bluuebunny/crossref_metadata_2025 huggingface dataset:
A CLIMATE AND PERSONALITY APPROACH TOWARDS CREATIVITY BEHAVIOURS: A MODERATED MEDIATION STUDY
Authors: GHAFOOR AZKA , HAAR JARROD
Published: January 2020

Organisations are interested in how to get the best performance out of their workforce and this study focuses on creativity behaviours. The present study focuses on psychological safety climate, which relates to shared beliefs amongst co-workers regarding the safety for risk-taking in their work teams. We combine this with another organisational factor and a psychological factor towards testing a robust model of employee creativity behaviours. These factors include organisational-based self-esteem (OBSE) as a mediator and climate for innovation as a moderator, and we then examine these in combination (moderated mediation). Using a sample of 269 diverse employees, we find psychological safety climate is positively related to creativity behaviours and OBSE, and OBSE influences creativity behaviours and fully mediates the effect of psychological safety climate. We also find a significant interaction effect, showing that the highest creativity behaviour is registered when there is high psychological safety climate and high climate for innovation. We also find a significant moderated mediation effect whereby the indirect effect of psychological safety climate on creativity behaviours (through OBSE) increases when climate for innovation gets stronger. We discuss the implications for managing people and teams.
Enhanced Energy Harvesting of a Nonlinear Energy Sink by Internal Resonance
Authors: Hou Shuai , Teng Ying-Yuan , Zhang Ye-Wei , Zang Jian
Published: January 2020

Given its essential nonlinearity, nonlinear energy sink (NES) has been extensively studied as a promising vibration energy harvesting device. Internal resonance, which is due to strong energy exchange between modes, also provides a valuable idea for vibration energy harvesting. Combining these two advantages, we put forward a 3:1 internal resonance system, which consists of an NES and a coupled linear oscillator, as an enhanced method for vibration energy harvesting. The multiscale method is applied to derive the relationship between amplitude and frequency response. Simulations are carried out to evaluate the performance of the proposed method. Results show that the internal resonance system can remarkably improve the vibration energy harvesting performance. The numerical solutions verify the accuracy of the analytical solutions. The results demonstrate that the internal resonance system with NES for energy harvesting has better output power and bandwidth compared with noninternal resonance system. Overall, the comprehensive design improves the performance of NES for vibration energy harvesting.
The Improved Complex Variable Element-Free Galerkin Method for Bending Problem of Thin Plate on Elastic Foundations
Authors: Wang Binhua , Ma Yongqi , Cheng Yumin
Published: January 2020

In this paper, the improved complex variable element-free Galerkin (ICVEFG) method is proposed for solving the bending problem of thin plate on elastic foundations. In the ICVEFG method, the approximation function regarding the deflection of thin plate is formed with the improved complex moving least-squares (ICVMLS) approximation, the discrete equation is obtained from Galerkin weak form of bending problem of thin plate on different elastic foundations, and essential boundary conditions are considered based on penalty method. As the ICVMLS approximation is based on the complex variable theory, it can obtain the shape function quickly with high precision. Three sample problems are used to discuss the advantages of the ICVEFG method, and the numerical results show that the ICVEFG method presented in this paper has a fast convergence speed and great computational accuracy.
Report of the 2nd International Workshop on Context-aware Autonomous and Smart Architectures (CASA@ECSA 2018)
Authors: Raibulet Claudia , Drira Khalil , Fugini MariaGrazia , Lo Genaina Nunes , Pelliccione Patrizio , Bures Tomás
Published: January 2020

The 2018 2nd International Workshop on Context-aware, Autonomous and Smart Architectures (CASA 2018) was held in conjunction with the 12th European Conference on Software Architecture (ECSA 2018), on September, 24th, 2018 in Madrid, Spain. The main topic of the workshop concerned the design of software architectures for dynamic, autonomous, and adaptive context-aware smart systems. Such systems address changes and cope with uncertainties at runtime. Therefore, the software architecture of such system should ensure the basis for their dynamicity, adaptivity, and autonomy. These basis should be solid because they represent the backbone of a system, and in the same time flexible because they address dynamicity during execution. The one-day workshop aimed to bring together researchers and practitioners from the academic and the industrial world to share and discuss their approaches, solutions, methodologies, ideas, and open questions about the software architecture design for context-aware, autonomous, and smart systems. The workshop enabled discussions and put the basis for future collaborations among the participants.
Software Qualities and their Dependencies Report on two editions of the workshop
Authors: Sentilles Severine , Boehm Barry , Trubiani Catia , Franch Xavier , Koziole Anne
Published: January 2020

New trends in software engineering recently emerged to cope with even more complex systems which in turns highlight problems software shortfalls and defects. The SQUADE (Software QUAlities and their DEpendencies) workshop focuses on increasing the understanding of the nature of Software Qualities (SQs), i.e., nonfunctional properties or extra-functional requirements (e.g., reliability, security, maintainability, etc.), and their interrelationships with the aim of bringing them into practice of software engineering. The topic is highly relevant due to the current trend of designing and developing software-intensive systems with larger complexity, increased autonomy, higher speed of changes, and growing need for interoperability within systems of systems. Unfortunately, this new trend comes with more software shortfalls and defects, which are widely and publicly spread. The primary goal of the workshop is to bring together researchers and practitioners to build more solid foundations when dealing with software qualities.
Optimization Algorithms for Large-Scale Systems
Authors: Azizan Navid
Published: January 2020

Brief Biography: Navid Azizan is a fifth-year PhD candidate in Computing and Mathematical Sciences (CMS) at the California Institute of Technology (Caltech), where he is co-advised by Adam Wierman and Babak Hassibi, and is a member of multiple research groups: DOLCIT, RSRG and SISL. During the summer of 2019, he was a research scientist intern at Google DeepMind. He received the B.Sc. degree in EE form Sharif University of Technology and the M.Sc. degree in ECE from the University of Southern California, in 2013 and 2015, respectively. His research interests broadly lie in mathematical optimization, machine learning, networks, and markets. He is the recipient of several awards, including the 2016 ACM GreenMetrics Best Student Paper Award, the Amazon Fellowship in Artificial Intelligence, the PIMCO Fellowship in Data Science, the Caltech CMS Fellowship, and the USC Provost's Fellowship.
Performance Modelling and Optimisation of NoSQL Database Systems
Authors: Dipietro Salvatore
Published: January 2020

Salvatore Dipietro is a final-year PhD candidate in Computing at Imperial College London. His current research focus is on performance modelling and optimization of NoSQL database systems. His work is supported by HiPEDS centre for doctoral training, funded by EPSRC. Before the PhD, Salvatore completed his MRes in Advance computing at Imperial College London (2015) and his MSc in computer security and forensics at Bedfordshire University (2013). Earlier he gained his undergraduate degree in computing engineering at Politecnico di Torino (2012). Besides, he also has extensive professional work experience as Cloud and DevOps engineer. His interest lies in performance and optimization, capacity planning, distributed applications and network security.
Scalable Dynamic Analysis of Browsers for Privacy and Performance
Authors: Pourghassemi Behnam
Published: January 2020

Brief Biography: Behnam Pourghassemi is a fth-year Ph.D. student in Computer Engineering at the University of California, Irvine. His research primarily revolves around performance analysis and privacy on the web including work- load characterization of web browsers, online advertising, and tracking ecosystem. He is interested in designing and developing scalable and low-overhead pro ling tools for pri- vacy and performance measurements. His previous research was in HPC and parallel computing with the focus on GPU acceleration and fault-tolerance. He earned his M.Sc. in Computer Engineering from UCI in 2017 and his B.Sc. in Electrical Engineering from Sharif University in 2015 with honor.
Defending Distributed Systems Against Adversarial Attacks
Authors: Su Lili
Published: January 2020

Brief Biography: I am a postdoc in the Computer Sci- ence and Arti cial Intelligence Laboratory (CSAIL) at MIT, hosted by Professor Nancy Lynch. She received a Ph.D. in Electrical and Computer Engineering from the University of Illinois at Urbana-Champaign in 2017, supervised by Pro- fessor Nitin H. Vaidya. Her research intersects distributed systems, learning, security, and brain computing. She was the runner-up for the Best Student Paper Award at DISC 2016, and she received the 2015 Best Student Paper Award at SSS 2015. She received UIUC's Sundaram Seshu Interna- tional Student Fellowship for 2016, and was invited to par- ticipate in Rising Stars in EECS (2018). She has served on TPC for several conferences including ICDCS and ICDCN.
Dynamic Responses of the Metro Train’s Bogie Frames: Field Tests and Data Analysis
Authors: He Xuhui , Yu Kehui , Cai Chenzhi , Zou Yunfeng
Published: January 2020

This paper focuses on the dynamic characteristics of the metro train’s bogie frames based on the field test data. The acceleration signals of both motor bogie frame and trailer bogie frame of a standard B-type metro train were measured. Running tests on the Metro line 21 of Guangzhou (China) were carried out. The acquired acceleration signals of bogie frames were analyzed through several methods to identify the dynamic characteristics of the motor and trailer bogies in the time-frequency domain. The spectral analysis and time-frequency representations show that noise components exist in the high-frequency domain of the original signal, especially for the acceleration signal of the motor bogie frame. Then, the soft thresholding process and discrete wavelet transform decomposition process are conducted to obtain a denoised version of the original signals in the time-frequency domain. The vibration frequency domain and energy distribution of bogie frames under different train speeds are analyzed. The track irregularity wavelength of the metro line is calculated and analyzed based on the measured bogie frames’ acceleration signals. The dynamic characteristics of the metro train’s bogie frames in this paper can be adopted as a reference in the track diagnosis of the elevated metro line.
Study on Control of Wall Deflection in Earth Stepped‐Twin Retaining Wall Using Anchor Method by means of Numerical Simulation
Authors: Maehara Kazuki , Hamanaka Akihiro , Sasaoka Takashi , Shimada Hideki , Sakuma Seiya
Published: January 2020

The demand for specific earth retaining wall methods is increasing along with the advancement and overcrowding of underground space use such as the presence of adjacent structures in an urban area. To cope with this, the method named earth stepped‐twin retaining wall is increasingly being applied. However, there is a concern about the workplace if the earth pressure causes a heaving and pressing phenomenon from both ends of the retaining wall in the earth stepped‐twin retaining wall. Therefore, we proposed the application of an anchor method that contains the inner and outer walls by using numerical simulation. The effects of the difference in soil properties, the horizontal distance between the outer and inner walls, and the depth of the outer wall embedment on the anchor were investigated. The results of this study show that the wall deflection of the inner wall could improve by adopting the anchor support. Besides, it was found that the inner wall can be efficiently suppressed by adopting the hybrid system with anchors and struts according to the soil properties, horizontal distance, and the depth of the outer wall.
Rotavirus VP6 Adjuvant Effect on Norovirus GII.4 Virus-Like Particle Uptake and Presentation by Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo
Authors: Tamminen Kirsi , Heinimäki Suvi , Vesikari Timo , Blazevic Vesna
Published: January 2020

We have previously shown that rotavirus (RV) inner capsid protein VP6 has an adjuvant effect on norovirus (NoV) virus-like particle- (VLP-) induced immune responses and studied the adjuvant mechanism in immortalized cell lines used as antigen-presenting cells (APCs). Here, we investigated the uptake and presentation of RV VP6 and NoV GII.4 VLPs by primary bone marrow-derived dendritic cells (BMDCs). The adjuvant effect of VP6 on GII.4 VLP presentation and NoV-specific immune response induction by BMDCin vivowas also studied. Intracellular staining demonstrated that BMDCs internalized both antigens, but VP6 more efficiently than NoV VLPs. Both antigens were processed and presented to antigen-primed T cells, which responded by robust interferonγsecretion. When GII.4 VLPs and VP6 were mixed in the same pulsing reaction, a subpopulation of the cells had uptaken both antigens. Furthermore, VP6 copulsing increased GII.4 VLP uptake by 37% and activated BMDCs to secrete 2-5-fold increased levels of interleukin 6 and tumor necrosis factorαcompared to VLP pulsing alone. Whenin vitro-pulsed BMDCs were transferred to syngeneic BALB/c mice, VP6 improved NoV-specific antibody responses. The results of this study support the earlier findings of VP6 adjuvant effectin vitroandin vivo.
Exercise Preconditioning Plays a Protective Role in Exhaustive Rats by Activating the PI3K‐Akt Signaling Pathway
Authors: Li Jingjing , Xu Peng , Wang Yang , Ping Zheng , Cao Xuebin , Zheng Yu
Published: January 2020

Objective. To investigate whether exercise preconditioning (EP) protects the rat heart from exhaustive exercise‐ (EE‐) induced injury by inducing the PI3K‐Akt signaling pathway. Methods. 84 male Sprague‐Dawley rats were randomly divided into 6 groups (n = 14 rats per group): control group (Con), exhaustive exercise group (EE), exercise preconditioning group (EP), exercise preconditioning + exhaustive exercise group (EP + EE), LY294002 (PI3K inhibitor) + exercise preconditioning + exhaustive exercise group (LY + EP + EE), and LY294002 group (LY). The Con and LY did not exercise. The remaining groups were subjected to treadmill running. The structure of myocardial tissue and serum biomarkers of myocardial injury were observed. Hemodynamic parameters were recorded with a pressure‐volume catheter. TUNEL assay was used to detect the apoptosis of cardiac myocytes, and the level of mitochondrial membrane permeability transforming pore (mPTP) in myocardium was evaluated using ELISA. Pathway and apoptosis‐related proteins in myocardium were assessed using western blotting. Results. Compared to the Con group, the EE group showed remarkable myocardial injury, such as cardiac dysfunction and myocardial apoptosis. Compared to the EE group, the injuries in the EP + EE group were improved. EP increased the PI3K‐Akt signaling pathway and regulated Bcl‐2 family to decrease the mPTP openness level. However, the cardioprotective effects of EP were attenuated when pretreated with the LY294002. Conclusions. EP protected the heart from EE‐induced injury, and it may improve the cardiac function and reduce the cardiomyocyte apoptosis by activating the PI3K‐Akt signaling pathway.
IKK Epsilon Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Inhibiting Inflammation, Oxidative Stress, and Apoptosis
Authors: Chai Hao , Tao ZhongHao , Qi YongChao , Qi HaoYu , Chen Wen , Xu YueYue , Zhang LeiYang , Chen HongWei , Chen Xin
Published: January 2020

Abdominal aortic aneurysm (AAA) is a vascular disorder that is considered a chronic inflammatory disease. However, the precise molecular mechanisms involved in AAA have not been fully elucidated. Recently, significant progress has been made in understanding the function and mechanism of action of inhibitor of kappa B kinase epsilon (IKKε) in inflammatory and metabolic diseases. The angiotensin II- (Ang II-) induced or pharmacological inhibitors were established to test the effects of IKKε on AAA in vivo. After mice were continuously stimulated with Ang II for 28 days, morphologically, we found that knockout of IKKε reduced AAA formation and drastically reduced maximal diameter and severity. We also observed a decrease in elastin degradation and medial destruction, which were independent of systolic blood pressure or plasma cholesterol concentrations. Western blot analyses and immunohistochemical staining were carried out to measure IKKε expression in AAA tissues and cell lines. AAA phenotype of mice was measured by ultrasound and biochemical indexes. In zymography, immunohistology staining, immunofluorescence staining, and reactive oxygen species (ROS) analysis, TUNEL assay was used to examine the effects of IKKε on AAA progression in AAA mice. IKKε deficiency significantly inhibited inflammatory macrophage infiltration, matrix metalloproteinase (MMP) activity, ROS production, and vascular smooth muscle cell (VSMC) apoptosis. We used primary mouse aortic VSMC isolated from apolipoprotein E (Apoe) −/− and Apoe−/−IKKε−/− mice. Mechanistically, IKKε deficiency blunted the activation of the ERK1/2 pathway. The IKKε inhibitor, amlexanox, has the same impact in AAA. Our results demonstrate a critical role of IKKε in AAA formation induced by Ang II in Apoe−/− mice. Targeting IKKε may constitute a novel therapeutic strategy to prevent AAA progression.
Statistical Experimental Design Optimization of Microbial Proteases Production under Co‐Culture Conditions for Chitin Recovery from Speckled Shrimp Metapenaeus monoceros By‐Product
Authors: Jabeur Fadoua , Mechri Sondes , Kriaa Mouna , Gharbi Ines , Bejaoui Nejla , Sadok Saloua , Jaouadi Bassem
Published: January 2020

This study was designed with the aim to produce microbial proteases in presence of speckled shrimp by‐product. For this reason, three strains belonging to Bacillus genus, namely, Aeribacillus pallidus VP3, Lysinibacillus fusiformis C250R, and Anoxybacillus kamchatkensis M1V were studied under co‐culture procedure. A Taguchi L27 experimental design was applied to optimize the co‐culture parameters. The experimental design was built with 9 factors (by‐product powder concentration, the pH of the medium, the temperature, the sucrose concentration, the agitation speed, the inoculum sizes of VP3, M1V, and C250R strains, and the culture volume) at three different levels. The obtained results showed that a total protease activity of 8,182 U/mL could be achieved after 24 h of incubation in presence of 20 g/L shrimp by‐product and 10 g/L sucrose, at an initial pH of 7, a 40°C temperature and absorbance, at 600 nm, of inoculum sizes of 0.1, 0.3, and 0.1 for VP3, M1V, and C250R strains, respectively. The agitation was set at 200 rpm, and the final volume was 25 mL. Taguchi’s design allowed the identification of temperature, the inoculum size for strain VP3, the inoculum size for strain M1V, and the final culture volume as the most influencing variables. A Box–Behnken design with 27 experiments was carried out for the optimization of these four selected factors. Following such design, the highest protease production reached was 11,300 U/mL. This yield was obtained in a final culture volume of 15 mL containing 20 g/L shrimp by‐product powder and 10 g/L sucrose and inoculated with VP3, C250R, and M1V strains at 0.05, 0.1, and 0.2, respectively. The flasks were incubated at 45°C for 24 h with shaking at 200 rpm. The efficiency of chitin extraction by co‐cultivation was investigated under the latter conditions. The chitin yield from shells by‐product was 16.7%. Fourier‐Transform Infrared (FTIR) analysis of the obtained chitin displayed characteristic profiles similar to that of the commercial α‐chitin.
Phenotypic and Genotypic Characterization of Extended-Spectrum Beta-Lactamases Produced by Escherichia coli Colonizing Pregnant Women
Authors: Ghaddar Nahed , Anastasiadis Elie , Halimeh Rawad , Ghaddar Ali , Matar Ghassan M. , Abou Fayad Antoine , Sherri Nour , Dhar Rita , AlFouzan Wadha , Yusef Hoda , El Chaar Mira
Published: January 2020

Introduction. Infections caused by extended spectrum beta lactamase (ESBL) producing bacteria continue to be a challenge for choosing the appropriate therapy since they may exhibit coresistance to many other classes of antibiotics. The aim of the study was to screen pregnant women for ESBL producing bacteria in Beirut, Lebanon, to examine their phenotypic and genotypic characterization and to study the association between ESBL colonization with adverse neonatal outcomes. Method. In this cross-sectional study, vaginal samples from 308 pregnant women at 35–37 weeks of gestation were studied during a one-year period. The samples were plated on MacConkey agar and selective MacConkey agar supplemented with ceftazidime. Phenotypic confirmation of ESBL production was performed by double-disc synergy test and all isolates were screened by PCR for the resistance genes blaSHV, blaTEM, and blaCTX-M. Clonal relatedness of Escherichia coli isolates was investigated by pulsed-field gel electrophoresis. Results. In total, 59 women out of 308 (19.1%) were colonized by ESBL producing gram negative bacteria. Two babies born to mothers colonized with ESBL were diagnosed with sepsis. The susceptibility rates of isolates to other antibiotics were 39% to co-trimoxazole, 49.2% to ciprofloxacin, 91.5% to gentamicin, 18.6% to aztreonam and 35.6% to cefepime. Most of isolates were highly sensitive to meropenem and imipenem, with a susceptibility of 93.2%. PCR was performed on all E. coli isolates to detect the most common ESBL producing genes; blaCTX-M was the predominant gene (90.7%), followed by blaTEM (88.4%) and finally blaSHV (44.2%). PFGE analysis of 34 E. coli isolates revealed 22 distinct clusters showing more than 85% similarity. Conclusion. In conclusion, this study showed that Lebanon has a high prevalence of ESBL carriage in pregnant women. Further studies that include a continuous screening of pregnant women and follow up of their newborn clinical status should be conducted to foresee the risk of transmission.
Hydrogen Sulfide Protects against Paraquat-Induced Acute Liver Injury in Rats by Regulating Oxidative Stress, Mitochondrial Function, and Inflammation
Authors: Liu Zhenning , Wang Xiaofeng , Li Lei , Wei Guigui , Zhao Min
Published: January 2020

In addition to the lung, the liver is considered another major target for paraquat (PQ) poisoning. Hydrogen sulfide (H2S) has been demonstrated to be effective in the inhibition of oxidative stress and inflammation. The aim of this study was to investigate the protective effect of exogenous H2S against PQ-induced acute liver injury. The acute liver injury model was established by a single intraperitoneal injection of PQ, evidenced by histological alteration and elevated serum aminotransferase levels. Different doses of NaHS were administered intraperitoneally one hour before exposure to PQ. Analysis of the data shows that exogenous H2S attenuated the PQ-induced liver injury and oxidative stress in a dose-dependent manner. H2S significantly suppressed reactive oxygen species (ROS) generation and the elevation of malondialdehyde content while it increased the ratio of GSH/GSSG and levels of antioxidant enzymes including SOD, GSH-Px, HO-1, and NQO-1. When hepatocytes were subjected to PQ-induced oxidative stress, H2S markedly enhanced nuclear translocation of Nrf2 via S-sulfhydration of Keap1 and resulted in the increase in IDH2 activity by regulating S-sulfhydration of SIRT3. In addition, H2S significantly suppressed NLRP3 inflammasome activation and subsequent IL-1β excretion in PQ-induced acute liver injury. Moreover, H2S cannot reverse the decrease in SIRT3 and activation of the NLRP3 inflammasome caused by PQ in Nrf2-knockdown hepatocytes. In summary, H2S attenuated the PQ-induced acute liver injury by enhancing antioxidative capability, regulating mitochondrial function, and suppressing ROS-induced NLRP3 inflammasome activation. The antioxidative effect of H2S in PQ-induced liver injury can at least partly be attributed to the promotion of Nrf2-driven antioxidant enzymes via Keap1 S-sulfhydration and regulation of SIRT3/IDH2 signaling via Nrf2-dependent SIRT3 gene transcription as well as SIRT3 S-sulfhydration. Thus, H2S supplementation can form the basis for a promising novel therapeutic strategy for PQ-induced acute liver injury.
Study and Simulation Analysis of Vehicle Rear-End Collision Model considering Driver Types
Authors: Luo Qiang , Chen Xinqiang , Yuan Jie , Zang Xiaodong , Yang Junheng , Chen Jing
Published: January 2020

The reasonable distance between adjacent cars is very crucial for roadway traffic safety. For different types of drivers or different driving environments, the required safety distance is different. However, most of the existing rear-end collision models do not fully consider the subjective factor such as the driver. Firstly, the factors affecting driving drivers’ characteristics, such as driver age, gender, and driving experience are analyzed. Then, on the basis of this, drivers are classified according to reaction time. Secondly, three main factors affecting driving safety are analyzed by using fuzzy theory, and the new calculation method of the reaction time is obtained. Finally, the improved car-following safety model is established based on different reaction time. The experimental results have shown that our proposed model obtained more accurate vehicle safety distance with varied traffic kinematic conditions (i.e., different traffic states, varied driver types, etc.). The findings can help traffic regulation departments issue early warnings to avoid potential traffic accidents on roads.
Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation
Authors: Aleka Yetemwork , Ibarra-Meneses Ana Victoria , Workineh Meseret , Tajebe Fitsumbrhan , Kiflie Amare , Tessema Mekibib Kassa , Melkamu Roma , Tadesse Azeb , Moreno Javier , van Griensven Johan , Carrillo Eugenia , Adriaensen Wim
Published: January 2020

Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with solubleLeishmaniaantigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γlevels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two mainLeishmaniaspecies. The levels of IFN-γ, IP-10, or TNF-αalso seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γand IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases.
SLAMF3-Mediated Signaling via ERK Pathway Activation Promotes Aggressive Phenotypic Behaviors in Multiple Myeloma
Authors: Ishibashi Mariko , Takahashi Risa , Tsubota Asako , Sasaki Makoto , Handa Hiroshi , Imai Yoichi , Tanaka Norina , Tsukune Yutaka , Tanosaki Sakae , Ito Shigeki , Asayama Toshio , Sunakawa Mika , Kaito Yuta , Kuribayashi-Hamada Yasuko , Onodera Asaka , Moriya Keiichi , Komatsu Norio , Tanaka Junji , Odajima Takeshi , Sugimori Hiroki , Inokuchi Koiti , Tamura Hideto
Published: January 2020

The signaling lymphocytic activation molecule family 3 (SLAMF3) is a member of the immunoglobulin superfamily expressed on T, B, and natural killer cells and modulates the activation and cytotoxicity of these cells. SLAMF3 is also expressed on plasma cells from patients with multiple myeloma (MM), although its role in MM pathogenesis remains unclear. This study found that SLAMF3 is highly and constitutively expressed on MM cells regardless of disease stage and that SLAMF3 knockdown/knockout suppresses proliferative potential and increases drug-induced apoptosis with decreased levels of phosphorylated ERK protein in MM cells. SLAMF3-overexpressing MM cells promote aggressive myeloma behavior in comparison with cytoplasmic domain-truncated SLAMF3 (ΔSLAMF3) cells. SLAMF3 interacts directly with adaptor proteins SH2 domain-containing phosphatase 2 (SHP2) and growth factor receptor bound 2 (GRB2), which also interact with each other. SLAMF3 knockdown, knockout, ΔSLAMF3, and SHP2 inhibitor-treated MM cells decreased phosphorylated ERK protein levels. Finally, serum soluble SLAMF3 (sSLAMF3) levels were markedly increased in advanced MM. Patients with high levels of sSLAMF3 progressed to the advanced stage significantly more often and had shorter progression-free survival times than those with low levels. This study revealed that SLAMF3 molecules consistently expressed on MM cells transmit MAPK/ERK signals mediated via the complex of SHP2 and GRB2 by self-ligand interaction between MM cells and induce a high malignant potential in MM. Furthermore, high levels of serum sSLAMF3 may reflect MM disease progression and be a useful prognostic factor.

Implications:

SLAMF3 may be a new therapeutic target for immunotherapy and novel agents such as small-molecule inhibitors.
Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell–Mediated Tumor Killing
Authors: Fan Jun-Bao , Miyauchi Sayuri , Xu Hui-Zhong , Liu Dan , Kim Leo J.Y. , Burkart Christoph , Cheng Hua , Arimoto Kei-ichiro , Yan Ming , Zhou Yu , Győrffy Balázs , Knobeloch Klaus-Peter , Rich Jeremy N. , Cang Hu , Fu Xiang-Dong , Zhang Dong-Er
Published: January 2020

Type I interferons (IFN), which activate many IFN-stimulated genes (ISG), are known to regulate tumorigenesis. However, little is known regarding how various ISGs coordinate with one another in developing antitumor effects. Here, we report that the ISG UBA7 is a tumor suppressor in breast cancer. UBA7 encodes an enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of another ISG (ISG15) to cellular proteins in a process known as “ISGylation.” ISGylation of other ISGs, including STAT1 and STAT2, synergistically facilitates production of chemokine-receptor ligands to attract cytotoxic T cells. These gene-activation events are further linked to clustering and nuclear relocalization of STAT1/2 within IFN-induced promyelocytic leukemia (PML) bodies. Importantly, this coordinated ISG–ISGylation network plays a central role in suppressing murine breast cancer growth and metastasis, which parallels improved survival in patients with breast cancer. These findings reveal a cooperative IFN-inducible gene network in orchestrating a tumor-suppressive microenvironment.

Significance:

We report a highly cooperative ISG network, in which UBA7-mediated ISGylation facilitates clustering of transcription factors and activates an antitumor gene-expression program. These findings provide mechanistic insights into immune evasion in breast cancer associated with UBA7 loss, emphasizing the importance of a functional ISG–ISGylation network in tumor suppression.

This article is highlighted in the In This Issue feature, p. 327
Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia
Authors: Pei Shanshan , Pollyea Daniel A. , Gustafson Annika , Stevens Brett M. , Minhajuddin Mohammad , Fu Rui , Riemondy Kent A. , Gillen Austin E. , Sheridan Ryan M. , Kim Jihye , Costello James C. , Amaya Maria L. , Inguva Anagha , Winters Amanda , Ye Haobin , Krug Anna , Jones Courtney L. , Adane Biniam , Khan Nabilah , Ponder Jessica , Schowinsky Jeffrey , Abbott Diana , Hammes Andrew , Myers Jason R. , Ashton John M. , Nemkov Travis , D'Alessandro Angelo , Gutman Jonathan A. , Ramsey Haley E. , Savona Michael R. , Smith Clayton A. , Jordan Craig T.
Published: January 2020

Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well as relapse following initial response demonstrates the need for a deeper understanding of resistance mechanisms. In the present study, we report that responses to venetoclax +azacitidine in patients with AML correlate closely with developmental stage, where phenotypically primitive AML is sensitive, but monocytic AML is more resistant. Mechanistically, resistant monocytic AML has a distinct transcriptomic profile, loses expression of venetoclax target BCL2, and relies on MCL1 to mediate oxidative phosphorylation and survival. This differential sensitivity drives a selective process in patients which favors the outgrowth of monocytic subpopulations at relapse. Based on these findings, we conclude that resistance to venetoclax + azacitidine can arise due to biological properties intrinsic to monocytic differentiation. We propose that optimal AML therapies should be designed so as to independently target AML subclones that may arise at differing stages of pathogenesis.

Significance:

Identifying characteristics of patients who respond poorly to venetoclax-based therapy and devising alternative therapeutic strategies for such patients are important topics in AML. We show that venetoclax resistance can arise due to intrinsic molecular/metabolic properties of monocytic AML cells and that such properties can potentially be targeted with alternative strategies.
Directing Traffic: How to Effectively Drive T Cells into Tumors
Authors: Anandappa Annabelle J. , Wu Catherine J. , Ott Patrick A.
Published: January 2020

Although immune checkpoint inhibitors (ICI) have demonstrated clinical activity in multiple tumor types, the majority of patients do not respond to ICI monotherapy. Mounting evidence suggests that ICI-mediated clinical responses rely upon tumor infiltration by T cells that are able to recognize and kill cancer cells. Here, we review therapeutic modalities that have been shown to promote T-cell infiltration into human tumors in studies to date, and discuss emerging data guiding how these modalities can be sequenced in order to optimize T-cell effector function and memory T-cell generation, while minimizing overactivation and potential toxicity.

Significance:

The lack of preexisting T-cell inflammation in tumors is a major barrier to effective cancer immunity. A deep understanding of the mechanisms that prevent T cells from trafficking into the tumor in a given individual will be critical for tailoring immunotherapy combinations that can overcome resistance to ICI in patients with cancer.
Pathology of the Fallopian Tube: Tubal Involvement by Ovarian Tumors and Incidental Findings in the Nontumoral Setting
Authors: Karpathiou Georgia , Chauleur Celine , Venet Melany , Clemenson Alix , Peoc’h Michel
Published: January 2020

The fallopian tube is thought to be the site of origin of most high-grade serous carcinomas (HGSCs). However, how often the tube is abnormal in the setting of other ovarian tumors is unknown. The aim of this study is to define the frequency of tubal abnormalities in the tumoral (n = 245) and nontumoral (n = 184) setting. We found that in ovarian tumors, 52.2% of the tubes were normal, while 39.2% were affected by the tumor. Abnormal tubes were found in 80% of HGSCs, in 21% of mucinous carcinomas, in 83.3% of seromucinous carcinomas, in 33.3% of endometrioid carcinomas, in 20% of clear-cell carcinomas, and in 10.5% of borderline tumors. Among normal tubes, almost 70% were histologically normal; transitional metaplasia was present in 17.4%, endometriosis in 8.1%, and adenofibroma in 2.2%, and 1.1% had an incidental serous intraepithelial tubal carcinoma. To conclude, the fallopian tube is abnormal in most serous carcinomas, and in a smaller number of endometrioid, clear-cell and mucinous carcinomas as well as borderline tumors. It is often abnormal in seromucinous tumors, but larger series are needed to study this rare subtype.
Cryo-Electron Microscopy Structure of the αIIbβ3-Abciximab Complex
Authors: Nešić Dragana , Zhang Yixiao , Spasic Aleksandar , Li Jihong , Provasi Davide , Filizola Marta , Walz Thomas , Coller Barry S.
Published: January 2020

Objective:

The αIIbβ3 antagonist antiplatelet drug abciximab is the chimeric antigen-binding fragment comprising the variable regions of murine monoclonal antibody 7E3 and the constant domains of human IgG1 and light chain κ. Previous mutagenesis studies suggested that abciximab binds to the β3 C177-C184 specificity-determining loop (SDL) and Trp129 on the adjacent β1-α1 helix. These studies could not, however, assess whether 7E3 or abciximab prevents fibrinogen binding by steric interference, disruption of either the αIIbβ3-binding pocket for fibrinogen or the β3 SDL (which is not part of the binding pocket but affects fibrinogen binding), or some combination of these effects. To address this gap, we used cryo-electron microscopy to determine the structure of the αIIbβ3-abciximab complex at 2.8 Å resolution.

Approach and Results:

The interacting surface of abciximab is comprised of residues from all 3 complementarity-determining regions of both the light and heavy chains, with high representation of aromatic residues. Binding is primarily to the β3 SDL and neighboring residues, the β1-α1 helix, and β3 residues Ser211, Val212 and Met335. Unexpectedly, the structure also indicated several interactions with αIIb. As judged by the cryo-electron microscopy model, molecular-dynamics simulations, and mutagenesis, the binding of abciximab does not appear to rely on the interaction with the αIIb residues and does not result in disruption of the fibrinogen-binding pocket; it does, however, compress and reduce the flexibility of the SDL.

Conclusions:

We deduce that abciximab prevents ligand binding by steric interference, with a potential contribution via displacement of the SDL and limitation of the flexibility of the SDL residues.
From Abramtsevo to Zakopane: Folk Art and National Ideals in Russia and Eastern Europe
Authors: Hilton Alison
Published: January 2020

Folk art revivals were incubators for modernist movements in painting, sculpture, architecture, applied arts, and performing arts. The upsurge of national sentiment in late Imperial Russia and official economic support of handicraft industries (known as kustar’) promoted the marketing of wood crafts and textiles made at Abramtsevo, Talashkino, and other centers in western Russia and Ukraine. Parallel developments drew upon both folk traditions and patriotic ideals in the central and eastern European countries that had suffered territorial encroachments by Russia, Prussia, and the Austro-Hungarian Empire. Artists’ groups and art colonies showed special respect for regional landscapes, peasant communities, and local artistic traditions. Their activities reflected nationalist ideologies, as well as practical, economic, and philanthropic concerns. The variety of circumstances and motivations sheds light on the phenomena of art colonies, new valuations of applied art forms, and the enduring importance of education in traditional crafts.
Revision of the genus Dziriblatta Chopard, 1936 (Blattodea, Ectobiidae, Ectobiinae). II. The species of the subgenera Pauciscleroblatta and Monoscleroblatta
Authors: BOHN HORST
Published: January 2020

The present paper is a continuation of the revision of the genus Dziriblatta started with definition and description of the nine subgenera of the genus (Bohn 2019). In that first part of the revision usually only one species of each subgenus was described; the remaining species should be treated in following papers of which this contribution is the first dealing with the species of the subgenera Pauciscleroblatta (6 species) and Monoscleroblatta (4 species). Five species are new to science: Dziriblatta (Pauciscleroblatta) cyprica, spec. nov., Dz. (P.) habbachii, spec. nov., Dz. (P.) stenoptera, spec. nov., Dz. (P.) multiporosa, spec. nov., and Dz. (Monoscleroblatta) aglandulosa, spec. nov.                The descriptions are illustrated by numerous figures and determination keys allow the discrimination of the species. The geographical distribution of the species is shown on several maps. The species of Pauciscleroblatta are distributed in Algeria, Tunisia, Israel, West Bank, Syria (Golan) and Cyprus, those of Monoscleroblatta are restricted to northwestern Morocco.
Diplommatina boessnecki n. sp. from Nepal (Gastropoda: Diplommatinidae)
Authors: WALTHER FRANK , HAUSDORF BERNHARD
Published: January 2020

Diplommatina Benson, 1849 (Caenogastropoda: Diplommatinidae) is a species-rich genus of terrestrial microsnails with a constriction near the beginning of the last whorl (Kobelt 1902). It includes several hundred species in eastern and southern continental Asia, Japan, Taiwan, Indonesia and the Philippines. Although known for more than a century from the Himalayas and other mountain ranges in India, the first Diplommatina from Nepal were reported not before 1997 (Kuznetsov & Schileyko 1997). A recent revision reported 16 species of the genus from Nepal (Budha et al. 2017).
The Regulatory Effect of Mir-149 on Bone Marrow Mesenchymal Stem Cells in Osteoporosis Rats and Its Related Mechanisms
Authors: Wang Long , Yu Jian
Published: January 2020

BMSCs play an important role in osteoporosis (OP) and their differentiation can lead to OP progression. Mir-149 can participate in the regulation of BMSCs. However, the effect of Mir-149 on BMSCs in osteoporosis remains unclear. SD rats were divided control group and OP group. OP rat
BMSCs were transfected with Mir-149 siRNA followed by analysis of Mir-149 expression by real time PCR, cell proliferation by MTT assay, apoptosis by flow cytometry, ERK/MAPK signaling protein expression by western blot, ALP activity, as well as expression of osteogenic genes Runx2 and OC by
real time PCR. Mir-149 expression was significantly increased in BMSCs of OP rats, cell proliferation was inhibited, apoptosis was increased, as well as p-ERK1/2 expression, ALP activity and expression of Runx2 and OC was decreased compared to control group (P < 0.05). Transfection
of Mir-149 siRNA into OP rat BMSCs reduced Mir-149 expression, promoted cell proliferation, decreased apoptotic rate, increased p-ERK1/2 expression, ALP activity and Runx2 and OC expression. Compared with OP group, the differences were statistically significant (P< 0.05). Mir-149
expression was increased in OP rat BMSCs. Down-regulation of Mir-149 promoted the activation of ERK/MAPK signaling pathway, inhibited apoptosis of BMSCs and promoted the proliferation and osteogenic differentiation of BMSCs in OP rats.
The Role of Life Events/Contextual Factors and Cannabis Use in Patterns of Other Drug Use Among Young Adult Cannabis Users in Los Angeles: A Qualitative Inquiry
Authors: Fedorova Ekaterina V. , Roth Alexis M. , Cepeda Alice , Wong Carolyn F. , Iverson Ellen , Lankenau Stephen E.
Published: January 2020

This analysis examined the role of impactful life events/stressful contextual factors and cannabis use in the patterns of illicit drug use. It utilized semi-structured qualitative interviews with 40 young adult medical cannabis patients and 22 non-patient users collected in Los Angeles during 2014–2015. Three patterns of illicit drug use emerged based on participants’ narratives: regular/problematic, recreational/occasional, and never users. Among regular/problematic users, a common theme was the lasting impact of traumatic life events or stressful contextual factors on transition to and away from problematic drug use, and using cannabis to cope with negative after effects of drug use. In contrast, most recreational/occasional and never users, who reported impactful life events or stressful contextual factors, used cannabis to cope with those experiences. Family history of addiction and acceptance of cannabis use within a family as protective factors against illicit drug use among some recreational/occasional and never users was an unexpected finding.
Restrained or constrained? Elections, communal conflicts, and variation in sexual violence
Authors: Krause Jana
Published: January 2020

Anecdotal evidence suggests that sexual violence varies significantly across cases of election violence and communal conflicts but systematic research is scarce. Post-election violence is particularly likely if electoral mobilization further polarizes longstanding communal conflicts and political elites do not instruct security forces to intervene decisively. I comparatively analyse two prominent cases of post-election violence in Kenya (2007/8) and Nigeria (2008) that exhibit stark variation in sexual violence. Patrimonial networks and norms of violent masculinity that increase the probability of (gang) rape were present in both cases and do not explain variation. Civil war research has identified three explanations for the variation in sexual violence: situational constraints; ordered sexual violence or restraint; and bottom-up dynamics of sexual violence or restraint. I examine these for the context of post-election violence. I argue that the type of communal conflict triggered by electoral mobilization explains variation in sexual violence. In Kenya, pogroms of a majority group against a minority allowed for the time and space to perpetrate widespread sexual violence while in Nigeria, dyadic clashes between similarly strong groups offered less opportunity but produced a significantly higher death toll. These findings have important implications for preventing election violence. They demonstrate that civilian vulnerability is gendered and that high levels of sexual violence do not necessarily correspond to high levels of lethal violence. Ignoring sexual violence means underestimating the real intensity of conflict and its impact on the political process.
Injuries, death and vehicle airbag deployment
Authors: O’Donovan Siobhan , van den Heuvel Corinna , Baldock Matthew , Byard Roger W
Published: January 2020

Airbags are impact-activated safety devices which deploy from the interior of vehicles to protect occupants from trauma during crashes. Although airbags effectively reduce the risk of death and injury, this it is not without issues. For example, high-impact unbelted rigid-barrier testing in the USA led to the adoption of powerful, large airbags that were associated with numerous airbag-related deaths and injuries. In contrast, European designs were tested and certified in conjunction with the use of three-point restraint systems, meaning that the airbags could be smaller with reduced ‘punch-out’ power. An overview is provided of the mechanism of action of airbags and the associated non-lethal and lethal injuries that may be sustained by vehicle occupants.