bluuebunny/crossref_metadata_2025 huggingface dataset:
The Bird Strike Challenge
Authors: Metz Isabel C. , Ellerbroek Joost , Mühlhausen Thorsten , Kügler Dirk , Hoekstra Jacco M.
Published: March 2020

Collisions between birds and aircraft pose a severe threat to aviation and avian safety. To understand and prevent these bird strikes, knowledge about the factors leading to these bird strikes is vital. However, even though it is a global issue, data availability strongly varies and is difficult to put into a global picture. This paper aims to close this gap by providing an in-depth review of studies and statistics to obtain a concise overview of the bird strike problem in commercial aviation on an international level. The paper illustrates the factors contributing to the occurrence and the potential consequences in terms of effect on flight and damage. This is followed by a presentation of the risk-reducing measures currently in place as well as their limitations. The paper closes with an insight into current research investigating novel methods to prevent bird strikes.
Effects of the Coupling between the Orbital Angular Momentum and the Temporal Degrees of Freedom in the Most Intense Ring of Ultrafast Vortices
Authors: Porras Miguel A.
Published: March 2020

It has recently been shown that the temporal and the orbital angular momentum (OAM) degrees of freedom in ultrafast (few-cycle) vortices are coupled. This coupling manifests itself with different effects in different parts of the vortex, as has been shown for the ring surrounding the vortex where the pulse energy is maximum, and also in the immediate vicinity of the vortex center. However, in many applications, the ring of maximum energy is not of primary interest, but the one where the peak intensity of the pulse is maximum, which is particularly true in nonlinear optics applications such as experiments with ultrafast vortices that excite high harmonics and attosecond pulses that also carry OAM. In this paper, the effects of the OAM-temporal coupling on the ring of maximum pulse peak intensity, which do not always coincide with the ring of maximum pulse energy, are described. We find that there is an upper limit to the magnitude of the topological charge that an ultrafast vortex with a prescribed pulse shape in its most intense ring can carry, and vice versa, a lower limit to the pulse duration in the most intense ring for a given magnitude of the topological charge. These limits imply that, with a given laser source spectrum, the duration of the synthesized ultrafast vortex increases with the magnitude of the topological charge. Explicit analytical expressions are given for the ultrafast vortices that contain these OAM-temporal couplings effects, which may be of interest in various applications, in particular in the study of their propagation and interaction with matter.
Color-Adjustable Devices Based on the Surface Plasmons Effect
Authors: Wen Kui , Jiang Xinpeng , He Jie , Li Guofeng , Yang Junbo
Published: March 2020

The optical response of a metamaterial can be engineered by manipulating the size, pattern, and composition of its cells. Here, we present a coloring device, which increases resolution while retaining adjustability. By adding different nanoparticles in the nanohole, the shift of the transmission peak in the visible regions is realizable and manageable, which means a series of different colors are revealed in this device. At the same time, it is also possible to fill the holes with dielectric materials of different refractive indices to achieve the purpose of color diversity. This method theoretically confirms the feasibility of designing a coloring device via surface plasmons-based metamaterial nanostructure, which holds great promise for future versatile utilization of multiple physical mechanisms to render multiple colors in a simple nanostructure.
Towards Secure and Usable Certificate-Based Authentication System Using a Secondary Device for an Industrial Internet of Things
Authors: Choi Jusop , Cho Junsung , Kim Hyoungshick , Hyun Sangwon
Published: March 2020

As the number of controllers and devices increases in Industrial Internet of Things (IIoT) applications, it is essential to provide a secure and usable user authentication system for human operators who have to manage tens or hundreds of controllers and devices with his/her password. In this paper, we propose a formally verified certificate-based authentication system using a secondary network device for such IIoT applications. In the proposed system, a user’s sign key is encrypted with a secret key that can be computed with his/her password and a secret parameter in a secondary device to securely protect the sign key. To demonstrate the feasibility of the proposed system, we implemented a prototype with standard cryptographic algorithms (AES-256, RSA-3072, and ECDSA-256). The experiment results demonstrated that the execution time overhead of the sign key recovery process was 0.039 and 0.073 s, respectively, for RSA-3072 and ECDSA-256, which was marginal compared with the total execution time (0.383 s for RSA-3072 and 0.319 s for ECDSA-256) of the conventional system. We also verified the security of the proposed protocol using a formal verification tool called ProVerif.
Exposure Therapy for Post-Traumatic Stress Disorder: Factors of Limited Success and Possible Alternative Treatment
Authors: Markowitz Sara , Fanselow Michael
Published: March 2020

Recent research indicates that there is mixed success in using exposure therapies on patients with post-traumatic stress disorder (PTSD). Our study argues that there are two major reasons for this: The first is that there are nonassociative aspects of PTSD, such as hyperactive amygdala activity, that cannot be attenuated using the exposure therapy; The second is that exposure therapy is conceptualized from the theoretical framework of Pavlovian fear extinction, which we know is heavily context dependent. Thus, reducing fear response in a therapist’s office does not guarantee reduced response in other situations. This study also discusses work relating to the role of the hippocampus in context encoding, and how these findings can be beneficial for improving exposure therapies.
Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer
Authors: Cavazzoni Andrea , Digiacomo Graziana , Alfieri Roberta , La Monica Silvia , Fumarola Claudia , Galetti Maricla , Bonelli Mara , Cretella Daniele , Barili Valeria , Zecca Alessandra , Giovannetti Elisa , Fiorentino Michelangelo , Tiseo Marcello , Petronini Pier Giorgio , Ardizzoni Andrea
Published: March 2020

Immunotherapy has significantly changed the treatment landscape for advanced non-small-cell lung cancer (NSCLC) with the introduction of drugs targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In particular, the addition of the anti-PD-1 antibody pembrolizumab to platinum-pemetrexed chemotherapy resulted in a significantly improved overall survival in patients with non-squamous NSCLC, regardless of PD-L1 expression. In this preclinical study, we investigated whether chemotherapy can modulate PD-L1 expression in non-squamous NSCLC cell lines, thus potentially affecting immunotherapy efficacy. Among different chemotherapeutic agents tested, only pemetrexed increased PD-L1 levels by activating both mTOR/P70S6K and STAT3 pathways. Moreover, it also induced the secretion of cytokines, such as IFN-γ and IL-2, by activated peripheral blood mononuclear cells PBMCs that further stimulated the expression of PD-L1 on tumor cells, as demonstrated in a co-culture system. The anti-PD-1/PD-L1 therapy enhanced T cell-mediated cytotoxicity of NSCLC cells treated with pemetrexed and expressing high levels of PD-L1 in comparison with untreated cells. These data may explain the positive results obtained with pemetrexed-based chemotherapy combined with pembrolizumab in PD-L1-negative NSCLC and can support pemetrexed as one of the preferable chemotherapy partners for immunochemotherapy combination regimens.
Statin Use and the Risk of Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies
Authors: Islam Md. Mohaimenul , Poly Tahmina Nasrin , Walther Bruno Andreas , Yang Hsuan-Chia , Li Yu-Chuan (Jack)
Published: March 2020

Background and Aims: Statins are the first-line medication to treating hypercholesterolemia. Several studies have investigated the impact of statins on the risk of hepatocellular carcinoma (HCC). However, the extent to which statins may prevent HCC remains uncertain. Therefore, we performed a meta-analysis of relevant studies to quantify the magnitude of the association between statins use and the risk of HCC. Methods: A systematic literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Scopus was performed for studies published between January 1, 1990, and September 1, 2019, with no restriction of language. Two reviewers independently evaluated the literature and included observational and experimental studies that reported the association between statin use and HCC risk. The random-effect model was used to calculate the overall risk ratio (RR) with a 95% confidence interval (CI), and the heterogeneity among the studies was assessed using the Q statistic and I2 statistic. The Newcastle Ottawa Scale (NOS) was also used to evaluate the quality of the included studies. Results: A total of 24 studies with 59,073 HCC patients was identified. Statin use was associated with a reduced risk of HCC development (RR: 0.54, 95% CI: 0.47–0.61, I2 = 84.39%) compared with nonusers. Moreover, the rate of HCC reduction was also significant among patients with diabetes (RR: 0.44, 95% CI: 0.28–0.70), liver cirrhosis (RR: 0.36, 95% CI: 0.30–0.42), and antiviral therapy (RR: 0.21, 95% CI: 0.08–0.59) compared with nonusers. Conclusion: This study serves as additional evidence supporting the beneficial inhibitory effect of statins on HCC incidence. The subgroup analyses of this study also highlight that statins are significantly associated with a reduced risk of HCC and may help to direct future prevention efforts. Additional large clinical studies are needed to determine whether statins are associated with a lower risk of HCC.
Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells
Authors: Moody Rhiane , Wilson Kirsty , Jaworowski Anthony , Plebanski Magdalena
Published: March 2020

Cancer-related deaths are approaching 10 million each year. Survival statistics for some cancers, such as ovarian cancer, have remained unchanged for decades, with women diagnosed at stage III or IV having over 80% chance of a lethal cancer recurrence after standard first-line treatment (reductive surgery and chemotherapy). New treatments and adjunct therapies are needed. In ovarian cancer, as in other cancers, the immune response, particularly cytotoxic (CD8+) T cells are correlated with a decreased risk of recurrence. As well as completely new antigen targets resulting from DNA mutations (neo-antigens), these T cells recognize cancer-associated overexpressed, re-expressed or modified self-proteins. However, there is concern that activation of self-reactive responses may also promote off-target pathology. This review considers the complex interplay between cancer-reactive and self-reactive immune cells and discusses the potential uses for various leading immunomodulatory compounds, derived from plant-based sources, as a cancer therapy option or to modulate potential autoimmune pathology. Along with reviewing well-studied compounds such as curcumin (from turmeric), epigallocatechin gallate (EGCG, from green tea) and resveratrol (from grapes and certain berries), it is proposed that compounds from novel sources, for example, native Australian plants, will provide a useful source for the fine modulation of cancer immunity in patients.
Tissue-Specific Metabolic Regulation of FOXO-Binding Protein: FOXO Does Not Act Alone
Authors: Kodani Noriko , Nakae Jun
Published: March 2020

The transcription factor forkhead box (FOXO) controls important biological responses, including proliferation, apoptosis, differentiation, metabolism, and oxidative stress resistance. The transcriptional activity of FOXO is tightly regulated in a variety of cellular processes. FOXO can convert the external stimuli of insulin, growth factors, nutrients, cytokines, and oxidative stress into cell-specific biological responses by regulating the transcriptional activity of target genes. However, how a single transcription factor regulates a large set of target genes in various tissues in response to a variety of external stimuli remains to be clarified. Evidence indicates that FOXO-binding proteins synergistically function to achieve tightly controlled processes. Here, we review the elaborate mechanism of FOXO-binding proteins, focusing on adipogenesis, glucose homeostasis, and other metabolic regulations in order to deepen our understanding and to identify a novel therapeutic target for the prevention and treatment of metabolic disorders.
From Rust to Quantum Biology: The Role of Iron in Retina Physiopathology
Authors: Picard Emilie , Daruich Alejandra , Youale Jenny , Courtois Yves , Behar-Cohen Francine
Published: March 2020

Iron is essential for cell survival and function. It is a transition metal, that could change its oxidation state from Fe2+ to Fe3+ involving an electron transfer, the key of vital functions but also organ dysfunctions. The goal of this review is to illustrate the primordial role of iron and local iron homeostasis in retinal physiology and vision, as well as the pathological consequences of iron excess in animal models of retinal degeneration and in human retinal diseases. We summarize evidence of the potential therapeutic effect of iron chelation in retinal diseases and especially the interest of transferrin, a ubiquitous endogenous iron-binding protein, having the ability to treat or delay degenerative retinal diseases.
Trend Analysis on Adoption of Virtual and Augmented Reality in the Architecture, Engineering, and Construction Industry
Authors: Noghabaei Mojtaba , Heydarian Arsalan , Balali Vahid , Han Kevin
Published: March 2020

With advances in Building Information Modeling (BIM), Virtual Reality (VR) and Augmented Reality (AR) technologies have many potential applications in the Architecture, Engineering, and Construction (AEC) industry. However, the AEC industry, relative to other industries, has been slow in adopting AR/VR technologies, partly due to lack of feasibility studies examining the actual cost of implementation versus an increase in profit. The main objectives of this paper are to understand the industry trends in adopting AR/VR technologies and identifying gaps within the industry. The identified gaps can lead to opportunities for developing new tools and finding new use cases. To achieve these goals, two rounds of a survey at two different time periods (a year apart) were conducted. Responses from 158 industry experts and researchers were analyzed to assess the current state, growth, and saving opportunities for AR/VR technologies for the AEC industry. The findings demonstrate that older generations are significantly more confident about the future of AR/VR technologies and they see more benefits in AR/VR utilization. Furthermore, the research results indicate that Residential and commercial sectors have adopted these tools the most, compared to other sectors and institutional and transportation sectors had the highest growth from 2017 to 2018. Industry experts anticipated a solid growth in the use of AR/VR technologies in 5 to 10 years, with the highest expectations towards healthcare. Ultimately, the findings show a significant increase in AR/VR utilization in the AEC industry from 2017 to 2018.
A Two-Stage Mutual Information Based Bayesian Lasso Algorithm for Multi-Locus Genome-Wide Association Studies
Authors: Guo Hongping , Yu Zuguo , An Jiyuan , Han Guosheng , Ma Yuanlin , Tang Runbin
Published: March 2020

Genome-wide association study (GWAS) has turned out to be an essential technology for exploring the genetic mechanism of complex traits. To reduce the complexity of computation, it is well accepted to remove unrelated single nucleotide polymorphisms (SNPs) before GWAS, e.g., by using iterative sure independence screening expectation-maximization Bayesian Lasso (ISIS EM-BLASSO) method. In this work, a modified version of ISIS EM-BLASSO is proposed, which reduces the number of SNPs by a screening methodology based on Pearson correlation and mutual information, then estimates the effects via EM-Bayesian Lasso (EM-BLASSO), and finally detects the true quantitative trait nucleotides (QTNs) through likelihood ratio test. We call our method a two-stage mutual information based Bayesian Lasso (MBLASSO). Under three simulation scenarios, MBLASSO improves the statistical power and retains the higher effect estimation accuracy when comparing with three other algorithms. Moreover, MBLASSO performs best on model fitting, the accuracy of detected associations is the highest, and 21 genes can only be detected by MBLASSO in Arabidopsis thaliana datasets.
Index Properties, Hydraulic Conductivity and Contaminant-Compatibility of CMC-Treated Sodium Activated Calcium Bentonite
Authors: Fan Ri-Dong , Reddy Krishna R. , Yang Yu-Ling , Du Yan-Jun
Published: March 2020

A typical sodium activated calcium bentonite (SACaB) was treated with carboxymethyl cellulose (CMC) polymer, called CMC-treated SACaB (CMC-SACaB), and it was investigated for its hydraulic conductivity and enhanced chemical compatibility. Index property and hydraulic conductivity tests were conducted on CMC-SACaB and SACaB with deionized water (DIW), heavy metals-laden water, and actual landfill leachate. Lead-zinc mixed (Pb-Zn) solution and hexavalent chromium (Cr(VI)) solution were selected as target heavy metals-laden water, and calcium (Ca) solution was tested for comparison purposes. The hydraulic conductivity (kMFL) was determined via the modified fluid loss (MFL) test. Liquid limit and swell index in DIW, heavy metal-laden water, and Ca solution increased with increasing CMC content. CMC treatment effectively decreased the kMFL of SACaB when exposed to Pb-Zn solutions with a metal concentration of 1 to 20 mmol/L and landfill leachate. An insignificant change in kMFL of CMC-SACaB occurred with exposure to Pb-Zn solutions with metal concentrations of 1 to 10 mmol/L, Cr(VI) and Ca solutions with metal concentration of 1 to 20 mmol/L, and landfill leachate. A slight increase in kMFL of CMC-SACaB was observed when Pb-Zn concentration increased to 20 mmol/L, and such an increment was more noticeable when the CMC content was lower than 10%. In the DIW, the measured kMFL values of CMC-SACaB and SACaB with a given range of void ratio were consistent with those obtained from the flexible-wall permeameter test.
Adaptation of TECCU App Based on Patients´ Perceptions for the Telemonitoring of Inflammatory Bowel Disease: A Qualitative Study Using Focus Groups
Authors: Del Hoyo Javier , Nos Pilar , Faubel Raquel , Bastida Guillermo , Muñoz Diana , Valero-Pérez Elena , Garrido-Marín Alejandro , Bella Pablo , Peña Beatriz , Savini Claudia , Aguas Mariam
Published: March 2020

Background: Despite the continuous adaptation of eHealth systems for patients with inflammatory bowel disease (IBD), a significant disconnection persists between users and developers. Since non-adherence remains high, it is necessary to better understand the patients’ perspective on telemonitoring for IBD. Accordingly, this study aimed to adapt the TECCU telemonitoring app to the preferences and needs of IBD patients. Methods: A qualitative study was carried out using successive focus groups of IBD patients. Meetings were audio-recorded and a thematic analysis was employed until data saturation was achieved. The first group included patients who had used the TECCU App in a pilot clinical trial, and subsequent meetings included patients with Crohn’s disease and ulcerative colitis recruited from the Spanish Confederation of patient associations. The information collected at each meeting guided consecutive changes to the platform. Results: Data saturation was reached after three focus groups involving a total of 18 patients. Three main themes emerged: (1) platform usability, (2) the communication process, and (3) platform content. All participants indicated that TECCU is easy to use, permitting continuous and personalized feedback. According to patients´ perspectives, the platform was adapted to foster a flexible follow-up and shared decision-making using open and safe communication networks. Many participants appreciated the educational elements and, consequently, the app was connected to reliable and continuously updated webpages. Conclusions: IBD patients valued the usability and personalized monitoring offered by the TECCU App. Improvements in the messaging system and continuously updated educational content were introduced to address patients´ needs and favor their engagement.
A Cross-Sectional Study on the Knowledge of Sexually Transmitted Diseases among Young Adults Living in Albaha, Saudi Arabia
Authors: Albanghali Mohammad A. , Othman Basim A.
Published: March 2020

Background: Sexually transmitted diseases (STDs) remain one of the most important health challenges in not only developing countries but also developed countries. Discussing STDs in the Saudi society is considered taboo, as social factors and ethics give rise to many obstacles. This study evaluates the knowledge of STDs among young adult students enrolled in Albaha University. Methods: This research is a cross-sectional study involving 1902 young adult students registered at Albaha University. STDs knowledge scores (STDs-KSs) were calculated using a predesigned and validated STDs knowledge questionnaire with 27 items adapted from previously developed questionnaires. Results: The estimated overall mean of STDs-KS was 7.95 ± 4.29. Female participants showed a significantly higher mean of STDs-KS, compared to males (8.51 ± 4.14 vs. 7.32 ± 4.38, p < 0.0001). Participants registered in health sciences programs showed higher STDs-KS, compared to participants from arts and sciences programs (p < 0.0001). Conclusions: Evidence from this study suggests a lack of STDs knowledge among young adults. To promote STDs awareness among this population, more health educational programs should be included in school curricula at the late stages of secondary education.
Indexing Mixed Aperture Icosahedral Hexagonal Discrete Global Grid Systems
Authors: Wang Rui , Ben Jin , Zhou Jianbin , Zheng Mingyang
Published: March 2020

Discrete global grid systems (DGGSs) are an emerging multiresolution 3D model used to integrate and analyze big earth data. The characteristic of multiresolution is usually realized by hierarchically subdividing cells on the sphere using certain refinement. This paper introduces mixed aperture three- and four- icosahedral hexagonal DGGSs using two types of refinement, the various combinations of which can provide more resolutions compared with pure aperture hexagonal DGGSs and can flexibly design the aperture sequence according to the target resolutions. A general hierarchy-based indexing method is first designed, and related indexing arithmetics and algorithm are developed based on the indexing method. Then, the grid structure on the surface of the icosahedron is described and by projection spherical grids are obtained. Experiments show that the proposed scheme is superior to pure aperture schemes in choosing grid resolutions and can reduce the data volume by 38.5% in representing 1-km resolution raster dataset; using the proposed indexing arithmetics to replace spherical geometry operations in generating discrete spherical vector lines based on hexagonal cells can improve the generation efficiency.
Distribution of Intracranial Major Artery Stenosis/Occlusion According to RNF213 Polymorphisms
Authors: Kim Jinkwon , Park Young Seok , Woo Min-Hee , An Hui Jeong , Kim Jung Oh , Park Han Sung , Ryu Chang Soo , Kim Ok Joon , Kim Nam Keun
Published: March 2020

Intracranial major artery stenosis/occlusion (ICASO) is the major cause of ischemic stroke. Recent studies have suggested that variants of RNF213, a susceptibility gene for moyamoya disease (MMD), are also related to non-MMD ICASO. Regarding the predominant involvement of steno-occlusion on anterior circulation in MMD, we hypothesized that the ICASO distribution pattern (anterior/posterior) in non-MMD may differ according to RNF213 variants. This study analyzed 1024 consecutive Korean subjects without MMD who underwent computed tomography angiography (CTA) or magnetic resonance angiography (MRA). We evaluated four single nucleotide polymorphisms (SNPs) in the exon region of RNF213: 4448G > A (rs148731719), 4810G > A (rs112735431), 4863G > A (rs760732823), and 4950G > A (rs371441113). Associations between RNF213 variants and anterior/posterior ICASO were examined using multivariate logistic regression analysis. Anterior ICASO was present in 23.0% of study subjects, and posterior ICASO was present in 8.2%. The GA genotype of RNF213 4810G > A (adjusted odds ratio (AOR) [95% confidence interval (CI)], 2.39 [1.14–4.87] compared to GG; p = 0.018) and GA genotype of RNF213 4950G > A (AOR [95% CI], 1.71 [1.11–2.63] compared to GG; p = 0.015) were more frequent in subjects with anterior ICASO. The genotype frequency of RNF213 4863G > A differed significantly according to the presence of posterior ICASO. Further investigations of the functional and biological roles of RNF213 will improve our understanding of the pathomechanisms of ICASO and cerebrovascular disease.
Circulating Tumor Necrosis Factor Receptors: A Potential Biomarker for the Progression of Diabetic Kidney Disease
Authors: Murakoshi Maki , Gohda Tomohito , Suzuki Yusuke
Published: March 2020

Despite considerable advancements in medicine, the optimal treatment for chronic kidney disease (CKD), especially diabetic kidney disease (DKD), remains a major challenge. More patients with DKD succumb to death due to cardiovascular events than due to progression to end-stage renal disease (ESRD). Moreover, patients with DKD and ESRD have remarkably poor prognosis. Current studies have appreciated the contribution of inflammation and inflammatory mediators, such as tumor necrosis factor (TNF)-related biomarkers, on the development/progression of DKD. The present review focuses on molecular roles, serum concentrations of TNF receptors (TNFRs), and their association with increased albuminuria, eGFR decline, and all-cause mortality in diabetes. Experimental studies have suggested that DKD progression occurs through the TNFα–TNFR2 inflammatory pathway. Moreover, serum TNFR levels were positively associated with albuminuria and negatively associated with estimated glomerular filtration rate (eGFR), while circulating levels of TNFRs exhibited an independent effect on all-cause mortality and eGFR decline, including ESRD, even after adjusting for existing risk factors. However, their precise function has yet to be elucidated and requires further studies.
The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer
Authors: Ding Lei , Cao Jiaqi , Lin Wen , Chen Hongjian , Xiong Xianhui , Ao Hongshun , Yu Min , Lin Jie , Cui Qinghua
Published: March 2020

Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in response to extracellular and intracellular signals. Not surprisingly, the dysregulation of CDKs is a hallmark of cancers, and inhibition of specific members is considered an attractive target in cancer therapy. In breast cancer (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, combined with other agents, were approved by the Food and Drug Administration (FDA) recently for the treatment of hormone receptor positive (HR+) advanced or metastatic breast cancer (A/MBC), as well as other sub-types of breast cancer. Furthermore, ongoing studies identified more selective CDK inhibitors as promising clinical targets. In this review, we focus on the roles of CDKs in driving cell-cycle progression, cell-cycle checkpoints, and transcriptional regulation, a highlight of dysregulated CDK activation in BC. We also discuss the most relevant CDK inhibitors currently in clinical BC trials, with special emphasis on CDK4/6 inhibitors used for the treatment of estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2−) M/ABC patients, as well as more emerging precise therapeutic strategies, such as combination therapies and microRNA (miRNA) therapy.
Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules
Authors: Rinne Sara S. , Dahlsson Leitao Charles , Saleh-nihad Zahra , Mitran Bogdan , Tolmachev Vladimir , Ståhl Stefan , Löfblom John , Orlova Anna
Published: March 2020

HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)3-ZHER3 and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)3-ZHER3-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [57Co]Co (surrogate for 55Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [57Co]Co-(HE)3-ZHER3-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA 3 h pi, [57Co]Co-(HE)3-ZHER3-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [57Co]Co–chelator complex influenced the uptake in tumors and normal tissue. [57Co]Co-(HE)3-ZHER3-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [57Co]Co-(HE)3-ZHER3-DOTA improved imaging contrast compared to early-time-point imaging with [68Ga]Ga-(HE)3-ZHER3-NODAGA.
Effects of Diaphorina citri Population Density on Daily Timing of Vibrational Communication Calls: Potential Benefits in Finding Forage
Authors: Mankin Richard W. , Patel Rikin , Grugnale Mason , Jetter Ethan
Published: March 2020

Adult Diaphorina citri (ACP) use visual and chemical cues to locate young citrus flush shoots on which they forage and oviposit, and they use vibrational communication duetting calls as cues to help locate mates. For individual pairs, calling and mating usually peaks between 10:00 and 15:00. To explore whether call rates (calls/h) are affected by interactions with nearby conspecifics, rates were compared in small citrus trees on which either 5 or 25 ACP female and male pairs had been released at 17:00 for later recording from sunrise (06:00) to 22:00. Final ACP locations were noted 40 h after release. Call rates were similar in both treatments during normal mating hours. However, rates were significantly higher for low- than high-density treatments between 06:00 and 10:00, which suggests calling during this period may be affected by conspecific density. Both sexes aggregated on flush at both densities. We discuss the potential that ACP producing calls near sunrise, outside of normal mating hours, might benefit from gains in reproductive fitness in low-density contexts if they call not only to locate mates but also to locate preferred flush—in which case, co-opting of vibrations to disrupt both mating and foraging may be feasible.
Alcohol Hangover Differentially Modulates the Processing of Relevant and Irrelevant Information
Authors: Opitz Antje , Beste Christian , Stock Ann-Kathrin
Published: March 2020

Elevated distractibility is one of the major contributors to alcohol hangover-induced behavioral deficits. Yet, the basic mechanisms driving increased distractibility during hangovers are still not very well understood. Aside from impairments in attention and psychomotor functions, changes in stimulus-response bindings may also increase responding to distracting information, as suggested by the theory of event coding (TEC). Yet, this has never been investigated in the context of alcohol hangover. Therefore, we investigated whether alcohol hangover has different effects on target-response bindings and distractor-response bindings using a task that allows to differentiate these two phenomena. A total of n = 35 healthy males aged 19 to 28 were tested once sober and once hungover after being intoxicated in a standardized experimental drinking setting the night before (2.64 gr of alcohol per estimated liter of body water). We found that alcohol hangover reduced distractor-response bindings, while no such impairment was found for target-response bindings, which appeared to be unaffected. Our findings imply that the processing of distracting information is most likely not increased, but in fact decreased by hangover. This suggests that increased distractibility during alcohol hangover is most likely not caused by modulations in distractor-response bindings.
Helicobacter pylori Gastritis in Children—The Link between Endoscopy and Histology
Authors: Domșa Ana-Maria Teodora , Lupușoru Raluca , Gheban Dan , Șerban Radu , Borzan Cristina Maria
Published: March 2020

Background: The management of Helicobacter pylori (H. pylori) infection raises important challenges, still being the most common chronic infection worldwide in all age groups. In high-prevalence regions, paediatric patients need a specific focus, as the acquisition of the infection takes place in childhood. The objective of this study was to analyze the endoscopic and histopathologic changes of the gastric mucosa in H. pylori infected children. Material and Methods: A retrospective study was performed on consecutive paediatric patients, ranging from 0 to 18 years of age, who underwent an upper gastrointestinal endoscopy (UGE) for a period of 5 years, regardless of their symptomatology. Endoscopy reports and histological slides were reviewed and clinical, endoscopic, and histologic data were recorded. Results: A total of 248 patients were included in the study, 82 (33.06%) of them being H. pylori infected. There was no difference in age and symptoms between the infected and noninfected group. A significant association was found between the H. pylori infection and histopathological parameters such as acute and chronic inflammatory infiltrate. The bacterial load influences the intensity of inflammation (p < 0.001). The chronic inflammation was predominant, only 23.2% of the patients displayed acute inflammation (p < 0.0001). The topographic distribution of inflammation was dominated by pangastritis (p = 0.04) with 58.6% of the patients presenting similar degrees of inflammation both in the antrum and corpus. Conclusion: Endoscopic features such as nodularity of the antral mucosa (p < 0.05) along with histological findings as lymphoid follicles (p < 0.05) are suggestive of H. pylori infection. However, the concordance between the endoscopic and histological diagnosis is still far from perfect (Cohen’s k coefficient = 0.42), maintaining the need for an invasive approach in children.
Long-Term Storage Considerations for Spacecraft Lubricants
Authors: Buttery Michael , Lewis Simon , Kent Anthony , Bingley Rachel , Cropper Matthew
Published: March 2020

Spacecraft mechanisms commonly undergo extended periods of storage, either on-ground, or in-flight and there are an increasing number of missions for which some element of long-term storage may be required. Despite the obvious potential for degradation of lubricants during storage which might impact mechanism functionality or life and so even become mission-threatening, today’s understanding of storage phenomena is rather incomplete. This paper provides consolidation and review of recent experimental studies in this area and considers the range of storage conditions and associated degradation phenomena which could impact different lubricants. Whilst some storage best practice guidelines exist, experimental verification of the impact of storage phenomena has rarely been carried out and test data is rather scarce and incomplete. Given the absence of comprehensive data to support design, lubricant selection or the development of storage protocols, it is shown that for all lubricant types careful control of storage and test environments combined with monitoring of the evolving tribological performance during periodic mechanism exercising are presently the most effective storage risk mitigations.
Using Digital Image Correlation on SEM Images of Strain Field after Ion Beam Milling for the Residual Stress Measurement of Thin Films
Authors: Chen Terry Yuan-Fang , Chou Yun-Chia , Wang Zhao-Ying , Lin Wen-Yen , Lin Ming-Tzer
Published: March 2020

The residual stress of thin films during the deposition process can cause the components to have unpredictable deformation and damage, which could affect the service life and reliability of the microsystems. Developing an accurate and reliable method for measuring the residual stress of thin films at the micrometer and nanometer scale is a great challenge. To analyze the residual stress regarding factors such as the mechanical anisotropy and preferred orientation of the materials, information related to the in-depth lattice strain function is required when calculating the depth profiles of the residual strain. For depth-resolved measurements of residual stress, it is strategically advantageous to develop a measurement procedure that is microstructurally independent. Here, by performing an incremental focused ion beam (FIB) ring-core drilling experiment with various depth steps, the digital image correlation (DIC) of the specimen images was obtained. The feasibility of DIC to FIB images was evaluated after the translation test, and an appropriate procedure for reliable results was established. Furthermore, the condition of the film in the function of residual stress was assessed and compared to elucidate the applicability of this technology.
Analysis of Selected Properties of Welded Joints of the HSLA Steels
Authors: Miletić Ivan , Ilić Andreja , Nikolić Ružica R. , Ulewicz Robert , Ivanović Lozica , Sczygiol Norbert
Published: March 2020

This paper presents research of the impact toughness and hardness distribution in specific zones of a ‘single V’butt multiple-pass welded joints of the high-strength low-alloyed steels. Obtained values of the impact toughness are analyzed in correlation with a microstructure in specific zones of the welded joint, together with the micro hardness distribution found in the related zones. Based on the carried out analysis and results obtained in experiments, the applied technology of welding was evaluated. The original conclusions on influence of the selected welding procedure manual metal arc (MMA) for the root passes and metal active gas (MAG) for the filling and covering passes) on impact toughness of the high-strength low-alloyed steels are drawn. The paper also presents discussion on the valid standards and recommendations related to welding of those steels, from the aspect of applications in design of steel welded constructions.
Effect of Single-Walled Carbon Nanotubes on Strength Properties of Cement Composites
Authors: Kang Jiayuan , Al-Sabah Salam , Théo Roger
Published: March 2020

This study aimed to investigate the effects of single-walled carbon nanotubes (SWCNTs) on strength the properties of cement composites when surfactant (SAA) was applied as the dispersion method. TritonX-100 (TX10) was used as the SAA to pretreat SWCNTs, which has been proved to perform well in dispersing the agglomerates of SWCNTs. In this study, four different concentration of SWCNTs, namely 0.00 wt%, 0.02 wt%, 0.04 wt%, and 0.06 wt% by the mass of cement, were used to prepare cement composite specimens. The compressive strength and flexural strength of specimens were tested and recorded. The results show that the compressive and flexural strengths of cement composites decreased with the increase in the concentration of SWCNTs without the addition of TX10. However, when SWCNT suspensions were pretreated with TX10, the strength variation pattern changed; the compressive and flexural strengths of cement composites increased as a function of the concentration of SWCNTs, although there were reductions compared to non-TX10-treated specimens at all concentrations of SWCNTs. Furthermore, the relationship between the strength of cement composites and bulk density of specimens was considered.
Pancreatic Hydatid Cyst Misdiagnosed as Mucinous Cystadenoma: CT and MRI Findings
Authors: Mitrovic Milica , Tadic Boris , Kovac Jelena , Grubor Nikola , Milosavljevic Vladimir , Jankovic Aleksandra , Khatkov Igor , Radenkovic Dejan , Matic Slavko
Published: March 2020

Isolated hydatid cysts of the pancreas are rare lesions, even in endemic regions. In this report, we present the case of a 76-year-old patient who was admitted to our clinic with a diagnosis of a cystic lesion in the tail of the pancreas. On preoperative computed tomography (CT) and magnetic resonance (MR) examination, the cyst was characterized as a mucinous cystadenoma. A laparoscopic distal pancreatectomy followed. A histopathological examination revealed a large hydatid cyst in the tail of the pancreas.
Epidemiology of Bladder Cancer
Authors: Saginala Kalyan , Barsouk Adam , Aluru John Sukumar , Rawla Prashanth , Padala Sandeep Anand , Barsouk Alexander
Published: March 2020

Based on the latest GLOBOCAN data, bladder cancer accounts for 3% of global cancer diagnoses and is especially prevalent in the developed world. In the United States, bladder cancer is the sixth most incident neoplasm. A total of 90% of bladder cancer diagnoses are made in those 55 years of age and older, and the disease is four times more common in men than women. While the average 5-year survival in the US is 77%, the 5-year survival for those with metastatic disease is a measly 5%. The strongest risk factor for bladder cancer is tobacco smoking, which accounts for 50–65% of all cases. Occupational or environmental toxins likewise greatly contribute to disease burden (accounting for an estimated 20% of all cases), though the precise proportion can be obscured by the fact bladder cancer develops decades after exposure, even if the exposure only lasted several years. Schistosomiasis infection is the common cause of bladder cancer in regions of Africa and the Middle East and is considered the second most onerous tropical pathogen after malaria. With 81% of cases attributable to known risk factors (and only 7% to heritable mutations), bladder cancer is a prime candidate for prevention strategies. Smoking cessation, workplace safety practices, weight loss, exercise and schistosomiasis prevention (via water disinfection and mass drug administration) have all been shown to significantly decrease the risk of bladder cancer, which poses a growing burden around the world.
Characterization of a Zn-Ca5(PO4)3(OH) Composite with a High Content of the Hydroxyapatite Particles Prepared by the Spark Plasma Sintering Process
Authors: Pinc Jan , Čapek Jaroslav , Kubásek Jiří , Průša Filip , Hybášek Vojtěch , Veřtát Petr , Sedlářová Ivona , Vojtěch Dalibor
Published: March 2020

Zinc and zinc alloys have been studied due to their corrosion properties as potentially biodegradable materials. In this study, a zinc/hydroxyapatite composite (Zn/HA) containing 16 wt % HA was prepared by spark plasma sintering and characterized in detail. The microstructure, mechanical and corrosion properties were studied and the mutual relations between properties and microstructure were found. The porosity was evaluated to be approximately 18%. The mechanical properties (ultimate compression strength = 65 MPa and ultimate flexural strength = 120 MPa) are sufficient for the potential scaffolding and augmentation of cancellous bone. The flexural properties of these materials were measured for the first time. Immersion tests and subsequent analyses confirmed no direct participation of hydroxyapatite in the corrosion process and an ideal corrosion rate of approximately 0.4 mm/year. The amount of released zinc was between 4–6 mg/day corresponding with the maximal usable surface area of 25 cm2. All the results suggest that the Zn/HA composite is suitable as a potential biodegradable material (from the point of view of mechanical and corrosion properties) for the replacement of cancellous bones.
Simultaneous Optimization of the Ultrasonic Extraction Method and Determination of the Antioxidant Activities of Hydroxysafflor Yellow A and Anhydrosafflor Yellow B from Safflower Using a Response Surface Methodology
Authors: Zhang Yangyang , Yu Li , Jin Weifeng , Li Chang , Wang Yu , Wan Haitong , Yang Jiehong
Published: March 2020

An evaluation of the ultrasonic extraction process and the antioxidant activities of hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) from safflower are presented herein. Using response surface methodology (RSM), based on a four-factor-three-level Box–Behnken design (BBD), the extraction parameters, namely, temperature, extraction time, solvent-to-material ratio, and extraction power, were optimized for maximizing the yields of HSYA and AHSYB. The maximum yield was obtained at a temperature of 66 °C with an extraction time of 36 min, solvent-to-material ratio of 16 mL/g, and the extraction power of 150 W, which was adjusted according to the actual conditions. The HSYA and AHSYB contents were determined using high performance liquid chromatography (HPLC). The yield and the comprehensive evaluation value of HSYA and AHSYB were calculated. The antioxidant activities of the extracts were determined using a ferric reducing antioxidant power (FRAP) kit and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. The results suggested that the safflower extracts possessed obvious ferric reducing and DPPH radical scavenging activities. The antioxidant activity increased with increasing concentration. The results suggested that optimizing the conditions of ultrasonic extraction using RSM can significantly increase the yields of HSYA and AHSYB from safflower. The safflower extracts showed better antioxidant activity. This study can encourage future research on cardiovascular and cerebrovascular diseases.