bluuebunny/crossref_metadata_2025 huggingface dataset:
Contemporary Guidance on Management of Road Safety Audits
Authors: Karndacharuk Auttapone , Hillier Paul
Published: August 2019

Although there is good awareness of road safety audit as a proactive technique for identifying and mitigating road safety related risks throughout Australasia and internationally, local practices in procuring, managing and conducting audits can vary between jurisdictions. This paper provides an overview of recent policy developments and practical guidance in managing road safety audits in Australia and New Zealand.

Based on the update (Austroads 2019) of Austroads Guide to Road Safety Part 6 (AGRS), the guidance aims at maximizing alignment with Safe System principles by integrating them into the audit process. This is achieved through improved awareness of practitioners new to the principles and concepts (especially project clients and project managers) and promoting the conduct of audits to realise their harm minimisation benefits.
For whom didn’t it click? A study of the non-use of seat belts in motor vehicle fatalities in New Zealand
Authors: Hirsch Lily , Mackie Hamish , Scott Richard , de Pont John , Douglas Simon , Thomsen Dylan
Published: August 2019

There is an increased risk of death or serious injury for occupants who did not wear a seat belt in a crash. In New Zealand, between 2006 and 2016, the non-use of seat belts accounted for 19-30% of the overall motor vehicle road deaths, and this figure shows no sign of decreasing. It is important to better understand the contextual factors associated with crashes where seat belts are not worn, so that more relevant and effective road safety interventions can be designed and implemented. The aim of this research was to determine the profiles for seat belt non-users who were killed in motor vehicle crashes in New Zealand between 2011 and 2015. An in-depth analysis of 200 fatalities where seat belts were not worn (186 crash cases) was carried out following a Safe System framework, using NZ Police reports. Following this, a Multiple Correspondence Analysis (MCA) developed five profiles of vehicle occupants who were killed in crashes where seat belts were not worn. While the stereotypical ‘young risky’ males were an important group, a range of other people and contexts emerged: ‘driving for work’; ‘elderly and retired’; ‘overseas passengers’; and ‘people driving in rural settings’. This has implications for tailored road safety interventions, as a variety of motivations and influences are likely to be at play, depending on the people involved.
The frequency and nature of aggressive acts on Australian roads
Authors: Stephens Amanda , Fitzharris Michael
Published: August 2019

To understand the current prevalence of aggressive acts on Australian roads, a large cross-sectional survey was conducted inviting drivers from all Australian jurisdictions to participate. A stratified sampling procedure was undertaken to ensure the age and gender distributions were representative of each jurisdiction. Participants were asked to report the frequency of aggressive driving behaviours as well as speeding, drink-driving and mobile phone usage while driving. Recent crash history was also obtained. The sample consisted of 2,916 drivers (males = 45%) with an average age of 42 (±16) years. Minor aggressive behaviours such as expressing annoyance to other drivers and sounding the horn in anger were reported by the majority of the sample (60% and 70% respectively). More extreme behaviour such as chasing another driver when angry was less common, however still reported by 18% of the overall sample. Aggressive driving behaviours were more common in younger, male drivers with 36% of drivers aged 22 to 39 reporting extreme aggression. Associations were found between aggressive driving with crash involvement and other forms of risky driving behaviour. The results show that aggressive driving is a problem on Australian roads. Further research is warranted to explore where aggressive driving fits within an overall risky driving pattern of behaviour, what attitudes drivers hold toward aggressive driving, and how to target the reduction of these behaviours.
PENGEMBANGAN BAHAN AJAR TEKS EKSPLANASI BERDASARKAN BERITA MEDIA MASSA CETAK
Authors: Rimayanti Ade Ina , Jaja Jaja
Published: August 2019

Penelitian ini bertujuan mengembangkan sebuah bahan ajar teks eksplanasi. Penelitian ini dilatarbelakangi permasalahan: (1) Bagaimanakah unsur dan kaidah kebahasaan yang terdapat dalam teks ekslanasi di berita media massa cetak? (2) Bagaimanakah rancangan bahan ajar tek eksplanasi berdasarkan media masa cetak dan implementasinya dalam pembelajaran teks eksplanasi ? (3) Bagaimanakah hasil implementasinya dari penggunaan bahan ajar teks eksplanasi berdasarkan media masa cetak dalam pembelajaran teks eksplanasi? Sumber Teks Eksplanasi media massa cetak koran dengan menganalisis isi, ketepatan penyajian, dan kesesuaian bahasanya, Instrumen angket hasil validasi dari ahli materi, dan Hasil pembelajaran. Berdasarkan penilaian  ahli  materi,  dan  guru  bahasa  Indonesia,  aspek kualitas pembelajaran memiliki rata-rata 3,33 (tingkat kelayakan 83,25%) yang termasuk dalam kategori sangat baik, dan layak digunakan. Kemudian, aspek penyajian  materi  pembelajaran  memiliki  rata-rata  3,22  (tingkat  kelayakan 80,5%) yang termasuk dalam kategori sangat baik dan layak digunakan.Selanjutnya, berdasarkan penilaian akhir ahli media, aspek desain tampilan  memiliki rata-rata 3,5 (tingkat kelayakan 87,5%) yang termasuk dalam kategori sangat  baik  dan  dapat  dikatakan  layak.  Kemudian,  aspek  pengoperasian memiliki  rata-rata  3,16  (tingkat  kelayakan  79,12%)  yang  termasuk  dalam kategori baik sehingga dapat dikatakan layak digunakan. Berdasarkan analisis tersebut dapat disimpulkan bahwa media pembelajaran teks  eksplanasi  dapat  digunakan  dalam  proses  pembelajaran  karena  telah memenuhi kriteria kelayakan.
PENGEMBANGAN BAHAN AJAR TEKS CERITA PENDEK DENGAN TEKNIK PAPAN CERITA BERGAMBAR UNTUK SMA
Authors: Susanti Eka
Published: August 2019

Melalui pengembangan bahan ajar menulis teks cerita pendek berdasaran teknik papan cerita bergambar dalam pembelajaran cerpen diharapkan dapat mengaktifkan dalam belajar, siswa akan terlatih menggunakan kemampuan berpikir dan bekerja sama dalam memecahkan masalah guna mencapai hasil yang maksimal.   Penelitian ini merupakan pengembangan atau Research & Development (R&D). Penelitian dan pengembangan merupakan metode penelitian yang digunakan untuk mengembangkan atau memvalidasi produk-produk yang digunakan dalam pendidikan dan pembelajaran. Penelitian ini mengembangkan produk berupa bahan ajar menulis cerpen berdasarkan teknik papan cerita bergambar untuk siswa SMA kelas XI. Penulis telah melakukan penelitian di kelas XI-7 Mipa, yaitu kelas eksperimen tentang pengembangan bahan ajar menulis cerita pendek berdasarkan teknik papan cerita bergambar dalam pembelajaran cerpen dengan kelas berjumlah 35 siswa. Teknik pengambilan data yang penulis gunakan adalah teknik wawancara, angket/kuesioner, telaah buku, tes tertulis dan observasi. Berdasarkan  hasil penelitian, diperoleh nilai rata-rata tes awal pada kelas eksperimen yaitu 58,62 sedangkan nilai rata-rata tes akhir adalah 79,25. Lain halnya dengan aktivitas siswa dalam pengembangan bahan ajar dengan teknik papan cerita bergambar yang dikategorikan baik dengan nilai probalititas 0,000 < nilai ᵅ (0.05), terdapat perbedaan yang signifikan yang menggunakan bahan ajar menyusun teks cerpen dengan teknik papan cerita bergambar. Berdasarkan data tersebut, dapat disimpulkan bahwa pengembangan bahan ajar menulis teks cerita pendek dengan teknik papan cerita bergambar di SMA kelas XI efektif. Guru Bahasa Indonesia dapat menggunakan bahan ajar yang dibuat oleh guru, khususnya pada materi pelajaran mengidentifikasi struktur dan unsur pembentuknya. Pengembangan bahan ajar dalam pembelajaran cerpen ini dapat memudahkan siswa dalam memahami pelajaran.
A Comprehensive Review on the Manipulation of the Sphingolipid Pathway by Pathogenic Bacteria
Authors: Rolando Monica , Buchrieser Carmen
Published: August 2019

Bacterial pathogens have developed many different strategies to hijack host cell responses to promote their own survival. The manipulation of lipid biogenesis and cell membrane stability is emerging as a key player in bacterial host cell control. Indeed, many bacterial pathogens such as Legionella, Pseudomonas, Neisseria, Staphylococci, Mycobacteria, Helicobacter, or Clostridia are able to manipulate and use host sphingolipids during multiple steps of the infectious process. Sphingolipids have long been considered only as structural components of cell membranes, however, it is now well known that they are also intracellular and intercellular signaling molecules that play important roles in many eukaryotic cell functions as well as in orchestrating immune responses. Furthermore, they are important to eliminate invading pathogens and play a crucial role in infectious diseases. In this review, we focus on the different strategies employed by pathogenic bacteria to hijack the sphingolipid balance in the host cell to promote cellular colonization.
Effect of High Potency Growth Implants on Average Daily Gain of Grass-Fattened Steers
Authors: Arias Rodrigo , Santa-Cruz Cristobal , Velásquez Alejandro
Published: August 2019

High potency growth promoter implants (HGPs) are widely used under feedlot conditions but there are few reports under grazing conditions. The study’s goal was to assess the effect of HGPs on the average daily gain of steers fattened in pastures. A total of 57 crossbreed steers (Hereford × Angus)—initial body weight = 356.65 kg ± 5.04 (SEM)—were randomly allocated to one of three groups: Control without HGP (n = 19), Synovex group (n = 17), and Revalor group (n = 21). The fattening period was 67 days using paddocks of Lolium perenne L. and Trifolium repens L. Body weight was recorded three times in the period. The data were analyzed using an analysis of covariance with a level of significance of 5%. The average daily gain (ADG) (1.55 ± 0.07 and 1.48 ± 0.09 kg/d) and the total weight gain (103.4 ± 4.9 and 99.2 ± 5.8 kg) were similar for Revalor and Synovex, respectively (p > 0.05). Moreover, HGP groups showed higher ADG and total weight gain (p < 0.01) than the control group (ADG = 0.93 ± 0.08 kg/d and a total weight gain of 62.2 ± 5.2 kg). Final body weights were 527.8 ± 8.5 kg and 512.2 ± 9.9 kg for Revalor and Synovex, respectively; and 479.9 ± 10.1 kg for Control. In conclusion, grazing-finished steers showed better performance when high potency HGPs were used, improving the ADG and final live body weight, generating a marginal income that justifies the use of the technology under grazing conditions
Effects of Supplementation of Branches and Leaves Trimmed from Tea Plant on Growth Performance, Rumen Fermentation and Meat Composition of Nanjiang Yellow Goats
Authors: Shah Ali Mujtaba , Cai Yimin , Zou Huawei , Zhang Xiangfei , Wang Lizhi , Xue Bai , Yu Peiqiang , Wang Zhisheng , Peng Quanhui
Published: August 2019

Thirty-two 6-month-old, healthy Nanjiang Yellow goats (34.6 ± 4.16 kg) were randomly divided into four treatments to evaluate the supplementary effects of branches and leaves trimmed from tea tree (BLTT) on growth performance, rumen fermentation characteristics, and meat composition in fattening goats. The control goats were fed a basal diet. Treatments 1, 2 and 3 were fed 2%, 4% and 6% of BLTT respectively. After a 60 d feeding trial, blood samples were collected for the analysis of the antioxidant profile and goats were slaughtered to obtain the rumen fluid and carcass samples for determination of rumen fermentation characteristics and meat composition perameters. Increased final body weight was observed in goats fed 4% BLTT compared with control. The activity of superoxide dismutase was increased in the 4% BLTT-treated group, while glutathione peroxidase and malondialdehyde followed the quadratic curve. Quadratic curves were also observed for villus height, crypt depth and the ratio of villus height to crypt depth in the jejunum. The quadratic effect was obtained for total essential amino acids, and individual amino acids threonine and leucine. The saturated fatty acid C16:0 was decreased with 4% of BLTT supplementation, and a quadratic effect was observed for polyunsaturated fatty acid C18:3 (n−3). To sum up, our findings revealed that BLTT supplementation has a positive effect on body antioxidative status, gastrointestinal development, rumen fermentation characteristics and overall growth performance and meat quality in goats.
Anti-Mycoplasma Activity of Daptomycin and Its Use for Mycoplasma Elimination in Cell Cultures of Rickettsiae
Authors: Tantibhedhyangkul Wiwit , Wongsawat Ekkarat , Matamnan Sutthicha , Inthasin Naharuthai , Sueasuay Jintapa , Suputtamongkol Yupin
Published: August 2019

Mycoplasma contamination detrimentally affects cellular functions and the growth of intracellular pathogens in cell cultures. Although several mycoplasmacidal agents are commercially available for sterile cell cultures, they are not applicable to rickettsia-infected cells. In our attempt to find an anti-mycoplasma drug for contaminated rickettsial cultures, we determined the susceptibilities of three common Mycoplasma species to daptomycin. Mycoplasma orale and M. arginini showed low-level resistance to daptomycin (minimum inhibitory concentration, MIC = 2 mg/L), whereas M. hyorhinis was high-level resistant (MIC = 32 mg/L). However, some Mycoplasma isolates developed higher resistance to daptomycin after failed treatments with inadequate doses or durations. An aminoglycoside (gentamicin) was still active against M. hyorhinis and could be used in Orientia cultures. For complete eradication of mycoplasmas in Rickettsia cultures, we recommend a 3-week treatment with daptomycin at 256 mg/L. In contaminated Orientia cultures, daptomycin at 32 mg/L was effective in eradicating M. orale, whereas either gentamicin or amikacin (100 mg/L) was effective in eradicating M. hyorhinis. Unlike each drug alone, the combinations of daptomycin plus clindamycin and/or quinupristin/dalfopristin proved effective in eradicating M. hyorhinis. In summary, our study demonstrated the in vitro anti-mycoplasma activity of daptomycin and its application as a new mycoplasma decontamination method for Rickettsia and Orientia cultures.
Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice
Authors: Kim Jung-Yeon , Jo Jungmin , Kim Kiryeong , An Hyun-Jin , Gwon Mi-Gyeong , Gu Hyemin , Kim Hyun-Ju , Yang A Young , Kim Sung-Woo , Jeon Eon Ju , Park Jae-Hyung , Leem Jaechan , Park Kwan-Kyu
Published: August 2019

Sirtuin 1 (Sirt1) is an essential modulator of cellular metabolism and has pleiotropic effects. It was recently reported that Sirt1 overexpression in kidney tubule ameliorates cisplatin-induced acute kidney injury (AKI). However, whether pharmacological activation of Sirt1 also has a beneficial effect against the disease remains unclear. In this study, we aimed to evaluate whether SRT1720, a potent and specific activator of Sirt1, could ameliorate cisplatin-induced AKI. We found that SRT1720 treatment ameliorated cisplatin-induced acute renal failure and histopathological alterations. Increased levels of tubular injury markers in kidneys were significantly attenuated by SRT1720. SRT1720 treatment also suppressed caspase-3 activation and apoptotic cell death. Increased expression of 4-hydroxynonenal, elevated malondialdehyde level, and decreased ratio of reduced glutathione/oxidized glutathione after cisplatin injection were significantly reversed by SRT1720. In addition, SRT1720 treatment decreased renal expression of pro-inflammatory cytokines and prevented macrophage infiltration into damaged kidneys. We also showed that the therapeutic effects of SRT1720 were associated with reduced acetylation of p53 and nuclear factor kappa-B p65 and preservation of peroxisome function, as evidenced by recovered expression of markers for number and function of peroxisome. These results suggest that Sirt1 activation by SRT1720 would be a useful therapeutic option for cisplatin-induced AKI.
Relationship between Kinematic Variables of Jump Throwing and Ball Velocity in Elite Handball Players
Authors: Akl Abdel-Rahman , Hassan Ibrahim , Hassan Amr , Bishop Phillip
Published: August 2019

The purpose of this pilot study was to evaluate the relationship between the kinematic variables of the right hand and left leg with ball velocity during jump-throwing phases in handball for better-informed training. We investigated ball velocity and the key kinematic variables of jump throwing during different throwing phases in three strides. Ten right-handed male handball professional players who had competed in the Egyptian Handball Super League participated in this study. Jump throwing performance was divided into three phases (cocking, acceleration and follow-through), which included eight events during the throwing. Five trials were captured for each player, and a 3D analysis was performed on the best trial. Results indicated that the velocity of the throwing hand was the most important variable during jump throwing, which was correlated with ball velocity during the three phases of performance in four events: Initial contact (IC) (r = 0.66*), initial flight (IF) (r = 63*), maximum height of the throwing hand (Max-HH) (r = 0.78*) and ground contact (GC) (r = 0.83*). In addition, the initial flight was the most important event in which players need to be using the best angles during performance, particularly the shoulder angle.
Seismic Control of SDOF Systems with Nonlinear Eddy Current Dampers
Authors: Liang Longteng , Feng Zhouquan , Chen Zhengqing
Published: August 2019

The nonlinear model and energy dissipation of a rotary axial eddy current damper (ECD) and the dynamic responses to harmonic and seismic base excitations of a linear elastic SDOF system with the nonlinear ECD (SDOF-ECD) are investigated. Firstly, the nonlinear force-velocity relationship of the ECD is studied using finite element simulation, experimental testing and mathematical model fitting. Secondly, the energy dissipated by the nonlinear ECD under a cycle of harmonic motion is derived analytically and its optimal critical velocity is determined such that the energy dissipation is maximized. Finally, the responses of the SDOF-ECDs subjected to harmonic and seismic base excitations are calculated using numerical algorithm, where the displacement and acceleration control performance and the energy dissipation capacity of the ECD are compared with those of the conventional fluid viscous dampers (FVDs). The results indicate that the seismic control performance of ECDs outperforms that of FVDs in most cases and it is anticipated that the ECDs can be used as good alternative devices to conventional FVDs for seismic control applications.
Cellulose Nanofibril (CNF) Films and Xylan from Hot Water Extracted Birch Kraft Pulps
Authors: Borrega Marc , Orelma Hannes
Published: August 2019

The effects of xylan extraction from birch kraft pulp on the manufacture and properties of cellulose nanofibril (CNF) films were here investigated. Hot water extractions of bleached and unbleached kraft pulps were performed in a flow-through system to remove and recover the xylan. After the extraction, the pulps were oxidized with 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) and fibrillated in a high-pressure microfluidizer. Compared to CNF from bleached kraft pulp, the CNF dispersions obtained from water-extracted pulps were less viscous and generally contained a higher amount of microfiber fragments, although smaller in size. In all cases, however, smooth and highly transparent films were produced from the CNF dispersions after the addition of sorbitol as plasticizer. The CNF films made from water-extracted pulps showed a lower tensile strength and ductility, probably due to their lower xylan content, but the stiffness was only reduced by the presence of lignin. Interestingly, the CNF films from water-extracted bleached pulps were less hydrophilic, and their water vapour permeability was reduced up to 25%. Therefore, hot water extraction of bleached birch kraft pulp could be used to produce CNF films with improved barrier properties for food packaging, while obtaining a high-purity xylan stream for other high-value applications.
Special Issue “Computational Methods for Fracture”
Authors: Rabczuk Timon
Published: August 2019

The prediction of fracture and material failure is of major importance for the safety and reliability of engineering structures and the efficient design of novel materials [...]
Docking Control of an Autonomous Underwater Vehicle Using Reinforcement Learning
Authors: Anderlini Enrico , Parker Gordon G. , Thomas Giles
Published: August 2019

To achieve persistent systems in the future, autonomous underwater vehicles (AUVs) will need to autonomously dock onto a charging station. Here, reinforcement learning strategies were applied for the first time to control the docking of an AUV onto a fixed platform in a simulation environment. Two reinforcement learning schemes were investigated: one with continuous state and action spaces, deep deterministic policy gradient (DDPG), and one with continuous state but discrete action spaces, deep Q network (DQN). For DQN, the discrete actions were selected as step changes in the control input signals. The performance of the reinforcement learning strategies was compared with classical and optimal control techniques. The control actions selected by DDPG suffer from chattering effects due to a hyperbolic tangent layer in the actor. Conversely, DQN presents the best compromise between short docking time and low control effort, whilst meeting the docking requirements. Whereas the reinforcement learning algorithms present a very high computational cost at training time, they are five orders of magnitude faster than optimal control at deployment time, thus enabling an on-line implementation. Therefore, reinforcement learning achieves a performance similar to optimal control at a much lower computational cost at deployment, whilst also presenting a more general framework.
Energy Management for Smart Homes—State of the Art
Authors: Lashkari Behzad , Chen Yuxiang , Musilek Petr
Published: August 2019

Smart home is a concept that aims to enhance the comfort of residents and facilitate household activities. The smart home is an application of ubiquitous computing which can provide the user with context-aware automated or assistive services in the form of ambient intelligence, remote control of home appliances, or automation. Smart homes attempt to integrate smartness into homes to guarantee the residents’ convenience, safety, and security, while conserving the energy. The capabilities of a smart home in the context of different applications, have been scrutinized for this investigation. Different proposed architectures, protocols, and infrastructures have been taken into consideration. As the data management process is a vital part of a smart home system, many procedures of data collection, storage, and analysis have been surveyed. Methods of data acquisition has also been discussed. Existing challenges, pros, and cons of proposed schemes along with future perspectives of smart homes are identified in this report, which is intended to promote future research directions.
On Watery Borders, Borderlands, and Tania Kovats’ Head to Mouth
Authors: Holt Ysanne
Published: August 2019

With a relational view of landscapes and natural environments as continuously “in process” and formed from the over-layered and interdependent connections between nature and culture, the human and the non-human, this paper considers some recent practices by artists who have worked in the largely rural border region of Northern England and Southern Scotland. Expanding from a focus on the artist Tania Kovats’ 2019 Berwick Visual Arts exhibition, Head to Mouth, and a wider frame of non-anthropocentric ecological thought in relation to the visual arts, it explores the significance of diverse creative engagements with water, here with the River Tweed, and their potential value in a current cross-border context of social and environmental challenges and concern.
Genetic Relationships Between Ethanol-Induced Conditioned Place Aversion and Other Ethanol Phenotypes in 15 Inbred Mouse Strains
Authors: Cunningham Christopher L.
Published: August 2019

The genetic relationships between different behaviors used to index the aversive effects of ethanol are unknown. To address this issue, ethanol-induced conditioned place aversion (CPA) was tested in a genetically diverse panel of 15 inbred mouse strains. Mice were exposed to an unbiased place conditioning procedure using ethanol doses of 0, 2, or 4 g/kg; all injections were given immediately after 5-min exposure to distinctive tactile cues. There were dose-dependent effects of ethanol on CPA and on the change in pre-injection activity rates between the first and last conditioning trials. Most strains (80%) developed CPA, demonstrating the generalizability of this behavior. Moreover, genotype had significant effects on CPA magnitude and locomotor activity rates. Strain means from this study and previously published studies were then used to examine genetic correlations. These analyses showed significant genetic correlations between CPA and ethanol intake/preference, conditioned taste aversion, and drug withdrawal (but not blood ethanol concentration or conditioned place preference), supporting the idea of commonality in the genes underlying CPA and each of these behaviors. The overall pattern of findings is consistent with previous data suggesting that genetic differences in sensitivity to ethanol’s aversive effects play a role in determining strain differences in ethanol drinking. The broader implication is that individuals who are more sensitive to the aversive effects of ethanol may be protected from developing the excessive drinking behaviors characteristic of alcohol use disorders.
Antioxidant Defenses: A Context-Specific Vulnerability of Cancer Cells
Authors: Cockfield Jordan A. , Schafer Zachary T.
Published: August 2019

Reactive oxygen species (ROS) are well known for their capacity to cause DNA damage, augment mutagenesis, and thereby promote oncogenic transformation. Similarly, agents that reduce ROS levels (antioxidants) are frequently thought to have anti-cancer properties given their propensity to minimize DNA damage and mutagenesis. However, numerous clinical studies focused on antioxidants suggest that this is a facile premise and that antioxidant capacity can be important for cancer cells in a similar fashion to normal cells. As a consequence of this realization, numerous laboratories have been motivated to investigate the biological underpinnings explaining how and when antioxidant activity can potentially be beneficial to cancer cells. Relatedly, it has become clear that the reliance of cancer cells on antioxidant activity in certain contexts represents a potential vulnerability that could be exploited for therapeutic gain. Here, we review some of the recent, exciting findings documenting how cancer cells utilized antioxidant activity and under what circumstances this activity could represent an opportunity for selective elimination of cancer cells.
The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo
Authors: Stakišaitis Donatas , Juknevičienė Milda , Damanskienė Eligija , Valančiūtė Angelija , Balnytė Ingrida , Alonso Marta Maria
Published: August 2019

Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in cancer cells’ mitochondria. Inhibition of pyruvate dehydrogenase kinases by DCA keeps the pyruvate dehydrogenase complex in the active form, resulting in decreased lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA’s effects on the cell pyruvate dehydrogenase deficiency, pyruvate mitochondrial oxidative phosphorylation, reactive oxygen species generation, and the Na+–K+–2Cl− cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human cancer xenografts in vivo in male and female animals. Preclinical cancer researchers report the synergistic effects of DCA combined with different drugs on cancer by reversing resistance to chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA’s effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad hormone dependency could be relevant for individualized therapy approaches so that gender-related differences in treatment response and safety can be proposed.
ADAM17: An Emerging Therapeutic Target for Lung Cancer
Authors: Saad Mohamed I. , Rose-John Stefan , Jenkins Brendan J.
Published: August 2019

Lung cancer is the leading cause of cancer-related mortality, which histologically is classified into small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all lung cancer diagnoses, with the majority of patients presenting with lung adenocarcinoma (LAC). KRAS mutations are a major driver of LAC, and are closely related to cigarette smoking, unlike mutations in the epidermal growth factor receptor (EGFR) which arise in never-smokers. Although the past two decades have seen fundamental progress in the treatment and diagnosis of NSCLC, NSCLC still is predominantly diagnosed at an advanced stage when therapeutic interventions are mostly palliative. A disintegrin and metalloproteinase 17 (ADAM17), also known as tumour necrosis factor-α (TNFα)-converting enzyme (TACE), is responsible for the protease-driven shedding of more than 70 membrane-tethered cytokines, growth factors and cell surface receptors. Among these, the soluble interleukin-6 receptor (sIL-6R), which drives pro-inflammatory and pro-tumourigenic IL-6 trans-signaling, along with several EGFR family ligands, are the best characterised. This large repertoire of substrates processed by ADAM17 places it as a pivotal orchestrator of a myriad of physiological and pathological processes associated with the initiation and/or progression of cancer, such as cell proliferation, survival, regeneration, differentiation and inflammation. In this review, we discuss recent research implicating ADAM17 as a key player in the development of LAC, and highlight the potential of ADAM17 inhibition as a promising therapeutic strategy to tackle this deadly malignancy.
Optimization of the Washcoat Slurry for Hydrotalcite-Based LNT Catalyst
Authors: Zhu Yue , Lv Gang , Song Chonglin , Li Bo , Zhu Yantao , Liu Ye , Zhang Wei , Wang Yuanhong
Published: August 2019

This work aimed to optimize the washcoat slurry for hydrotalcite-based lean NOx trap (LNT) catalyst. The effects of the slurry properties including pH, solid content, binder and additive on the hydrotalcite-based slurry viscosity were investigated. The particle size distribution of the optimal hydrotalcite-based slurry was measured. A cordierite material was used to coat the optimal slurry, and the washcoat was characterized by X-ray diffraction, scanning electron microscopy and N2 adsorption. The optimal slurry containing Pt and Ba was coated on the cordierite for the preparation of hydrotalcite-based LNT catalyst, and the performances of this catalyst were evaluated by NOx storage test, temperature programmed desorption and NOx reduction. For comparison, the performance of the commercial LNT catalyst with Pt/BaO/Al2O3 was analyzed. After coating, the hydrotalcite-based washcoat was closely contacted with the support, being the main phase MgO and presenting a specific surface area of 86.3 m2/g. The hydrotalcite-based LNT catalyst had better NOx storage and desorption ability, selectivity to N2 and LNT efficiency than the Pt/BaO/Al2O3 catalyst.
BKCa (Slo) Channel Regulates Mitochondrial Function and Lifespan in Drosophila melanogaster
Authors: Gururaja Rao Shubha , Bednarczyk Piotr , Towheed Atif , Shah Kajol , Karekar Priyanka , Ponnalagu Devasena , Jensen Haley N. , Addya Sankar , Reyes Beverly A.S. , Van Bockstaele Elisabeth J. , Szewczyk Adam , Wallace Douglas C. , Singh Harpreet
Published: August 2019

BKCa channels, originally discovered in Drosophila melanogaster as slowpoke (slo), are recognized for their roles in cellular and organ physiology. Pharmacological approaches implicated BKCa channels in cellular and organ protection possibly for their ability to modulate mitochondrial function. However, the direct role of BKCa channels in regulating mitochondrial structure and function is not deciphered. Here, we demonstrate that BKCa channels are present in fly mitochondria, and slo mutants show structural and functional defects in mitochondria. slo mutants display an increase in reactive oxygen species and the modulation of ROS affected their survival. We also found that the absence of BKCa channels reduced the lifespan of Drosophila, and overexpression of human BKCa channels in flies extends life span in males. Our study establishes the presence of BKCa channels in mitochondria of Drosophila and ascertains its novel physiological role in regulating mitochondrial structural and functional integrity, and lifespan.
Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells
Authors: Datta Keshava K. , Patil Shankargouda , Patel Krishna , Babu Niraj , Raja Remya , Nanjappa Vishalakshi , Mangalaparthi Kiran Kumar , Dhaka Bharti , Rajagopalan Pavithra , Deolankar Sayali Chandrashekhar , Kannan Ramakrishnan , Kumar Prashant , Prasad T. S. Keshava , Mathur Premendu P. , Kumari Anjali , Manoharan Malini , Coral Karunakaran , Murugan Saktivel , Sidransky David , Gupta Ravi , Gupta Rohit , Khanna-Gupta Arati , Chatterjee Aditi , Gowda Harsha
Published: August 2019

Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form. An understanding of molecular alterations associated with chewing tobacco exposure is vital for identifying molecular markers and potential targets. We developed an in vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over an eight-month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth, indicating cell transformation. Molecular alterations associated with chewing tobacco exposure were characterized by carrying out exome sequencing and quantitative proteomic profiling of parental cells and chewing tobacco exposed cells. Quantitative proteomic analysis revealed increased expression of cancer stem cell markers in tobacco treated cells. In addition, tobacco exposed cells showed the Oxidative Phosphorylation (OXPHOS) phenotype with decreased expression of enzymes associated with glycolytic pathway and increased expression of a large number of mitochondrial proteins involved in electron transport chain as well as enzymes of the tricarboxylic acid (TCA) cycle. Electron micrographs revealed increase in number and size of mitochondria. Based on these observations, we propose that chronic exposure of esophageal epithelial cells to tobacco leads to cancer stem cell-like phenotype. These cells show the characteristic OXPHOS phenotype, which can be potentially targeted as a therapeutic strategy.
Mechanisms of Energy Metabolism in Skeletal Muscle Mitochondria Following Radiation Exposure
Authors: Kim Eun Ju , Lee Minyoung , Kim Da Yeon , Kim Kwang Il , Yi Jae Youn
Published: August 2019

An understanding of cellular processes that determine the response to ionizing radiation exposure is essential for improving radiotherapy and assessing risks to human health after accidental radiation exposure. Radiation exposure leads to many biological effects, but the mechanisms underlying the metabolic effects of radiation are not well known. Here, we investigated the effects of radiation exposure on the metabolic rate and mitochondrial bioenergetics in skeletal muscle. We show that ionizing radiation increased mitochondrial protein and mass and enhanced proton leak and mitochondrial maximal respiratory capacity, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, mice and cells treated with radiation became energetically efficient and displayed increased fatty acid and amino acid oxidation metabolism through the citric acid cycle. Finally, we demonstrate that radiation-induced alterations in mitochondrial energy metabolism involved adenosine monophosphate-activated kinase signaling in skeletal muscle. Together, these results demonstrate that alterations in mitochondrial mass and function are important adaptive responses of skeletal muscle to radiation.
The Influence of Electrophoretic Deposition Parameters and Heat Treatment on the Microstructure and Tribological Properties of Nanocomposite Si3N4/PEEK 708 Coatings on Titanium Alloy
Authors: Fiołek Aleksandra , Zimowski Sławomir , Kopia Agnieszka , Moskalewicz Tomasz
Published: August 2019

Nanocomposite Si3N4/PEEK 708 coatings were successfully fabricated on the Ti-6Al-4V alloy substrate by electrophoretic deposition (EPD) and post-EPD heat treatment. The addition of chitosan polyelectrolyte into ethanolic-based suspensions enabled the cathodic co-deposition of ceramic and polymeric particles. Zeta potential measurements allowed the elaboration of stable suspensions. The selection of the optimal EPD voltage and time enabled uniform coatings to be obtained. Heating above the PEEK melting point and cooling with a furnace or in water resulted in the formation of dense coatings with semi-crystalline or amorphous polymer structures, respectively. Both coatings with a thickness in the range of 90–105 µm had good adhesion and scratch resistance to the substrates, despite the presence of relatively high degrees of open porosity. The coatings improved the tribological properties of the titanium alloy. However, a strong relationship between the polymeric matrix structure and wear resistance was observed. Semi-crystalline coatings proved to be significantly more wear resistant than amorphous ones.
Recent Advances on Topical Application of Ceramides to Restore Barrier Function of Skin
Authors: Kahraman Emine , Kaykın Melis , Şahin Bektay Hümeyra , Güngör Sevgi
Published: August 2019

Human skin is the largest organ of the body and is an effective physical barrier keeping it from environmental conditions. This barrier function of the skin is based on stratum corneum, located in the uppermost skin. Stratum corneum has corneocytes surrounded by multilamellar lipid membranes which are composed of cholesterol, free fatty acids and ceramides (CERs). Alterations in ceramide content of the stratum corneum are associated with numerous skin disorders. In recent years, CERs have been incorporated into conventional and novel carrier systems with the purpose of exogenously applying CERs to help the barrier function of the skin. This review provides an overview of the structure, function and importance of CERs to restore the barrier function of the skin following their topical application.
Electrically Tunable-Focusing Liquid Crystal Microlens Array with Simple Electrode
Authors: Tian Li-Lan , Chu Fan , Dou Hu , Li Lei , Wang Qiong-Hua
Published: August 2019

An electrically tunable-focusing liquid crystal (LC) microlens array exhibiting a wide-range tunable focal length is proposed. The lower substrate has strip indium tin oxide (ITO) electrodes, the upper substrate has periodic ITO electrodes with a certain gap coated on the inner surface., and an LC microlens is generated between the two strip electrodes. For each LC microlens, the gap between the top planar electrodes is directly above the center of the microlens. Unlike the conventional LC lens, the individual LC microlens is not coated with ITO electrodes on the central part of its upper and lower substrates, which helps to maintain the LC’s horizontal orientation. In the voltage-off state, the focal length of the microlens array is infinity because of the homogeneous LC alignment. At a given operating voltage, an ideal gradient refractive index distribution is induced over the homogeneous LC layer, which leads to the focusing effect. The simulation result shows that the focal length of the LC microlens could be gradually drawn to 0.381 mm with a change of voltage.
Wing Design, Fabrication, and Analysis for an X-Wing Flapping-Wing Micro Air Vehicle
Authors: Cheaw Boon Hong , Ho Hann Woei , Abu Bakar Elmi
Published: August 2019

Flapping-wing Micro Air Vehicles (FW-MAVs), inspired by small insects, have limitless potential to be capable of performing tasks in urban and indoor environments. Through the process of mimicking insect flight, however, there are a lot of challenges for successful flight of these vehicles, which include their design, fabrication, control, and propulsion. To this end, this paper investigates the wing design and fabrication of an X-wing FW-MAV and analyzes its performance in terms of thrust generation. It was designed and developed using a systematic approach. Two pairs of wings were fabricated with a traditional cut-and-glue method and an advanced vacuum mold method. The FW-MAV is equipped with inexpensive and tiny avionics, such as the smallest Arduino controller board, a remote-control receiver, standard sensors, servos, a motor, and a 1-cell battery. Thrust measurement was conducted to compare the performance of different wings at full throttle. Overall, this FW-MAV produces maximum vertical thrust at a pitch angle of 10 degrees. The wing having stiffeners and manufactured using the vacuum mold produces the highest thrust among the tested wings.
Modelling Thermally Induced Non-Equilibrium Gas Flows by Coupling Kinetic and Extended Thermodynamic Methods
Authors: Yang Weiqi , Gu Xiao-Jun , Emerson David R. , Zhang Yonghao , Tang Shuo
Published: August 2019

Thermally induced non-equilibrium gas flows have been simulated in the present study by coupling kinetic and extended thermodynamic methods. Three different types of thermally induced gas flows, including temperature-discontinuity- and temperature-gradient-induced flows and radiometric flow, have been explored in the transition regime. The temperature-discontinuity-induced flow case has shown that as the Knudsen number increases, the regularised 26 (R26) moment equation system will gradually loss its accuracy and validation. A coupling macro- and microscopic approach is employed to overcome these problems. The R26 moment equations are used at the macroscopic level for the bulk flow region, while the kinetic equation associated with the discrete velocity method (DVM) is applied to describe the gas close to the wall at the microscopic level, which yields a hybrid DVM/R26 approach. The numerical results have shown that the hybrid DVM/R26 method can be faithfully used for the thermally induced non-equilibrium flows. The proposed scheme not only improves the accuracy of the results in comparison with the R26 equations, but also extends their capability with a wider range of Knudsen numbers. In addition, the hybrid scheme is able to reduce the computational memory and time cost compared to the DVM.
Editorial of Energy-Efficient and Reliable Information Processing: Computing and Storage
Authors: Kim Yongjune
Published: August 2019

Recently, artificial intelligence (AI) systems have begun to approach and exceed human performance in many intelligent tasks: AlexNet [...]
Overpressure Generation Mechanisms and Its Distribution in the Paleocene Shahejie Formation in the Linnan Sag, Huimin Depression, Eastern China
Authors: Li Chao , Luo Xiaorong , Zhang Likuan , Wang Bing , Guan Xiaoyan , Luo Hongmei , Lei Yuhong
Published: August 2019

The Linnan Sag is one of the main oil-producing units in the Huimin Depression, Eastern China, and the pore pressure gradients obtained from drill stem tests (DSTs) range from 9.0 to 16.0 MPa/km. Uncertainty about the origin and distribution of abnormally high pressures in the Linnan Sag has led to different interpretations of hydrocarbon accumulation and resource assessments, and it interferes with safe drilling. In the Linnan Sag, mudstone compaction curves are substantially affected by several non-compaction factors, and the normal trend of the compaction curve is difficult to determine. The determination of the origin and distribution of overpressure in the Linnan Sag is a challenge. In this study, the factors that may affect mudstone compaction—such as the shale volume, higher calcareous, and organic matter content—were carefully examined and processed. The pressures in the mudstones were estimated by the corrected mudstone compaction curves, which were compiled from acoustic, density, and neutron logs, and calibrated using DST and mud weight data. The log response–vertical effective stress and acoustic velocity-density crossplots were used to identify the mechanisms that generate overpressure. The comprehensive compaction curve shows that the mudstones in the overpressured layer exhibit clear disequilibrium compaction characteristics. The logging response crossplots demonstrate that those overpressured points were consistent with the loading curve. The findings suggest that, the fundamental mechanism resulting in overpressures is the disequilibrium compaction of thick Paleocene mudstones. Hydrocarbon generation and vertical transfer of overpressure may be the main unloading mechanisms, which corresponds to the overpressure points that deviate from the loading curves. Since organic matter cracking may occur in formations at depths greater than 4000 m (Ro > 1.0%), the contribution of hydrocarbon generation to overpressuring is expected to be limited. The transfer of overpressure through opening faults is therefore considered to be the main cause of higher overpressure in local sandstones. The overpressures in the mudstones are characterized by a gradual decrease from the center to the margin in the Linnan Sag. The pressure in the isolated sand bodies are generally similar to that in the surrounding mudstones, whereas it can be lower or higher when the overpressure in the sand bodies are vertically transferred by faults to other pressure systems. The results of this analysis provide an indication of the magnitude, mechanism, and distribution of overpressure in the Linnan Sag. This insight can be used to guide further exploration of the Linnan Sag and similar geological basins.