bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights into the Clinical Implications of Yes-Associated Protein in Lung Cancer: Roles in Drug Resistance, Tumor Immunity, Autophagy, and Organoid Development
Authors: Yoo Geon , Park Dongil , Kim Yoonjoo , Chung Chaeuk
Published: June 2021

Despite significant innovations in lung cancer treatment, such as targeted therapy and immunotherapy, lung cancer is still the principal cause of cancer-associated death. Novel strategies to overcome drug resistance and inhibit metastasis in cancer are urgently needed. The Hippo pathway and its effector, Yes-associated protein (YAP), play crucial roles in lung development and alveolar differentiation. YAP is known to mediate mechanotransduction, an important process in lung homeostasis and fibrosis. In lung cancer, YAP promotes metastasis and confers resistance against chemotherapeutic drugs and targeted agents. Recent studies revealed that YAP directly controls the expression of programmed death-ligand 1 (PD-L1) and modulates the tumor microenvironment (TME). YAP not only has a profound relationship with autophagy in lung cancer but also controls alveolar differentiation, and is responsible for tubular structure formation in lung organoids. In this review, we discuss the various roles and clinical implications of YAP in lung cancer and propose that targeting YAP can be a promising strategy for treating lung cancer.
Targeted Therapies and Immune Checkpoint Inhibitors in Primary CNS Lymphoma
Authors: Wirsching Hans-Georg , Weller Michael , Balabanov Stefan , Roth Patrick
Published: June 2021

This review article outlines the current development of emerging treatment strategies for primary central nervous system lymphoma, a rare brain tumor with, thus far, limited therapeutic options. Small molecule targeted tyrosine kinase inhibitors, immunomodulatory agents, and immune checkpoint inhibitors will be discussed. The mechanisms of action, results of completed clinical studies, ongoing clinical trials, and future perspectives are summarized. Among the most promising clinical developments in the field of CNS lymphomas is ibrutinib, an inhibitor of Bruton’s tyrosine kinase, which relays activation of nuclear factor kappa B upon integration of constitutive B cell receptor and Toll-like receptor signals. Down-stream of nuclear factor kappa B, the thalidomide analogs lenalidomide and pomalidomide exert immunomodulatory functions and are currently explored against CNS lymphomas. Finally, immune checkpoint inhibitors, such as drugs targeting the PD-1 pathway, may become novel therapeutic options to unleash anti-tumor immunity in patients with primary CNS lymphoma.
Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors
Authors: LaPlante Gabriel , Zhang Wei
Published: June 2021

The ubiquitin-proteasome system (UPS) is a critical regulator of cellular protein levels and activity. It is, therefore, not surprising that its dysregulation is implicated in numerous human diseases, including many types of cancer. Moreover, since cancer cells exhibit increased rates of protein turnover, their heightened dependence on the UPS makes it an attractive target for inhibition via targeted therapeutics. Indeed, the clinical application of proteasome inhibitors in treatment of multiple myeloma has been very successful, stimulating the development of small-molecule inhibitors targeting other UPS components. On the other hand, while the discovery of potent and selective chemical compounds can be both challenging and time consuming, the area of targeted protein degradation through utilization of the UPS machinery has seen promising developments in recent years. The repertoire of proteolysis-targeting chimeras (PROTACs), which employ E3 ligases for the degradation of cancer-related proteins via the proteasome, continues to grow. In this review, we will provide a thorough overview of small-molecule UPS inhibitors and highlight advancements in the development of targeted protein degradation strategies for cancer therapeutics.
Are Borrmann’s Types of Advanced Gastric Cancer Distinct Clinicopathological and Molecular Entities? A Western Study
Authors: Díaz del Arco Cristina , Ortega Medina Luis , Estrada Muñoz Lourdes , Molina Roldán Elena , Cerón Nieto M. Ángeles , García Gómez de las Heras Soledad , Fernández Aceñero M. Jesús
Published: June 2021

Most studies on the clinicopathological impact of Borrmann classification for gastric cancer (GC) have been performed in Asian patients with type IV tumors, and immunohistochemical features of Borrmann types have scarcely been analyzed. We assessed the clinicopathological, molecular features and prognostic value of Borrmann types in all patients with advanced GC resected in a Western institution (n = 260). We observed a significant relationship between Borrmann types and age, systemic symptoms, tumor size, Laurén subtype, presence of signet-ring cells, infiltrative growth, high grade, tumor necrosis, HERCEPTEST positivity, microsatellite instability (MSI) and molecular subtypes. Polypoid GC showed systemic symptoms, intestinal-type histology, low grade, expansive growth and HERCEPTEST positivity. Fungating GC occurred in symptomatic older patients. It presented intestinal-type histology, infiltrative growth and necrosis. Ulcerated GC showed smaller size, intestinal-type histology, high grade and infiltrative growth. Most polypoid and ulcerated tumors were stable-p53-not overexpressed or microsatellite unstable. Flat lesions were high-grade diffuse tumors with no MSI, and occurred in younger and less symptomatic patients. No association was found between Borrmann classification and prognosis. According to our results, Borrmann types may represent distinct clinicopathological and biological entities. Further research should be conducted to confirm the role of Borrmann classification in the stratification of patients with advanced GC.
Hematopoietic Stem Cell Transplantation-Associated Neurological Complications and Their Brain MR Imaging Findings in a Pediatric Population
Authors: Shin Hyewon , Yum Mi-Sun , Kim Min-Jee , Suh Jin Kyung , Im Ho Joon , Kim Hyery , Koh Kyung-Nam , Ko Tae-Sung
Published: June 2021

Purpose: To determine the prognostic indicators for hematopoietic stem cell transplantation (HSCT)-associated neurological complications, the clinical characteristics and brain magnetic resonance imaging (MRI) lesions in pediatric HSCT recipients were reviewed. Methods: This retrospective study included 51 patients who had underwent a brain MRI due to newly developed neurological symptoms or infection signs during chemotherapy or HSCT. We reviewed the demographics, received treatments, treatment-related morbidities, laboratory findings and brain MRI findings, which were compared between good and poor neurologic outcome groups. Results: Thirty-seven patients (72.5%) fully recovered from the neurologic deficits and fourteen (27.5%) persisted or aggravated. The children with an underlying malignant disease had significantly poorer neurological outcomes (p = 0.015). The neurologic complications associated with infection were more frequent in the poor outcome group (p = 0.038). In the neuroimaging findings, the extent of the white matter lesions was significantly higher in the poor outcome group, as was that of abnormal enhancement, ventriculomegaly, cortical change, deep gray matter abnormalities and cerebellar abnormalities. Conclusion: Most children with neurologic complications and neuroimaging abnormalities during HSCT had recovered. However, children with neurologic complications associated with infectious causes, malignant disease or severe brain MRI abnormalities should be more carefully monitored during HSCT.
B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer
Authors: Pylaeva Ekaterina , Ozel Irem , Squire Anthony , Spyra Ilona , Wallner Charlotte , Korek Magdalena , Korschunow Georg , Domnich Maksim , Siakaeva Elena , Goetz Moritz , Bankfalvi Agnes , Lang Stephan , Kansy Benjamin , Jablonska Jadwiga
Published: June 2021

The role of neutrophils during cancer formation and elimination is diverse. Here, for the first time, we investigate neutrophil helper cells (NBH), their influence on B cell activity in the regional lymph nodes (RLN) of head-and-neck cancer patients and the effect of this neutrophil/B cell interaction on patient prognosis. Circulating and RLN neutrophils of patients with stage I–IV head-and-neck squamous cell carcinoma were investigated with flow cytometry and qPCR. In addition, neutrophil/B cell co-localization in RLNs was evaluated using immunohistochemistry. B cell proliferation was assessed and correlated with the distance to neutrophils. Patient survival was evaluated. Neutrophils with the helper cell phenotype were identified in the RLN of HNC patients. B cells in close proximity to such NBH showed significantly higher proliferation rates, together with elevated activation-induced cytidine deaminase (AID) expression. Notably, patient survival was significantly higher in individuals with high NBH frequencies in the B follicles of RLNs. Neutrophils in RLN can support T cell-independent activation of the adaptive immune system through B cell stimulation, capturing helper cell phenotype character. The presence of such helper neutrophils in the RLNs of HNC patients positively correlates with patient prognosis.
Renal Safety of [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function
Authors: Rosar Florian , Kochems Niklas , Bartholomä Mark , Maus Stephan , Stemler Tobias , Linxweiler Johannes , Khreish Fadi , Ezziddin Samer
Published: June 2021

Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, patients with significantly impaired baseline kidney function before initiation of therapy were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [177Lu]Lu-PSMA-617. Methods: Twenty-two mCRPC patients with impaired renal function (glomerular filtration rate (GFR) ≤ 60 mL/min) who received more than two cycles of [177Lu]Lu-PSMA-617 RLT (median 5 cycles and median 6-week time interval between consecutive cycles) were analyzed in this study. Patients were treated within a prospective patient registry (REALITY Study, NCT04833517). Cumulative administered activities ranged from 17.1 to 85.6 GBq with a median activity of 6.5 GBq per cycle. Renal function was closely monitored during and after PSMA-RLT. Results: Mean pre-treatment GFR was 45.0 ± 10.7 mL/min. After two (22/22 patients), four (20/22 patients), and six cycles (10/22 patients) of RLT, a significant increase of GFR was noted (each p < 0.05). End-of-treatment GFR (54.1 ± 16.7 mL/min) was significantly higher than baseline GFR (p = 0.016). Only one patient experienced deterioration of renal function (change of CTCAE grade 2 to 3). The remaining patients showed no significant reduction of GFR, including follow-up assessments (6, 9, and 12 months), and even showed improved (10/22 patients) or unchanged (11/22 patients) CTCAE-based renal impairment grades during and after the end of PSMA-RLT. No significant correlation between the change in GFR and per-cycle (p = 0.605) or cumulative (p = 0.132) administered activities were found. Conclusions: As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [177Lu]Lu-PSMA-617 RLT may be overestimated and not of clinical priority in the setting of palliative treatment in mCRPC. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment.
Distinct Characteristics and Clinical Outcomes to Predict the Emergence of MET Amplification in Patients with Non-Small Cell Lung Cancer Who Developed Resistance after Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Authors: Ahn Beung-Chul , Lee Ji Hyun , Kim Min Hwan , Pyo Kyoung-Ho , Lee Choong-kun , Lim Sun Min , Kim Hye Ryun , Cho Byoung Chul , Hong Min Hee
Published: June 2021

Objectives: Patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) ultimately acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) during treatment. In 5–22% of these patients, resistance is mediated by aberrant mesenchymal epithelial transition factor (MET) gene amplification. Here, we evaluated the emergence of MET amplification after EGFR-TKI treatment failure based on clinical parameters. Materials and Methods: We retrospectively analyzed 186 patients with advanced EGFR-mutant NSCLC for MET amplification status by in situ hybridization (ISH) assay after EGFR-TKI failure. We collected information including baseline patient characteristics, metastatic locations and generation, line, and progression-free survival (PFS) of EGFR-TKI used before MET evaluation. Multivariate logistic regression analysis was conducted to evaluate associations between MET amplification status and clinical variables. Results: Regarding baseline EGFR mutations, exon 19 deletion was predominant (57.5%), followed by L858R mutation (37.1%). The proportions of MET ISH assays performed after first/second-generation and third-generation TKI failure were 66.7% and 33.1%, respectively. The median PFS for the most recent EGFR-TKI treatment was shorter in MET amplification-positive patients than in MET amplification-negative patients (median PFS 7.0 vs. 10.4 months, p = 0.004). Multivariate logistic regression demonstrated that a history of smoking, short PFS on the most recent TKI, and less intracranial progression were associated with a high probability of MET amplification (all p < 0.05). Conclusions: Our results demonstrated the distinct clinical characteristics of patients with MET amplification-positive NSCLC after EGFR-TKI therapy. Our clinical prediction can aid physicians in selecting patients eligible for MET amplification screening and therapeutic targeting.
Gender-Specific Efficacy Revealed by Head-to-Head Comparison of Pasireotide and Octreotide in a Representative In Vivo Model of Nonfunctioning Pituitary Tumors
Authors: Gulde Sebastian , Wiedemann Tobias , Schillmaier Mathias , Valença Isabel , Lupp Amelie , Steiger Katja , Yen Hsi-Yu , Bäuerle Stephen , Notni Johannes , Luque Raul , Schmid Herbert , Schulz Stefan , Ankerst Donna P. , Schilling Franz , Pellegata Natalia S.
Published: June 2021

Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail against NFPTs. Thus, identifying effective therapies is clinically relevant. As NFPTs express SSTR3 at high levels, pasireotide, a multireceptor-targeted SSA, might be beneficial. Here we evaluated pasireotide in the only representative model of spontaneous NFPTs (MENX rats) in vivo. Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. While tumors in placebo-treated rats increased in volume over time, PTs in drug-treated rats displayed significant growth suppression, and occasional tumor shrinkage. Pasireotide elicited stronger growth inhibition. Radiological responses correlated with tumors’ proliferation rates. Both SSAs, but especially pasireotide, were more effective in female vs. male rats. Basal Sstr3 expression was significantly higher in the former group. It is noteworthy that female human NFPTs patients also have a trend towards higher SSTR3 expression. Altogether, our studies provide the rationale for testing pasireotide in patients with residual/recurrent NFPTs. If confirmed, the sex-related SSTR3 expression might be used as criteria to stratify NFPTs patients for treatment with pasireotide.
Pentose Phosphate Pathway Reactions in Photosynthesizing Cells
Authors: Sharkey Thomas D.
Published: June 2021

The pentose phosphate pathway (PPP) is divided into an oxidative branch that makes pentose phosphates and a non-oxidative branch that consumes pentose phosphates, though the non-oxidative branch is considered reversible. A modified version of the non-oxidative branch is a critical component of the Calvin–Benson cycle that converts CO2 into sugar. The reaction sequence in the Calvin–Benson cycle is from triose phosphates to pentose phosphates, the opposite of the typical direction of the non-oxidative PPP. The photosynthetic direction is favored by replacing the transaldolase step of the normal non-oxidative PPP with a second aldolase reaction plus sedoheptulose-1,7-bisphosphatase. This can be considered an anabolic version of the non-oxidative PPP and is found in a few situations other than photosynthesis. In addition to the strong association of the non-oxidative PPP with photosynthesis metabolism, there is recent evidence that the oxidative PPP reactions are also important in photosynthesizing cells. These reactions can form a shunt around the non-oxidative PPP section of the Calvin–Benson cycle, consuming three ATP per glucose 6-phosphate consumed. A constitutive operation of this shunt occurs in the cytosol and gives rise to an unusual labeling pattern of photosynthetic metabolites while an inducible shunt in the stroma may occur in response to stress.
Eritoran Attenuates Hepatic Inflammation and Fibrosis in Mice with Chronic Liver Injury
Authors: Hsieh Yun-Cheng , Lee Kuei-Chuan , Wu Pei-Shan , Huo Teh-Ia , Huang Yi-Hsiang , Hou Ming-Chih , Lin Han-Chieh
Published: June 2021

Toll-like receptor 4 (TLR4) signaling plays a key role in liver inflammation and fibrosis. The therapeutic effects of eritoran, a TLR4 antagonist, in mice with chronic liver injury remained unclear. C57BL/6 mice were fed a fast-food diet (FFD) or treated with carbon tetrachloride (CCl4) to induce chronic liver injury. Eritoran (10 mg/kg) or a vehicle was randomly intraperitoneally administered to the FFD-fed mice and the CCl4-injured mice. Primary mouse liver cells were cultured with lipopolysaccharide (LPS) or eritoran. In both FFD and CCl4 mouse models, eritoran significantly reduced serum ALT levels and decreased hepatic inflammatory cell infiltration without altering hepatic steatosis. Additionally, eritoran attenuated liver fibrosis by decreasing hepatic stellate cells (HSCs) activation and the abundance of α-smooth muscle actin and transforming growth factor-β1. Hepatic TLR4 downstream signaling including MyD88 expression, NF-κB p65 nuclear translocation, p38 and JNK phosphorylation were successfully inhibited by eritoran. In the in vitro study, LPS-induced nuclear translocation of NF-κB in primary HSCs and Kupffer cells was significantly suppressed by eritoran. In conclusion, eritoran attenuated hepatic inflammation and fibrosis by inhibition of the TLR4 signaling pathway in mice with chronic liver injury. Eritoran may serve as a potential drug for chronic liver disease.
Scaling of Droplet Breakup in High-Pressure Homogenizer Orifices. Part II: Visualization of the Turbulent Droplet Breakup
Authors: Mutsch Benedikt , Preiss Felix Johannes , Dagenbach Teresa , Karbstein Heike Petra , Kähler Christian J.
Published: June 2021

Emulsion formation is of great interest in the chemical and food industry and droplet breakup is the key process. Droplet breakup in a quiet or laminar flow is well understood, however, actual in-dustrial processes are always in the turbulent flow regime, leading to more complex droplet breakup phenomena. Since high resolution optical measurements on microscopic scales are extremely dif-ficult to perform, many aspects of the turbulent droplet breakup are physically unclear. To over-come this problem, scaled experimental setups (with scaling factors of 5 and 50) are used in con-junction with an original scale setup for reference. In addition to the geometric scaling, other non-dimensional numbers such as the Reynolds number, the viscosity ratio and the density ratio were kept constant. The scaling allows observation of the phenomena on macroscopic scales, whereby the objective is to show that the scaling approach makes it possible to directly transfer the findings from the macro- to the micro-/original scale. In this paper, which follows Part I where the flow fields were compared and found to be similar, it is shown by breakup visualizations that the turbulent droplet breakup process is similar on all scales. This makes it possible to transfer the results of detailed parameter variations investigated on the macro scale to the micro scale. The evaluation and analysis of the results imply that the droplet breakup is triggered and strongly influenced by the intensity and scales of the turbulent flow motion.
Identification of the Wear Process of a Silver-Plating Layer by Dual Acoustic Emission Sensing
Authors: Hase Alan , Sato Yousuke , Shinohara Keisuke , Arai Kentaro
Published: June 2021

A method based on acoustic emission (AE) sensing in which two AE sensors are used to measure the tribological characteristics of two interacting friction materials simultaneously in real time was assessed for the in situ measurement and evaluation of the wear process of silver plating. AE sensors were attached to a silver-plated pin and a silver-plated plate, and the two AE signals were measured simultaneously on a pin-on-plate-type reciprocating sliding tester. The resulting changes in the AE signal could be classified into three phases. Surface observations and energy-dispersive X-ray spectroscopy analyses showed that the wear of the silver-plating layer progressed in Phase I, the nickel intermediate layer was exposed and wear of the nickel progressed in Phase II, and the contact electrical resistance increased and the copper substrate was exposed in Phase III. In summary, the wear process of a silver-plating layer, which cannot be identified from the changes in the frictional resistance or the contact electric resistance, can be detected from changes in the dual AE signals. Furthermore, changes in the wear state of both the pin and plate specimens can be identified from differences in the amplitudes of the AE signals and the timing of their detection.
Effect of Chitosan Composite Coatings with Salicylic Acid and Titanium Dioxide Nanoparticles on the Storage Quality of Blackcurrant Berries
Authors: Xing Yage , Yue Tianyi , Wu Yu , Xu Qinglian , Guo Xunlian , Wang Xiaomin , Yang Shuang , Xu Lin , Yang Ping
Published: June 2021

The use of chitosan and chitosan composite coatings for the preservation of fruits and vegetables during storage is attracting increasing attention. In this study, a chitosan-based edible coating, as well as a second chitosan-based edible coating containing salicylic acid (CTS + SA), a third containing nanosized titanium dioxide particles (CTS + TiO2), and a fourth containing a combination of these two (CTS + SA + TiO2) were evaluated in terms of their effects on the postharvest quality of blackcurrant fruit during storage at 4 °C. The results showed that compared with the other three treatment groups, the blackcurrants treated with CTS + SA + TiO2 underwent the smallest changes in weight loss, total soluble solids, titratable acidity, vitamin C, and total anthocyanin content, and retained the highest total flavonoid content. This combined treatment significantly inhibited polyphenol oxidase activity during storage, and the CTS + SA + TiO2 samples also displayed the lowest malondialdehyde content. These results, thus, indicate that the CTS + SA + TiO2 composite coating could maintain the nutrient composition of blackcurrants, thereby playing a significant role in preserving the quality of this fruit at 4 °C.
The Effect of Nickel Contents on the Microstructure Evolution and Toughness of 800 MPa Grade Low Carbon Bainite Deposited Metal
Authors: Liu Jingwu , Sun Jian , Wei Shitong , Lu Shanping
Published: June 2021

In this work, three deposited metals with different nickel (Ni) contents were produced by active gas metal arc welding (GMAW) in order to explore the influence of Ni on the microstructure evolution and toughness of 800 MPa grade low carbon bainite deposited metal. The results showed that microstructure of the deposited metals mainly consisted of lath bainite, lath martensite, coalesced bainite (CB), and retained austenite (RA), and that the toughness was closely related to two factors: CB and RA. RA in deposited metal could improve the toughness, while the CB would deteriorate the toughness of deposited metal. As the Ni content increased, a large amount of CB was generated in the deposited metals. The RA content increased from 1.5% to 5.7% with the content of Ni increasing from 5.5% to 6.5%. However, the RA content did not increase when the Ni content increased from 6.5% to 7.5%. Additionally, the smallest control unit of toughness in 800 MPa grade low carbon bainite deposited metals is the Bain Packet (BP) from the perspective of crystallography characteristics. This work provided a reference for the chemical composition design of 800 MPa grade steel welding consumables and showed that the toughness of the deposited metal could be improved effectively by increasing the RA content while suppressing the formation of CB.
Quasi-Continuous Production and Separation of Lysozyme Crystals on an Integrated Laboratory Plant
Authors: Dobler Timo , Radel Benjamin , Gleiss Marco , Nirschl Hermann
Published: June 2021

Vacuum crystallization with subsequent solid–liquid separation is a suitable method to produce and separate the temperature-sensitive protein lysozyme. The conventional process is performed batch-wise and on different devices, which in turn leads to disadvantages in terms of energy efficiency, contamination risk and process control. This publication therefore focuses on the application of the previously multistage process to a quasi-continuous, integrated single plant. The transfer occurs successively and starts with the substitution of the batch vessel by a process chamber. Afterwards, the filtration scale is increased and the formerly deployed membrane is replaced by an industrial filter cloth. Based on the results of these experiments, the complete process chain is successfully transferred to an integrated laboratory plant.
Multi-View 2D/3D Switchable Display with Cylindrical Liquid Crystal Lens Array
Authors: Chu Fan , Wang Di , Liu Chao , Li Lei , Wang Qiong-Hua
Published: June 2021

We propose a multi-view 2D/3D switchable display by using cylindrical liquid crystal (LC) lens array with a low operating voltage and fast response time. The cylindrical LC lens array is composed of three parts: the LC layer, a top-plane indium tin oxide (ITO) electrode, and bottom periodic strip ITO electrodes. In the voltage-off state, the cylindrical LC lens array is equivalent to a transparent glass substrate and the viewers can see a clear 2D image. In the 3D mode, the cylindrical LC lens array can be used as a cylindrical lens array under a suitable operating voltage. As a result, the 2D and 3D images can be switched according to the state of the cylindrical LC lens array. The experimental result shows that the 2D/3D switchable display with the cylindrical LC lens array has a wider viewing angle, has no moiré pattern, and is much thinner compared to the other 2D/3D switchable display devices.
Band-Gap Properties of Finite Locally Resonant Beam Suspended Periodically with Two-Degree-of-Freedom Force Type Resonators
Authors: Lv Hangyuan , Li Shangjie , Huang Xianzhen , Yu Zhongliang
Published: June 2021

The propagation properties of waves in finite Timoshenko locally resonant (LR) beams resting on forced vibrations and periodically attached two-degree-of-freedom force-type resonators are studied by the wave-based analysis approach. By calculating the motion equations of the beam, the transmission and reflection matrices of waves at the resonator attached point are first derived, and the forced vibration response of the finite periodic beam is deduced by the wave-based approach. Several examples are also analyzed by the finite element method to verify the high accuracy of the developed wave-based analysis approach. Numerical results show that wider low-frequency band-gaps exist in this type of LR beams. It was also found that the resonator masses and spring stiffnesses caused different effects on the band-gap properties of the combined LR beam. The desired band-gap widths of the LR beam can be tuned by adjusting the mass blocks and spring stiffness in the resonators based on the results.
Genetic Diversity of Ancient Camellia sinensis (L.) O.Kuntze in Sandu County of Guizhou Province in China
Authors: Zhao Yichen , Wang Runying , Liu Qing , Dong Xuan , Zhao De-Gang
Published: June 2021

The ancient tea plant germplasm is an important resource for breeding new tea plant varieties and has great economic value. However, due to man-made and natural disturbances, it has become endangered. In order to have a better management of the conserved tea plant germplasm, it is a requirement to understand the genetic and phenotypic diversity. The aim of this study was to evaluate the genetic and phenotypic diversity of 145 ancient tea plant germplasm resources from five populations in Sandu County of Guizhou province in China. To explore the population genetics of tea plant, we successfully identified 15 simple sequence repeat (SSR) markers, which were highly polymorphic. Additionally, we applied traditional phenotypic methods to evaluate the tea plant diversity. The results suggested that the genetic and phenotypic diversity were relatively high. A total of 96 alleles were identified, and the mean polymorphic information content (PIC) value was found to be 0.66. The analysis of molecular variance (AMOVA) showed that genetic variation within the populations was greater than among the populations. Overall, our results are the valuable baseline data in developing more efficient management and breeding plans for one of the most popular non-alcoholic beverage crops, the tea plant species.
Diversity of Macrophytes and Environmental Assessment of the Ljubljanica River (Slovenia)
Authors: Germ Mateja , Janež Vanja , Gaberščik Alenka , Zelnik Igor
Published: June 2021

The present research aimed to determine the diversity of macrophyte taxa in the Ljubljanica River and its relationship with environmental parameters. In each of the 19 river sections, the presence and abundance of plant taxa were recorded, and basic physical and chemical parameters were measured. Additionally, selected environmental parameters were assessed using a modified version of the Riparian, Channel and Environmental (RCE) method. We compared the obtained data set with survey data from the year 2004. In 2019, a total of 34 macrophyte taxa were recorded. The dominant taxa with the highest abundance were Sparganium emersum, Callitriche sp., and the invasive alien species Elodea canadensis. The species richness and diversity of macrophytes decreased with distance from the source, an increase in pH, and alterations of the riverbed structure due to interference in the riverine ecosystem in the lower part of the Ljubljanica River and its catchment. The comparison of 2004 and 2019 surveys revealed a decrease in the overall presence and abundance of P. natans and in the frequency of occurrence of the species Myriophyllum spicatum and an increase in the presence and abundance of the invasive alien species Elodea canadensis.
The Sliding Window and SHAP Theory—An Improved System with a Long Short-Term Memory Network Model for State of Charge Prediction in Electric Vehicle Application
Authors: Gu Xinyu , See KW , Wang Yunpeng , Zhao Liang , Pu Wenwen
Published: June 2021

The state of charge (SOC) prediction for an electric vehicle battery pack is critical to ensure the reliability, efficiency, and life of the battery pack. Various techniques and statistical systems have been proposed in the past to improve the prediction accuracy, reduce complexity, and increase adaptability. Machine learning techniques have been vigorously introduced in recent years, to be incorporated into the existing prediction algorithms, or as a stand-alone system, with a large amount of recorded past data to interpret the battery characteristics, and further predict for the present and future. This paper presents an overview of the machine learning techniques followed by a proposed pre-processing technique employed as the input to the long short-term memory network (LSTM) algorithm. The proposed pre-processing technique is based on the time-based sliding window algorithm (SW) and the Shapley additive explanation theory (SHAP). The proposed technique showed improvement in accuracy, adaptability, and reliability of SOC prediction when compared to other conventional machine learning models. All the data employed in this investigation were extracted from the actual driving cycle of five different electric vehicles driven by different drivers throughout a year. The computed prediction error, as compared to the original SOC data extracted from the vehicle, was within the range of less than 2%. The proposed enhanced technique also demonstrated the feasibility and robustness of the prediction results through the persistent computed output from a random selection of the data sets, consisting of different driving profiles and ambient conditions.
The Brown Seaweeds of Scotland, Their Importance and Applications
Authors: Al-Dulaimi Omar , Rateb Mostafa E. , Hursthouse Andrew S. , Thomson Gary , Yaseen Mohammed
Published: June 2021

More than 50% of the UK coastline is situated in Scotland under legislative jurisdiction; therefore, there is a great opportunity for regionally focused economic development by the rational use of sustainable marine bio-sources. We review the importance of seaweeds in general, and more specifically, wrack brown seaweeds which are washed from the sea and accumulated in the wrack zone and their economic impact. Rules and regulations governing the harvesting of seaweed, potential sites for harvesting, along with the status of industrial application are discussed. We describe extraction and separation methods of natural products from these seaweeds along with their phytochemical profiles. Many potential applications for these derivatives exist in agriculture, energy, nutrition, biomaterials, waste treatment (composting), pharmaceuticals, cosmetics and other applications. The chemical diversity of the natural compounds present in these seaweeds is an opportunity to further investigate a range of chemical scaffolds, evaluate their biological activities, and develop them for better pharmaceutical or biotechnological applications. The key message is the significant opportunity for the development of high value products from a seaweed processing industry in Scotland, based on a sustainable resource, and locally regulated.
Mechanical Mastication Reduces Fuel Structure and Modelled Fire Behaviour in Australian Shrub Encroached Ecosystems
Authors: Grant Madeleine A. , Duff Thomas J. , Penman Trent D. , Pickering Bianca J. , Cawson Jane G.
Published: June 2021

Shrub encroachment of grassland and woodland ecosystems can alter wildfire behaviour and threaten ecological values. Australian fire managers are using mechanical mastication to reduce the fire risk in encroached ecosystems but are yet to evaluate its effectiveness or ecological impact. We asked: (1) How does fuel load and structure change following mastication?; (2) Is mastication likely to affect wildfire rates of spread and flame heights?; and (3) What is the impact of mastication on flora species richness and diversity? At thirteen paired sites (masticated versus control; n = 26), located in Victoria, Australia, we measured fuel properties (structure, load and hazard) and floristic diversity (richness and Shannon’s H) in 400 mP2 plots. To quantify the effects of mastication, data were analysed using parametric and non-parametric paired sample techniques. Masticated sites were grouped into two categories, 0–2 and 3–4 years post treatment. Fire behaviour was predicted using the Dry Eucalypt Forest Fire Model. Mastication with follow-up herbicide reduced the density of taller shrubs, greater than 50 cm in height, for at least 4 years. The most recently masticated sites (0–2 years) had an almost 3-fold increase in dead fine fuel loads and an 11-fold increase in dead coarse fuel loads on the forest floor compared with the controls. Higher dead coarse fuel loads were still evident after 3–4 years. Changes to fuel properties produced a reduction in predicted flame heights from 22 m to 5–6 m under severe fire weather conditions, but no change in the predicted fire rate of spread. Reductions in flame height would be beneficial for wildfire suppression and could reduce the damage to property from wildfires. Mastication did not have a meaningful effect on native species diversity, but promoted the abundance of some exotic species.
Numerical Simulation of Self-Propelled Steady Jet Propulsion at Intermediate Reynolds Numbers: Effects of Orifice Size on Animal Jet Propulsion
Authors: Jiang Houshuo
Published: June 2021

Most marine jet-propelled animals have low swimming efficiencies and relatively small jet orifices. Motivated by this, the present computational fluid dynamics study simulates the flow for a jet-propelled axisymmetric body swimming steadily at intermediate Reynolds numbers of order 1–1000. Results show that swimming-imposed flow field, drag coefficients, swimming efficiencies, and performance index (a metric comparing swimming speeds sustained by differently sized orifices ejecting the same volume flow rate) all depend strongly on orifice size, and orifice size affects the configuration of oppositely signed body vorticity and jet vorticity, thereby affecting wake and efficiency. As orifice size decreases, efficiencies decrease considerably, while performance index increases substantially, suggesting that, for a given jet volume flow rate, a smaller orifice supports faster swimming than a larger one does, albeit at reduced efficiency. These results support the notion that most jet-propelled animals having relatively small jet orifices may be an adaptation to deal with the physical constraint of limited total volume of water available for jetting, while needing to compete for fast swimming. Finally, jet orifice size is discussed regarding the role of jet propulsion in jet-propelled animal ecology, particularly for salps that use two relatively large siphons to respectively draw in and expel water.
Detection of Peanut Allergen by Real-Time PCR: Looking for a Suitable Detection Marker as Affected by Processing
Authors: Sanchiz Africa , Sánchez-Enciso Paulina , Cuadrado Carmen , Linacero Rosario
Published: June 2021

Peanut (Arachis hypogaea) contains allergenic proteins, which make it harmful to the sensitised population. The presence of peanut in foods must be indicated on label, to prevent accidental consumption by allergic population. In this work, we use chloroplast markers for specific detection of peanut by real-time PCR (Polymerase Chain Reaction), in order to increase the assay sensitivity. Binary mixtures of raw and processed peanut flour in wheat were performed at concentrations ranging from 100,000 to 0.1 mg/kg. DNA isolation from peanut, mixtures, and other legumes was carried out following three protocols for obtaining genomic and chloroplast-enrich DNA. Quantity and quality of DNA were evaluated, obtaining better results for protocol 2. Specificity and sensitivity of the method has been assayed with specific primers for three chloroplast markers (mat k, rpl16, and trnH-psbA) and Ara h 6 peanut allergen-coding region was selected as nuclear low-copy target and TaqMan probes. Efficiency and linear correlation of calibration curves were within the adequate ranges. Mat k chloroplast marker yielded the most sensitive and efficient detection for peanut. Moreover, detection of mat K in binary mixtures of processed samples was possible for up to 10 mg/kg even after boiling, and autoclave 121 °C 15 min, with acceptable efficiency and linear correlation. Applicability of the method has been assayed in several commercial food products.
Effects of Bacillus Subtilis-Fermented White Sword Bean Extract on Adipogenesis and Lipolysis of 3T3-L1 Adipocytes
Authors: Choi Yujeong , Kim Da-Som , Lee Min-Chul , Park Seulgi , Lee Joo-Won , Om Ae-Son
Published: June 2021

To investigate the adipogenesis and lipolysis effects of the Bacillus subtilis-fermented white sword bean extract (FWSBE) on 3T3-L1 adipocytes, we treated 3T3-L1 preadipocytes before and after differentiation with FWSBE and measured triglyceride, free glycerol, mRNA, and protein levels. First, FWSBE reduced the cell viability of 3T3-L1 pre-adipocytes under 1000 µg/mL conditions. Triglyceride accumulation in 3T3-L1 pre-adipocytes was suppressed, and free glycerol content in mature 3T3-L1 adipocytes was increased in the FWSBE treatment groups, indicating that FWSBE has anti-obesity effects. Further, FWSBE suppressed adipogenesis in 3T3-L1 pre-adipocytes by lowering the protein levels of C/EBPα, PPARγ, and FAS and increasing the level of pACC and pAMPK. Additionally, FWSBE promoted lipolysis in mature 3T3-L1 adipocytes by increasing the transcription levels of Ppara, Acox, and Lcad and the protein levels of pHSL and ATGL. Thus, we suggest that FWSBE can be a potential dietary supplement because of its anti-obesity properties.
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome
Authors: Vasko Ashley , Drivas Theodore G. , Schrier Vergano Samantha A.
Published: June 2021

Coffin-Siris syndrome (CSS, MIM 135900) is a multi-system intellectual disability syndrome characterized by classic dysmorphic features, developmental delays, and organ system anomalies. Genes in the BRG1(BRM)-associated factors (BAF, Brahma associated factor) complex have been shown to be causative, including ARID1A, ARID1B, ARID2, DPF2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, and SOX4. In order to describe more robust genotype-phenotype correlations, we collected data from 208 individuals from the CSS/BAF complex registry with pathogenic variants in seven of these genes. Data were organized into cohorts by affected gene, comparing genotype groups across a number of binary and quantitative phenotypes. We determined that, while numerous phenotypes are seen in individuals with variants in the BAF complex, hypotonia, hypertrichosis, sparse scalp hair, and hypoplasia of the distal phalanx are still some of the most common features. It has been previously proposed that individuals with ARID-related variants are thought to have more learning and developmental struggles, and individuals with SMARC-related variants, while they also have developmental delay, tend to have more severe organ-related complications. SOX-related variants also have developmental differences and organ-related complications but are most associated with neurodevelopmental differences. While these generalizations still overall hold true, we have found that all individuals with BAF-related conditions are at risk of many aspects of the phenotype, and management and surveillance should be broad.
Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study
Authors: Vancheri Chiara , Morini Elena , Prandi Francesca Romana , Alkhoury Elie , Celotto Roberto , Romeo Francesco , Novelli Giuseppe , Amati Francesca
Published: June 2021

Primary prevention is crucial for coronary heart disease (CAD) and the identification of new reliable biomarkers might help risk stratification or predict adverse coronary events. Alternative splicing (AS) is a less investigated genetic factors implicated in CAD etiology. We performed an RNA-seq study on PBMCs from CAD patients and control subjects (CTR) and observed 113 differentially regulated AS events (24 up and 89 downregulated) in 86 genes. The RECK (Reversion-inducing-cysteine-rich protein with Kazal motifs) gene was further analyzed in a larger case study (24 CTR subjects, 72 CAD and 32 AMI patients) for its Splicing-Index FC (FC = −2.64; p = 0.0217), the AS event involving an exon (exon 18), and its role in vascular inflammation and remodeling. We observed a significant downregulation of Long RECK splice variant (containing exon 18) in PBMCs of AMI compared to CTR subjects (FC = −3.3; p < 0.005). Interestingly, the Short RECK splice variant (lacking exon 18) was under-expressed in AMI compared to both CTR (FC = −4.5; p < 0.0001) and CAD patients (FC = −4.2; p < 0.0001). A ROC curve, constructed combining Long and Short RECK expression data, shows an AUC = 0.81 (p < 0.001) to distinguish AMI from stable CAD patients. A significant negative correlation between Long RECK and triglycerides in CTR group and a positive correlation in the AMI group was found. The combined evaluation of Long and Short RECK expression levels is a potential genomic biomarker for the discrimination of AMI from CAD patients. Our results underline the relevance of deeper studies on the expression of these two splice variants to elucidate their functional role in CAD development and progression.
QTL Analysis of Stem Elongation and Flowering Time in Lettuce Using Genotyping-by-Sequencing
Authors: Lee O New , Fukushima Keita , Park Han Yong , Kawabata Saneyuki
Published: June 2021

Lettuce plants tend to undergo floral initiation by elongation of flower stalks (bolting) under high-temperature and long-day conditions, which is a serious problem for summer lettuce production. Our objective was to generate a high-density genetic map using SNPs obtained from genotyping-by-sequencing (GBS) analysis of F5 recombinant inbred lines (RILs) and to map QTLs involved in stem growth and flowering time in lettuce. A set of 127 intra-specific RIL mapping populations derived from a cross between two varieties, green and red leaf lettuce, were used to identify QTLs related to the number of days from sowing to bolting (DTB), to flowering of the first flower (DTF), to seed-setting of the first flower (DTS), and the total number of leaves (LN), plant height (PH), and total number of branches of main inflorescence (BN) for two consecutive years. Of the 15 QTLs detected, one that controls DTB, DTF, DTS, LN, and PH detected on LG 7, and another QTL that controls DTF, DTS, and PH detected on LG 1. Analysis of the genomic sequence corresponding to the QTL detected on LG 7 led to the identification of 22 putative candidate genes. A consistent QTL related to bolting and flowering time, and corresponding candidate genes has been reported. This study will be valuable in revealing the genetic basis of stem growth and flowering time in lettuce.