bluuebunny/crossref_metadata_2025 huggingface dataset:
LmjF.22.0810 from Leishmania major Modulates the Th2-Type Immune Response and Is Involved in Leishmaniasis Outcome
Authors: Vacas Andrés , Fernández-Rubio Celia , Larrea Esther , Peña-Guerrero José , Nguewa Paul A.
Published: October 2020

A novel serine/threonine protein kinase, LmjF.22.0810, was recently described in Leishmania major. After generating an L. major cell line overexpressing LmjF.22.0810 (named LmJ3OE), the ability of this novel protein to modulate the Th2-type immune response was analyzed. Our results suggest that the protein kinase LmjF.22.0810 might be involved in leishmaniasis outcomes. Indeed, our study outlined the LmJ3OE parasites infectivity in vitro and in vivo. Transgenic parasites displayed lower phagocytosis rates in vitro, and their promastigote forms exhibited lower expression levels of virulence factors compared to their counterparts in control parasites. In addition, LmJ3OE parasites developed significantly smaller footpad swelling in susceptible BALB/c mice. Hematoxylin–eosin staining allowed the observation of a lower inflammatory infiltrate in the footpad from LmJ3OE-infected mice compared to animals inoculated with control parasites. Gene expression of Th2-associated cytokines and effectors revealed a dramatically lower induction in interleukin (IL)-4, IL-10, and arginase 1 (ARG1) mRNA levels at the beginning of the swelling; no expression change was found in Th1-associated cytokines except for IL-12. Accordingly, such results were validated by immunohistochemistry studies, illustrating a weaker expression of ARG1 and a similar induction for inducible NO synthase (iNOS) in footpads from LmJ3OE-infected mice compared to control L. major infected animals. Furthermore, the parasite burden was lower in footpads from LmJ3OE-infected mice. Our analysis indicated that such significant smaller footpad swellings might be due to an impairment of the Th2 immune response that subsequently benefits Th1 prevalence. Altogether, these studies depict LmjF.22.0810 as a potential modulator of host immune responses to Leishmania. Finally, this promising target might be involved in the modulation of infection outcome.
Fast Deoxynivalenol Determination in Cereals Using a White Light Reflectance Spectroscopy Immunosensor
Authors: Anastasiadis Vasileios , Raptis Ioannis , Economou Anastasios , Kakabakos Sotirios , Petrou Panagiota
Published: October 2020

Deoxynivalenol (DON) is a mycotoxin produced by certain Fusarium species and found in a high percentage of wheat and maize grains cultured worldwide. Although not so toxic as other mycotoxins, it exhibits both chronic and acute toxicity, and therefore methods for its fast and accurate on-site determination are highly desirable. In the current work, we employ an optical immunosensor based on White Light Reflectance Spectroscopy (WLRS) for the fast and sensitive immunochemical label-free determination of DON in wheat and maize samples. The assay is completed in 12 min and has a quantification limit of 2.5 ng/mL in buffer corresponding to 125 μg/kg in whole grain which is lower than the maximum allowable concentrations set by the regulatory authorities for grains intended for human consumption. Several extraction protocols have been compared, and the highest recovery (>90%) was achieved employing distilled water. In addition, identical calibration curves were received in buffer and wheat/maize extraction matrix providing the ability to analyze the grain samples using calibrators in buffer. Recoveries of DON from spiked wheat and maize grain samples ranged from 92.0(±4.0) to 105(±4.0)%. The analytical performance of the WLRS immunosensor, combined with the short analysis time and instrument portability, supports its potential for on-site determinations.
Studying Individual Differences in Spatial Cognition Through Differential Item Functioning Analysis
Authors: Lopez Antonella , Caffò Alessandro O. , Tinella Luigi , Postma Albert , Bosco Andrea
Published: October 2020

Background: In the field of spatial cognition, the study of individual differences represents a typical research topic. Gender and age have been prominently investigated. A promising statistical technique used to identify the different responses to items in relation to different group memberships is the Differential Item Functioning Analysis (DIF). The aim of the present study was to investigate the DIF of the Landmark positioning on a Map (LPM) task, across age groups (young and elderly) and gender, in a sample of 400 healthy human participants. Methods: LPM is a hometown map completion test based on well-known and familiar landmarks used to assess allocentric mental representations. DIF was assessed on LPM items two times: on categorical (i.e., positions) and coordinate (i.e., distances) scores, separately. Results: When positions and distances were difficult to assess with respect to the intended reference point, the probability to endorse the items seemed to get worse for the elderly compared to the younger participants. Instead other features of landmarks (high pleasantness, restorativeness) seemed to improve the elderly performance. A gender-related improvement of probability to endorse distance estimation of some landmarks, favoring women, emerged, probably associated with their repeated experiences with those landmarks. Overall, the complexity of the task seemed to have a differential impact on young and elderly people while gender-oriented activities and places seemed to have a differential impact on men and women. Conclusions: For the first time DIF was applied to a spatial mental representation task, based on the schematic sketch maps of the participants. The application of DIF to the study of individual differences in spatial cognition should become a systematic routine to early detect differential items, improving knowledge, as well as experimental control, on individual differences.
The Prevalence of Different Types of Headache in Patients with Subjective Tinnitus and Its Influence on Tinnitus Parameters: A Prospective Clinical Study
Authors: Nowaczewska Magdalena , Wiciński Michał , Straburzyński Marcin , Kaźmierczak Wojciech
Published: October 2020

Both tinnitus and headache are very prevalent conditions in the general population, with bidirectional co-occurrence of them. A number of studies revealed a high prevalence of headache in tinnitus patients; however, most of them used self-reported symptoms, questionnaires, or health databases and were retrospective. The aim of this study was to evaluate the prevalence of different types of headache in a cohort of tinnitus patients and to assess the influence of headache on tinnitus parameters, focusing on appropriate headache and tinnitus diagnosis verified by clinical examination. This prospective study involved 286 patients diagnosed with subjective non-pulsating tinnitus. Patients’ clinical information was thoroughly assessed by the multidisciplinary team, including tinnitus characteristics and severity according to the Tinnitus Handicap Inventory (THI), loudness assessed by the Visual Analogue Scale (VAS), audiometry, type of headache diagnosed according to the third edition of the International Classification of Headache Disorders, severity of headache assessed by the Numeric Rating Scale (NRS), and impact of headache using the Headache Impact Test (HIT). In total, 141 (49.3%) tinnitus patients were diagnosed with headache, most of them with tension-type headache or migraine. They were significantly younger; mostly women; had bilateral tinnitus, vertigo, and depression more frequently; and had hearing loss less frequently as compared with the non-headache group. In total, 82 (58.16%) patients had the same localization of tinnitus and headache. Younger age, female gender, higher tinnitus burden measured by THI, and coexistence of hearing loss were independent variables connected with the occurrence of headache in the tinnitus group. According to our study, headaches impact tinnitus on many different levels and may be an important co-factor for tinnitus subtyping. We recommend screening for headache coexistence in all tinnitus patients.
Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management
Authors: Jentzsch Valerie , Davis James , Djamgoz Mustafa
Published: October 2020

The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating ‘western’ clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main ‘hallmarks of cancer’. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials.
Gemcitabine and Rapamycin Exhibit Additive Effect against Osteosarcoma by Targeting Autophagy and Apoptosis
Authors: Ando Takashi , Ichikawa Jiro , Fujimaki Taro , Taniguchi Naofumi , Takayama Yoshihiro , Haro Hirotaka
Published: October 2020

The overall prognosis for sarcoma-based cancer patients has remained largely unchanged over the past 10 years. Because there is no effective anticancer drug for patients with chemoresistant osteosarcoma (OS), novel approaches are needed to improve the prognosis. Here, we investigated whether rapamycin (Rapa) could enhance the anti-tumor effects of gemcitabine (Gem) in OS. Gem dose-dependently killed the OS cells, but exhibited much lower cytotoxicity on osteoblasts. Treatment with a combination Gem and Rapa was much more effective than that of either single agent with respect to reducing cell viability, cell invasion, cell migration, and vascular endothelial growth factor production in vitro. Moreover, the combination of these agents suppressed tumor growth, angiogenesis, and lung metastasis in allograft and xenograft murine models of OS with minimal adverse effects. Overall, the combination therapy prolonged the overall survival of tumor-bearing mice. Mechanistically, Gem induced apoptosis and increased the levels of cleaved caspases, while Rapa induced autophagy and microtubule-associated protein light chain 3 (LC3)-I/LC3-II expression both in vitro and in vivo. Our findings suggest that chemotherapy using Gem combined with Rapa may be a novel and promising therapeutic approach for the treatment of OS.
Transforming Growth Factor-β: A Multifunctional Regulator of Cancer Immunity
Authors: Xue Vivian Weiwen , Chung Jeff Yat-Fai , Córdoba Cristina Alexandra García , Cheung Alvin Ho-Kwan , Kang Wei , Lam Eric W.-F. , Leung Kam-Tong , To Ka-Fai , Lan Hui-Yao , Tang Patrick Ming-Kuen
Published: October 2020

Transforming growth factor-β (TGF-β) was originally identified as an anti-tumour cytokine. However, there is increasing evidence that it has important roles in the tumour microenvironment (TME) in facilitating cancer progression. TGF-β actively shapes the TME via modulating the host immunity. These actions are highly cell-type specific and complicated, involving both canonical and non-canonical pathways. In this review, we systemically update how TGF-β signalling acts as a checkpoint regulator for cancer immunomodulation. A better appreciation of the underlying pathogenic mechanisms at the molecular level can lead to the discovery of novel and more effective therapeutic strategies for cancer.
Non-Canonical Functions of the Gamma-Tubulin Meshwork in the Regulation of the Nuclear Architecture
Authors: Corvaisier Matthieu , Alvarado-Kristensson Maria
Published: October 2020

The nuclear architecture describes the organization of the various compartments in the nucleus of eukaryotic cells, where a plethora of processes such as nucleocytoplasmic transport, gene expression, and assembly of ribosomal subunits occur in a dynamic manner. During the different phases of the cell cycle, in post-mitotic cells and after oncogenic transformation, rearrangements of the nuclear architecture take place, and, among other things, these alterations result in reorganization of the chromatin and changes in gene expression. A member of the tubulin family, γtubulin, was first identified as part of a multiprotein complex that allows nucleation of microtubules. However, more than a decade ago, γtubulin was also characterized as a nuclear protein that modulates several crucial processes that affect the architecture of the nucleus. This review presents the latest knowledge regarding changes that arise in the nuclear architecture of healthy cells and under pathological conditions and, more specifically, considers the particular involvement of γtubulin in the modulation of the biology of the nuclear compartment.
Validation of Prognostic Stage and Anatomic Stage in the American Joint Committee on Cancer 8th Edition for Inflammatory Breast Cancer
Authors: Kida Kumiko , Hess Kenneth R. , Lim Bora , Iwase Toshiaki , Chainitikun Sudpreeda , Valero Vicente , Lucci Anthony , Le-Petross Huong Carisa , Woodward Wendy A. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Ueno Naoto T.
Published: October 2020

The AJCC updated its breast cancer staging system to incorporate biological factors in the “prognostic stage”. We undertook this study to validate the prognostic and anatomic stages for inflammatory breast cancer (IBC). We established two cohorts of IBC diagnosed without distant metastasis: (1) patients treated at The University of Texas MD Anderson Cancer Center between 1991 and 2017 (MDA cohort) and (2) patients registered in the national Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 (SEER cohort). For prognostic staging, estrogen receptor (ER)+/progesterone receptor (PR)+/ human epidermal growth factor receptor-2 (HER2)+/grade 1–2 was staged as IIIA; ER+/PR−/HER2−/grade 3, ER−/PR+/HER2−/grade 3, and triple-negative cancers as IIIC; and all others as IIIB. Endpoints were breast cancer-specific survival (BCSS), overall survival (OS), and disease-free survival (DFS). We studied 885 patients in the MDA cohort and 338 in the SEER cohort. In the MDA cohort, the prognostic stage showed significant predictive power for BCSS, OS, and DFS (all p < 0.0001), although the anatomic stage did not. In both cohorts, the Harrell concordance index (C index) was significantly higher in the prognostic stage than the anatomic stage for all endpoints. In conclusion, the prognostic stage provided more accurate prognostication for IBC than the anatomic stage. Our results show that the prognostic staging is applicable in IBC.
The Immune Phenotype of Isolated Lymphoid Structures in Non-Tumorous Colon Mucosa Encrypts the Information on Pathobiology of Metastatic Colorectal Cancer
Authors: Mungenast Felicitas , Meshcheryakova Anastasia , Beer Andrea , Salzmann Martina , Tamandl Dietmar , Gruenberger Thomas , Pietschmann Peter , Koperek Oskar , Birner Peter , Kirsch Ilan , Robins Harlan , Mittlboeck Martina , Jaritz Markus , Bergmann Michael , Zimmermann Philip , Mechtcheriakova Diana
Published: October 2020

The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.
Biological Aging Marker p16INK4a in T Cells and Breast Cancer Risk
Authors: Shen Jie , Song Renduo , Fuemmeler Bernard F. , McGuire Kandace P. , Chow Wong-Ho , Zhao Hua
Published: October 2020

Prior research has demonstrated that altered telomere length, a well-known marker for biological aging, is associated with various types of human cancer. However, whether such association extends to additional hallmarks of biological aging, including cellular senescence, has not been determined yet. In this two-stage study, we assessed the association between p16INK4a mRNA expression in T cells, a marker of cellular senescence, and breast cancer risk. The discovery stage included 352 breast cancer patients and 324 healthy controls. p16INK4a mRNA expression was significantly higher in individuals who were older, Black, and had family history of cancer than their counterparts in both cases and controls. p16INK4a mRNA expression also differed by marital status, annual income, and smoking status in cases. In the discovery stage, we found that increased p16INK4a mRNA expression was associated with 1.40-fold increased risk of breast cancer (OR = 1.40; 95%CI: 1.21, 1.68; p < 0.001). A marginally significant association was further observed in the validation stage with 47 cases and 48 controls using pre-diagnostic samples (OR = 1.28; 95%CI: 0.98, 2.97; p = 0.053). In addition, we found that p16INK4a mRNA expression was higher in tumors with selected aggressive characteristics (e.g., poorly differentiated and large tumors) than their counterparts. In summary, our results demonstrate that higher p16INK4a mRNA expression in T cells is a risk factor for breast cancer and further support the role of biological aging in the etiology of breast cancer development. Novelty and Impact Statements: The results from this study provide evidence that cellular senescence, a process of biological aging, plays a role in breast cancer etiology. In addition, our results also support that social demographics may modify cellular senescence and biological aging.
Unravelling the Epigenome of Myelodysplastic Syndrome: Diagnosis, Prognosis, and Response to Therapy
Authors: Bond Danielle R. , Lee Heather J. , Enjeti Anoop K.
Published: October 2020

Myelodysplastic syndrome (MDS) is a malignancy that disrupts normal blood cell production and commonly affects our ageing population. MDS patients are diagnosed using an invasive bone marrow biopsy and high-risk MDS patients are treated with hypomethylating agents (HMAs) such as decitabine and azacytidine. However, these therapies are only effective in 50% of patients, and many develop resistance to therapy, often resulting in bone marrow failure or leukemic transformation. Therefore, there is a strong need for less invasive, diagnostic tests for MDS, novel markers that can predict response to therapy and/or patient prognosis to aid treatment stratification, as well as new and effective therapeutics to enhance patient quality of life and survival. Epigenetic modifiers such as DNA methylation, long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs) are perturbed in MDS blasts and the bone marrow micro-environment, influencing disease progression and response to therapy. This review focusses on the potential utility of epigenetic modifiers in aiding diagnosis, prognosis, and predicting treatment response in MDS, and touches on the need for extensive and collaborative research using single-cell technologies and multi-omics to test the clinical utility of epigenetic markers for MDS patients in the future.
Safety, Efficacy and Pharcacokinetics of Targeted Therapy with The Liposomal RNA Interference Therapeutic Atu027 Combined with Gemcitabine in Patients with Pancreatic Adenocarcinoma. A Randomized Phase Ib/IIa Study
Authors: Schultheis Beate , Strumberg Dirk , Kuhlmann Jan , Wolf Martin , Link Karin , Seufferlein Thomas , Kaufmann Joerg , Feist Mathilde , Gebhardt Frank , Khan Mike , Stintzing Sebastian , Pelzer Uwe
Published: October 2020

Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences the expression of protein kinase N3 (PKN3) in the vascular endothelium. This trial was designed to assess the safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: In total, 23 patients (pts) with inoperable APC were randomly assigned to gemcitabine combined with two different Atu027 schedules (0.235 mg/kg once weekly vs. 0.235 mg/kg twice weekly). ClinicalTrials.gov Identifier: NCT01808638. Results: The treatment was well-tolerated. There were Grade 3 adverse events (AEs) in 9/11 pts (arm 1) and 11/12 pts (arm 2), while Grade 4 AEs were reported for two pts in each arm. The AEs were mainly laboratory abnormalities without clinical significance. The median progression-free survival reached statistical significance in patients who had metastatic disease (1.6 vs. 2.9 months, p = 0.025). Disease control during treatment was achieved in 4/11 pts (arm 1) and in 7/12 pts (arm 2). Pts in arm 1 experienced stable global health status while pts in arm 2 reported improvement. Conclusions: Combining Atu027 with gemcitabine is safe and well tolerated. In pts with metastatic APC, twice-weekly Atu027 is associated with significantly improved outcomes. Our clinical results support the significant involvement of the vascular endothelium in the spread of cancer, and thus the further investigation of its target role.
Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease
Authors: Atlante Anna , Amadoro Giuseppina , Bobba Antonella , Latina Valentina
Published: October 2020

A new epoch is emerging with intense research on nutraceuticals, i.e., “food or food product that provides medical or health benefits including the prevention and treatment of diseases”, such as Alzheimer’s disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuroprotective effects; in particular, they are able to provide protection against mitochondrial damage, oxidative stress, toxicity of β-amyloid and Tau and cell death. They have been shown to influence the composition of the intestinal microbiota significantly contributing to the discovery that differential microorganisms composition is associated with the formation and aggregation of cerebral toxic proteins. Further, the routes of interaction between epigenetic mechanisms and the microbiota–gut–brain axis have been elucidated, thus establishing a modulatory role of diet-induced epigenetic changes of gut microbiota in shaping the brain. This review examines recent scientific literature addressing the beneficial effects of some natural products for which mechanistic evidence to prevent or slowdown AD are available. Even if the road is still long, the results are already exceptional.
Nuclear Isoforms of Neurofibromin Are Required for Proper Spindle Organization and Chromosome Segregation
Authors: Peta Charoula , Tsirimonaki Emmanouella , Samouil Dimitris , Georgiadou Kyriaki , Mangoura Dimitra
Published: October 2020

Mitotic spindles are highly organized, microtubule (MT)-based, transient structures that serve the fundamental function of unerring chromosome segregation during cell division and thus of genomic stability during tissue morphogenesis and homeostasis. Hence, a multitude of MT-associated proteins (MAPs) regulates the dynamic assembly of MTs in preparation for mitosis. Some tumor suppressors, normally functioning to prevent tumor development, have now emerged as significant MAPs. Among those, neurofibromin, the product of the Neurofibromatosis-1 gene (NF1), a major Ras GTPase activating protein (RasGAP) in neural cells, controls also the critical function of chromosome congression in astrocytic cellular contexts. Cell type- and development-regulated splicings may lead to the inclusion or exclusion of NF1exon51, which bears a nuclear localization sequence (NLS) for nuclear import at G2; yet the functions of the produced NLS and ΔNLS neurofibromin isoforms have not been previously addressed. By using a lentiviral shRNA system, we have generated glioblastoma SF268 cell lines with conditional knockdown of NLS or ΔNLS transcripts. In dissecting the roles of NLS or ΔNLS neurofibromins, we found that NLS-neurofibromin knockdown led to increased density of cytosolic MTs but loss of MT intersections, anastral spindles featuring large hollows and abnormal chromosome positioning, and finally abnormal chromosome segregation and increased micronuclei frequency. Therefore, we propose that NLS neurofibromin isoforms exert prominent mitotic functions.
The Tubulin Code in Mitosis and Cancer
Authors: Lopes Danilo , Maiato Helder
Published: October 2020

The “tubulin code” combines different α/β-tubulin isotypes with several post-translational modifications (PTMs) to generate microtubule diversity in cells. During cell division, specific microtubule populations in the mitotic spindle are differentially modified, but only recently, the functional significance of the tubulin code, with particular emphasis on the role specified by tubulin PTMs, started to be elucidated. This is the case of α-tubulin detyrosination, which was shown to guide chromosomes during congression to the metaphase plate and allow the discrimination of mitotic errors, whose correction is required to prevent chromosomal instability—a hallmark of human cancers implicated in tumor evolution and metastasis. Although alterations in the expression of certain tubulin isotypes and associated PTMs have been reported in human cancers, it remains unclear whether and how the tubulin code has any functional implications for cancer cell properties. Here, we review the role of the tubulin code in chromosome segregation during mitosis and how it impacts cancer cell properties. In this context, we discuss the existence of an emerging “cancer tubulin code” and the respective implications for diagnostic, prognostic and therapeutic purposes.
Effect of Annealing on the Structural, Magnetic, Surface Energy and Optical Properties of Co32Fe30W38 Films Deposited by Direct-Current Magnetron Sputtering
Authors: Liu Wen-Jen , Chang Yung-Huang , Ou Sin-Liang , Chen Yuan-Tsung , Li Wei-Hsuan , Jhou Tian-Yi , Chu Chun-Lin , Wu Te-Ho , Tseng Shih-Wen
Published: October 2020

In this study, a 10–50 nm Co32Fe30W38 alloy thin film sputtered on glass substrates was annealed at different temperatures for 1 h including room temperature (RT), 300, 350, and 400 °C. The structure, magnetic properties, surface energy, and optical properties of the Co32Fe30W38 alloy were studied. X-ray diffraction (XRD) patterns of the as-deposited Co32Fe30W38 thin films showed the amorphous structure. The apparent body-centered cubic (BCC) CoFe (110) structure was exhibited after 300 °C annealing for 1 h. The 300 °C annealed Co32Fe30W38 thin film showed the highest CoFe (110) peak compared with other temperatures. Furthermore, the thicker the Co32Fe30W38 thin film, the higher the CoFe (110) peak. The CoFe (110) peak revealed magneto-crystalline anisotropy, which was related to the strong low-frequency alternative-current magnetic susceptibility (χac) and induced an increasing trend of saturation magnetization (Ms) as the thickness (tf) increased. Due to the thermal disturbance, the χac and Ms for the 350 and 400 °C annealed Co32Fe30W38 thin film decreased. The contact angles of the Co32Fe30W38 thin films were less than 90°. For all temperatures, the surface energy increased when the film thickness increased from 10 to 50 nm. In addition, the surface energies for annealed samples were comparatively higher than the as-deposited samples. The higher surface energy of 28 mJ/mm2 was obtained for the 50 nm Co32Fe30W38 thin film annealed at 300 °C. The transmittance percentage (%) of the as-deposited Co32Fe30W38 film was higher than other annealed conditions. This result contributed to the fact that higher crystallization, due to perfect band structures, may inhibit the transmission of photon signals through the film, resulting in low transmittance and high absorption.
Preparation of Cellulose Nanocrystal-Reinforced Physical Hydrogels for Actuator Application
Authors: Kim Jaehwan , Jayaramudu Tippabattini , Zhai Lindong , Kim Hyun Chan , Agumba Dickens Owino
Published: October 2020

In the present investigation, we prepared cellulose nanocrystal (CNC)-reinforced polyvinyl alcohol-cellulose (PVA-Cell) physical hydrogels using a simple blending method for actuator application. The prepared hydrogels were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and the surface and cross-section were studied by scanning electron microscopy. CNCs were well dispersed in the PVA-Cell hydrogel. In the preparation process, surface hydroxyl groups of the CNC and PVA-Cell matrix hydroxyl groups were interacted to produce uniform dispersion of CNCs in the hydrogels. Swelling behavior and compression studies revealed that the increase of the CNCs reinforced the crosslinking. The actuation test of the prepared hydrogels showed that the displacement linearly increased with the voltage, and the immense output displacement was observed at low CNC concentration. The prepared hydrogels are applicable for soft robot actuators and active lens.
Approaching Adversarial Example Classification with Chaos Theory
Authors: Pedraza Anibal , Deniz Oscar , Bueno Gloria
Published: October 2020

Adversarial examples are one of the most intriguing topics in modern deep learning. Imperceptible perturbations to the input can fool robust models. In relation to this problem, attack and defense methods are being developed almost on a daily basis. In parallel, efforts are being made to simply pointing out when an input image is an adversarial example. This can help prevent potential issues, as the failure cases are easily recognizable by humans. The proposal in this work is to study how chaos theory methods can help distinguish adversarial examples from regular images. Our work is based on the assumption that deep networks behave as chaotic systems, and adversarial examples are the main manifestation of it (in the sense that a slight input variation produces a totally different output). In our experiments, we show that the Lyapunov exponents (an established measure of chaoticity), which have been recently proposed for classification of adversarial examples, are not robust to image processing transformations that alter image entropy. Furthermore, we show that entropy can complement Lyapunov exponents in such a way that the discriminating power is significantly enhanced. The proposed method achieves 65% to 100% accuracy detecting adversarials with a wide range of attacks (for example: CW, PGD, Spatial, HopSkip) for the MNIST dataset, with similar results when entropy-changing image processing methods (such as Equalization, Speckle and Gaussian noise) are applied. This is also corroborated with two other datasets, Fashion-MNIST and CIFAR 19. These results indicate that classifiers can enhance their robustness against the adversarial phenomenon, being applied in a wide variety of conditions that potentially matches real world cases and also other threatening scenarios.
TNT: An Interpretable Tree-Network-Tree Learning Framework using Knowledge Distillation
Authors: Li Jiawei , Li Yiming , Xiang Xingchun , Xia Shu-Tao , Dong Siyi , Cai Yun
Published: October 2020

Deep Neural Networks (DNNs) usually work in an end-to-end manner. This makes the trained DNNs easy to use, but they remain an ambiguous decision process for every test case. Unfortunately, the interpretability of decisions is crucial in some scenarios, such as medical or financial data mining and decision-making. In this paper, we propose a Tree-Network-Tree (TNT) learning framework for explainable decision-making, where the knowledge is alternately transferred between the tree model and DNNs. Specifically, the proposed TNT learning framework exerts the advantages of different models at different stages: (1) a novel James–Stein Decision Tree (JSDT) is proposed to generate better knowledge representations for DNNs, especially when the input data are in low-frequency or low-quality; (2) the DNNs output high-performing prediction result from the knowledge embedding inputs and behave as a teacher model for the following tree model; and (3) a novel distillable Gradient Boosted Decision Tree (dGBDT) is proposed to learn interpretable trees from the soft labels and make a comparable prediction as DNNs do. Extensive experiments on various machine learning tasks demonstrated the effectiveness of the proposed method.
Optimization of Selective Assembly for Shafts and Holes Based on Relative Entropy and Dynamic Programming
Authors: Xing Mingyi , Zhang Qiushuang , Jin Xin , Zhang Zhijing
Published: October 2020

Selective assembly is the method of obtaining high precision assemblies from relatively low precision components. For precision instruments, the geometric error on mating surface is an important factor affecting assembly accuracy. Different from the traditional selective assembly method, this paper proposes an optimization method of selective assembly for shafts and holes based on relative entropy and dynamic programming. In this method, relative entropy is applied to evaluate the clearance uniformity between shafts and holes, and dynamic programming is used to optimize selective assembly of batches of shafts and holes. In this paper, the case studied has 8 shafts and 20 holes, which need to be assembled into 8 products. The results show that optimal combinations are selected, which provide new insights into selective assembly optimization and lay the foundation for selective assembly of multi-batch precision parts.
Non-Uniform Discretization-based Ordinal Regression for Monocular Depth Estimation of an Indoor Drone
Authors: Zhang Xiangzhu , Zhang Lijia , Lewis Frank L. , Pei Hailong
Published: October 2020

At present, the main methods of solving the monocular depth estimation for indoor drones are the simultaneous localization and mapping (SLAM) algorithm and the deep learning algorithm. SLAM requires the construction of a depth map of the unknown environment, which is slow to calculate and generally requires expensive sensors, whereas current deep learning algorithms are mostly based on binary classification or regression. The output of the binary classification model gives the decision algorithm relatively rough control over the unmanned aerial vehicle. The regression model solves the problem of the binary classification, but it carries out the same processing for long and short distances, resulting in a decline in short-range prediction performance. In order to solve the above problems, according to the characteristics of the strong order correlation of the distance value, we propose a non-uniform spacing-increasing discretization-based ordinal regression algorithm (NSIDORA) to solve the monocular depth estimation for indoor drone tasks. According to the security requirements of this task, the distance label of the data set is discretized into three major areas—the dangerous area, decision area, and safety area—and the decision area is discretized based on spacing-increasing discretization. Considering the inconsistency of ordinal regression, a new distance decoder is produced. Experimental evaluation shows that the root-mean-square error (RMSE) of NSIDORA in the decision area is 33.5% lower than that of non-uniform discretization (NUD)-based ordinal regression methods. Although it is higher overall than that of the state-of-the-art two-stream regression algorithm, the RMSE of the NSIDORA in the top 10 categories of the decision area is 21.8% lower than that of the two-stream regression algorithm. The inference speed of NSIDORA is 3.4 times faster than that of two-stream ordinal regression. Furthermore, the effectiveness of the decoder has been proved through ablation experiments.
A Deep Learning Instance Segmentation Approach for Global Glomerulosclerosis Assessment in Donor Kidney Biopsies
Authors: Altini Nicola , Cascarano Giacomo Donato , Brunetti Antonio , De Feudis Irio , Buongiorno Domenico , Rossini Michele , Pesce Francesco , Gesualdo Loreto , Bevilacqua Vitoantonio
Published: October 2020

The histological assessment of glomeruli is fundamental for determining if a kidney is suitable for transplantation. The Karpinski score is essential to evaluate the need for a single or dual kidney transplant and includes the ratio between the number of sclerotic glomeruli and the overall number of glomeruli in a kidney section. The manual evaluation of kidney biopsies performed by pathologists is time-consuming and error-prone, so an automatic framework to delineate all the glomeruli present in a kidney section can be very useful. Our experiments have been conducted on a dataset provided by the Department of Emergency and Organ Transplantations (DETO) of Bari University Hospital. This dataset is composed of 26 kidney biopsies coming from 19 donors. The rise of Convolutional Neural Networks (CNNs) has led to a realm of methods which are widely applied in Medical Imaging. Deep learning techniques are also very promising for the segmentation of glomeruli, with a variety of existing approaches. Many methods only focus on semantic segmentation—which consists in segmentation of individual pixels—or ignore the problem of discriminating between non-sclerotic and sclerotic glomeruli, so these approaches are not optimal or inadequate for transplantation assessment. In this work, we employed an end-to-end fully automatic approach based on Mask R-CNN for instance segmentation and classification of glomeruli. We also compared the results obtained with a baseline based on Faster R-CNN, which only allows detection at bounding boxes level. With respect to the existing literature, we improved the Mask R-CNN approach in sliding window contexts, by employing a variant of the Non-Maximum Suppression (NMS) algorithm, which we called Non-Maximum-Area Suppression (NMAS). The obtained results are very promising, leading to improvements over existing literature. The baseline Faster R-CNN-based approach obtained an F-Measure of 0.904 and 0.667 for non-sclerotic and sclerotic glomeruli, respectively. The Mask R-CNN approach has a significant improvement over the baseline, obtaining an F-Measure of 0.925 and 0.777 for non-sclerotic and sclerotic glomeruli, respectively. The proposed method is very promising for the instance segmentation and classification of glomeruli, and allows to make a robust evaluation of global glomerulosclerosis. We also compared Karpinski score obtained with our algorithm to that obtained with pathologists’ annotations to show the soundness of the proposed workflow from a clinical point of view.
Location Proof Systems for Smart Internet of Things: Requirements, Taxonomy, and Comparative Analysis
Authors: Zafar Faheem , Khan Abid , Anjum Adeel , Maple Carsten , Shah Munam Ali
Published: October 2020

In the current hyper-connected, data-driven era, smart devices are providing access to geolocation information, enabling a paradigm shift in diverse domains. Location proof systems utilize smart devices to provide witnessed proof of location to enable secure location-based services (LBS). Applications of location proof systems include safety, asset management and operations monitoring in health care, supply chain tracking, and Internet-of-Things (IoT)-based location intelligence in businesses. In this paper, we investigate the state of the art in location proof systems, examining design challenges and implementation considerations for application in the real world. To frame the analysis, we have developed a taxonomy of location proof systems and performed a comparative analysis over the common attributes, highlighting their strength and weaknesses. Furthermore, we have identified future trends for this increasingly important area of investigation and development.
Resonant Network Design Method to Reduce Influence of Mutual Inductance between Receivers in Multi-Output Omnidirectional Wireless Power Transfer Systems
Authors: Woo Dong-Hun , Cha Hwa-Rang , Kim Rae-Young
Published: October 2020

Many studies have been conducted on multi-output systems that transfer power to multiple receivers in conventional planar-type wireless power transfer (WPT) systems; however, few studies and analyses have taken into account the mutual inductance between receivers in multi-output omnidirectional WPT systems. In this paper, the correlation between the mutual inductance between receivers and the power transfer efficiency (PTE) in a multi-output omnidirectional WPT system is analyzed, and a limitation in terms of a reduction in the PTE with an increase in the influence of the mutual inductance between the receivers is presented. To solve this problem, a resonant network design method is proposed to reduce the influence of mutual inductance between receivers, and appropriate canceling capacitor values are selected using the weighted sum method among multi-objective optimization methods. The proposed method is through simulations and experiments, and it presents the potential for improvement in the problems that occur when transferring power to multiple receivers.
Analytical Study of the Solidification of a Phase Change Material in an Annular Space
Authors: Lipnicki Zygmunt , Małolepszy Tomasz
Published: October 2020

In this study, the process of the solidification of a PCM (phase change material) liquid in an annular space was analytically investigated with the use of a simplified quasi-steady-state model. This model described the phase change phenomenon with the cylindrical solidification front and with the solidification liquid overheated above the solidification temperature. One of the important novelties of the applied model was the determination of the coefficient of the heat transfer between the liquid and the solidified layer on the solidification surface, which was calculated as a function of the location of the solidification front. A method for calculating the variable coefficient of heat transfer on the surface of the solidification front during the solidification process is presented. The contact layer between the cold wall and the solidified layer was incorporated into the model and played an important role. The theoretical analytical method describing the solidification process based on the quasi-steady model was used in the study. Moreover, the main problem considered in this work could be reduced to a conjugate system of differential equations, allowing it to be solved numerically. From this perspective, the influence of various dimensionless parameters on the solidification process could be clearly seen. The obtained numerical results are presented in graphical form. The results of the theoretical research were compared with the experimental research of one of the author’s earlier works and they showed a significant agreement. Finally, the simple analytical approach presented in this work can be used for designing annular heat accumulators.
Laboratory Measurements of the Relative Permeability of Coal: A Review
Authors: Shen Shaicheng , Fang Zhiming , Li Xiaochun
Published: October 2020

The relative permeability of coal to gas and water is an essential parameter for characterizing coalbed methane (CBM) reservoirs and predicting coal seam gas production, particularly in numerical simulations. Although a variety of studies related to the relative permeability of coals have been conducted, the results hardly meet the needs of practical engineering applications. To track the dynamic development of relative permeability measurements in the laboratory, discover the deficiencies, and discuss further work in this field, this paper investigates the relative permeability measurement preparation work and laboratory methods and summarizes the development of techniques used to determine the water saturation during experimentation. The previously determined relative permeability curves are also assembled and classified according to coal rank and the absolute permeability. It is found that the general operations in the relative permeability measurement process are still not standardized. The techniques applied to determine the water saturation of coal in experiments have been refined to some extent, but no optimal technique has been recognized yet. New techniques, such as the incorporation of high-precision differential pressure gauges, can be used to determine the water production during relative permeability measurement. In addition, the existing relative permeability data are limited, and no study has focused on supercritical carbon dioxide-water and mixed gas (methane and carbon dioxide)-water relative permeability measurements. To meet the requirements of actual projects, further research on this topic must be conducted.