bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinematic and Aerodynamic Investigation of the Butterfly in Forward Free Flight for the Butterfly-Inspired Flapping Wing Air Vehicle
Authors: Zhang Yixin , Wang Xingjian , Wang Shaoping , Huang Wenhao , Weng Qiwang
Published: March 2021

To ensure the stability of flight, the butterfly needs to flap its wings and simultaneously move its main body to achieve all kinds of flying motion, such as taking off, hovering, or reverse flight. The high-speed camera is used to record the swing of the abdomen, the movement of the wings, and the pitch angle of the body for butterflies during their free flight; the comprehensive biokinetic observations show that the butterfly’s wings and body are coupled in various flight states. The swing of the abdomen and the flap of the fore wing affect the pitch motion significantly. For theoretical analysis of the butterfly flight, a three-dimensional multi-rigid butterfly model based on real butterfly dimension is established, and the aerodynamic of the butterfly flight is simulated and analyzed via computational fluid dynamics methods to obtain an optimal kinematic model of butterfly forward flight. Moreover, the formation and development of three-dimensional vortex structures in the forward flight are also presented. The detailed structures of vortices and their dynamic behavior show that the wing’s flap and the abdominal swing play a key role in reorienting and correcting the “clap and peel” mechanism, and the force generation mechanisms are evaluated. The research indicates that longitudinal flight performance is mainly related to the kinematic parameters of the wing and body, and it can lead to the development of butterfly-inspired flapping wing air vehicles.
Theoretical Investigation on Performance Characteristics of Aerostatic Journal Bearings with Active Displacement Compensator
Authors: Kodnyanko Vladimir , Shatokhin Stanislav , Kurzakov Andrey , Pikalov Yuri , Brungardt Maxim , Strok Lilia , Pikalov Iakov
Published: March 2021

Active aerostatic bearings are capable of providing negative compliance, which can be successfully used to automatically compensate for deformation of the machine tool system in order to reduce the time and improve the quality of metalworking. The article considers an aerostatic radial bearing with external combined throttling systems and an elastic displacement compensator, which is an alternative to aerostatic bearings with air flow rate compensators. The results of the mathematical modeling and theoretical research of stationary and nonstationary modes of operation of bearings with slotted and diaphragm throttling systems are presented. A counter-matrix sweep method has been developed for solving linear and nonlinear boundary value problems in partial derivatives with respect to the function of the square of the pressure in the bearing gap and inter-throttling bearing cavities for any values of the relative shaft eccentricity. A numerical method is proposed for calculating the dynamic quality criteria, and the transfer function of the dynamic compliance of a bearing with small displacements is considered as a linear automatic control system with distributed parameters. An experimental verification of the theoretical characteristics of the bearing was carried out, which showed a satisfactory correspondence among the compared data. It is shown that bearings with a throttle system have the best quantitative and qualitative load characteristics. The possibility of optimal determination of the values of a number of important parameters that provide the bearing with optimal performance and a high stability margin is established. It is shown that bearings with an elastic suspension of the movable sleeve allow one to compensate for significant movements, which can be larger than the size of the air gap by an order of magnitude or more. In these conditions, similar bearings with air flow compensators would be obviously inoperative.
3D DNA Nanostructures: The Nanoscale Architect
Authors: Fu Daniel , Reif John
Published: March 2021

Structural DNA nanotechnology is a pioneering biotechnology that presents the opportunity to engineer DNA-based hardware that will mediate a profound interface to the nanoscale. To date, an enormous library of shaped 3D DNA nanostructures have been designed and assembled. Moreover, recent research has demonstrated DNA nanostructures that are not only static but can exhibit specific dynamic motion. DNA nanostructures have thus garnered significant research interest as a template for pursuing shape and motion-dependent nanoscale phenomena. Potential applications have been explored in many interdisciplinary areas spanning medicine, biosensing, nanofabrication, plasmonics, single-molecule chemistry, and facilitating biophysical studies. In this review, we begin with a brief overview of general and versatile design techniques for 3D DNA nanostructures as well as some techniques and studies that have focused on improving the stability of DNA nanostructures in diverse environments, which is pivotal for its reliable utilization in downstream applications. Our main focus will be to compile a wide body of existing research on applications of 3D DNA nanostructures that demonstrably rely on the versatility of their mechanical design. Furthermore, we frame reviewed applications into three primary categories, namely encapsulation, surface templating, and nanomechanics, that we propose to be archetypal shape- or motion-related functions of DNA nanostructures found in nanoscience applications. Our intent is to identify core concepts that may define and motivate specific directions of progress in this field as we conclude the review with some perspectives on the future.
Influence of Material-Dependent Damping on Brake Squeal in a Specific Disc Brake System
Authors: Úradníček Juraj , Musil Miloš , Gašparovič L’uboš , Bachratý Michal
Published: March 2021

The connection of two phenomena, nonconservative friction forces and dissipation-induced instability, can lead to many interesting engineering problems. We study the general material-dependent damping influence on the dynamic instability of disc brake systems leading to brake squeal. The effect of general damping is demonstrated on minimal and complex models of a disc brake. Experimental analyses through the frequency response function (FRF) show different damping of the brake system coalescent modes, indicating possible dissipation-induced instability. A complex system including material-dependent damping is defined in commercial finite element (FE) software. A FE model validated by experimental data on the brake-disc test bench is used to compute the influence of a pad and disc damping variations on the system stability using complexe igenvalue analysis (CEVA). Numerical analyses show a significant sensitivity of the experimentally verified unstable mode of the system to the ratio of the damping between the disc and the friction material components.
Enhancing the Iterative Smoothed Particle Hydrodynamics Method
Authors: Francomano Elisa
Published: March 2021

Motivated by recent research on the iterative approach proposed for the smoothed particle hydrodynamics (ISPH) method, some ideas to improve the process are introduced. The standard procedure is enhanced iterating on the residuals preserving the matrix-free nature of the process. The method is appealing providing reasonable results with disordered data distribution too and no kernel variations are needed in the approximation. This work moves forward with a novel formulation requiring a lower number of iterations to reach a desired accuracy. The computational procedure is described and some results are introduced to appreciate the proposed formulation.
Improved Hot Smoke Processing of Chub Mackerel (Scomber japonicus) Promotes Sensorial, Physicochemical and Microbiological Characteristics
Authors: Rana Md. Masud , Mohibbullah Md. , Won Na Eun , Baten Md. Abdul , Sohn Jae Hak , Kim Jin-Soo , Choi Jae-Suk
Published: March 2021

Chub mackerel (CM), Scomber japonicus, is a commercially important fish species in pacific countries including South Korea and its rapid quality deterioration by various spoilage mechanisms while marketed has been reported, leading to a dramatic decline of the market price. To overcome this problem, a combination of superheated steam roasting (270 °C for 4 min) and hot smoking (70 °C) on CM fillets was applied to impart extending shelf-life at the market level. Using different sawdust with time-dependent smoking revealed that Oak sawdust at 25 min of optimized smoking time significantly (p < 0.05) provided the highest sensory properties (appearance, odor, color, texture and overall preferences), improved physicochemical, microbial, and nutritional properties, and subsequently, promoted shelf life of processed CM during the storage period at 10 °C for up to 34 days. Moreover, the processed CM offered high nutritional value, especially, essential and non-essential amino acids were found to be 13.14 and 15.48 g/100 g of CM fillets, and also reduced the trimethylamine-N-oxide level to an acceptable limit, indicating its quality and safety with high nutritional standards to end-point users upon consumption.
Fire Safety Risk Analysis of Conventional Submarines
Authors: Depetro Aidan , Gamble Grant , Moinuddin Khalid
Published: March 2021

Conventional (diesel-electric) submarines can provide improved stealth compared to nuclear submarines once submerged. This is because nuclear submarines are generally larger and are required to operate their nuclear reactors at all times, unlike diesel-electric submarines which are generally smaller and can run exclusively on batteries when submerged which generally requires fewer moving parts. These characteristics normally result in a smaller acoustic, thermal and magnetic signature which afford diesel-electric submarines greater stealth when submerged. However, the current underwater range and endurance is limited by the energy storage or generation for submerged operation. The application of emerging energy storage technology seeks to address this limitation and provide significant tactical and operational advantages to the conventional submarine operator. From a fire safety perspective, the potential addition of technologies such as rechargeable lithium-ion batteries, Air Independent Propulsion (AIP) systems and increasingly sophisticated electronic equipment dramatically changes the risk space in an already challenging and unforgiving underwater environment. This study reviews the functions, failure modes and maturity of emerging technologies that have serious submarine fire safety implications. A semi-quantitative assessment of the fire risk associated with potential large future conventional submarine design options for batteries and AIP is provided. This assessment concludes that lithium-ion batteries pose the greatest challenge with regard to integration into conventional submarines without compromising reliability or safety.
Collective Memory: Transposing Pavlov’s Experiment to Robot Swarms
Authors: Campo Alexandre , Nicolis Stamatios C. , Deneubourg Jean-Louis
Published: March 2021

Remembering information is a fundamental aspect of cognition present in numerous natural systems. It allows adaptation of the behavior as a function of previously encountered situations. For instance, many living organisms use memory to recall if a given situation incurred a penalty or a reward and rely on that information to avoid or reproduce that situation. In groups, memory is commonly studied in the case where individual members are themselves capable of learning and a few of them hold pieces of information that can be later retrieved for the benefits of the group. Here, we investigate how a group may display memory when the individual members have reactive behaviors and can not learn any information. The well known conditioning experiments of Pavlov illustrate how single animals can memorize stimuli associated with a reward and later trigger a related behavioral response even in the absence of reward. To study and demonstrate collective memory in artificial systems, we get inspiration from the Pavlov experiments and propose a setup tailored for testing our robotic swarm. We devised a novel behavior based on the fundamental process of aggregation with which robots exhibit collective memory. We show that the group is capable of encoding, storing, and retrieving information that is not present at the level of the individuals.
Global Solar Radiation Transfer and Its Loss in the Atmosphere
Authors: Bai Jianhui , Zong Xuemei
Published: March 2021

Based on the analysis of solar radiation and meteorological parameters measured at a subtropical forest in China during 2013–2016, a new empirical model of global solar irradiance has been developed. It can calculate global solar irradiance at the ground and at the top of the atmosphere (TOA); both are in agreement with the observations. This model is used to calculate the extinction of global solar irradiance in the atmosphere and the contributions from absorbing and scattering substances. The loss of global solar irradiance is dominated by absorbing and absorbing substances. The results show clear seasonal and interannual variations during the observation period. Sensitivity analysis indicates that global solar irradiance is more sensitive to changes in scattering, quantified by the S/G factor (S and G are diffuse and global solar radiation, respectively), than to changes in absorption. The relationships between the extinction factor (AF) of G and S/G and between the AF and the aerosol optical depth (AOD) are determined and used to estimate S/G and the AOD from the measured AF. This empirical model is applied to calculate the albedos at the TOA and the ground. This empirical model is useful to study global solar radiation and the energy–atmosphere interactions.
Experimental Quantum Message Authentication with Single Qubit Unitary Operation
Authors: Kang Min-Sung , Kim Yong-Su , Choi Ji-Woong , Yang Hyung-Jin , Han Sang-Wook
Published: March 2021

We have developed a quantum message authentication protocol that provides authentication and integrity of an original message using single qubit unitary operations. Our protocol mainly consists of two parts: quantum encryption and a correspondence check. The quantum encryption part is implemented using linear combinations of wave plates, and the correspondence check is performed using Hong–Ou–Mandel interference. By analyzing the coincidence counts of the Hong–Ou–Mandel interference, we have successfully proven the proposed protocol experimentally, and also showed its robustness against an existential forgery.
Torrefaction Characteristics of Blended Ratio of Sewage Sludge and Sugarcane Bagasse for Energy Production
Authors: Nwabunwanne Nwokolo , Vuyokazi Tonga , Olagoke Adeniji , Mike Ojemaye , Patrick Mukumba , Anthony Okoh
Published: March 2021

Torrefaction is a thermal pretreatment technique usually adopted for improving biomass properties to be on par with that of coal for energy production. In this study, the torrefaction characteristics of blended fuel of sewage sludge (SS) and sugarcane bagasse (BG) biomass were investigated for the purpose of gasification. The thermal degradation behavior of the blended biomass sample was tested in an inert atmosphere from ambient temperature to 900 °C using thermogravimetric analysis (TGA). The obtained TGA data aided in the determination of thermochemical parameters that are of necessity in gasification. Morphological changes in the blended torrefied samples were examined through scanning electron microscopy. Further changes in the chemical structure of the samples were investigated through Fourier-transform infrared analysis. The blend ratio of 75% SS + 25% BG torrefied at 350 °C gave the highest energy value (HHV) of 23.62 MJ/kg, fixed carbon of 51.37 wt % and fuel ratio of 1.70. The obtained fuel ratio is comparable to that required for optimum combustion performance of coal. The morphological structure of the samples showed that there was an aggregation of the biomass particles into small lumps at higher torrefaction temperature for 50% SS + 50% BG and 75% SS + 25% BG blend indicating a better grind ability of the biomass material. Thus, it can be concluded that the blend and torrefaction enhanced the properties of the biomass materials.
Effect of 13-Hydroperoxyoctadecadienoic Acid (13-HPODE) Treatment on the Transcriptomic Profile of Poorly-Differentiated Caco-2 Cells
Authors: Faizo Nisreen , Narasimhulu Chandrakala Aluganti , Forsman Anna , Yooseph Shibu , Parthasarathy Sampath
Published: March 2021

Dietary lipid peroxides (LOOHs) have been linked to gut pathologies including inflammatory bowel disease and cancer. As poorly differentiated (PDiff) intestinal epithelial (Caco-2) cells represent tumor cells and could model intestinal crypt cells, we investigated the cellular response of PDiff Caco-2 cells to the most common dietary LOOH, 13-hydroperoxyoctadecadienoic acid (13-HPODE), using RNA sequencing (RNA-seq). Further, we compared the results with the transcriptomic profiles of PDiff cells exposed to linoleic acid (LA) or hydrogen peroxide (H2O2). The results showed that 13-HPODE treatment induces expression of genes related to detoxification and several metabolic pathways including glycogen and amino acid metabolism, which may create a tumorigenic environment despite the downregulation of some proliferation-related genes. 13-HPODE also enhanced peroxisome proliferator-activated receptor signaling involved in lipid metabolism, homeostasis, and inflammation. Additionally, results indicated that 13-HPODE impacts ribosome biogenesis, phagosome, and mitochondrial function through disrupted electron transport chain, which may contribute to disease development or progression. RNA-seq results were validated using qRT-PCR. This study provides an understanding of PDiff Caco-2 cell response to 13-HPODE and the mechanisms by which 13-HPODE modulates cellular processes that may contribute to disease development or progression.
Characterizing Bushfire Occurrences over Jamaica Using the MODIS C6 Fire Archive 2001–2019
Authors: Charlton Candice S. , Stephenson Tannecia S. , Taylor Michael A. , Douglas Christina A.
Published: March 2021

There is an increasing need to develop bushfire monitoring and early warning systems for Jamaica and the Caribbean. However, there are few studies that examine fire variability for the region. In this study the MODIS C6 Fire Archive for 2001–2019 is used to characterize bushfire frequencies across Jamaica and to relate the variability to large-scale climate. Using additive mixed model and backward linear regression, the MODIS represents 80% and 73% of the local Jamaica Fire Brigade (JFB) data variability for 2010–2015, respectively. However, the MODIS values are smaller by a factor of approximately 30. The MODIS climatology over Jamaica reveals a primary peak in March and a secondary maximum in July, coinciding with months of minimum rainfall. A significant positive linear trend is observed for July-August bushfire events over 2001–2019 and represents 29% of the season’s variability. Trends in all-island totals in other seasons or annually were not statistically significant. However, positive annual trends in Zone 2 (eastern Jamaica) are statistically significant and may support an indication that a drying trend is evolving over the east. Significant 5-year and 3.5-year periodicities are also evident for April–June and September–November variability, respectively. Southern Jamaica and particularly the parish of Clarendon, known for its climatological dryness, show the greatest fire frequencies. The study provides evidence of linkages between fire occurrences over Jamaica and oceanic and atmospheric variability over the Atlantic and Pacific. For example, all-island totals show relatively strong association with the Atlantic Multidecadal Oscillation. The study suggests that development of an early warning system for bushfire frequency that includes climate indices is possible and shows strong potential for fire predictions.
Testing the Drop-Size Distribution-Based Separation of Stratiform and Convective Rain Using Radar and Disdrometer Data from a Mid-Latitude Coastal Region
Authors: Thurai Merhala , Bringi Viswanathan , Wolff David , Marks David , Pabla Charanjit
Published: March 2021

Stratiform and convective rain are associated with different microphysical processes and generally produce drop-size distributions (DSDs) with different characteristics. Previous studies using data from (a) a tropical coastal location, (b) a mid-latitude continental location with semi-arid climate, and (c) a sub-tropical continental location, found that the two rain types could be separated in the NW–Dm space, where Dm is the mass-weighted mean diameter and NW is the normalized intercept parameter. In this paper, we investigate the same separation technique using data and observations from a mid-latitude coastal region. Three-minute DSDs from disdrometer measurements are used for the NW- versus Dm-based classification and are compared with simultaneous observations from an S-band polarimetric radar 38 km away from the disdrometer site. Specifically, RHI (range-height indicator) scans over the disdrometer were used for confirmation. Results show that there was no need to modify the separation criteria from previous studies. Three-minute DSDs from the same location were used as input to scattering calculations to derive retrieval equations for NW and Dm for the S-band radar using an improved technique and applied to the RHI scans to identify convective and stratiform rain regions. Two events are shown as illustrative examples.
Changes Occurring on the Activity of Salivary Alpha-Amylase Proteoforms in Two Naturalistic Situations Using a Spectrophotometric Assay
Authors: Contreras-Aguilar María D. , Mateo Sandra V. , Tecles Fernando , Hirtz Christophe , Escribano Damián , Cerón Jose J.
Published: March 2021

This study aimed to evaluate the changes in the activity of total salivary alpha-amylase (TsAA) and both the non-glycosylated and glycosylated salivary alpha-amylase proteoforms (NGsAA and GsAA, respectively) in physical and psychological stress models, estimated using a simple and easily set-up method. The method used was a spectrophotometric assay with 2-chloro-4-nitrophenyl-α-D-maltotriose (CNPG3) as a substrate, incubated with Concanavalin A (ConA) to remove most of the glycosylated protein from the sample. This method allowed the measurement of TsAA and estimation of NGsAA and GsAA activities with imprecision lower than 10%. When this method was applied to two different stress models, differences in the responses of the proteoforms were observed, with the NGsAA activity showing changes of higher magnitude after stress induction than the GsAA activity, and the highest correlation with the State–Trait Anxiety Inventory Scale in the Trier Social Stress Test (TSST). In conclusion, the activity of the two main sAA proteoforms can be easily estimated in saliva, and their measurement can provide additional information on TsAA activity in physical or psychological stress situations.
Paeoniflorin Enhances Endometrial Receptivity through Leukemia Inhibitory Factor
Authors: Park Hye-Rin , Choi Hee-Jung , Kim Bo-Sung , Chung Tae-Wook , Kim Keuk-Jun , Joo Jong-Kil , Ryu Dongryeol , Bae Sung-Jin , Ha Ki-Tae
Published: March 2021

Despite advances in assisted reproductive technology, treatment for deficient endometrial receptivity is a major clinical unmet need. In our previous study, the water extract of Paeonia lactiflora Pall. enhanced endometrial receptivity in vitro and in vivo via induction of leukemia inhibitory factor (LIF), an interleukin (IL)-6 family cytokine. In the present study, we found that paeoniflorin, a monoterpene glycoside, is the major active compound of P. lactiflora. Paeoniflorin significantly improved the embryo implantation rate in a murine model of mifepristone (RU486)-induced implantation failure. In addition, paeoniflorin increased the adhesion of human trophectoderm-derived JAr cells to endometrial Ishikawa cells through the expression of LIF in vitro. Moreover, using the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database of the human endometrium, we confirmed that LIF signaling is a key regulator for improving human endometrial receptivity. Therefore, these results suggest that paeoniflorin might be a potent drug candidate for the treatment of endometrial implantation failure by enhancing endometrial receptivity.
The Effects of 10 Hz and 20 Hz tACS in Network Integration and Segregation in Chronic Stroke: A Graph Theoretical fMRI Study
Authors: Chen Cheng , Yuan Kai , Chu Winnie Chiu-wing , Tong Raymond Kai-yu
Published: March 2021

Transcranial alternating current stimulation (tACS) has emerged as a promising technique to non-invasively modulate the endogenous oscillations in the human brain. Despite its clinical potential to be applied in routine rehabilitation therapies, the underlying modulation mechanism has not been thoroughly understood, especially for patients with neurological disorders, including stroke. In this study, we aimed to investigate the frequency-specific stimulation effect of tACS in chronic stroke. Thirteen chronic stroke patients underwent tACS intervention, while resting-state functional magnetic resonance imaging (fMRI) data were collected under various frequencies (sham, 10 Hz and 20 Hz). The graph theoretical analysis indicated that 20 Hz tACS might facilitate local segregation in motor-related regions and global integration at the whole-brain level. However, 10 Hz was only observed to increase the segregation from whole-brain level. Additionally, it is also observed that, for the network in motor-related regions, the nodal clustering characteristic was decreased after 10 Hz tACS, but increased after 20 Hz tACS. Taken together, our results suggested that tACS in various frequencies might induce heterogeneous modulation effects in lesioned brains. Specifically, 20 Hz tACS might induce more modulation effects, especially in motor-related regions, and they have the potential to be applied in rehabilitation therapies to facilitate neuromodulation. Our findings might shed light on the mechanism of neural responses to tACS and facilitate effectively designing stimulation protocols with tACS in stroke in the future.
Kinetics of Renal Function during Induction in Newly Diagnosed Multiple Myeloma: Results of Two Prospective Studies by the German Myeloma Study Group DSMM
Authors: Bachmann Friederike , Schreder Martin , Engelhardt Monika , Langer Christian , Wolleschak Denise , Mügge Lars Olof , Dürk Heinz , Schäfer-Eckart Kerstin , Blau Igor Wolfgang , Gramatzki Martin , Liebisch Peter , Grube Matthias , v Metzler Ivana , Bassermann Florian , Metzner Bernd , Röllig Christoph , Hertenstein Bernd , Khandanpour Cyrus , Dechow Tobias , Hebart Holger , Jung Wolfram , Theurich Sebastian , Maschmeyer Georg , Salwender Hans , Hess Georg , Bittrich Max , Rasche Leo , Brioli Annamaria , Eckardt Kai-Uwe , Straka Christian , Held Swantje , Einsele Hermann , Knop Stefan
Published: March 2021

Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
The Potential of Artificial Intelligence to Detect Lymphovascular Invasion in Testicular Cancer
Authors: Ghosh Abhisek , Sirinukunwattana Korsuk , Khalid Alham Nasullah , Browning Lisa , Colling Richard , Protheroe Andrew , Protheroe Emily , Jones Stephanie , Aberdeen Alan , Rittscher Jens , Verrill Clare
Published: March 2021

Testicular cancer is the most common cancer in men aged from 15 to 34 years. Lymphovascular invasion refers to the presence of tumours within endothelial-lined lymphatic or vascular channels, and has been shown to have prognostic significance in testicular germ cell tumours. In non-seminomatous tumours, lymphovascular invasion is the most powerful prognostic factor for stage 1 disease. For the pathologist, searching multiple slides for lymphovascular invasion can be highly time-consuming. The aim of this retrospective study was to develop and assess an artificial intelligence algorithm that can identify areas suspicious for lymphovascular invasion in histological digital whole slide images. Areas of possible lymphovascular invasion were annotated in a total of 184 whole slide images of haematoxylin and eosin (H&E) stained tissue from 19 patients with testicular germ cell tumours, including a mixture of seminoma and non-seminomatous cases. Following consensus review by specialist uropathologists, we trained a deep learning classifier for automatic segmentation of areas suspicious for lymphovascular invasion. The classifier identified 34 areas within a validation set of 118 whole slide images from 10 patients, each of which was reviewed by three expert pathologists to form a majority consensus. The precision was 0.68 for areas which were considered to be appropriate to flag, and 0.56 for areas considered to be definite lymphovascular invasion. An artificial intelligence tool which highlights areas of possible lymphovascular invasion to reporting pathologists, who then make a final judgement on its presence or absence, has been demonstrated as feasible in this proof-of-concept study. Further development is required before clinical deployment.
The Feasibility Study of Hypofractionated Radiotherapy with Regional Hyperthermia in Soft Tissue Sarcomas
Authors: Spałek Mateusz Jacek , Borkowska Aneta Maria , Telejko Maria , Wągrodzki Michał , Niebyłowska Daria , Uzar Aldona , Białobrzeska Magdalena , Rutkowski Piotr
Published: March 2021

Introduction: Management of marginally resectable or unresectable soft tissue sarcomas (STS) in patients who are not candidates for neoadjuvant chemotherapy due to chemoresistant pathology or contraindications remains a challenge. Therefore, in these indications, we aimed to investigate a feasibility of 10x 3.25 Gy radiotherapy combined with regional hyperthermia (HT) that could be followed by surgery or 4x 4 Gy radiotherapy with HT. Materials and methods: We recruited patients with locally advanced marginally resectable or unresectable STS who (1) presented chemoresistant STS subtype, or (2) progressed after neoadjuvant chemotherapy, or (3) were unfit for chemotherapy. The primary endpoint was the feasibility of the proposed regimen. Results: Thirty patients were enrolled. All patients received the first part of the treatment, namely radiotherapy with HT. Among them, 14 received the second part of radiotherapy with HT whereas 13 patients underwent surgery. Three patients did not complete the treatment protocol. The feasibility criteria were fulfilled in 90% of patients. Two patients developed distant metastases. One patient died due to distant progression. One patient developed rapid local recurrence after surgery. Conclusions: Hypofractionated radiotherapy with HT is a feasible treatment for marginally resectable or unresectable STS in patients who are not candidates for chemotherapy. Results of this clinical trial support the further validation of RT and HT combinations in STS.
The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review
Authors: Liu Ye , Mohri Zahra , Alsheikh Wissal , Cheema Umber
Published: March 2021

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.
Radiomics in Renal Cell Carcinoma—A Systematic Review and Meta-Analysis
Authors: Mühlbauer Julia , Egen Luisa , Kowalewski Karl-Friedrich , Grilli Maurizio , Walach Margarete T. , Westhoff Niklas , Nuhn Philipp , Laqua Fabian C. , Baessler Bettina , Kriegmair Maximilian C.
Published: March 2021

Radiomics may increase the diagnostic accuracy of medical imaging for localized and metastatic RCC (mRCC). A systematic review and meta-analysis was performed. Doing so, we comprehensively searched literature databases until May 2020. Studies investigating the diagnostic value of radiomics in differentiation of localized renal tumors and assessment of treatment response to ST in mRCC were included and assessed with respect to their quality using the radiomics quality score (RQS). A total of 113 out of 1098 identified studies met the criteria and were included in qualitative synthesis. Median RQS of all studies was 13.9% (5.0 points, IQR 0.25–7.0 points), and RQS increased over time. Thirty studies were included into the quantitative synthesis: For distinguishing angiomyolipoma, oncocytoma or unspecified benign tumors from RCC, the random effects model showed a log odds ratio (OR) of 2.89 (95%-CI 2.40–3.39, p < 0.001), 3.08 (95%-CI 2.09–4.06, p < 0.001) and 3.57 (95%-CI 2.69–4.45, p < 0.001), respectively. For the general discrimination of benign tumors from RCC log OR was 3.17 (95%-CI 2.73–3.62, p < 0.001). Inhomogeneity of the available studies assessing treatment response in mRCC prevented any meaningful meta-analysis. The application of radiomics seems promising for discrimination of renal tumor dignity. Shared data and open science may assist in improving reproducibility of future studies.
A Drastic Shift in Lipid Adducts in Colon Cancer Detected by MALDI-IMS Exposes Alterations in Specific K+ Channels
Authors: Garate Jone , Maimó-Barceló Albert , Bestard-Escalas Joan , Fernández Roberto , Pérez-Romero Karim , Martínez Marco A. , Payeras Mª Antònia , Lopez Daniel H. , Fernández José Andrés , Barceló-Coblijn Gwendolyn
Published: March 2021

Even though colorectal cancer (CRC) is one of the most preventable cancers, it is one of the deadliest, and recent data show that the incidence in people <50 years has unexpectedly increased. While new techniques for CRC molecular classification are emerging, no molecular feature is as yet firmly associated with prognosis. Imaging mass spectrometry (IMS) lipidomic analyses have demonstrated the specificity of the lipid fingerprint in differentiating pathological from healthy tissues. During IMS lipidomic analysis, the formation of ionic adducts is common. Of particular interest is the [Na+]/[K+] adduct ratio, which already functions as a biomarker for homeostatic alterations. Herein, we show a drastic shift of the [Na+]/[K+] adduct ratio in adenomatous colon mucosa compared to healthy mucosa, suggesting a robust increase in K+ levels. Interrogating public databases, a strong association was found between poor diagnosis and voltage-gated potassium channel subunit beta-2 (KCNAB2) overexpression. We found this overexpression in three CRC molecular subtypes defined by the CRC Subtyping Consortium, making KCNAB2 an interesting pharmacological target. Consistently, its pharmacological inhibition resulted in a dramatic halt in commercial CRC cell proliferation. Identification of potential pharmacologic targets using lipid adduct information emphasizes the great potential of IMS lipidomic techniques in the clinical field.
Autocrine TGFβ1 Opposes Exogenous TGFβ1-Induced Cell Migration and Growth Arrest through Sustainment of a Feed-Forward Loop Involving MEK-ERK Signaling
Authors: Ungefroren Hendrik , Christl Jessica , Eiden Caroline , Wellner Ulrich F. , Lehnert Hendrik , Marquardt Jens-Uwe
Published: March 2021

Autocrine transforming growth factor β (aTGFβ) has been implicated in the regulation of cell invasion and growth of several malignant cancers such as pancreatic ductal adenocarcinoma (PDAC) or triple-negative breast cancer (TNBC). Recently, we observed that endogenous TGFB1 can inhibit rather than stimulate cell motility in cell lines with high aTGFβ production and mutant KRAS, i.e., Panc1 (PDAC) and MDA-MB-231 (TNBC). The unexpected anti-migratory role prompted us to evaluate if aTGFβ1 may be able to antagonize the action of exogenous (recombinant human) TGFβ (rhTGFβ), a well-known promoter of cell motility and growth arrest in these cells. Surprisingly, RNA interference-mediated knockdown of the endogenous TGFB1 sensitized genes involved in EMT and cell motility (i.e., SNAI1) to up-regulation by rhTGFβ1, which was associated with a more pronounced migratory response following rhTGFβ1 treatment. Ectopic expression of TGFB1 decreased both basal and rhTGFβ1-induced migratory activities in MDA-MB-231 cells but had the opposite effect in Panc1 cells. Moreover, silencing TGFB1 reduced basal proliferation and enhanced growth inhibition by rhTGFβ1 and induction of cyclin-dependent kinase inhibitor, p21WAF1. Finally, we show that aTGFβ1 promotes MEK-ERK signaling and vice versa to form a self-perpetuating feedforward loop that is sensitive to SB431542, an inhibitor of the TGFβ type I receptor, ALK5. Together, these data suggest that in transformed cells an ALK5-MEK-ERK-aTGFβ1 pathway opposes the promigratory and growth-arresting function of rhTGFβ1. This observation has profound translational implications for TGFβ signaling in cancer.
How Chaotic Is Genome Chaos?
Authors: Shapiro James A.
Published: March 2021

Cancer genomes evolve in a punctuated manner during tumor evolution. Abrupt genome restructuring at key steps in this evolution has been called “genome chaos.” To answer whether widespread genome change is truly chaotic, this review (i) summarizes the limited number of cell and molecular systems that execute genome restructuring, (ii) describes the characteristic signatures of DNA changes that result from activity of those systems, and (iii) examines two cases where genome restructuring is determined to a significant degree by cell type or viral infection. The conclusion is that many restructured cancer genomes display sufficiently unchaotic signatures to identify the cellular systems responsible for major oncogenic transitions, thereby identifying possible targets for therapies to inhibit tumor progression to greater aggressiveness.
The Prognostic Role of LRIG Proteins in Endometrial Cancer
Authors: Razumova Zoia , Oda Husam , Govorov Igor , Lundin Eva , Östensson Ellinor , Lindquist David , Mints Miriam
Published: March 2021

Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor proteins in EC. The initial study cohort included 100 women with EC who were treated at the Department of Women’s and Children’s Health, Karolinska University Hospital Solna, between 2007 and 2012. We assessed the associations between LRIG protein expression and type, grade, and stage of EC, as well as progression-free and overall survival. Immunohistochemistry results revealed that most women in the analytical sample had >50% LRIG1-, LRIG2- and LRIG3-positive cells. A statistically significant association was observed between having a high number of LRIG3-positive cells and superior overall survival (incidence rate ratio = 0.977; 95% confidence interval: 0.958–0.996, p = 0.019). Moreover, positive LRIG3 staining of the cell membrane was associated with reducing in the risk of death (hazard ratio = 0.23; 95% confidence interval: 0.09–0.57). Our results show that LRIG3 expression might be a prognostic factor in EC. The role of LRIG1 and LRIG2 expression remains to be further investigated.
The MAMs Structure and Its Role in Cell Death
Authors: Wang Nan , Wang Chong , Zhao Hongyang , He Yichun , Lan Beiwu , Sun Liankun , Gao Yufei
Published: March 2021

The maintenance of cellular homeostasis involves the participation of multiple organelles. These organelles are associated in space and time, and either cooperate or antagonize each other with regards to cell function. Crosstalk between organelles has become a significant topic in research over recent decades. We believe that signal transduction between organelles, especially the endoplasmic reticulum (ER) and mitochondria, is a factor that can influence the cell fate. As the cellular center for protein folding and modification, the endoplasmic reticulum can influence a range of physiological processes by regulating the quantity and quality of proteins. Mitochondria, as the cellular “energy factory,” are also involved in cell death processes. Some researchers regard the ER as the sensor of cellular stress and the mitochondria as an important actuator of the stress response. The scientific community now believe that bidirectional communication between the ER and the mitochondria can influence cell death. Recent studies revealed that the death signals can shuttle between the two organelles. Mitochondria-associated membranes (MAMs) play a vital role in the complex crosstalk between the ER and mitochondria. MAMs are known to play an important role in lipid synthesis, the regulation of Ca2+ homeostasis, the coordination of ER-mitochondrial function, and the transduction of death signals between the ER and the mitochondria. Clarifying the structure and function of MAMs will provide new concepts for studying the pathological mechanisms associated with neurodegenerative diseases, aging, and cancers. Here, we review the recent studies of the structure and function of MAMs and its roles involved in cell death, especially in apoptosis.
Signaling Pathways in Cancer: Therapeutic Targets, Combinatorial Treatments, and New Developments
Authors: Yip Hon Yan Kelvin , Papa Antonella
Published: March 2021

Molecular alterations in cancer genes and associated signaling pathways are used to inform new treatments for precision medicine in cancer. Small molecule inhibitors and monoclonal antibodies directed at relevant cancer-related proteins have been instrumental in delivering successful treatments of some blood malignancies (e.g., imatinib with chronic myelogenous leukemia (CML)) and solid tumors (e.g., tamoxifen with ER positive breast cancer and trastuzumab for HER2-positive breast cancer). However, inherent limitations such as drug toxicity, as well as acquisition of de novo or acquired mechanisms of resistance, still cause treatment failure. Here we provide an up-to-date review of the successes and limitations of current targeted therapies for cancer treatment and highlight how recent technological advances have provided a new level of understanding of the molecular complexity underpinning resistance to cancer therapies. We also raise three basic questions concerning cancer drug discovery based on molecular markers and alterations of selected signaling pathways, and further discuss how combination therapies may become the preferable approach over monotherapy for cancer treatments. Finally, we consider novel therapeutic developments that may complement drug delivery and significantly improve clinical response and outcomes of cancer patients.
Novel Gene Regulation in Normal and Abnormal Spermatogenesis
Authors: Du Li , Chen Wei , Cheng Zixin , Wu Si , He Jian , Han Lu , He Zuping , Qin Weibing
Published: March 2021

Spermatogenesis is a complex and dynamic process which is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulating the normal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubular myoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.
Effect of Calcium Carbonate Particle Size on the Scratch Resistance of Rapid Alkyd-Based Wood Coatings
Authors: Ersoy Orkun , Fidan Sinan , Köse Harun , Güler Dilek , Özdöver Ömer
Published: March 2021

Polymer-based wood coatings are used for aesthetic purposes as well as to protect wood surfaces, especially under external conditions. High-hardness mineral fillers are thought to enhance the resistance of these polymer coatings to wear and scratching. However, recent studies suggest that the relatively low-hardness mineral calcite (CaCO3, Mohs hardness of 3) performs similarly to harder minerals under external conditions. It can replace more expensive hard minerals, thus driving research interest in its use. In this study, CaCO3 powders with different grain sizes were applied to rapid alkyd-based coating formulations, and the effect of CaCO3 particle size on the scratch behavior of the coatings was investigated under identical test conditions. The scratch morphologies, scratch hardness, and roughness values of the scratched surfaces indicated that the surfaces of the rapid alkyd-based wood coatings including finer-grained CaCO3 experienced plastic plowing-type deformation in the form of regular, narrow, and shallow scratches, showing high scratch resistance. Coatings using coarser-grained CaCO3 experienced more extensive plastic deformation of the plowing–tearing type owing to the weaker filler–polymer interface and the breakage of larger coating pieces from the coating surface.