bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of Scanning Strategies and Optimization Experiments for Laser Beam Powder Bed Fusion of Ti-6Al-4V Titanium Alloys
Authors: Shi Wentian , Li Jihang , Jing Yanlong , Liu Yude , Lin Yuxiang , Han Yufan
Published: July 2022

This paper studies the effects of different combinations of scanning strategies between layers on the surface quality, tensile properties, and microstructure of samples in a laser beam powder bed fusion (L-PBF) formation experiment of Ti-6Al-4V titanium alloy. The purpose of this experiment was to improve the comprehensive performance of the piece by selecting the optimal combination of scanning strategies. The results show that the surface roughness of the L-PBF specimen was the lowest under the combination of the CHESS scanning strategy, reaching 14 μm. The surface hardness of the samples was generally higher with the LINE scanning strategy and the angle offset of 90°, reaching 409 HV. The overall density of the samples was higher under the combination of CHESS scanning strategies, reaching 99.88%. Among them, the CHESS&45° sample had the best comprehensive properties, with a density of 99.85%, a tensile strength of up to 1125 MPa, a yield strength of 912 MPa, and an elongation of 8.2%. The fractured form was a ductile fracture, with many dimple structures. Compared with the CHESS scanning strategy, the tensile properties of the CHESS&45° samples were improved by 12.8%. The microstructure of the L-PBF sample was mainly composed of the primary β phase and α’ martensite phase. The upper surface of the CHESS scanning strategy combination sample had a clear melt channel, and the distribution of each phase was uniform. A certain number of columnar β crystals were distributed in the longitudinal section of the sample, which was paralleled to the build direction. The columnar β crystals of CHESS&45° were relatively coarse, which enhanced the tensile properties of the sample.
Investigation of Quantitative Evaluation Method and Engineering Application of Shallow Buried Tunnel Face Stability
Authors: Zhou Guan-Nan , Yang Teng-Tian , Sun Ze , Li Heng , Cheng Yun , Song Zhan-Ping , Han Jing-Jing
Published: July 2022

The stability of a tunnel face and the rationality of its supporting structures are the guarantees for safe tunnel construction. This paper established a quantitative analysis model of tunnel face stability, obtained the calculation formula of the tunnel face stability coefficient based on the silo theory of surrounding rock, and then realized the quantitative description of stability of the tunnel face under the condition of a pipe roofing support, bolting support, grouting support and reserved core soil. Finally, a tunnel face stability discrimination and support optimization system was developed, its supporting effects were quantitatively evaluated, and the support measures were optimized based on a buried tunnel of Chongqing rail transit passing through the suburban expressway. The results show that the grouting support increased the stability coefficient by 103~412%, and its supporting effect is the most significant. The reinforcement with reserved core soil has the lowest cost. The tunnel face stability discrimination and support optimization system carries out a rapid judgment of tunnel face stability, and then provides a quantitative evaluation method for the assessment of the tunnel face. On-site monitoring indicates that the cumulative displacement gradually increased with monitoring time; the farther from the tunnel surface, the smaller the cumulative displacement. The cumulative displacement reached 34.50 mm before the optimization of the reinforcement scheme. The optimization scheme of pipe roofing support + reserved core soil + grouting support led to the gradual convergence of cumulative displacement. The final surface settlement displacement was reduced to 15.50 mm, which was about 44.93% of that before the optimization of reinforcement scheme, ensuring the safe construction of the buried tunnel. This research has a certain theoretical significance for the quantitative evaluation and analysis of the tunnel face stability of shallow buried tunnels.
Simulating 3D Human Postural Stabilization in Vibration and Dynamic Driving
Authors: Mirakhorlo Mojtaba , Kluft Nick , Desai Raj , Cvetković Marko , Irmak Tugrul , Shyrokau Barys , Happee Riender
Published: July 2022

In future automated vehicles we will often engage in non-driving tasks and will not watch the road. This will affect postural stabilization and may elicit discomfort or even motion sickness in dynamic driving. Future vehicles will accommodate this with properly designed seats and interiors, whereas comfortable vehicle motion will be achieved with smooth driving styles and well-designed (active) suspensions. To support research and development in dynamic comfort, this paper presents the validation of a multi-segment full-body human model, including visuo-vestibular and muscle spindle feedback, for postural stabilization. Dynamic driving is evaluated using a “sickening drive”, including a 0.2 Hz 4 m/s2 slalom. Vibration transmission is evaluated with compliant automotive seats, applying 3D platform motion and evaluating 3D translation and rotation of pelvis, trunk and head. The model matches human motion in dynamic driving and reproduces fore–aft, lateral and vertical oscillations. Visuo-vestibular and muscle spindle feedback are shown to be essential, in particular, for head–neck stabilization. Active leg muscle control at the hips and knees is shown to be essential to stabilize the trunk in the high-amplitude slalom condition but not with low-amplitude horizontal vibrations. However, active leg muscle control can strongly affect 4–6 Hz vertical vibration transmission. Compared to the vibration tests, the dynamic driving tests show enlarged postural control gains to minimize trunk and head roll and pitch and to align head yaw with driving direction. Human modelling can enable the insights required to achieve breakthrough comfort enhancements, while enabling efficient developments for a wide range of driving conditions, body sizes and other factors. Hence, modelling human postural control can accelerate the innovation of seats and vehicle motion-control strategies for (automated) vehicles.
Rationalizing Structural Hierarchy in the Design of Fuel Cell Electrode and Electrolyte Materials Derived from Metal-Organic Frameworks
Authors: Kumar Aniket , Purwar Prashant , Sonkaria Sanjiv , Khare Varsha
Published: July 2022

Metal-organic frameworks (MOFs) are arguably a class of highly tuneable polymer-based materials with wide applicability. The arrangement of chemical components and the bonds they form through specific chemical bond associations are critical determining factors in their functionality. In particular, crystalline porous materials continue to inspire their development and advancement towards sustainable and renewable materials for clean energy conversion and storage. An important area of development is the application of MOFs in proton-exchange membrane fuel cells (PEMFCs) and are attractive for efficient low-temperature energy conversion. The practical implementation of fuel cells, however, is faced by performance challenges. To address some of the technical issues, a more critical consideration of key problems is now driving a conceptualised approach to advance the application of PEMFCs. Central to this idea is the emerging field MOF-based systems, which are currently being adopted and proving to be a more efficient and durable means of creating electrodes and electrolytes for proton-exchange membrane fuel cells. This review proposes to discuss some of the key advancements in the modification of PEMs and electrodes, which primarily use functionally important MOFs. Further, we propose to correlate MOF-based PEMFC design and the deeper correlation with performance by comparing proton conductivities and catalytic activities for selected works.
The Impact of High-Resolution SRTM Topography and Corine Land Cover on Lightning Calculations in WRF
Authors: de Meij Alexander , Ojha Narendra , Singh Narendra , Singh Jaydeep , Poelman Dieter Roel , Pozzer Andrea
Published: July 2022

The goal of this study is to investigate the impact of high-resolution SRTM and Corine Land Cover on the number of cloud–ground lightning flashes and their spatial distribution simulated by a numerical weather-prediction model. Two lightning episodes were selected: (1) over a non-complex terrain and (2) over a complex terrain, the Alps. Significant discrepancies were found in the geographical distribution of the land-cover classes and also in the topography between Corine Land Cover and 30-arc seconds USGS. In general, the timing and the spatial distribution of Cloud-to-Ground (CG) lightning by the model were well-represented when compared to the observations. In general, more CG flashes were calculated by the simulation with USGS Land Cover and topography than the simulation with Corine Land Cover and SRTM topography. It appears that the differences in sensible and latent heat fluxes between the simulations were caused by the differences in land-cover classes. Moreover, differences in the vertical wind speeds, specific humidity, temperature and the convective available potential energy were found when compared to observations, resulting in the differences in cloud–ground lightning flashes between the simulation with the SRTM topography and Corine Land Cover and the simulation with the USGS Land Cover and topography. Using the high-resolution land cover and topography data may help to reduce uncertainties in CG lightning calculations by the model.
Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk
Authors: D’Amuri Andrea , Sanz Juana Maria , Lazzer Stefano , Pišot Rado , Šimunič Bostjan , Biolo Gianni , Zuliani Giovanni , Gasparini Mladen , Narici Marco , Grassi Bruno , Reggiani Carlo , Dalla Nora Edoardo , Passaro Angelina
Published: July 2022

The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.
A Flexible Ultrasound Array for Local Pulse Wave Velocity Monitoring
Authors: Xu Lirui , Wang Peng , Xia Pan , Wu Pang , Chen Xianxiang , Du Lidong , Liu Jiexin , Xue Ning , Fang Zhen
Published: July 2022

Pulse wave velocity (PWV) measured at a specific artery location is called local PWV, which provides the elastic characteristics of arteries and indicates the degree of arterial stiffness. However, the large and cumbersome ultrasound probes require an appropriate sensor position and pressure maintenance, introducing usability constraints. In this paper, we developed a light (0.5 g) and thin (400 μm) flexible ultrasound array by encapsulating 1–3 composite piezoelectric transducers with a silicone elastomer. It can capture the distension waveforms of four arterial positions with a spacing of 10 mm and calculate the local PWV by multi-point fitting. This is illustrated by in vivo experiments, where the local PWV value of five normal subjects ranged from 3.07 to 4.82 m/s, in agreement with earlier studies. The beat-to-beat coefficient of variation (CV) is 12.0% ± 3.5%, showing high reliability. High reproducibility is shown by the results of two groups of independent measurements of three subjects (the error between the mean values is less than 0.3 m/s). These properties of the developed flexible ultrasound array enable the bandage-like application of local PWV monitoring to skin surfaces.
A Pilot Study Assessing the Effects of Goal Management Training on Cognitive Functions among Individuals with Major Depressive Disorder and the Effect of Post-Traumatic Symptoms on Response to Intervention
Authors: Boyd Jenna E. , Sanger Brahm D. , Cameron Duncan H. , Protopopescu Alina , McCabe Randi E. , O’Connor Charlene , Lanius Ruth A. , McKinnon Margaret C.
Published: July 2022

Recent meta-analyses highlight alterations in cognitive functioning among individuals with major depressive disorder (MDD), with performance deficits observed across multiple cognitive domains including executive functioning, memory, and attention. Moreover, impaired concentration is a formal diagnostic criterion for a major depressive episode. Notably, cognitive impairment is reported frequently in MDD and is associated with poor treatment response. Despite this knowledge, research examining the effectiveness of top-down, adjunctive treatments for cognitive dysfunction in MDD remains in its infancy. The primary aim of the present study was to perform a pilot investigation of the implementation of a standardized cognitive remediation program, Goal Management Training (GMT), among individuals with a primary diagnosis of MDD. A secondary aim was to explore how comorbid symptoms of post-traumatic stress disorder (PTSD) among those MDD patients exposed to trauma may affect treatment response. A final sample of thirty individuals were randomized to either participate in the nine-week GMT program (active group; n = 16) or to complete a nine-week waiting period (waitlist control; n = 14). One participant was excluded from the GMT group analysis following study completion due to meeting an exclusion criteria. In total, 60% of the individuals allocated to the GMT program were trauma exposed (n = 9). Groups were assessed at baseline, post-treatment, and at three-month follow-up. The assessment comprised neuropsychological tasks assessing a variety of cognitive domains, subjective measures of functioning and symptom severity, as well as a clinical interview to establish a primary diagnosis of MDD. Significant gains in processing speed, attention/concentration, and response inhibition were observed for the participants in the GMT condition relative to participants in the waitlist control condition. Individuals in the GMT condition also reported improvements in subjective cognitive functioning from baseline to post-treatment. Heightened PTSD symptom severity was associated with reduced response to treatment with respect to the domain of processing speed. The results of this pilot investigation highlight not only the potential utility of GMT as an augmentative treatment in MDD, but also highlight the contribution of comorbid symptoms of PTSD to diminished treatment response among trauma-exposed individuals with MDD. The study is limited primarily by its small pilot sample and the absence of a program evaluation component to gauge participant opinions and feedback of the treatment protocol.
Variations of Sensorimotor Representation (Structure): The Functional Interplay between Object Features and Goal-Directed Grasping Actions
Authors: Cienfuegos Miguel , Kim Taeho , Schack Thomas
Published: July 2022

This study investigated the structure of sensorimotor representations during goal-directed grasping actions and explored their relationship with object features. Sixteen 3D-printed spheres that varied in size (i.e., a diameter of 20 mm, 40 mm, 60 mm, 80 mm) and weight (i.e., 40 g, 52 g, 76 g, 91 g) were used as experimental stimuli. The Structural Dimensional Analysis of Mental Representation (SDA-M) method was used to assess the sensorimotor representation structure during grasping. Participants were instructed in each trial to weigh, lift, or transport sets of two different spheres and to judge the similarity of the objects’ features, taking into account the executed grasping movement. Each participant performed a total of 240 trials, and object presentation was randomized. The results suggest that the functional interplay between object features and goal-directed actions accounts for the significant variations in the structure of sensorimotor representations after grasping. Specifically, the relevance of the perceived objects’ size and weight is closely interrelated to the grasping task demands and movement dynamics of the executed action. Our results suggest that distinct sensorimotor representations support individual grasping actions according to top-down influences modulated by motor intentions, functional task demands, and task-relevant object features.
Skin Surface Dose for Whole Breast Radiotherapy Using Personalized Breast Holder: Comparison with Various Radiotherapy Techniques and Clinical Experiences
Authors: Chen Chiu-Ping , Lin Chi-Yeh , Kuo Chia-Chun , Chen Tung-Ho , Lin Shao-Chen , Tseng Kuo-Hsiung , Cheng Hao-Wen , Chao Hsing-Lung , Yen Sang-Hue , Lin Ruo-Yu , Feng Chen-Ju , Lu Long-Sheng , Chiou Jeng-Fong , Hsu Shih-Ming
Published: July 2022

Purpose: Breast immobilization with personalized breast holder (PERSBRA) is a promising approach for normal organ protection during whole breast radiotherapy. The aim of this study is to evaluate the skin surface dose for breast radiotherapy with PERSBRA using different radiotherapy techniques. Materials and methods: We designed PERSBRA with three different mesh sizes (large, fine and solid) and applied them on an anthropomorphic(Rando) phantom. Treatment planning was generated using hybrid, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques to deliver a prescribed dose of 5000 cGy in 25 fractions accordingly. Dose measurement with EBT3 film and TLD were taken on Rando phantom without PERSBRA, large mesh, fine mesh and solid PERSBRA for (a) tumor doses, (b) surface doses for medial field and lateral field irradiation undergoing hybrid, IMRT, VMAT techniques. Results: The tumor dose deviation was less than five percent between the measured doses of the EBT3 film and the TLD among the different techniques. The application of a PERSBRA was associated with a higher dose of the skin surface. A large mesh size of PERSBRA was associated with a lower surface dose. The findings were consistent among hybrid, IMRT, or VMAT techniques. Conclusions: Breast immobilization with PERSBRA can reduce heart toxicity but leads to a build-up of skin surface doses, which can be improved with a larger mesh design for common radiotherapy techniques.
Testing for Dihydropyrimidine Dehydrogenase Deficiency to Individualize 5-Fluorouracil Therapy
Authors: Diasio Robert B. , Offer Steven M.
Published: July 2022

Severe adverse events (toxicity) related to the use of the commonly used chemotherapeutic drug 5-fluorouracil (5-FU) affect one in three patients and are the primary reason cited for premature discontinuation of therapy. Deficiency of the 5-FU catabolic enzyme dihydropyrimidine dehydrogenase (DPD, encoded by DPYD) has been recognized for the past 3 decades as a pharmacogenetic syndrome associated with high risk of 5-FU toxicity. An appreciable fraction of patients with DPD deficiency that receive 5-FU-based chemotherapy die as a result of toxicity. In this manuscript, we review recent progress in identifying actionable markers of DPD deficiency and the current status of integrating those markers into the clinical decision-making process. The limitations of currently available tests, as well as the regulatory status of pre-therapeutic DPYD testing, are also discussed.
Defining Models to Classify between Benign and Malignant Adnexal Masses Using Routine Laboratory Parameters
Authors: Reiser Elisabeth , Pils Dietmar , Grimm Christoph , Hoffmann Ines , Polterauer Stephan , Kranawetter Marlene , Aust Stefanie
Published: July 2022

Discrimination between benign and malignant adnexal masses is essential for optimal treatment planning, but still remains challenging in a routine clinical setting. In this retrospective study, we aimed to compare albumin as a single parameter to calculate models by analyzing laboratory parameters of 1552 patients with an adnexal mass (epithelial ovarian cancer (EOC): n= 294; borderline tumor of the ovary (BTO): n = 66; benign adnexal mass: n = 1192) undergoing surgery. Models comprising classical laboratory parameters show better accuracies (AUCs 0.92–0.93; 95% CI 0.90–0.95) compared to the use of single markers, and could easily be implemented in clinical practice by containing only readily available markers. This has been incorporated into a nomogram.
Multiple Basal Cell Carcinomas in Immunocompetent Patients
Authors: Savoia Paola , Veronese Federica , Camillo Lara , Tarantino Vanessa , Cremona Ottavio , Zavattaro Elisa
Published: July 2022

Background: The onset of multiple BCCs is a relatively common condition, not only among patients undergoing chronic treatment with immunosuppressant drugs, but also in the general population, although specific risk factors for immunocompetent patients have not been identified. A putative role of somatic mutations in the hedgehog pathway should be considered. Methods: This study is a retrospective observation of all patients diagnosed and surgically treated for BCCs during 5 years at our Dermatological Division. For these patients, we evaluated clinical and histopathological characteristics and data about possible risk factors for BCC. Results: Five-hundred and six patients affected by multiple BCCs, accounting for the 24.2% of the entire sample, have been identified. In these patients, the total number of BCCs was 1516, ranging from 2 to 11. Subjects affected by multiple BCCs were more frequently males, with an older age at diagnosis; multiple BCCs developed mainly on the trunk and were often represented by a nodular histotype. The multivariate analysis highlighted that male gender, older age, nodular BCC, or face involvement at the first diagnosis are risk factors for the development of multiple BCCs. Conclusions: The frequency of multiple BCCs even among the non-immunocompromised population underlines the need to subject patients to a close surveillance program, to allow early diagnosis and treatment of additional cancers.
Tensin2 Is a Novel Diagnostic Marker in GIST, Associated with Gastric Location and Non-Metastatic Tumors
Authors: Salmikangas Sami , Böhling Tom , Merikoski Nanna , Jagdeo Joanna , Sampo Mika , Vesterinen Tiina , Sihto Harri
Published: July 2022

GIST is a rare soft tissue sarcoma, for which KIT and DOG1 are used as highly sensitive diagnostic markers. Other diagnostic markers include CD34, protein kinase C θ, deficiency of succinate dehydrogenase complex subunit B, carbonic anhydrase II, and type I insulin-like growth factor receptor. We investigated the role of TNS2 as a diagnostic biomarker by using immunohistochemistry in 176 GISTs and 521 other sarcomas. All GISTs expressed TNS2, with intermediate or high expression in 71.4% of samples. The majority (89.8%) of other sarcomas were negative for TNS2, and intermediate to strong staining was only seen in 2.9% of samples. Strong TNS2 staining was associated with gastric location (gastric 52.8% vs. non-gastric 7.2%; p < 0.001), absence of metastases (non-metastatic tumors 44.3% vs. metastatic tumors 5.9%; p = 0.004), female sex (female 45.9% vs. male 33.8%; p = 0.029), and tumors of lower risk categories (very low or low 46.9% vs. intermediate 51.7% vs. high 29.0%; p = 0.020). TNS2 expression did not correlate with overall survival or metastasis-free survival. No associations between TNS2 expression and KIT/PDGFRA mutation status, tumor size, mitotic count, or age of the patient were detected. The results provide conclusive evidence for the value of TNS2 as a sensitive and specific diagnostic biomarker for GIST.
Combining Molecular, Imaging, and Clinical Data Analysis for Predicting Cancer Prognosis
Authors: Lobato-Delgado Barbara , Priego-Torres Blanca , Sanchez-Morillo Daniel
Published: July 2022

Cancer is one of the most detrimental diseases globally. Accordingly, the prognosis prediction of cancer patients has become a field of interest. In this review, we have gathered 43 state-of-the-art scientific papers published in the last 6 years that built cancer prognosis predictive models using multimodal data. We have defined the multimodality of data as four main types: clinical, anatomopathological, molecular, and medical imaging; and we have expanded on the information that each modality provides. The 43 studies were divided into three categories based on the modelling approach taken, and their characteristics were further discussed together with current issues and future trends. Research in this area has evolved from survival analysis through statistical modelling using mainly clinical and anatomopathological data to the prediction of cancer prognosis through a multi-faceted data-driven approach by the integration of complex, multimodal, and high-dimensional data containing multi-omics and medical imaging information and by applying Machine Learning and, more recently, Deep Learning techniques. This review concludes that cancer prognosis predictive multimodal models are capable of better stratifying patients, which can improve clinical management and contribute to the implementation of personalised medicine as well as provide new and valuable knowledge on cancer biology and its progression.
The Mechanism of Action of Biguanides: New Answers to a Complex Question
Authors: Di Magno Laura , Di Pastena Fiorella , Bordone Rosa , Coni Sonia , Canettieri Gianluca
Published: July 2022

Biguanides are a family of antidiabetic drugs with documented anticancer properties in preclinical and clinical settings. Despite intensive investigation, how they exert their therapeutic effects is still debated. Many studies support the hypothesis that biguanides inhibit mitochondrial complex I, inducing energy stress and activating compensatory responses mediated by energy sensors. However, a major concern related to this “complex” model is that the therapeutic concentrations of biguanides found in the blood and tissues are much lower than the doses required to inhibit complex I, suggesting the involvement of additional mechanisms. This comprehensive review illustrates the current knowledge of pharmacokinetics, receptors, sensors, intracellular alterations, and the mechanism of action of biguanides in diabetes and cancer. The conditions of usage and variables affecting the response to these drugs, the effect on the immune system and microbiota, as well as the results from the most relevant clinical trials in cancer are also discussed.
Iron Chelator VLX600 Inhibits Mitochondrial Respiration and Promotes Sensitization of Neuroblastoma Cells in Nutrition-Restricted Conditions
Authors: Jakobsson Amanda Westergren , Kundu Snehangshu , Guo Jing , Chowdhury Azazul , Zhao Miao , Lindell Emma , Bergsten Peter , Swartling Fredrik J. , Sjöblom Tobias , Zhang Xiaonan
Published: July 2022

Neuroblastoma, the most common solid tumor in children, is characterized by amplification of the MYCN proto-oncogene, a high-risk aggressive clinical marker associated with treatment failure. MYCN plays an important role in cell growth, proliferation, metabolism, and chemoresistance. Here, we show for the first time that in neuroblastoma, iron chelator VLX600 inhibits mitochondrial respiration, decreases expression levels of MYCN/LMO1, and induces an efficient cell death regardless of MYCN status in both 2D and 3D culture conditions. Moreover, insufficient induction of autophagy was observed in cells treated with VLX600, which is essential as a protective response in the event of ATP synthesis disruption. Further inhibition of glucose uptake using DRB18, a pan-GLUT (glucose transporter) inhibitor, synergized the effect of VLX600 and no significant cell death was found in immortalized epithelial cells under this combination treatment. Our results demonstrate that inhibition of mitochondrial respiration by iron chelator VLX600 accompanied by autophagy deficiency promotes sensitivity of neuroblastoma cells in a nutrition-restricted microenvironment regardless of MYCN status, indicating that MYCN expression level is an essential clinical marker but might not be a necessary target for the treatment of neuroblastoma which warrants further investigation. VLX600 has been studied in Phase I clinical trials; combining VLX600 with conventional chemotherapy could be an innovative therapeutic strategy for neuroblastoma.
Biochemical Characterisation and Structure Determination of a Novel Cold-Active Proline Iminopeptidase from the Psychrophilic Yeast, Glaciozyma antarctica PI12
Authors: Kamaruddin Shazilah , Ahmad Redzuan Rohaiza , Minor Nurulermila , Seman Wan Mohd Khairulikhsan Wan , Md Tab Mahzan , Jaafar Nardiah Rizwana , Ahmad Rodzli Nazahiyah , Jonet Mohd Anuar , Bharudin Izwan , Yusof Nur Athirah , Xia Doris Quay Huai , Mahadi Nor Muhammad , Abdul Murad Abdul Munir , Abu Bakar Farah Diba
Published: July 2022

Microbial proteases constitute one of the most important groups of industrially relevant enzymes. Proline iminopeptidases (PIPs) that specifically release amino-terminal proline from peptides are of major interest for applications in food biotechnology. Proline iminopeptidase has been extensively characterised in bacteria and filamentous fungi. However, no similar reports exist for yeasts. In this study, a protease gene from Glaciozyma antarctica designated as GaPIP was cloned and overexpressed in Escherichia coli. Sequence analyses of the gene revealed a 960 bp open reading frame encoding a 319 amino acid protein (35,406 Da). The purified recombinant GaPIP showed a specific activity of 3561 Umg−1 towards L-proline-p-nitroanilide, confirming its identity as a proline iminopeptidase. GaPIP is a cold-active enzyme with an optimum activity of 30 °C at pH 7.0. The enzyme is stable between pH 7.0 and 8.0 and able to retain its activity at 10–30 °C. Although GaPIP is a serine protease, only 25% inhibition by the serine protease inhibitor, phenylmethanesulfonylfluoride (PMSF) was recorded. This enzyme is strongly inhibited by the presence of EDTA, suggesting that it is a metalloenzyme. The dimeric structure of GaPIP was determined at a resolution of 2.4 Å. To date, GaPIP is the first characterised PIP from yeasts and the structure of GaPIP is the first structure for PIP from eukaryotes.
High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota
Authors: Xiao Jason , Xie Bingqing , Dao David , Spedale Melanie , D’Souza Mark , Theriault Betty , Hariprasad Seenu M. , Sulakhe Dinanath , Chang Eugene B. , Skondra Dimitra
Published: July 2022

Relationships between retinal disease, diet, and the gut microbiome have started to emerge. In particular, high-fat diets (HFDs) are associated with the prevalence and progression of several retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR). These effects are thought to be partly mediated by the gut microbiome, which modulates interactions between diet and host homeostasis. Nevertheless, the effects of HFDs on the retina and adjacent retinal pigment epithelium (RPE) and choroid at the transcriptional level, independent of gut microbiota, are not well-understood. In this study, we performed the high-throughput RNA-sequencing of germ-free (GF) mice to explore the transcriptional changes induced by HFD in the RPE/choroid. After filtering and cleaning the data, 649 differentially expressed genes (DEGs) were identified, with 616 genes transcriptionally upregulated and 33 genes downregulated by HFD compared to a normal diet (ND). Enrichment analysis for gene ontology (GO) using the DEGs was performed to analyze over-represented biological processes in the RPE/choroid of GF-HFD mice relative to GF-ND mice. GO analysis revealed the upregulation of processes related to angiogenesis, immune response, and the inflammatory response. Additionally, molecular functions that were altered involved extracellular matrix (ECM) binding, ECM structural constituents, and heparin binding. This study demonstrates novel data showing that HFDs can alter RPE/choroid tissue transcription in the absence of the gut microbiome.
Alpha-Synuclein and Its Role in Melanocytes
Authors: Rachinger Nicole , Mittag Nora , Böhme-Schäfer Ines , Xiang Wei , Kuphal Silke , Bosserhoff Anja K.
Published: July 2022

Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson’s disease (PD). In PD, alpha-Synuclein (aSyn) has been shown to be involved in the pigmentation of neurons. The presynaptic protein is intensively investigated for its pathological role in PD, but its physiological function remains unknown. We hypothesized that aSyn is both involved in melanocytic differentiation and melanosome trafficking processes. We detected a strong expression of aSyn in human epidermal melanocytes (NHEMs) and observed its regulation in melanocytic differentiation via the microphthalmia-associated transcription factor (MITF), a central regulator of differentiation. Moreover, we investigated its role in pigmentation by performing siRNA experiments but found no effect on the total melanin content. We discovered a localization of aSyn to melanosomes, and further analysis of aSyn knockdown revealed an important role in melanocytic morphology and a reduction in melanosome release. Additionally, we found a reduction of transferred melanosomes in co-culture experiments of melanocytes and keratinocytes but no complete inhibition of melanosome transmission. In summary, this study highlights a novel physiological role of aSyn in melanocytic morphology and its so far unknown function in the pigment secretion in melanocytes.
LIM Kinases, Promising but Reluctant Therapeutic Targets: Chemistry and Preclinical Validation In Vivo
Authors: Berabez Rayan , Routier Sylvain , Bénédetti Hélène , Plé Karen , Vallée Béatrice
Published: July 2022

LIM Kinases are important actors in the regulation of cytoskeleton dynamics by controlling microtubule and actin filament turnover. The signaling pathways involving LIM kinases for actin filament remodeling are well established. They are downstream effectors of small G proteins of the Rho-GTPases family and have become promising targets for the treatment of several major diseases because of their position at the lower end of these signaling cascades. Cofilin, which depolymerizes actin filaments, is the best-known substrate of these enzymes. The phosphorylation of cofilin to its inactive form by LIM kinases avoids actin filament depolymerization. The balance between phosphorylated and non-phosphorylated cofilin is thought to play an important role in tumor cell invasion and metastasis. Since 2006, many small molecules have been developed for LIMK inhibition, and in this review article, we will discuss the structure–activity relationships of the few inhibitor families that have been tested in vivo on different pathological models.
Hepatoprotective Effect of Silver Nanoparticles at Two Different Particle Sizes: Comparative Study with and without Silymarin
Authors: Elfaky Mahmoud A. , Sirwi Alaa , Ismail Sameh H. , Awad Heba H. , Gad Sameh S.
Published: July 2022

Silver nanoparticles have been used for numerous therapeutic purposes because of their increased biodegradability and bioavailability, yet their toxicity remains questionable as they are known to interact easily with biological systems because of their small size. This study aimed to investigate and compare the effect of silver nanoparticles’ particle size in terms of their potential hazard, as well as their potential protective effect in an LPS-induced hepatotoxicity model. Liver slices were obtained from Sprague Dawley adult male rats, and the thickness of the slices was optimized to 150 μm. Under regulated physiological circumstances, freshly cut liver slices were divided into six different groups; GP1: normal, GP2: LPS (control), GP3: LPS + AgNpL (positive control), GP4: LPS + silymarin (standard treatment), GP5: LPS + AgNpS + silymarin (treatment I), GP6: LPS + AgNpL + silymarin (treatment II). After 24 h of incubation, the plates were gently removed, and the supernatant and tissue homogenate were all collected and then subjected to the following biochemical parameters: Cox2, NO, IL-6, and TNF-α. The LPS elicited marked hepatic tissue injury manifested by elevated cytokines and proinflammatory markers. Both small silver nanoparticles and large silver nanoparticles efficiently attenuated LPS hepatotoxicity, mainly via preserving the cytokines’ level and diminishing the inflammatory pathways. In conclusion, large silver nanoparticles exhibited effective hepatoprotective capabilities over small silver nanoparticles.
Association of Single Nucleotide Polymorphisms from Angiogenesis-Related Genes, ANGPT2, TLR2 and TLR9, with Spontaneous Preterm Labor
Authors: Wujcicka Wioletta Izabela , Kacerovsky Marian , Krygier Adrian , Krekora Michał , Kaczmarek Piotr , Grzesiak Mariusz
Published: July 2022

In this study, we hypothesized that the changes localized at angiopoietin-2 (ANGPT2), granulocyte-macrophage colony-stimulating factor (CSF2), fms-related tyrosine kinase 1 (FLT1) and toll-like receptor (TLR) 2, TLR6 and TLR9 genes were associated with spontaneous preterm labor (PTL), as well as with possible genetic alterations on PTL-related coagulation. This case-control genetic association study aimed to identify single nucleotide polymorphisms (SNPs) for the aforementioned genes, which are correlated with genetic risk or protection against PTL in Polish women. The study was conducted in 320 patients treated between 2016 and 2020, including 160 women with PTL and 160 term controls in labor. We found that ANGPT2 rs3020221 AA homozygotes were significantly less common in PTL cases than in controls, especially after adjusting for activated partial thromboplastin time (APTT) and platelet (PLT) parameters. TC heterozygotes for TLR2 rs3804099 were associated with PTL after correcting for anemia, vaginal bleeding, and history of threatened miscarriage or PTL. TC and CC genotypes in TLR9 rs187084 were significantly less common in women with PTL, compared to the controls, after adjusting for bleeding and gestational diabetes. For the first time, it was shown that three polymorphisms—ANGPT2 rs3020221, TLR2 rs3804099 and TLR9 rs187084 —were significantly associated with PTL, adjusted by pregnancy development influencing factors.
Comparison of Self-Assembled Monolayers on SiO2 and Porous SiOCH Dielectrics by Decyltrimethoxysilane Vapor Treatment
Authors: Cheng Yi-Lung , Peng Wei-Fan , Lee Chih-Yen , Chen Giin-Shan , Fang Jau-Shiung
Published: July 2022

Self-assembled monolayers (SAMs) are emerging as materials that are candidates of barriers used in back-end-of–line interconnects of integrated circuits for future generations. In this study, SAMs were formed on the SiO2 and porous SiOCH (p-SiOCH) films by using decyltrimethoxysilane (DTMOS) precursor in vapor phase at a temperature of 100 °C. The effects of the formation of SAMs at the surfaces of SiO2 and p-SiOCH films on the electrical characteristics were characterized and compared. With O2 plasma irradiation, SAMs could successfully form on both SiO2 and p-SiOCH films, thereby enhancing the adhesion and dielectric breakdown field. In the p-SiOCH films, SAMs sealed the surface pores and had higher coverage, promoting the effectiveness of the Cu barrier. In the Cu/porous low-k integrated interconnects for advanced technological nodes, therefore, SAMs are promising emerging materials acting as a barrier and adhesive. On the other hand, for SiO2 films, SAMs weakened the barrier; however, they can act as an interfacial adhesion enhancer.
A Novel Approach for Wind Turbine Blade Erosion Characterization: An Investigation Using Surface Gloss Measurement
Authors: Leishman Grant , Nash David , Yang Liu , Dyer Kirsten
Published: July 2022

Wind turbine blade erosion is typically assessed in situ using visual inspection, which is a rudimentary qualitative assessment of the condition of the blade coating system. On coated test specimens in laboratory test conditions, mass loss can provide a better understanding of the stage of erosion, but cannot be extended to real world applications. In this work, by using analysis of photographs, microscopy images, mass data, and gloss data together, it was found that gloss measurements can effectively quantify changes in coating microstructure as a result of rain erosion. This was achieved by correlating and comparing mass loss measurements over time with surface gloss and verifying the erosion stages with photographs and microscopy images. As such, gloss was shown to represent the erosion stages with greater accuracy than the current industry methods. This novel technique has been shown to identify the incubation period, that is the onset of erosion damage, by detecting microstructure changes which are not visible to the naked eye, nor is determinable by mass loss. The quantitative output from the gloss methodology thus allows wind turbine owners and operators to assess, manage, and plan more efficiently for costly erosion repairs and future inspections. The system is presently being used in a laboratory setting, though it has the potential to be combined with drones or climber robots to be remotely used within the wind farm.
Challenges and Opportunities for the Blue Perovskite Quantum Dot Light-Emitting Diodes
Authors: Weng Shuchen , Yu Guicheng , Zhou Chao , Lin Fang , Han Yonglei , Wang Hao , Huang Xiaoxi , Liu Xiaoyuan , Hu Hanlin , Liu Wei , Wang Yongfei , Lin Haoran
Published: July 2022

Perovskite quantum dots (PQDs), as the promising materials for the blue light-emitting diodes (LEDs), own huge advantages as ultra-high color purity, flexibility and whole-spectrum tunability. Through dimensional and compositional engineering, PQD-LEDs have shown superiority in deep-blue light emission. However, compared with the fast development of red and green PeLEDs, the electroluminescent performance of PQD-LEDs has faced more obstacles. In this review, we aim to explore and state the uniqueness and the possible solutions for the bottleneck problems of the PQD-LEDs.
How to Recognize the Universal Aspects of Mott Criticality?
Authors: Tan Yuting , Dobrosavljević Vladimir , Rademaker Louk
Published: July 2022

In this paper we critically discuss several examples of two-dimensional electronic systems displaying interaction-driven metal-insulator transitions of the Mott (or Wigner–Mott) type, including dilute two-dimension electron gases (2DEG) in semiconductors, Mott organic materials, as well as the recently discovered transition-metal dichalcogenide (TMD) moiré bilayers. Remarkably similar behavior is found in all these systems, which is starting to paint a robust picture of Mott criticality. Most notable, on the metallic side a resistivity maximum is observed whose temperature scale vanishes at the transition. We compare the available experimental data on these systems to three existing theoretical scenarios: spinon theory, Dynamical Mean Field Theory (DMFT) and percolation theory. We show that the DMFT and percolation pictures for Mott criticality can be distinguished by studying the origins of the resistivity maxima using an analysis of the dielectric response.
Population Genetic Structure of Endemic Fish Species Facilitating Their Survival in Changing Environments—A Case Study on the Genus Telestes in Croatia
Authors: Buj Ivana , Marčić Zoran , Flauder Elena , Šanda Radek , Vukić Jasna
Published: July 2022

The genus Telestes primarily comprises freshwater fish distributed mostly in the Mediterranean area. Recent investigation of the evolutionary history of this genus revealed that it originated in southern Europe, where the most ancient Telestes species are still present. The isolation of rivers in the karstic region facilitated allopatric speciation, resulting in a high number of Telestes species and a great portion of endemic species in freshwater systems of Croatia and Bosnia and Herzegovina. Most of the endemic Telestes species have very small distribution areas, inhabiting a single river or a few water bodies in a single karstic field, making them extremely vulnerable to anthropogenic changes. In order to contribute to practical conservation of the endemic Telestes species through the design of conservational measures that are likely to be the most effective in ensuring the future viability and undisturbed evolutionary course of those species, we have investigated their population genetic structure and estimated their viabilities. Population viability analyses were carried out based on the current state of populations and their habitats, as well as recognized threats. Several scenarios also included potential threats. Our results show that invasive species pose the biggest threat to the future survival of the endemic Telestes species. Contrary to previous opinions that a reduced genetic diversity is characteristic for small populations, high intraspecific genetic diversity was revealed inside most of the investigated species, which might enable most of the populations to cope with future changes and mitigate negative effects.
DNA Barcoding and Distribution of Gastropods and Malacostracans in the Lower Danube Region
Authors: Menabit Selma , Begun Tatiana , Teacă Adrian , Mureşan Mihaela , Lavin Paris , Purcarea Cristina
Published: July 2022

This survey reports the spatial distribution of gastropods belonging to Caenogastropoda, Architaenioglossa, Littorinimorpha, Cycloneritida and Hygrophila orders, and malacostracans from Amphipoda and Mysida orders in the lower sector of the Danube River, Romania, using DNA barcoding based on the cytochrome C oxidase I (COI) gene sequence. Sampling was performed for eight locations of Danube Delta branches and Bechet area during three consecutive years (2019–2021). Molecular identification of sixteen gastropods and twelve crustacean individuals was confirmed to the species level, providing the first molecular identification of gastropods from the Lower Danube sector. Phylogenetic analysis showed that species of gastropods and crustaceans clustered in monophyletic groups. Among gastropods, Microcolpia daudebartii acicularis, Viviparus viviparus, Bithynia tentaculata, Physa fontinalis, Ampullaceana lagotis and Planorbarius corneus were identified in Chilia and Sulina branches; and the Bechet area was populated by Holandriana holandrii, Theodoxus transversalis and Gyraulus parvus. The amphipods and mysids were present along the three main Danube branches. The calculated density of these species revealed an abundant community of crustacean Chelicorophium robustum on Sulina branch, and Dikerogammarus haemobaphes and D. villosus in extended areas of the Danube Delta. The presence of these invertebrates along Danube River was reported in relation to the sediment type and water depth.
A Hepatogastrophrenic Trunk, Celiacomesenteric Trunk, and a Middle Mesenteric Artery in a 68-Year-Old White Male Donor
Authors: Sheridan Ariana , Reynolds Elizabeth , Maynes Elizabeth , Wind Gary , Leighton Maria Ximena , Granite Guinevere
Published: July 2022

A detailed understanding of the enteric vascular supply is of great importance for pre-operative planning. In the case of this 68-year-old white male donor, the following variations were observed: a hepatogastrophrenic trunk, a celiacomesenteric trunk, and a middle mesenteric artery. Literature review was conducted to understand the frequency and clinical significance of these variations.