatitis C virus (HCV) infection causes 500,000 deaths annually, in association with end-stage liver diseases. Investigations of the HCV life cycle have widened the knowledge of virology, and here we discovered that two piperazinylbenzenesulfonamides inhibit HCV entry into liver cells. The entry of HCV into host cells is a complex process that is not fully understood but is characterized by multiple spatially and temporally regulated steps involving several known host factors. Through a high-content virus infection screening analysis with a library of 1,120 biologically active chemical compounds, we identified SB258585, an antagonist of serotonin receptor 6 (5-HT6), as a new inhibitor of HCV entry in liver-derived cell lines as well as primary hepatocytes. A functional characterization suggested a role for this compound and the compound SB399885, which share similar structures, as inhibitors of a late HCV entry step, modulating the localization of the coreceptor tight junction protein claudin-1 (CLDN1) in a 5-HT6-independent manner. Both chemical compounds induced an intracellular accumulation of CLDN1, reflecting export impairment. This regulation correlated with the modulation of protein kinase A (PKA) activity. The PKA inhibitor H89 fully reproduced these phenotypes. Furthermore, PKA activation resulted in increased CLDN1 accumulation at the cell surface. Interestingly, an increase of CLDN1 recycling did not correlate with an increased interaction with CD81 or HCV entry. These findings reinforce the hypothesis of a common pathway, shared by several viruses, which involves G-protein-coupled receptor-dependent signaling in late steps of viral entry.

IMPORTANCEThe HCV entry process is highly complex, and important details of this structured event are poorly understood. By screening a library of biologically active chemical compounds, we identified two piperazinylbenzenesulfonamides as inhibitors of HCV entry. The mechanism of inhibition was not through the previously described activity of these inhibitors as antagonists of serotonin receptor 6 but instead through modulation of PKA activity in a 5-HT6-independent manner, as proven by the lack of 5-HT6 in the liver. We thus highlighted the involvement of the PKA pathway in modulating HCV entry at a postbinding step and in the recycling of the tight junction protein claudin-1 (CLDN1) toward the cell surface. Our work underscores once more the complexity of HCV entry steps and suggests a role for the PKA pathway as a regulator of CLDN1 recycling, with impacts on both cell biology and virology.
Asymmetric Modification of Hepatitis B Virus (HBV) Genomes by an Endogenous Cytidine Deaminase inside HBV Cores Informs a Model of Reverse Transcription
Authors: Nair Smita , Zlotnick Adam
Published: February 2018

Cytidine deaminases inhibit replication of a broad range of DNA viruses by deaminating cytidines on single-stranded DNA (ssDNA) to generate uracil. While several lines of evidence have revealed hepatitis B virus (HBV) genome editing by deamination, it is still unclear which nucleic acid intermediate of HBV is modified. Hepatitis B virus has a relaxed circular double-stranded DNA (rcDNA) genome that is reverse transcribed within virus cores from a RNA template. The HBV genome also persists as covalently closed circular DNA (cccDNA) in the nucleus of an infected cell. In the present study, we found that in HBV-producing HepAD38 and HepG2.2.15 cell lines, endogenous cytidine deaminases edited 10 to 25% of HBV rcDNA genomes, asymmetrically with almost all mutations on the 5′ half of the minus strand. This region corresponds to the last half of the minus strand to be protected by plus-strand synthesis. Within this half of the genome, the number of mutations peaks in the middle. Overexpressed APOBEC3A and APOBEC3G could be packaged in HBV capsids but did not change the amount or distribution of mutations. We found no deamination on pregenomic RNA (pgRNA), indicating that an intact genome is encapsidated and deaminated during or after reverse transcription. The deamination pattern suggests a model of rcDNA synthesis in which pgRNA and then newly synthesized minus-sense single-stranded DNA are protected from deaminase by interaction with the virus capsid; during plus-strand synthesis, when enough dsDNA has been synthesized to displace the remaining minus strand from the capsid surface, the single-stranded DNA becomes deaminase sensitive.

IMPORTANCE
Host-induced mutation of the HBV genome by APOBEC proteins may be a path to clearing the virus. We examined cytidine-to-thymidine mutations in the genomes of HBV particles grown in the presence or absence of overexpressed APOBEC proteins. We found that genomes were subjected to deamination activity during reverse transcription, which takes place within the virus capsid. These observations provide a direct insight into the mechanics of reverse transcription, suggesting that newly synthesized dsDNA displaces ssDNA from the capsid walls, making the ssDNA accessible to deaminase activity.
Can doctors and patients correctly estimate cardiovascular risk? A cross-sectional study in primary care
Authors: Liew Su May , Lee Wai Khew , Khoo Ee Ming , Ismail Irmi Zarina , Ambigapathy Subashini , Omar Mimi , Suleiman Siti Zaleha , Saaban Juwita , Mohd Zaidi Nur Farhana , Yusoff Harmy
Published: February 2018

Objective

Accurate cardiovascular risk estimations by patients and doctors are important as these affect health behaviour and medical decision making. We aimed to determine if doctors and patients were accurately estimating the absolute cardiovascular risk of patients in primary care.

Methods

A cross-sectional study was carried out in primary care clinics in Malaysia in 2014. Patients aged 35 years and above without known cardiovascular disease (CVDs) were included. Face-to-face interviews with a structured questionnaire were used to collect sociodemographic and clinical data as well as patients’ perception and doctors’ estimate of the patients’ CVD risk. Associations were tested using χ2, correlation and independent t-tests.

Results

We recruited 1094 patients and 57 doctors. Using the Framingham Risk Score (FRS) alone, 508 patients (46.4%) were in the high-risk group. When diabetes was included as high risk, the number increased to 776 (70.9%). Only 34.4% of patients and 55.7% of doctors correctly estimated the patient’s CVD risk in comparison with the reference FRS.

Of the high-risk patients, 664 (85.6%) underestimated their CV risk. Factors associated with underestimation by patients included not having family history of CVD (adjusted OR (AOR): 2.705, 95% CI 1.538 to 4.757), smaller waist circumference (AOR: 0.979,95% CI 0.960 to 0.999) and ethnicity in comparison with the Malay as reference group (indigenous/others: AOR: 0.129, 95% CI 0.071 to 0.235). Doctors underestimated risk in 59.8% of the high-risk group. Factors associated with underestimation by doctors were patients factors such as being female (AOR: 2.232, 95% CI 1.460 to 3.410), younger age (AOR: 0.908, 95% CI 0.886 to 0.930), non-hypertensive (AOR: 1.731, 95% CI 1.067 to 2.808), non-diabetic (AOR: 1.931, 95% CI 1.114 to 3.348), higher high-density lipoprotein levels (AOR: 3.546, 95% CI 2.025 to 6.209), lower systolic blood pressure (AOR: 0.970, 95% CI 0.957 to 0.982), non-smoker (AOR: 2.246, 95% CI 1.354 to 3.726) and ethnicity in comparison with the Malay as reference group (Indian: AOR: 0.430, 95% CI 0.257 to 0.720; indigenous/others: AOR: 2.498, 95% CI 1.346 to 4.636).

Conclusions

The majority of consultations occurring between doctors and patients are being informed by inaccurate cardiovascular risk estimation.
Electroacupuncture for poststroke spasticity (EAPSS): protocol for a randomised controlled trial
Authors: Cai Yiyi , Zhang Claire Shuiqing , Ouyang Wenwei , Li Jianmin , Nong Wenheng , Zhang Anthony Lin , Xue Charlie Changli , Wen Zehuai
Published: February 2018

Introduction

Spasticity is a common complication of stroke. Current therapies for poststroke spasticity (PSS) have been reported to be associated with high costs, lack of long-term benefit and unwanted adverse events (AEs). Electroacupuncture (EA) has been used for PSS, however, its efficacy and safety is yet to be confirmed by high-quality clinical studies. This study is designed to evaluate the add-on effects and safety profile of EA when used in combination with usual care (UC).

Methods and analysis

This study is a parallel group randomised controlled trial. A total of 136 participants will be included and randomly assigned to either the treatment group (EA plus UC) or the control group (UC alone). Prior to the main trial, a pilot study involving 30 participants will be conducted to assess the feasibility of the trial protocol. EA will be administered by registered acupuncturists for 20min to 30 min, three times per week for 4 weeks. The primary outcome measure (Modified Ashworth Scale) and secondary outcome measures (Fugl-Meyer Assessment and Barthel Index) will be evaluated at baseline, the end of treatment (week 4) and the end of follow-up (week 8). AEs will be monitored, recorded and reported, and their causality will be explored.

Ethics and dissemination

Ethics approval was obtained from the ethics committees of Guangdong Provincial Hospital of Chinese Medicine and RMIT University in December 2016. The results will be disseminated in a peer-reviewed journal, and PhD theses and might be presented at international conferences.

Trial registration number

ChiCTR-IOR-16010283; Pre-results.
Reliability of wireless monitoring using a wearable patch sensor in high-risk surgical patients at a step-down unit in the Netherlands: a clinical validation study
Authors: Breteler Martine J M , Huizinga Erik , van Loon Kim , Leenen Luke P H , Dohmen Daan A J , Kalkman Cor J , Blokhuis Taco J
Published: February 2018

Background and objectives

Intermittent vital signs measurements are the current standard on hospital wards, typically recorded once every 8 hours. Early signs of deterioration may therefore be missed. Recent innovations have resulted in ‘wearable’ sensors, which may capture patient deterioration at an earlier stage. The objective of this study was to determine whether a wireless ‘patch’ sensor is able to reliably measure respiratory and heart rate continuously in high-risk surgical patients. The secondary objective was to explore the potential of the wireless sensor to serve as a safety monitor.

Design

In an observational methods comparisons study, patients were measured with both the wireless sensor and bedside routine standard for at least 24 hours.

Setting

University teaching hospital, single centre.

Participants

Twenty-five postoperative surgical patients admitted to a step-down unit.

Outcome measures

Primary outcome measures were limits of agreement and bias of heart rate and respiratory rate. Secondary outcome measures were sensor reliability, defined as time until first occurrence of data loss.

Results

1568 hours of vital signs data were analysed. Bias and 95% limits of agreement for heart rate were −1.1 (−8.8 to 6.5) beats per minute. For respiration rate, bias was −2.3 breaths per minute with wide limits of agreement (−15.8 to 11.2 breaths per minute). Median filtering over a 15 min period improved limits of agreement of both respiration and heart rate. 63% of the measurements were performed without data loss greater than 2 min. Overall data loss was limited (6% of time).

Conclusions

The wireless sensor is capable of accurately measuring heart rate, but accuracy for respiratory rate was outside acceptable limits. Remote monitoring has the potential to contribute to early recognition of physiological decline in high-risk patients. Future studies should focus on the ability to detect patient deterioration on low care environments and at home after discharge.
Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis
Authors: James Brandon , Chang Andrew D , McTaggart Ryan A , Hemendinger Morgan , Mac Grory Brian , Cutting Shawna M , Burton Tina M , Reznik Michael E , Thompson Bradford , Wendell Linda , Mahta Ali , Siket Matthew , Madsen Tracy E , Sheth Kevin N , Nouh Amre , Furie Karen L , Jayaraman Mahesh V , Khatri Pooja , Yaghi Shadi
Published: February 2018

Objectives

Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA.

Methods

We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups.

Results

We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008).

Conclusion

Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach.
Association ofinterleukin-10gene single nucleotide polymorphisms with rheumatoid arthritis in a Chinese population
Authors: Zhang Tian-Ping , Lv Tian-Tian , Xu Shu-Zhen , Pan Hai-Feng , Ye Dong-Qing
Published: February 2018

Purpose of the study

Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility.

Study design

We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA.

Results

The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes.

Conclusions

The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA.
A New Versatile Universal Biquad Configuration for Emerging Signal Processing Applications
Authors: Chaturvedi Bhartendu , Mohan Jitendra , Kumar Atul
Published: February 2018

The paper introduces a new versatile universal biquadratic configuration based on two fully differential second generation current conveyors without need of input matching conditions. The proposed circuit consists of two fully differential second generation current conveyors, four resistors and two grounded capacitors. The proposed biquad configuration provides all five standard filtering responses: low-pass, high-pass, band-pass, band-reject and all-pass in voltage-mode, transadmittance-mode, current-mode and transimpedance-mode. The proposed circuit is single-input multiple-outputs type, so all responses are available simultaneously. Moreover, extra inverting amplifier and double-type amplifier are also not required in the proposed circuit for any filtering response. The nonideal and parasitic effects of fully differential second generation current conveyor on the proposed circuit have also been investigated. HSPICE simulation results have been incorporated to validate the proposal.
Best of Both Worlds? Persistent Hybrid Entrepreneurship
Authors: Viljamaa Anmari , Varamäki Elina , Joensuu-Salo Sanna
Published: February 2018

Hybrid entrepreneurs (HEs) represent a considerable share of all entrepreneurial activity. Yet little is known about the phenomenon. In this study we examine the differences between transitory HEs, who expect to make the transition to full-time entrepreneurship, and persistent HEs, who view their part-time status as permanent. With data collected from 848 academic HEs we find that only a small minority considers full self-employment likely in the near future and that self-fulfillment is the most significant motive for entrepreneurial activities. The results suggest that persistent hybrid entrepreneurship should be viewed as a form of entrepreneurship in its own right, and that even partial entrepreneurship has the potential to lengthen careers and improve wellbeing at work. Hybrid entrepreneurship offers the entrepreneurially inclined employees the best of both worlds.
Entrepreneurial Orientation in Family Firms: Looking at a European Outermost Region
Authors: Pimentel Duarte , Couto João Pedro , Scholten Marc
Published: February 2018

This study addresses a current debate in the family business literature involving the extent to which the family business context hinders or promotes entrepreneurial behavior. The empirical evidence is provided by 155 small-sized firms, 82 family-controlled and 73 nonfamily-controlled, operating in an outermost region, the Autonomous Region of the Azores. This study analyzes the differences between family and nonfamily firms in regard to entrepreneurial orientation and how it is influenced by family participation. Results show that there are differences in entrepreneurship orientation and in two of its three dimensions, while revealing that family participation is negatively associated with entrepreneurial orientation and its three dimensions.
The computation of factorization invariants for affine semigroups
Authors: García-Sánchez Pedro A. , O’Neill Christopher , Webb Gautam
Published: February 2018

We present several new algorithms for computing factorization invariant values over affine semigroups. In particular, we give (i) the first known algorithm to compute the delta set of any affine semigroup, (ii) an improved method of computing the tame degree of an affine semigroup, and (iii) a dynamic algorithm to compute catenary degrees of affine semigroup elements. Our algorithms rely on theoretical results from combinatorial commutative algebra involving Gröbner bases, Hilbert bases, and other standard techniques. Implementation in the computer algebra system GAP is discussed.
Sensitive Manipulation: Manipulation Through Tactile Feedback
Authors: Torres-Jara Eduardo , Natale Lorenzo
Published: February 2018

Object grasping and manipulation in robotics has been largely approached using visual feedback. Human studies on the other hand have demonstrated the importance of tactile and force feedback to guide the interaction between the fingers and the objects. Inspired by these observations, we propose an approach that consists in guiding a robot’s actions mainly by tactile feedback, with remote sensing such as vision, used only as a complement. Directly sensing the interaction forces between the object, the environment, and the robot’s hand enables it to obtain information relevant to the task that can be used to perform it more reliably. This approach (that we call sensitive manipulation) requires important changes in the hardware and in the way the robot is programmed. At the hardware level, we exploit compliant actuators and novel sensors that allow to safely interact and detect the environment. We developed strategies to perform manipulation tasks that take advantage of these new sensing and actuation capabilities. In this paper, we demonstrate that using these strategies the humanoid robot Obrero can safely find, reach and grab unknown objects that are neither held in place by a fixture nor placed in a specific orientation. The robot can also make insertions by “feeling” the hole without specialized mechanisms such as a remote center of compliance (RCC).
Ionic conductivity and relaxation studies in PVDF-HFP:PMMA-based gel polymer blend electrolyte with LiClO4salt
Authors: Gohel Khushbu , Kanchan D. K.
Published: February 2018

Poly(vinylidene fluoride-hexafluropropylene) (PVDF-HFP) and poly(methyl methacrylate) (PMMA)-based gel polymer electrolytes (GPEs) comprising propylene carbonate and diethyl carbonate mixed plasticizer with variation of lithium perchlorate (LiClO4) salt concentrations have been prepared using a solvent casting technique. Structural characterization has been carried out using XRD wherein diffraction pattern reveals the amorphous nature of sample up to 7.5[Formula: see text]wt.% salt and complexation of polymers and salt have been studied by FTIR analysis. Surface morphology of the samples has been studied using scanning electron microscope. Electrochemical impedance spectroscopy in the temperature range 303–363[Formula: see text]K has been carried out for electrical conductivity. The maximum room temperature conductivity of 2.83[Formula: see text][Formula: see text]S cm[Formula: see text] has been observed for the GPE incorporating 7.5[Formula: see text]wt.% LiClO4. The temperature dependence of ionic conductivity obeys the Arrhenius relation. The increase in ionic conductivity with change in temperatures and salt content is observed. Transport number measurement is carried out by Wagner’s DC polarization method. Loss tangent (tan [Formula: see text]) and imaginary part of modulus ([Formula: see text]) corresponding to dielectric relaxation and conductivity relaxation respectively show faster relaxation process with increasing salt content up to optimum value of 7.5[Formula: see text]wt.% LiClO4. The modulus ([Formula: see text]) shows that the conductivity relaxation is of non-Debye type (broader than Debye peak).
Maximising the value of Portable XRF data in exploration: An example from Marirongoe, Mozambique
Authors: Sterk René , Gazley Michael F. , Wood Matthew P. , Collins Katie S. , Collis Geoff
Published: February 2018

Here we present a portable X-ray fluorescence (pXRF) dataset collected
in situ
(
n
 = 1591) and a laboratory dataset (
n
 
=
 226) from a soil sampling campaign in Marirongoe, Mozambique, to document the strength of rapid geochemical data collection in the field during mineral exploration. Real-time mapping of the geochemistry of underlying granite by utilising pXRF analysis of soil samples identified variation in granitic composition, thus allowing exploration to rapidly focus on the most prospective areas for Ta-Nb-U-REE mineralization. Principal components analysis and clustering protocols are applied to the centred log-ratio transform of a selection of eight elements (Ca, Fe, K, Rb, Sr, Ti, Mn, and Zr) to identify rocks of the same geochemical affinity
a posteriori.
Maps of these clusters reveal a map pattern that provides an interpretation of the underlying geology. One of the limitations of pXRF is false elemental concentrations being detected due to spectral overlaps between elements. We provide a possible solution to this problem through statistical data analysis using a probabilistic modelling approach. We propose a binary approach whereby the pXRF data for these elements, such as Sn, can be considered in the context of presence (detected; >150 ppm) or absence (not detected; <150 ppm) as comparison to laboratory data shows that the concentration of Sn is reliably detected at concentrations >150 ppm. A kernel density estimator and Bayes conditional probability can provide an effective method for calculating the probability of a sample having elevated content of elements, such as Sn, which may be variably detected by pXRF (depending on matrix and concentration). Utilising statistical approaches to treat large geochemical datasets, such as those that can be generated by pXRF, as they are collected, can provide timely and significant insights that might otherwise not have been apparent in elemental concentration maps alone.
Background values of gold, potentially toxic elements and emerging high-tech critical elements in surface water collected in a remote northern European environment
Authors: Reimann Clemens , Birke Manfred , Flem Belinda , Eggen Ola A. , Gasser Deta
Published: February 2018

A geochemical surfacewater survey, focused on 2nd and 3rd order streams, was carried out in the Oppdal/Berkåk area in Norway. Stream water was collected at 168 sample sites, covering a 1500-km
2
survey area. Electrical conductivity, pH, alkalinity and temperature were recorded in the field. Electrical conductivity and pH were also determined once more in the laboratory. The cations Br, Cl, F, NO
2
, NO
3
, PO
4
and SO
4
were determined by ion-chromatography (IC) on unacidified, laboratory filtered samples. Inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) was used to analyse field filtered and acidified samples for 63 elements. In addition, inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to determine 27 elements.

One aim of the survey was to test whether today's ICP-QMS analyses are sensitive enough to directly use surface water efficiently for gold prospecting. The two known gold occurrences in the area are marked by low level Au anomalies in stream water (0.006 µg/l). These values are just above the detection limit of 0.001 µg/l and it must be concluded that today's detection limits are still not low enough to use stream water for routine Au (and In) prospecting. The anions as determined by IC were most problematic in terms of number of samples below detection limit.

Increased anthropogenic activities in the lowlands are marked by slightly enhanced NO
3
values in the streams. An As, Mo, Sb, V anomaly marks the main skiing area near Oppdal but is probably geogenic. In general surface water geochemistry of, for example, Ca, Ce, Cu, K, La, Rb, SO
4
and Sr reflects the geology of the area well. Methodological tests indicate that it should be sufficient to take unfiltered samples in the field and to filter and acidify these in the evening at home base. The dataset provides a good overview of background concentrations and variation of almost 70 chemical elements in stream water from a remote northern European survey area.

Supplementary material:
Table S1 showing the analytical program, isotopes measured and detection limits, Table S2 with analytical results of the international reference materials used for quality control and Fig. S1 with geochemical maps for all elements are available at:
https://doi.org/10.6084/m9.figshare.c.4012885
CO
2
sublimation in Martian gullies: laboratory experiments at varied slope angle and regolith grain sizes
Authors: Sylvest Matthew E. , Dixon John C. , Conway Susan J. , Patel Manish R. , McElwaine Jim N. , Hagermann Axel , Barnes Adam
Published: February 2018

Martian gullies were initially hypothesized to be carved by liquid water, due to their resemblance to gullies on Earth. Recent observations have highlighted significant sediment transport events occurring in Martian gullies at times and places where CO
2
ice should be actively sublimating. Here we explore the role of CO
2
sublimation in mobilizing sediment through laboratory simulation. In our previous experimental work, we reported the first observations of sediment slope movement triggered by the sublimation of CO
2
frost. We used a Mars regolith simulant near the angle of repose. The current study extends our previous work by including two additional substrates, fine and coarse sand, and by testing slope angles down to 10°. We find that the Mars regolith simulant is active down to 17°, the fine sand is active only near the angle of repose and the coarse sand shows negligible movement. Using an analytical model, we show that under Martian gravity motion should be possible at even lower slope angles. We conclude that these mass-wasting processes could be involved in shaping Martian gullies at the present day and intriguingly the newly reported CO
2
-creep process could provide an alternative explanation for putative solifluction lobes on Mars.
Nrf2 deletion from adipocytes, but not hepatocytes, potentiates systemic metabolic dysfunction after long-term high-fat diet-induced obesity in mice
Authors: Chartoumpekis Dionysios V. , Palliyaguru Dushani L. , Wakabayashi Nobunao , Fazzari Marco , Khoo Nicholas K. H. , Schopfer Francisco J. , Sipula Ian , Yagishita Yoko , Michalopoulos George K. , O’Doherty Robert M , Kensler Thomas W.
Published: February 2018

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a canonical regulator of cytoprotective gene expression, but evidence of its cross talk with other pathways, including metabolic ones, is ever increasing. Pharmacologic or systemic genetic activation of the Nrf2 pathway partially protects from obesity in mice and ameliorates fasting hyperglycemia in mice and humans. However, systemic Nrf2 deletion also protects from diet-induced obesity and insulin resistance in mice. To further investigate the effect of the disruption of Nrf2 on obesity in a tissue-specific manner, we focused on adipocytes and hepatocytes with targeted deletion of Nrf2. To this end, mice with cell-specific deletion of Nrf2 in adipocytes (ANKO) or hepatocytes (HeNKO) were fed a high-fat diet (HFD) for 6 mo and showed similar increases in body weight and body fat content. ANKO mice showed a partially deteriorated glucose tolerance, higher fasting glucose levels, and higher levels of cholesterol and nonesterified fatty acids compared with their Control counterparts. The HeNKO mice, though, had lower insulin levels and trended toward improved insulin sensitivity without having any difference in liver triglyceride accumulation. This study compared for the first time two conditional Nrf2 knockout models in adipocytes and in hepatocytes during HFD-induced obesity. None of these models could completely recapitulate the unexpected protection against obesity observed in the whole body Nrf2 knockout mice, but this study points out the differential roles that Nrf2 may play, beyond cytoprotection, in different target tissues and rather suggests systemic activation of the Nrf2 pathway as an effective means of prevention and treatment of obesity and type 2 diabetes.
Numerical Method for Predicting the Blast Wave in Partially Confined Chamber
Authors: Xu Wei-zheng , Kong Xiang-shao , Zheng Cheng , Wu Wei-guo
Published: February 2018

Blast waves generated by cylindrical TNT explosives in partially confined chamber were studied numerically and experimentally. Based on the classical fifth-order weighted essentially nonoscillatory finite difference schemes (fifth-order WENO schemes), the 1D, 2D, and 3D codes for predicting the evolution of shock waves were developed. A variety of benchmark-test problems, including shock tube problem, interacting blast wave, shock entropy wave interaction, and double Mach reflection, were studied. Experimental tests of explosion events in a partially confined chamber were conducted. Then, the 3D code was employed to predict the overpressure-time histories of certain points of chamber walls. Through comparing, a good agreement between numerical prediction and experimental results was achieved. The studies in this paper provide a reliable means to predict the blast load in confined space.
Synthesis of Carbon Nanomaterials from Rice Husk via Microwave Oven
Authors: Asnawi Muhammad , Azhari Saman , Hamidon Mohd Nizar , Ismail Ismayadi , Helina Intan
Published: February 2018

Microwave oven was utilized to fabricate carbon nanostructure, specifically CNTs, from waste RH powders. It has been shown that the use of carbon source, catalyst, and commercial microwave oven to induce plasma is necessary to carry on this synthesis. The plasma enhances and speeds up the catalytic decomposition of RH in presence of ferrocene. FESEM, TGA, and Raman spectroscopy were utilized to confirm the presence and quality of produced carbon nanomaterials. In addition, these results suggest the conversion of ferrocene to iron(II, III) oxide with notable conversion rate.
Analysis of Dietary Related Factors of Recurrent Aphthous Stomatitis among College Students
Authors: Du Qian , Ni Shenglou , Fu Yanling , Liu Sanhai
Published: February 2018

Objective. We investigated the occurrence of recurrent aphthous stomatitis (RAS) among college students and its potential influence by dietary habits. Methods. Study of dietary habits and RAS among students in Beijing University of Chinese Medicine was carried by homemade questionnaire. Multivariate binary logistic regression analysis was used to identify RAS risk factors and explore their relations. Results. Among 1011 investigated college students, family history (odds ratio (OR) 1.678, 95% confidence intervals (CI) 1.192 to 2.364, p < 0.05), bed late (OR 1.515, 95% CI 1.005 to 2.285, p < 0.05), frequent thirst (OR 1.842, 95% CI 1.393 to 2.435, p < 0.001), and frequent drinking carbonated beverages (OR 1.369, 95% CI 1.029 to 1.821, p < 0.05) were independent risk factors for RAS, but preference for nuts (OR 0.607, 95% CI 0.448 to 0.824, p < 0.001) was a protective factor. There was no statistical difference in fruit intake between RAS and non‐RAS groups (χ2 = 5.249, p > 0.05). Conclusions. Among college students, frequent drinking carbonated beverages or frequent thirst will increase its possibility, whereas preference for nuts provides protection. In addition, fruit intake does not have a positive effect.
Defending against the Advanced Persistent Threat: An Optimal Control Approach
Authors: Li Pengdeng , Yang Xiaofan , Xiong Qingyu , Wen Junhao , Tang Yuan Yan
Published: February 2018

The new cyberattack pattern of advanced persistent threat (APT) has posed a serious threat to modern society. This paper addresses the APT defense problem, that is, the problem of how to effectively defend against an APT campaign. Based on a novel APT attack-defense model, the effectiveness of an APT defense strategy is quantified. Thereby, the APT defense problem is modeled as an optimal control problem, in which an optimal control stands for a most effective APT defense strategy. The existence of an optimal control is proved, and an optimality system is derived. Consequently, an optimal control can be figured out by solving the optimality system. Some examples of the optimal control are given. Finally, the influence of some factors on the effectiveness of an optimal control is examined through computer experiments. These findings help organizations to work out policies of defending against APTs.
Acute Intoxication following Dimethyltryptamine Ingestion
Authors: Bilhimer Matthew H. , Schult Rachel F. , Higgs Kristan V. , Wiegand Timothy J. , Gorodetsky Rachel M. , Acquisto Nicole M.
Published: February 2018

Ayahuasca is a hallucinogenic tea that is most commonly comprised of the vine Banisteriopsis caapi alone or in combination with other plants such as Psychotria viridis. This concoction results in an orally active form of dimethyltryptamine (DMT), a hallucinogenic amine. Despite use in South America as a medicinal agent and component in religious ceremonies, interest in its recreational use and spiritual effects has led to increased use in the United States. We describe a unique case following ingestion of ayahuasca tea in a patient with history of schizophrenia resulting in personal injury and property damage. A review of ayahuasca toxicity and evaluation of serious adverse effects is also presented.
On Surface Completion and Image Inpainting by Biharmonic Functions: Numerical Aspects
Authors: Damelin S. B. , Hoang N. S.
Published: February 2018

Numerical experiments with smooth surface extension and image inpainting using harmonic and biharmonic functions are carried out. The boundary data used for constructing biharmonic functions are the values of the Laplacian and normal derivatives of the functions on the boundary. Finite difference schemes for solving these harmonic functions are discussed in detail.
Vehicle Reference Generator for Collision-Free Trajectories in Hazardous Maneuvers
Authors: Acosta Lúa Cuauhtémoc , De Jesus Díaz Gerardo , Di Gennaro Stefano , Kabbani Tarek
Published: February 2018

This paper presents a reference generator for ground vehicles, based on potential fields adapted to the case of vehicular dynamics. The reference generator generates signals to be tracked by the vehicle, corresponding to a trajectory avoiding collisions with obstacles. This generator integrates artificial forces of potential fields of the object surrounding the vehicle. The reference generator is used with a controller to ensure the tracking of the accident-free reference. This approach can be used for vehicle autonomous driving or for active control of manned vehicles. Simulation results, presented for the autonomous driving, consider a scenario inspired by the so-called moose (or elk) test, with the presence of other collaborative vehicles.
Nonlinear Dynamics of the High-Speed Rotating Plate
Authors: Yao Minghui , Ma Li , Zhang Wei
Published: February 2018

High speed rotating blades are crucial components of modern large aircraft engines. The rotating blades under working condition frequently suffer from the aerodynamic, elastic and inertia loads, which may lead to large amplitude nonlinear oscillations. This paper investigates nonlinear dynamic responses of the blade with varying rotating speed in supersonic airflow. The blade is simplified as a pre-twist and presetting cantilever composite plate. Warping effect of the rectangular cross-section of the plate is considered. Based on the first-order shear deformation theory and von-Karman nonlinear geometric relationship, nonlinear partial differential dynamic equations of motion for the plate are derived by using Hamilton’s principle. Galerkin approach is applied to discretize the partial differential governing equations of motion to ordinary differential equations. Asymptotic perturbation method is exploited to derive four-degree-of-freedom averaged equation for the case of 1 : 3 internal resonance-1/2 sub-harmonic resonance. Based on the averaged equation, numerical simulation is used to analyze the influence of the perturbation rotating speed on nonlinear dynamic responses of the blade. Bifurcation diagram, phase portraits, waveforms and power spectrum prove that periodic motion and chaotic motion exist in nonlinear vibration of the rotating cantilever composite plate.
SAI: Safety Application Identifier Algorithm at MAC Layer for Vehicular Safety Message Dissemination Over LTE VANET Networks
Authors: Ansari Shuja , Sánchez Marvin , Boutaleb Tuleen , Sinanovic Sinan , Gamio Carlos , Krikidis Ioannis
Published: February 2018

Vehicular safety applications have much significance in preventing road accidents and fatalities. Among others, cellular networks have been under investigation for the procurement of these applications subject to stringent requirements for latency, transmission parameters, and successful delivery of messages. Earlier contributions have studied utilization of Long‐Term Evolution (LTE) under single cell, Friis radio, or simplified higher layer. In this paper, we study the utilization of LTE under multicell and multipath fading environment and introduce the use of adaptive awareness range. Then, we propose an algorithm that uses the concept of quality of service (QoS) class identifiers (QCIs) along with dynamic adaptive awareness range. Furthermore, we investigate the impact of background traffic on the proposed algorithm. Finally, we utilize medium access control (MAC) layer elements in order to fulfill vehicular application requirements through extensive system‐level simulations. The results show that, by using an awareness range of up to 250 m, the LTE system is capable of fulfilling the safety application requirements for up to 10 beacons/s with 150 vehicles in an area of 2 × 2 km2. The urban vehicular radio environment has a significant impact and decreases the probability for end‐to‐end delay to be ≤100 ms from 93%–97% to 76%–78% compared to the Friis radio environment. The proposed algorithm reduces the amount of vehicular application traffic from 21 Mbps to 13 Mbps, while improving the probability of end‐to‐end delay being ≤100 ms by 20%. Lastly, use of MAC layer control elements brings the processing of messages towards the edge of network increasing capacity of the system by about 50%.
Sufficient Condition for the Parallel Flow Problem of Electromagnetic Loop Networks
Authors: Yang Yi , Guo Zhizhong
Published: February 2018

Electromagnetic loop networks (EMLNs) are pervasive in power networks. Their major characteristic is parallel flow. EMLNs with substantial parallel flow are considered to have a parallel flow problem. There is currently a serious disagreement about whether EMLNs have a parallel flow problem, which has resulted in different configurations of national grids. Therefore, this paper proposes a general model of EMLNs and derives the parallel current function, which formulates parallel flow, from the network equations of both the high and low voltage sides of an EMLN. Accordingly, the high and low voltage sides of an EMLN are equivalent to two sets of parallel identical multi-transmission lines. Finally, this paper considers operating margins and derives the sufficient condition under which parallel flow can be ignored. The sufficient condition not only determines whether an EMLN has a parallel flow problem but also reveals simple approaches to visually diminishing parallel flow. If the EMLN satisfies the sufficient condition, parallel flow can be ignored; otherwise, the EMLN needs to operate in a restricted way or to adopt open loop planning.
A Tricin Derivative from Deschampsia antarctica Desv. Inhibits Colorectal Carcinoma Growth and Liver Metastasis through the Induction of a Specific Immune Response
Authors: Malvicini Mariana , Gutierrez-Moraga Ana , Rodriguez Marcelo M. , Gomez-Bustillo Sofia , Salazar Lorena , Sunkel Carlos , Nozal Leonor , Salgado Antonio , Hidalgo Manuel , Lopez-Casas Pedro P. , Novella Jose Luis , Vaquero Juan Jose , Alvarez-Builla Julio , Mora Adda , Gidekel Manuel , Mazzolini Guillermo
Published: February 2018

In colorectal carcinoma patients, distant metastatic disease is present at initial diagnosis in nearly 25% of them. The majority of patients with metastatic colorectal carcinoma have incurable disease; therefore, new therapies are needed. Agents derived from medicinal plants have already demonstrated therapeutic activities in human cancer cells. Antartina is an antitumor agent isolated from Deschampsia antarctica Desv. This study aimed to evaluate the antitumor properties of Antartina in colorectal carcinoma models. We used human and murine colorectal carcinoma cell lines for investigating proliferation, apoptosis, and cell-cycle effects of Antartina therapy in vitro. Avatar and immunocompetent colorectal carcinoma animal models were applied for evaluating the effects of Antartina in vivo. Immune response against colorectal carcinoma model was investigated using CTL assay, analyzing dendritic cell activation and intratumor T-cell subpopulation, and by tumor rechallenge experiments. Antartina inhibits in vitro human colorectal carcinoma cell proliferation; however, in vivo experiments in Avatar colorectal carcinoma model Antartina display a limited antitumor effect. In an immunocompetent colorectal carcinoma mice model, Antartina potently inhibited tumor growth and liver metastases, leading to complete tumor regressions in >30% of mice and increased animal survival. In addition, Antartina induced a potent specific cytotoxic T-cell response against colorectal carcinoma and a long-lasting antitumor immunity. Interestingly, Antartina increased tumor immunogenicity and stimulated dendritic cell activation. No toxic effects were observed at the doses employed. Our findings showed that Antartina has the ability to induce antitumor immunity against colorectal carcinoma and can be used to develop new tools for the treatment of colorectal carcinoma. Mol Cancer Ther; 17(5); 966–76. ©2018 AACR.
Combined Inhibition of mTOR and CDK4/6 Is Required for Optimal Blockade of E2F Function and Long-term Growth Inhibition in Estrogen Receptor–positive Breast Cancer
Authors: Michaloglou Chrysiis , Crafter Claire , Siersbaek Rasmus , Delpuech Oona , Curwen Jon O. , Carnevalli Larissa S. , Staniszewska Anna D. , Polanska Urszula M. , Cheraghchi-Bashi Azadeh , Lawson Mandy , Chernukhin Igor , McEwen Robert , Carroll Jason S. , Cosulich Sabina C.
Published: February 2018

The cyclin dependent kinase (CDK)–retinoblastoma (RB)–E2F pathway plays a critical role in the control of cell cycle in estrogen receptor–positive (ER+) breast cancer. Small-molecule inhibitors of CDK4/6 have shown promise in this tumor type in combination with hormonal therapies, reflecting the particular dependence of this subtype of cancer on cyclin D1 and E2F transcription factors. mTOR inhibitors have also shown potential in clinical trials in this disease setting. Recent data have suggested cooperation between the PI3K/mTOR pathway and CDK4/6 inhibition in preventing early adaptation and eliciting growth arrest, but the mechanisms of the interplay between these pathways have not been fully elucidated. Here we show that profound and durable inhibition of ER+ breast cancer growth is likely to require multiple hits on E2F-mediated transcription. We demonstrate that inhibition of mTORC1/2 does not affect ER function directly, but does cause a decrease in cyclin D1 protein, RB phosphorylation, and E2F-mediated transcription. Combination of an mTORC1/2 inhibitor with a CDK4/6 inhibitor results in more profound effects on E2F-dependent transcription, which translates into more durable growth arrest and a delay in the onset of resistance. Combined inhibition of mTORC1/2, CDK4/6, and ER delivers even more profound and durable regressions in breast cancer cell lines and xenografts. Furthermore, we show that CDK4/6 inhibitor–resistant cell lines reactivate the CDK–RB–E2F pathway, but remain sensitive to mTORC1/2 inhibition, suggesting that mTORC1/2 inhibitors may represent an option for patients that have relapsed on CDK4/6 therapy. Mol Cancer Ther; 17(5); 908–20. ©2018 AACR.