bluuebunny/crossref_metadata_2025 huggingface dataset:
The growth and morphology of microgreens is associated with modified ascorbate and anthocyanin profiles in response to the intensity of sole-source light-emitting diodes
Authors: Jones-Baumgardt Chase , Ying Qinglu , Zheng Youbin , Bozzo Gale G.
Published: September 2020

Sole-source light-emitting diodes (LEDs) are alternatives to fluorescent tubes and high intensity discharge lamps that are routinely used for indoor cultivation of horticultural commodities, including microgreens. This study examined the effect of photosynthetic photon flux density (PPFD) from LEDs on phytochemical profiles of organically grown kale, cabbage, arugula, and mustard microgreens, and their association with growth and morphological attributes. LEDs were used to deliver a 15% blue light and 85% red light mixture to microgreens at varying PPFDs between 100 and 600 μmol·m−2·s−1. For all microgreens, increased concentrations of ascorbate (total and reduced) and total anthocyanin were proportional to PPFD. Total phenolic concentrations were elevated in all four microgreens at high PPFDs, whereas chlorophyll concentrations declined in arugula, cabbage, and mustard. A principal component analysis revealed anthocyanins and phenolics were associated with ascorbate levels in all microgreens, but not with chlorophylls or carotenoids. At high PPFDs photosynthetic pigment levels were negatively associated with fresh and dry weight to varying degrees. Anthocyanins, phenolics, and ascorbate were negatively correlated with hypocotyl length and the colour attribute hue angle in all microgreens. These results indicate that microgreen growth and morphology are associated with altered phytochemical profiles during cultivation under sole-source LEDs.
Review of nuclear techniques for planetary science
Authors: Parsons Ann M.
Published: September 2020

Spaceflight instruments that measure the energy and intensity of gamma rays and neutrons emitted by the surfaces of planetary bodies have been included in planetary science missions since 1966. These instruments use nuclear techniques to determine the elemental composition and related information about planetary surface and near-surface materials from the analysis of these gamma ray and neutron data. This paper provides a short review of these nuclear techniques as they have been used in current and past orbital and landed missions. A description of the nuclear instrumentation on many such missions is provided. Finally, descriptions of future missions that will employ gamma ray and neutron instruments will be presented.
Absolute calibration for film dosimetry
Authors: Casolaro Pierluigi , Campajola Luigi , Breglio Giovanni , Buontempo Salvatore , Consales Marco , Cusano Andrea , Cutolo Antonello , Di Capua Francesco , Fienga Francesco , Vaiano Patrizio
Published: September 2020

Recent results in the field of film dosimetry demonstrated that the Green–Saunders equation, a solution of the logistic equation describing phenomena of kinetics of chemical reactions, is the absolute calibration function for all radiochromic film types. Taking advantage of the new opto-electronics-based radiochromic film reading method, which allows real-time measurements of the spectral response of radiochromic films, we confirm that the film darkening is ruled by the Green–Saunders equation independently both from the reading instrument or the choice of the observable used for the calibration. In order to demonstrate it, we exposed an XR-QA2 Gafchromic film to 90Sr/90Y beta rays up to 1400 mGy. Film spectra are recorded in real-time. The calibration is performed by means of two analytic methods: evaluation of the integral under the curves from 500 nm to 645 nm and evaluation of the intensity at 570, 600 and 643 nm. Experimental data fit to the Green–Saunders equation for both methods.
Particle therapy and radioprotection in space with the FOOT experiment
Authors: Mengarelli Alberto
Published: September 2020

The evaluation of nuclear fragmentation contribution on the delivered dose during particle therapy treatment is still an open point. The FOOT (FragmentatiOn Of Target) experiment aims to improve the actual knowledge of nuclear physics by measuring the differential cross section as a function of the energy and angle of the fragments produced when an external particle beam interacts with patent tissues during hadrontherapy treatment. Depending on the beam energy, the purpose of the measurements is dual: in the range of 150–400 MeV/u, they will be used to evaluate the side effects of the nuclear fragmentation in the hadrontherapy treatment, while in the range of 700–1000 MeV/u (typical of cosmic galactic rays) they will be used to optimize the shielding of the spaceship for long term space missions. The FOOT detector includes a pre-target region with a first plastic scintillator for time of flight (TOF) and trigger purpose, and a beam monitor drift chamber to evaluate the beam direction (necessary for the inverse kinematic approach); a magnetic spectrometer to measure the momentum of fragments; and finally a second plastic scintillator for deposited energy (ΔE) and TOF measurements, and a scintillating crystal calorimeter to measure the kinetic energy of fragments. These measurements will be combined to accurately identify the charge and mass of fragments. The experiment, funded by the INFN since September 2017, is in the construction phase. It has performed several test beams, while the full detector data taking is scheduled in the next few years. A full description of the different setups together with the performances obtained with the latest geometry studies are reported here.
Effects of electron irradiation on spectrometric properties of Schottky barrier CdTe radiation detectors
Authors: Sedlačková Katarína , Zaťko Bohumír , Pavlovič Márius , Šagátová Andrea , Nečas Vladimír
Published: September 2020

High detection efficiency and good room temperature performance of Schottky barrier CdTe semiconductor detectors make them well suited especially for X-ray and gamma-ray detectors. In this contribution, we studied the effect of electron irradiation on the spectrometric performance of the Schottky barrier CdTe detectors manufactured from the chips of size [Formula: see text] mm3 with In/Ti anode and Pt cathode electrodes (Acrorad Co., Ltd.). Electron irradiation of the detectors was performed by 5 MeV electrons at RT using a linear accelerator UELR 5-1S. Different accumulated doses from 0.5 kGy up to 1.25 kGy were applied and the consequent degradation of the spectrometric properties was evaluated by measuring the pulse-height gamma-spectra of [Formula: see text] radioisotope source. The spectra were collected at different reverse voltages from 300 V up to 500 V. The changes of selected significant parameters, like energy resolution, peak position, detection efficiency and leakage current were monitored and evaluated to quantify the radiation hardness of the studied detectors. The results showed remarkable worsening of their spectrometric parameters even at relatively low applied doses of 1.25 kGy.
A Combined Finite Element Method with Normal Mode for the Elastic Structural Acoustic Radiation in Shallow Water
Authors: An Buchao , Zhang Chao , Shang Dejiang , Xiao Yan , Khan Imran Ullah
Published: September 2020

A combined Finite Element Method with Normal Mode (FEM-NM) is proposed for calculation of the acoustic field radiated by a three-dimensional structural source in shallow water. The FEM is used to calculate the near range acoustic field, then the modes expansion at the vertical and azimuthal direction is performed at a certain coupling range. Hence, the true three-dimensional acoustic field at any range is obtained rapidly by the NM theory. The numerical examples show the efficiency and accuracy of this method. The coupling range and the truncation of the vertical modes hardly affect the far field results.
Modulation of the inflammatory response to LPS by the recruitment and activation of brown and brite adipocytes in mice
Authors: Munro Patrick , Dufies Océane , Rekima Samah , Loubat Agnès , Duranton Christophe , Boyer Laurent , Pisani Didier F.
Published: September 2020

Recruitment and activation of brown and brite adipocytes in the adipose tissue of mice lead to a local low-grade anti-inflammatory phenotype in response to acute endotoxemia without alteration of adipocyte phenotype and function.
An obesogenic maternal environment impairs mouse growth patterns, satellite cell activation, and markers of postnatal myogenesis
Authors: Mikovic Jasmine , Brightwell Camille , Lindsay Angus , Wen Yuan , Kowalski Greg , Russell Aaron P. , Fry Christopher S. , Lamon Séverine
Published: September 2020

Skeletal muscle is sensitive to environmental cues that are first present in utero. Maternal overnutrition is a model of impaired muscle development leading to structural and metabolic dysfunction in adult life. In this study, we investigated the effect of an obesogenic maternal environment on growth and postnatal myogenesis in the offspring. Male C57BL/6J mice born to chow- or high-fat-diet-fed mothers were allocated to four different groups at the end of weaning. For the following 10 wk, half of the pups were maintained on the same diet as their mother and half of the pups were switched to the other diet (chow or high-fat). At 12 wk of age, muscle injury was induced using an intramuscular injection of barium chloride. Seven days later, mice were humanely killed and muscle tissue was harvested. A high-fat maternal diet impaired offspring growth patterns and downregulated satellite cell activation and markers of postnatal myogenesis 7 days after injury without altering the number of newly synthetized fibers over the whole 7-day period. Importantly, a healthy postnatal diet could not reverse any of these effects. In addition, we demonstrated that postnatal myogenesis was associated with a diet-independent upregulation of three miRNAs, mmu-miR-31–5p, mmu-miR-136–5p, and mmu-miR-296–5p. Furthermore, in vitro analysis confirmed the role of these miRNAs in myocyte proliferation. Our findings are the first to demonstrate that maternal overnutrition impairs markers of postnatal myogenesis in the offspring and are particularly relevant to today’s society where the incidence of overweight/obesity in women of childbearing age is increasing.
Entanglement Research for the Coupled Superconducting Phase Qubit and a Two-Level System
Authors: Shi Jianxin
Published: September 2020

Entanglement can exist not only in the microscopic system (e.g., atom, photon, and ion trap) but also in macroscopic systems. According to recent research, entanglement can be achieved and controlled in superconducting devices. The quantum dynamics and entanglement mechanism of the coupled superconducting phase qubit and a two-level system (TLS) were demonstrated when the bipartite system was under microwave driving. Besides, the results reveal that when the system was experiencing decoherence, entanglement (concurrence) of the coupled superconducting phase qubit and TLS would oscillate damply with microwave driving time, even exhibiting concurrence sudden death and revival. The coupling effect of the superconducting qubit and TLS system and the resonant microwave together help to achieve entanglement, while concurrence death and concurrence revival are dependent on the decoherence source and mechanism, for example, the resonant microwave driving time acting on the bipartite coupling system. Furthermore, the simulation results show the entanglement of the coupled qubit and TLS system also depends on the purity of the initial states of the system. The article carried out a numerical simulation on the entanglement of different initial states, and the results showed that the entanglement of the coupled system changes with different initial states. For different initial states, entanglement, sudden death, and rejuvenation are still visible.
Digital PCR for the Analysis of MYC Copy Number Variation in Lung Cancer
Authors: Brik Alexander , Weber Daniel G. , Casjens Swaantje , Rozynek Peter , Meier Swetlana , Behrens Thomas , Stamatis Georgios , Darwiche Kaid , Theegarten Dirk , Brüning Thomas , Johnen Georg
Published: September 2020

Background. MYC (v-myc avian myelocytomatosis viral oncogene homolog) is one of the most frequently amplified genes in lung tumors. For the analysis of gene copy number variations, dPCR (digital PCR) is an appropriate tool. The aim of our study was the assessment of dPCR for the detection of MYC copy number variations (CNV) in lung tissue considering clinicopathological parameters. Material and Methods. MYC status was analyzed with dPCR as well as qPCR (quantitative PCR) using gDNA (genomic DNA) from tumor and adjacent nontumor tissue samples of lung cancer patients. The performance of MYC was estimated based on the AUC (area under curve). Results. The results of the MYC amplification correlated significantly between dPCR and qPCR (rS=0.81, P<0.0001). The MYC copy number revealed by dPCR showed statistically significant differences between tumor and adjacent nontumor tissues. For discrimination, a sensitivity of 43% and a specificity of 99% were calculated, representing 55 true-positive and one false-positive tests. No statistically significant differences could be observed for age, sex, and smoking status or the clinicopathological parameters (histological subtype, grade, and stage). Conclusion. The results of the study show that dPCR is an accurate and reliable method for the determination of MYC copy numbers. The application is characterized by high specificity and moderate sensitivity. MYC amplification is a common event in lung cancer patients, and it is indicated that the determination of the MYC status might be useful in clinical diagnostics.
Calibration of MEMS Triaxial Accelerometers Based on the Maximum Likelihood Estimation Method
Authors: Sun Yifan , Xu Xiang
Published: September 2020

As a widely used inertial device, a MEMS triaxial accelerometer has zero-bias error, nonorthogonal error, and scale-factor error due to technical defects. Raw readings without calibration might seriously affect the accuracy of inertial navigation system. Therefore, it is necessary to conduct calibration processing before using a MEMS triaxial accelerometer. This paper presents a MEMS triaxial accelerometer calibration method based on the maximum likelihood estimation method. The error of the MEMS triaxial accelerometer comes into question, and the optimal estimation function is established. The calibration parameters are obtained by the Newton iteration method, which is more efficient and accurate. Compared with the least square method, which estimates the parameters of the suboptimal estimation function established under the condition of assuming that the mean of the random noise is zero, the parameters calibrated by the maximum likelihood estimation method are more accurate and stable. Moreover, the proposed method has low computation, which is more functional. Simulation and experimental results using the consumer low-cost MEMS triaxial accelerometer are presented to support the abovementioned superiorities of the maximum likelihood estimation method. The proposed method has the potential to be applied to other triaxial inertial sensors.
Application of Multispectral Imaging in the Human Tympanic Membrane
Authors: Tran Van Tien , Lu Thi Thao Mi , Bui Mai Quynh Linh , Phan Ngoc Khuong Cat , Huynh Quang Linh
Published: September 2020

Multispectral imaging has recently shown good performance in determining information about physiology, morphology, and composition of tissue. In the endoscopy field, many researches have shown the ability to apply multispectral or narrow-band images in surveying vascular structure based on the interaction of light wavelength with tissue composition. However, there has been no mention to assess the contrast between other components in the middle ear such as the tympanic membrane, malleus, and the surrounding area. Using CT, OCT, or ODT can clearly describe the tympanic membrane structure; nevertheless, these approaches are expensive, more complex, and time-consuming and are not suitable for most common middle ear diagnoses. Here, we show the potential of using the multispectral imaging technique to enhance the contrast of the tympanic membrane compared to the surrounding tissue. The optical absorption and scattering of biological tissues constituents are not the same at different wavelengths. In this pilot study, multiwavelength images of the tympanic membrane were captured by using the otoscope with LED light source at three distinct spectral regions: 450 nm, 530 nm, and 630 nm. Subsequently, analyses of the intensity images as well as the histogram of these images point out that the 630 nm illumination image features an evident contrast in the intensity of the tympanic membrane and malleus compared to the surrounding area. Analysis of such images could facilitate the boundary determination and segmentation of the tympanic membrane (TM) with high precision.
Distributed Congestion Control via Outage Probability Model for Delay-Constrained Flying Ad Hoc Networks
Authors: Wen Shaojie , Deng Lianbing , Shi Shuo , Fan Xiying , Li Hao
Published: September 2020

Drastic changes in network topology of Flying Ad Hoc Networks (FANETs) result in the instability of the single-hop delay and link status accordingly. Therefore, it is difficult to implement the congestion control with delay-sensitive traffic according to the instantaneous link status. To solve the above difficulty effectively, we formulate the delay-aware congestion control as a network utility maximization, which considers the link capacity and end-to-end delay as constraints. Next, we combine the Lagrange dual method and delay auxiliary variable to decouple the link capacity and delay threshold constraints, as well as to update single-hop delay bound with the delay-outage mode. Built on the methods above, a distributed optimization algorithm is proposed in this work by considering the estimated single-hop delay bound for each transmission, which only uses the local channel information to limit the end-to-end delay. Finally, we deduce the relationship between the primal and dual solutions to underpin the advantages of the proposed algorithm. Simulation results demonstrate that the proposed algorithm effectively can improve network performances in terms of packet time-out rate and network throughput.
Experimental Study on Inverse Model-Based Force Tracking Control of MR Damper
Authors: Wei Shuli , Wang Jian , Ou Jinping
Published: September 2020

An explicit inverse model of a magnetorheological (MR) damper is established to track the desired force in real time through experimental analysis and mathematical modeling. An algebraic hyperbolic tangent model is used to present the nonlinear behavior of MR dampers to avoid dynamic evolution due to effortless invertibility. A characteristic method is utilized to obtain the initial parameters of this algebraic hyperbolic tangent model; subsequently, the main parameters of the algebraic model are selected as quadratic functions of the applied current such that the closed-form expressions of the inverse model can be obtained. Then, the response time including communication and electromagnetic interactions in the experiment is investigated and modeled. By combining the force-current and electromagnetic models, an inverse model-based force tracking scheme is proposed. A series of validated tests are performed to study the force tracking performance. The proposed model exhibits high fidelity for tracking variable desired forces in experiments. Further analysis on force tracking errors demonstrates the mitigation of errors in various current fluctuating methods.
Metallic Contamination of the Muscles of Three Fish Species from the Moulouya River (Lower Moulouya, Eastern Morocco)
Authors: Mahjoub Mohammed , El Maadoudi Mohammed , Smiri Youssef
Published: September 2020

This study introduces a spatiotemporal evaluation of the metallic contamination with three trace metals (mercury, lead, and cadmium) in the muscles of three fish species (Lepomis macrochirus, Barbus callensis, and Barbus nasus), of which the samples were taken from three stations in the Moulouya River: the confluence of the Moulouya River and the Sebra River (station 1), the neighbourhood of the farms in the region of Aklim downstream from confluence of Lakhmis river (station 2), and the level of ancient bridge of Ras El Ma-Moulouya (station 3), during the period from July 2017 to May 2018. The results have allowed us to highlight rather high contents of lead and mercury in the fish muscles, mainly in station 1, which receives domestic and industrial discharges. The contents of cadmium in all fish species in different stations are very low. Moreover, all concentrations assessed in different fish species do not exceed the maximum limit recommended by European Community (EC) Commission Regulation No. 1881/2006.
Multiprocessor Scheduling of Sensor Transactions for Real-Time Data Quality Maintenance
Authors: Bai Tian , Li Zhijie , Fan Bo
Published: September 2020

In cyber-physical systems, sensor transactions should be effectively scheduled to maintain the temporal validity of real-time data objects. Previous studies on sensor transaction scheduling mainly focus on uniprocessor systems. In this paper, we study the problem of data quality-based scheduling of sensor transactions on multiprocessor platforms. The data quality is defined to describe the validity degree of real-time data objects. Two methods, named the Partitioned Scheduling for Quality Maximization (P-QM) and the improved P-QM scheduling (IP-QM), are proposed. P-QM maximizes the data quality by judiciously determining the preallocated computation time of each sensor transaction and assigns the transactions to different processors. IP-QM improves the data quality obtained from P-QM by adaptively executing transaction instances on each processor based on the current status of the system. It is demonstrated through experiments that IP-QM can provide higher data quality than P-QM under different system workloads.
Assessing the Risk Probability of the Embankment Seismic Damage Using Monte Carlo Method
Authors: Che Fa , Yin Chao , Zhang Han , Tang Gangting , Hu Zhinan , Liu Dong , Li Ying , Huang Zhanfang
Published: September 2020

There are few systematic studies on the risk probability assessment, although embankment seismic damages are extremely serious. Meanwhile, retaining walls and other retaining structures play positive roles in improving the embankment seismic performance, but relevant quantitative study is rarely reported. In particular, there are few existing studies on the seismic damage characteristics of the embankment fill‐soil foundation system and the retaining structure‐embankment fill‐soil foundation system under different seismic actions. In view of this, the Xi’an‐Baoji expressway K1125 + 470 embankment was taken as the research object, the risk probability assessment of the embankment seismic damage was conducted on the basis of the seismic fragility and seismic hazard assessment, the positive role of the retaining wall in improving the embankment seismic performance was verified, and the seismic damage evolution processes of the retaining wall‐embankment fill‐soil foundation system and the embankment fill‐soil foundation system were analyzed. The research results show that the risk probabilities of the severe damage and destruction of the embankment fill‐soil foundation system are 29.07% and 7.62% in the next 50 years, while of the retaining wall‐embankment fill‐soil foundation system are 19.30% and 3.46% and are reduced by 33.61% and 54.60%, respectively. The influence of the retaining wall on the embankment seismic performance mainly occurs at the middle stage of a violent earthquake, but the seismic damages of the retaining wall itself are also very serious, and the engineering disturbance of the retaining wall is reduced greatly or even lost completely at the final stage of the violent earthquake.
Numerical Modelling of Interaction between Hydraulic Fractures and Natural Fractures by Using the Extended Finite Element Method
Authors: Li Peilun , Dong Yan , Wang Sheng , Li Peichao
Published: September 2020

Natural fractures usually develop in shale reservoirs. Thereby, in the process of hydraulic fracturing, it is inevitable that hydraulic fractures will intersect with natural fractures. In order to reveal the interaction mechanism between hydraulic‐induced fractures and natural fractures, a two‐dimensional fracture intersection model based on the extended finite element method (XFEM) is proposed, and the different types of intersecting criteria reported in the literature are compared. Then, the effects of natural fracture azimuth, fluid pressure in hydraulic fracture, and in situ principal stress difference on hydraulic fracturing are studied in detail. The results show that the fracture morphology is different under different criteria and working conditions. And the stress concentration phenomenon mainly concentrates on the tip in the obtuse angle side of natural fracture. Meanwhile, different fluid pressures in hydraulic fracture can also induce different intersection patterns. The obtained results in this work are of great benefit to understand the intersection mechanism between hydraulic fractures and natural fractures.
Sevoflurane-Induced Thrombocytopenia in Post-Robotic-Assisted Paraesophageal Hernia Repair
Authors: Alhaj Sara , Tran James , Nazim Muhammad , Tumula Praveen , Ahmed Hassan
Published: September 2020

Background. Transient transaminitis is an expected outcome from liver retraction after foregut surgeries. However, severe thrombocytopenia is usually not a sequela of that. We present a case in which sevoflurane is suspected of inducing thrombocytopenia as it was the only newly introduced medication to the patient during the hospital course. Thrombocytopenia may present in a variety of settings in hospitalized patients. However, managing this occurrence requires deep exploration of pathophysiology that can cause decreased platelets, which may be a challenging task in certain circumstances. The liver plays an important role in thrombopoiesis by releasing megakaryocyte growth factors. Therefore, liver dysfunction can present as thrombocytopenia or other platelet dysfunctions. Objective. To describe a presentation of thrombocytopenia possibly associated with anesthesia-induced transaminitis after a robotic paraesophageal hernia repair with mesh and fundoplasty with intraoperative esophagogastroduodenoscopy (EGD). Methods. A 55-year-old presented to the ED with abdominal pain and was found to have a large type IV paraesophageal hernia that was surgically treated with a robotic paraesophageal hernia repair with mesh. However, on the first postoperative day (POD) (#1), the patient developed new onset thrombocytopenia with transaminitis. Workup for thrombocytopenia failed to determine an etiology. With platelet transfusion, platelet count showed an upward trend. The patient was then evaluated and cleared for discharge by POD#5. Results. The patient’s POD#1 daily labs showed elevated values for liver function tests and a low platelet count of 10,000 platelets per microliter with an international normalized value (INR) of 1.3. She had received two doses of intravenous acetaminophen just prior to surgery. Her platelet count responded to two units of platelets but decreased again immediately after. She continued to have transaminitis with down-trending liver enzymes. Peripheral smear on review showed no evidence of schistocytes. A heparin-induced thrombocytopenia (HIT) screening was negative. The patient was regularly evaluated, and the platelets stabilized and slowly started to trend up. The patient recovered by the morning of her POD#5 and was cleared for discharge. Conclusion. We are reporting on a case of acute postoperative thrombocytopenia that was associated with transaminitis and elevated liver enzymes. We are linking the role of the liver dysfunction in noncirrhotic patients with surgical abdominal procedures. Although liver retraction transaminitis possibly played a role in the laboratory findings in the patient, the acute drop in her platelet count could be closely related to the use of sevoflurane anesthetic considering its potential hepatotoxic side effects. We also cannot rule out the sevoflurane directly affecting the platelet count.
Effect of Emotion on Prospective Memory in Those of Different Age Groups
Authors: Xian Jinhua , Wang Yan , Han Buxin
Published: September 2020

The effect of emotion on prospective memory on those of different age groups and its neural mechanism in Chinese adults are still unclear. The present study investigated the effect of emotion on prospective memory during the encoding and retrieval phases in younger and older adults by using event-related potentials (ERPs). In the behavioral results, a shorter response time was found for positive prospective memory cues only in older group. In the ERP results, during the encoding phase, an increased late positive potential (LPP) was found for negative prospective memory cues in younger adults, while the amplitude of the LPP was marginally greater for positive prospective memory cues than for negative prospective memory cues in older adults. Correspondingly, younger adults showed an increased parietal positivity for negative prospective memory cues, while an elevated parietal positivity for positive prospective memory cues was found in older adults during the retrieval phase. This finding reflects the increased attentional processing of encoding and the more cognitive resources recruited to carry out a set of processes that are associated with the realization of delayed intentions when the prospective memory cues are emotional. The results reveal the effect of emotion on prospective memory during the encoding and retrieval phases in Chinese adults, modulated by aging, as shown by a positivity effect on older adults and a negativity bias in younger adults.
CHD7 Regulates Osteogenic Differentiation of Human Dental Follicle Cells via PTH1R Signaling
Authors: Liu Caojie , Li Qiwen , Xiao Qingyue , Gong Ping , Kang Ning
Published: September 2020

Chromodomain helicase DNA-binding protein 7 (CHD7) is an ATP-dependent chromatin remodeling enzyme, functioning as chromatin reader to conduct epigenetic modification. Its effect on osteogenic differentiation of human dental follicle cells (hDFCs) remains unclear. Here, we show the CHD7 expression increases with osteogenic differentiation. The knockdown of CHD7 impairs the osteogenic ability of hDFCs, characterized by reduced alkaline phosphatase activity and mineralization, and the decreased expression of osteogenesis-related genes. Conversely, the CHD7 overexpression enhances the osteogenic differentiation of hDFCs. Mechanically, RNA-seq analyses revealed the downregulated enrichment of PTH (parathyroid hormone)/PTH1R (parathyroid hormone receptor-1) signaling pathway after CHD7 knockdown. We found the expression of PTH1R positively correlates with CHD7. Importantly, the overexpression of PTH1R in CHD7-knockdown hDFCs partially rescued the impaired osteogenic differentiation. Our research demonstrates that CHD7 regulates the osteogenic differentiation of hDFCs by regulating the transcription of PTH1R.
Management of a Splenic Artery Aneurysm in the Third Trimester of Pregnancy
Authors: Zarudskaya Oxana , Subash Madanika , Tamirisa Anita , Docheva Nikolina , Reddy Balaji , Zoorob Dani
Published: September 2020

Background. Splenic artery aneurysm (SAA) is a rare but potentially fatal complication associated with high maternal and fetal mortality when occurring during pregnancy. Case. A 29-year-old G4P3003 at 34 4/7 weeks of gestation was admitted with left upper quadrant pain and newly diagnosed SAA in the hilum. She was scheduled for embolization of the SAA but the night before went into labor. A multidisciplinary team discussion was held, and the patient underwent successful primary low transverse c-section via Pfannenstiel skin incision followed by laparoscopic splenectomy under general anesthesia. She delivered a male newborn with birth weight of 2855 and Apgar score of 8/5. Summary and Conclusion. Early diagnosis and management of SAA are key for improved maternal and fetal outcomes. Our case demonstrates that through a multidisciplinary approach and anticipation of the possible clinical scenarios, good outcomes can be achieved.
Brittle Characteristic and Microstructure of Sandstone under Freezing‐Thawing Weathering
Authors: Yu Songtao , Deng Junren , Deng Hongwei , Gao Feng , Li Jielin
Published: September 2020

As an important property of rock material, brittleness plays a vital role in rock engineering. This paper raised the concept of elastic strain energy release rate and proposed an elastic strain energy release rate based brittleness index based on the most acceptable definition of brittleness. Mechanical and Nuclear Magnetic Resonance parameters of sandstone under various Freezing‐Thawing (F‐T) cycles are also acquired and analyzed. Then, the proposed brittleness index is used to compare with two recently proposed brittleness indices to verify its correctness and applicability. Finally, the brittleness index is applied to evaluate the brittle behavior of F‐T cycles treated sandstone under uniaxial compression. The results show that elastic modulus, value of the postpeak modulus, and peak stress decrease with F‐T cycles, and the porosity and microstructure develop with F‐T cycles. The proposed brittleness index is highly related to F‐T cycles, peak stress, porosity, and elastic modulus of sandstone that suffered recurrent F‐T cycles. It declines exponentially with F‐T cycles and porosity increase while growing exponentially with peak stress and elastic modulus increase.
A Novel Convex Clustering Method for High-Dimensional Data Using Semiproximal ADMM
Authors: Chen Huangyue , Kong Lingchen , Li Yan
Published: September 2020

Clustering is an important ingredient of unsupervised learning; classical clustering methods include K-means clustering and hierarchical clustering. These methods may suffer from instability because of their tendency prone to sink into the local optimal solutions of the nonconvex optimization model. In this paper, we propose a new convex clustering method for high-dimensional data based on the sparse group lasso penalty, which can simultaneously group observations and eliminate noninformative features. In this method, the number of clusters can be learned from the data instead of being given in advance as a parameter. We theoretically prove that the proposed method has desirable statistical properties, including a finite sample error bound and feature screening consistency. Furthermore, the semiproximal alternating direction method of multipliers is designed to solve the sparse group lasso convex clustering model, and its convergence analysis is established without any conditions. Finally, the effectiveness of the proposed method is thoroughly demonstrated through simulated experiments and real applications.
PET Reporter Gene Imaging and Ganciclovir-Mediated Ablation of Chimeric Antigen Receptor T Cells in Solid Tumors
Authors: Murty Surya , Labanieh Louai , Murty Tara , Gowrishankar Gayatri , Haywood Tom , Alam Israt S. , Beinat Corinne , Robinson Elise , Aalipour Amin , Klysz Dorota D. , Cochran Jennifer R. , Majzner Robbie G. , Mackall Crystal L. , Gambhir Sanjiv S.
Published: September 2020

Imaging strategies to monitor chimeric antigen receptor (CAR) T-cell biodistribution and proliferation harbor the potential to facilitate clinical translation for the treatment of both liquid and solid tumors. In addition, the potential adverse effects of CAR T cells highlight the need for mechanisms to modulate CAR T-cell activity. The herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene has previously been translated as a PET reporter gene for imaging of T-cell trafficking in patients with brain tumor. The HSV1-TK enzyme can act as a suicide gene of transduced cells through treatment with the prodrug ganciclovir. Here we report the molecular engineering, imaging, and ganciclovir-mediated destruction of B7H3 CAR T cells incorporating a mutated version of the HSV1-tk gene (sr39tk) with improved enzymatic activity for ganciclovir. The sr39tk gene did not affect B7H3 CAR T-cell functionality and in vitro and in vivo studies in osteosarcoma models showed no significant effect on B7H3 CAR T-cell antitumor activity. PET/CT imaging with 9-(4-[18F]-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG) of B7H3-sr39tk CAR T cells in an orthotopic model of osteosarcoma revealed tumor homing and systemic immune expansion. Bioluminescence and PET imaging of B7H3-sr39tk CAR T cells confirmed complete tumor ablation with intraperitoneal ganciclovir administration. This imaging and suicide ablation system can provide insight into CAR T-cell migration and proliferation during clinical trials while serving as a suicide switch to limit potential toxicities.

Significance:

This study showcases the only genetically engineered system capable of serving the dual role both as an effective PET imaging reporter and as a suicide switch for CAR T cells.
Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment
Authors: Subramani Elavarasan , Radoul Marina , Najac Chloe , Batsios Georgios , Molloy Abigail R. , Hong Donghyun , Gillespie Anne Marie , Santos Romelyn Delos , Viswanath Pavithra , Costello Joseph F. , Pieper Russell O. , Ronen Sabrina M.
Published: September 2020

Although lower grade gliomas are driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene and are less aggressive than primary glioblastoma, they nonetheless generally recur. IDH1-mutant patients are increasingly being treated with temozolomide, but early detection of response remains a challenge and there is a need for complementary imaging methods to assess response to therapy prior to tumor shrinkage. The goal of this study was to determine the value of magnetic resonance spectroscopy (MRS)–based metabolic changes for detection of response to temozolomide in both genetically engineered and patient-derived mutant IDH1 models. Using 1H MRS in combination with chemometrics identified several metabolic alterations in temozolomide-treated cells, including a significant increase in steady-state glutamate levels. This was confirmed in vivo, where the observed 1H MRS increase in glutamate/glutamine occurred prior to tumor shrinkage. Cells labeled with [1–13C]glucose and [3–13C]glutamine, the principal sources of cellular glutamate, showed that flux to glutamate both from glucose via the tricarboxylic acid cycle and from glutamine were increased following temozolomide treatment. In line with these results, hyperpolarized [5–13C]glutamate produced from [2–13C]pyruvate and hyperpolarized [1–13C]glutamate produced from [1–13C]α-ketoglutarate were significantly higher in temozolomide-treated cells compared with controls. Collectively, our findings identify 1H MRS-detectable elevation of glutamate and hyperpolarized 13C MRS-detectable glutamate production from either pyruvate or α-ketoglutarate as potential translatable metabolic biomarkers of response to temozolomide treatment in mutant IDH1 glioma.

Significance:

These findings show that glutamate can be used as a noninvasive, imageable metabolic marker for early assessment of tumor response to temozolomide, with the potential to improve treatment strategies for mutant IDH1 patients.
Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC)
Authors: Musher Benjamin L. , Melson Joshua E. , Amato Gianni , Chan David , Hill Marisa , Khan Iftekhar , Kochuparambil Samith T. , Lyons Susan E. , Orsini James , Pedersen Susanne K. , Robb Bruce , Saltzman Joel , Silinsky Jennifer , Gaur Snigdha , Tuck Melissa K. , LaPointe Lawrence C. , Young Graeme P.
Published: September 2020

Background:

Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes.

Methods:

Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored.

Results:

322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4–80.6] and 48% (CI, 28.7–68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7–94.4) and 96.3% (CI, 93.4–98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity.

Conclusions:

COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit.

Impact:

This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.
Strategizing Screening for Melanoma in an Era of Novel Treatments: A Model-Based Approach
Authors: Gogebakan Kemal Caglar , Berry Elizabeth G. , Geller Alan C. , Sonmez Kemal , Leachman Sancy A. , Etzioni Ruth
Published: September 2020

Background:

Benefit–harm tradeoffs of melanoma screening depend on disease risk and treatment efficacy. We developed a model to project outcomes of screening for melanoma in populations with different risks under historic and novel systemic treatments.

Methods:

Computer simulation model of a screening program with specified impact on overall and advanced-stage incidence. Inputs included meta-analyses of treatment trials, cancer registry data, and a melanoma risk prediction study

Results:

Assuming 50% reduction in advanced stage under screening, the model projected 59 and 38 lives saved per 100,000 men under historic and novel treatments, respectively. With 10% increase in stage I, the model projects 2.9 and 4.7 overdiagnosed cases per life saved and number needed to be screened (NNS) equal to 1695 and 2632 under historical and novel treatments. When screening was performed only for the 20% of individuals with highest predicted risk, 34 and 22 lives per 100,000 were saved under historic and novel treatments. Similar results were obtained for women, but lives saved were lower.

Conclusions:

Melanoma early detection programs must shift a substantial fraction of cases from advanced to localized stage to be sustainable. Advances in systemic therapies for melanoma might noticeably reduce benefits of screening, but restricting screening to individuals at highest risk will likely reduce intervention efforts and harms while preserving >50% of the benefit of nontargeted screening.

Impact:

Our accessible modeling framework will help to guide population melanoma screening programs in an era of novel treatments for advanced disease.
Replication and Genetic Risk Score Analysis for Pancreatic Cancer in a Diverse Multiethnic Population
Authors: Bogumil David , Conti David V. , Sheng Xin , Xia Lucy , Shu Xiao-ou , Pandol Stephen J. , Blot William J. , Zheng Wei , Le Marchand Loïc , Haiman Christopher A. , Setiawan Veronica Wendy
Published: September 2020

Background:

Genome-wide association studies (GWAS) have identified several SNPs associated with pancreatic cancer. No studies yet have attempted to replicate these SNPs in US minority populations. We aimed to replicate the associations of 31 GWAS-identified SNPs with pancreatic cancer and build and test a polygenic risk score (PRS) for pancreatic cancer in an ethnically diverse population.

Methods:

We evaluated 31 risk variants in the Multiethnic Cohort and the Southern Community Cohort Study. We included 691 pancreatic ductal adenocarcinoma (PDAC) cases and 13,778 controls from African-American, Japanese-American, Latino, Native Hawaiian, and white participants. We tested the association between each SNP and PDAC, established a PRS using the 31 SNPs, and tested the association between the score and PDAC risk.

Results:

Eleven of the 31 SNPs were replicated in the multiethnic sample. The PRS was associated with PDAC risk [OR top vs. middle quintile = 2.25 (95% confidence interval, 1.73–2.92)]. Notably, the PRS was associated with PDAC risk in all ethnic groups except Native Hawaiian (OR per risk allele ranged from 1.33 in Native Hawaiians to 1.91 in African Americans; P heterogeneity = 0.12).

Conclusions:

This is the first study to replicate 11 of the 31 GWAS-identified risk variants for pancreatic cancer in multiethnic populations, including African Americans, Japanese Americans, and Latinos. Our results also suggest a potential utility of PRS with GWAS-identified risk variants for the identification of individuals at increased risk for PDAC across multiple ethnic groups.

Impact:

PRS can potentially be used to stratify pancreatic cancer risk across multiple ethnic groups.
Siglec-15 as an Emerging Target for Next-generation Cancer Immunotherapy
Authors: Sun Jingwei , Lu Qiao , Sanmamed Miguel F. , Wang Jun
Published: September 2020

Immunomodulatory agents blocking the PD-1/PD-L1 pathway have shown a new way to treat cancer. The explanation underlying the success of these agents may be the selective expression of PD-L1 with dominant immune-suppressive activities in the tumor microenvironment (TME), supporting a more favorable tumor response-to-toxicity ratio. However, despite the big success of these drugs, most patients with cancer show primary or acquired resistance, calling for the identification of new immune modulators in the TME. Using a genome-scale T-cell activity array in combination with bioinformatic analysis of human cancer databases, we identified Siglec-15 as a critical immune suppressor with broad upregulation on various cancer types and a potential target for cancer immunotherapy. Siglec-15 has unique molecular features compared with many other known checkpoint inhibitory ligands. It shows prominent expression on macrophages and cancer cells and a mutually exclusive expression with PD-L1, suggesting that it may be a critical immune evasion mechanism in PD-L1–negative patients. Interestingly, Siglec-15 has also been identified as a key regulator for osteoclast differentiation and may have potential implications in bone disorders not limited to osteoporosis. Here, we provide an overview of Siglec-15 biology, its role in cancer immune regulation, the preliminary and encouraging clinical data related to the first-in-class Siglec-15 targeting mAb, as well as many unsolved questions in this pathway. As a new player in the cancer immunotherapeutic arena, Siglec-15 may represent a novel class of immune inhibitors with tumor-associated expression and divergent mechanisms of action to PD-L1, with potential implications in anti-PD-1/PD-L1–resistant patients.