bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical study of supersonic plasma torch
Authors: Yuan Xing-Qiu  , Li Hui  , Zhao Tai-Zhe  , Wang Fei  , Guo Wen-Kang  , Xu Ping  ,   复旦大学现代物理研究所,上海 200433
Published: December 2020

The magnetic hydrodynamics(MHD) model which is used to describe the heat and fluid flow inside the plasma torch under atmosphere condition was presented. Numerical simulation of the plasma torch with convergence-divergence nozzle shape was carried out by using a two-dimensional mathematical model. Plasma temperature, velocity, pressure, Mach number contours,which describe the characteristic of heat and fluid flow inside the plasma torch, were obtained. Results show that the plasma field can be divided into three regions named subsonic region, transonic region, and the supersonic region.
The study of self-simulating properties of spherical shock front attenuation
Authors: Bian Bao-Min  , Yang Ling  , Li Zhen-Hua  , Chen Xiao  , He An-Zhi  , Shen Zhong-Hua  ,   南京理工大学应用物理系,南京 210094
Published: December 2020

In an isotropic medium the self-simulating theory is used in characterizing the spherical shock front attenuation. We first deduce the self-simulating equation of decaying spherical shock front propagation. Then the decaying propagation equation of the spherical shock front is shown in good agreement with experimental data.
Superconductivity and negative temperature coefficient of the resistivity of bulk metallic glass Zr46.75Ti8.25Cu7.5Ni10Be27.5
Authors: Li Yong  , Wen Ping  , Liu Zhen-Xing  , Jing Xiu-Nian  , Wang Wan-Lu  , Bai Hai-Yang  ,   (1)中国科学院物理研究所,北京 100080; (2)重庆大学应用物理系,重庆 400044; (3)重庆大学应用物理系,重庆 400044;中国科学院物理研究所,北京 100080
Published: December 2020

Electrical-resistivity measurements between 1.5 K and 300 K were performed on the Zr46.75Ti8.25Cu7.5Ni10Be27.5 bulk metallic glasses (BMGs) before and after annealing. Results of the superconducting transition temperature measurements are presented for the BMG Zr46.75Ti8.25Cu7.5Ni10Be27.5. The superconducting critical temperature Tc is 1.84K for the as-prepared metallic glassy sample and 3.76K for the annealed sample at zero magnetic fields. The as-prepared metallic glassy sample exhibits negative temperature coefficient of the resistivity in the temperature range from 5 to 300 K. The negative temperature coefficient of the resistivity of the as-prepared metallic glassy sample can be reasonably understood with the extended Faber-Ziman theory in terms of the diffraction model for metallic glasses if it is assumed that Zr, Ti, Cu, Ni and Be contribute 1.5, 1.5, 0.5, 0.5 and 2 conduction electrons, respectively. The R(T) of the BMG Zr46.75Ti8.25Cu7.5Ni10Be27.5 over the temperature range from 5 to 300 K was analyzed by fitting it to a polynomial using a least-squares procedure.
Photoluminescence centers and shift of ZnO films deposited by rf magnetron sputtering
Authors: Li Huo-Quan  , Ning Zhao-Yuan  , Cheng Shan-Hua  , Jiang Mei-Fu  ,   苏州大学物理科学与技术学院薄膜材料江苏省重点实验室，苏州 215006
Published: December 2020

ZnO films deposited by rf magnetron sputtering with different stoichimetries were made by varing Ar/O2 flow rate during the depositions, and annealed in vacuum. The photoluminescence measurements show that the films have strong blue emission. As O2 gas flow decreases, the blue emission peak moves to long wavelength side. The blue emission may correspond to the electron transition from the bottom of the conduction band to the acceptor level composed of zinc defects.
Generation of high repetition rate femtosecond Ti:sapphire regenerative amplified pulse of high beam quality for ultra-precision machining
Authors: Wang Yi-Shan  , Cheng Guang-Hua  , Liu Qing  , Sun Chuan-Dong  , Zhao Wei  , Chen Guo-Fu  ,   中国科学院西安光学精密机械研究所瞬态光学技术国家重点实验室，西安 710068
Published: December 2020

On the basis of calculation and analysis on femtosecond amplification gain saturation and femtosecond pulse stretching, we believe it is possible to achieve moderate energy femtosecond regenerative amplification without stretcher if the amplifying cavity parameters is optimized and the pumping pulse energy is changed. According to the conclusion, applying low pumping energy and Ti:sapphire off-focusing technique to the amplifier, we do the experiment about high repetition rate femtosecond Ti:sapphire regenerative amplification and compressing without the stretcher. The femtosecond amplified pulse of perfect beam quality is obtained. The energy of amplified pulse is more than 100μJ.The amplified pulse repetition is 1kHz. The spectrum FWHM is 7.7nm.After the compressing,the pulsewidth is 500fs.
A new search method to solve the magnetoencephalography inverse problem
Authors: Zhu Hong-Yi  , Shen Jian-Qi  , Li Jun  ,   浙江大学光通讯联合实验室，现代光学仪器国家重点实验室，光及电磁波研究中心,杭州 310027
Published: December 2020

A new search method is presented to solve the magnetoencephalography(MEG) inverse problem in a realistic head model. This method is based on the relationship between the magnetic fields generated by two closely located current dipoles. If we know the magnetic field produced by a current dipole, we can get the magnetic field generated by another current dipole located in somewhere close to it through this relationship. Doing it again and again, we can calculate the magnetic field generated by the dipole located anywhere in the brain, and obtain the difference between the calculated magnetic field and the measured magnetic field. The place where the square of the difference is the least will be the solution to our problem. Compared with boundary element method, this method can get the accurate solution to MEG inverse problem simpler, as well as costing less time.
On constitutive models of oxygen-free high-conductivity copper at high pressure and high strain rates
Authors: Chen Da-Nian  , Fan Chun-Lei  , Hu Jin-Wei  , Tan Hua  , Wang Huan-Ran  , Wu Shan-Xing  , Yu Yu-Ying  ,   (1)宁波大学力学与材料科学研究中心，宁波  315211; (2)中国工程物理研究院流体物理研究所冲击波与爆轰物理重点实验室，绵阳  621900
Published: December 2020

In this paper, seven constitutive models for oxygenfree high conductivity copper at high pressure and high strain rate are constructed based on Y/G=constant and on G/B=constant, respectively （Y denoting the yield strength, G the shear modulus, B the bulk modulus）. The variations of longitudinal stress, transverse stress and yield strength of oxygenfree high conductivity copper with time under planar shock loading are obtained using the manganin stress gauge and compared with the predicted values by the constructed seven constitutive models. It is indicated that the pressure, density, temperature and plastic strain dependence of the yield strength for oxygenfree high conductivity copper under planar shock loading is essential to the constitutive description. It seems that the strength models of oxygenfree high conductivity copper obtained from SHPB tests and torsion tests are unavailing to the planar shock loading.
Effects of visual inputs on neural dynamics for coding of location and running speed in medial entorhinal cortex
Authors: Dannenberg Holger , Lazaro Hallie , Nambiar Pranav , Hoyland Alec , Hasselmo Michael E
Published: December 2020

Neuronal representations of spatial location and movement speed in the medial entorhinal cortex during the ‘active’ theta state of the brain are important for memory-guided navigation and rely on visual inputs. However, little is known about how visual inputs change neural dynamics as a function of running speed and time. By manipulating visual inputs in mice, we demonstrate that changes in spatial stability of grid cell firing correlate with changes in a proposed speed signal by local field potential theta frequency. In contrast, visual inputs do not alter the running speed-dependent gain in neuronal firing rates. Moreover, we provide evidence that sensory inputs other than visual inputs can support grid cell firing, though less accurately, in complete darkness. Finally, changes in spatial accuracy of grid cell firing on a 10 s time scale suggest that grid cell firing is a function of velocity signals integrated over past time.
Kinetic Resolution and Desymmetrization of Alcohols and Amines by Nonenzymatic, Enantioselective Acylation
Authors: Frost Aileen B. , Greenhalgh Mark D. , Munday Elizabeth S. , Musolino Stefania F. , Taylor James E. , Smith Andrew D.
Published: December 2020

Enantiomerically pure alcohols and amines are ubiquitous throughout Nature and are found within numerous biologically active compounds. This chapter provides a comprehensive overview of strategies for the nonenzymatic acylative kinetic resolution and desymmetrization of alcohols and amines, which have emerged as powerful methods for the preparation of a range of enantiomerically enriched alcohol and amine derivatives. The use of both stoichiometric chiral acylating agents and the use of small‐molecule catalysts for such processes is discussed. The chapter provides an overview of the variety of substrates that can be effectively resolved using the range of enantioselective acylation methods available. Key mechanistic considerations within each class of acylation and the origin of stereoselectivity are also discussed.
The Piancatelli Reaction
Authors: Marin Lucile , Schulz Emmanuelle , Lebœuf David , Gandon Vincent
Published: December 2020

The Piancatelli reaction allows the synthesis of 4‐substituted cyclopentenone derivatives from furylcarbinols and various nucleophiles such as water, alcohols, or amines. Easily accessible classes of products produced by this methodology include 4‐hydroxy‐, 4‐alkoxy‐ and 4‐aminocyclopent‐2‐enones. Cascade Piancatelli reactions involving intramolecular conjugate additions to the resulting enone moiety can lead to polycyclic products. Since the development of catalytic versions of the reaction using Lewis and Brønsted acids, the methodology has attracted considerable attention and has found several applications in the synthesis of complex molecules, including natural products. Enantioselective Piancatelli reactions are also possible by utilizing chiral Brønsted acids as catalysts. This chapter describes in detail the proposed mechanisms as well as the scope and limitations of the Piancatelli reaction.
Fostering knowledge building in learning by teaching: A test of the drawing‐facilitates‐explaining hypothesis
Authors: Fiorella Logan
Published: December 2020

Learning by teaching can be effective, yet many students fail to engage in knowledge building, in which they actively generate inferences and connect the material to their existing knowledge. Recent research suggests creating drawings while orally explaining to others fosters knowledge building and long‐term learning; however, the mechanisms underlying this effect—generation, visualization, or both—remain unclear. In the present study, college students will learn about the human respiratory system and then explain what they learned on video to a fictitious peer. Following a 2 × 2 between‐subjects design, students will either generate their own words or visuals on a whiteboard while explaining aloud, or they will view instructor‐provided words or visuals while explaining aloud. We expect access to visuals (generated or provided) will foster knowledge building and learning outcomes better than access to words. We will also test competing hypotheses regarding potential unique benefits of explaining instructor‐provided versus learner‐generated visuals.
Discriminating deceptive from truthful statements using the verifiability approach: A meta‐analysis
Authors: Verschuere Bruno , Bogaard Glynis , Meijer Ewout
Published: December 2020

The Verifiability Approach predicts that truth tellers will include details that can be verified by the interviewer, whereas liars will refrain from providing such details. A meta‐analysis revealed that truth tellers indeed provided more verifiable details (k = 28, d = 0.49, 95% CI [0.25; 0.74], BF10 = 93.28), and a higher proportion of verifiable details (k = 26, d = 0.49 95% CI: 0.25, 0.74, p < .001, BF10 = 81.49) than liars. We found no evidence that liars would include more unverifiable details than truth tellers (k = 20, d = −0.31, 95% CI [−0.02; 0.64], BF10 = 1.12) Moderator analysis revealed the verifiable detail effect was substantially larger when the statement is the suspect's alibi, but smaller when an incentive to appear credible was used. Our findings support the main prediction behind the Verifiability Approach, but also stress the need for larger sample sizes and independent replications.
Beyond the emergency department: Effects of COVID‐19 on emergency medicine resident education
Authors: Ford Tabitha R. , Fix Megan L. , Shappell Eric , Egan Daniel J. , Mannix Alexandra , Bailitz John , Li Xian , Gottlieb Michael
Published: December 2020

Background

In December 2019, a novel coronavirus (COVID‐19) caused widespread clinical disease, triggering limited in‐person gatherings and social‐distancing guidelines to minimize transmission. These regulations led most emergency medicine (EM) residency training programs to rapidly transition to virtual didactics. We sought to evaluate EM resident perceptions of the effects of COVID‐19 on their didactic and clinical education.

Methods

We performed a cross‐sectional survey study at seven EM residency programs using a mixed‐methods approach designed to understand resident perceptions regarding the impact of COVID‐19 on their educational experience. Quantitative data were presented as percentages with comparison of subgroups, while open‐ended responses were analyzed using qualitative methodology.

Results

We achieved a 59% response rate (187/313). The majority of respondents (119/182, 65.4%) reported that the COVID‐19 pandemic had a negative impact on their residency education with junior residents disproportionately affected. A total of 81 of 182 (44.5%) participants reported that one or more of their clinical rotations were partially or completely canceled due to the pandemic. Additionally, we identified four themes and 34 subthemes highlighting the contextual effects of the pandemic, which were then divided into positive and negative influences on the residency experience. The four themes include systems experience, clinical experience, didactic experience, and wellness.

Conclusion

Our study examined the impact of COVID‐19 on residents’ educational experiences. We found overall mixed responses with a slightly negative impact on residency education, wellness, and clinical rotations, while satisfaction with EM as a career choice was increased. Factors influencing this included systems, clinical, and didactic experiences as well as overall wellness.
Genetic insights into the evolution of genera with the eastern Asia–eastern North America floristic disjunction: a transcriptomics analysis
Authors: Melton Anthony E. , Chen Shichao , Zhao Yunpeng , Fu Chengxin , Xiang Qiu‐Yun (Jenny) , Cheng Shifeng , Wong Gane K.‐S. , Soltis Pamela S. , Soltis Douglas E. , Gitzendanner Matthew A.
Published: December 2020

Premise

Large disjunctions in species distributions provide excellent opportunities to study processes that shape biogeographic patterns. One such disjunction is the eastern Asia–eastern North America (EA‐ENA) floristic disjunction. For many genera with this disjunction, species richness is greater in EA than in ENA; this pattern has been attributed, in part, to higher rates of molecular evolution and speciation in EA. Longer branch lengths have been found in some EA clades, relative to their ENA sister clades, suggesting that the EA lineages have evolved at a higher rate, possibly due to environmental heterogeneity, potentially contributing to the species richness anomaly.

Methods

To evaluate whether rates of molecular evolution are elevated in EA relative to ENA, we used transcriptomes from species in 11 genera displaying this disjunction. Rates of molecular evolution were estimated for up to 385 orthologous nuclear loci per genus.

Results

No statistically significant differences were identified in pairwise comparisons between EA and ENA sister species, suggesting equal rates of molecular evolution for both species; the data also suggest similar selection pressures in both regions. For larger genera, evidence likewise argues against more species‐rich clades having higher molecular evolutionary rates, regardless of region. Our results suggest that genes across multiple gene ontology categories are evolving at similar rates under purifying selection in species in both regions.

Conclusions

Our data support the hypothesis that greater species richness in EA than ENA is due to factors other than an overall increase in rates of molecular evolution in EA.
Dangers in the dark: Calling for a safer practice of transvaginal ultrasonography
Authors: Collins Kelly , Hamlyn Tina , Bruxner George , Kothari Alka
Published: December 2020

Background

The intimate examination is an important component of the assessment of a patient presenting with obstetric or gynaecological concerns. Ultrasound practitioners, like any other medical practitioner, are in a unique and privileged position. During the examination, the sonographers engage in a very close and personal interaction with an individual whom they have likely never met. They are also most likely unfamiliar with their social situation, cultural background, previous experiences with the healthcare profession and more importantly, any history of sexual trauma. It is an extremely sensitive area of practice which places a great deal of responsibility on the clinician to ensure that they not only protect their patient from psychological distress, but also themselves, from the threat of litigation arising from such distress.

Aims

This paper highlights the current governance requirements for sonographers and makes suggestions to support them in safeguarding their patients and themselves from allegations of unprofessional conduct, until such a regulatory body exists.

Materials and Methods

A wide‐ranging review of the literature exploring the perceptions of female patients regarding intimate sonographic examination was performed using standard search engines. Additionally, grey literature was searched for policy statements and government regulatory documents for guidance on the topic.

Results

Although much research has been undertaken in this field across diverse cultures and knowledge in this area is ever increasing; however, the guidelines for sonographers appear to be site specific and variable. At present, there is no overarching governance for sonographers, as there is with practitioners registered with the Australian Health Practitioner Regulation Agency.

Discussion

While there are practice standards for the purposes of Medicare set out by the Diagnostic Imaging Accreditation Scheme, there is no regulatory professional standard that sonographers are held accountable to. This is problematic and has the potential for inadvertent boundary transgression by the practitioner, as there is also no existing framework for management of such incidents in an equitable manner.

Conclusion

The intimate examination is generally well tolerated; however, there is a subset of the population who are vulnerable to psychological distress arising from the examination. The sonographer must be astute to signs of distress and act in accordance with the intimate examination guidelines set out by AHPRA, for the dual purpose of protecting their patients against harm and also themselves from the threat of litigation.
Biofabricated 3D in vitro model of fibrosis‐induced abnormal hepatoblast/biliary progenitors' expansion of the developing liver
Authors: Brovold Matthew , Keller Dale , Devarasetty Mahesh , Dominijanni Anthony , Shirwaiker Rohan , Soker Shay
Published: December 2020

Congenital disorders of the biliary tract are the primary reason for pediatric liver failure and ultimately for pediatric liver transplant needs. Not all causes of these disorders are well understood, but it is known that liver fibrosis occurs in many of those afflicted. The goal of this study is to develop a simple yet robust model that recapitulates physico‐mechanical and cellular aspects of fibrosis mediated via hepatic stellate cells (HSCs) and their effects on biliary progenitor cells. Liver organoids were fabricated by embedding various HSCs, with distinctive abilities to generate mild to severe fibrotic environments, together with undifferentiated liver progenitor cell line, HepaRG, within a collagen I hydrogel. The fibrotic state of each organoid was characterized by examination of extracellular matrix (ECM) remodeling through quantitative image analysis, rheometry, and qPCR. In tandem, the phenotype of the liver progenitor cell and cluster formation was assessed through histology. Activated HSCs (aHSCs) created a more severe fibrotic state, exemplified by a more highly contracted and rigid ECM, as well higher relative expression of TGF‐β, TIMP‐1, LOXL2, and COL1A2 as compared to immortalized HSCs (LX‐2). Within the more severe fibrotic environment, generated by the aHSCs, higher Notch signaling was associated with an expansion of CK19+ cells as well as the formation of larger, more densely populated cell biliary like‐clusters as compared to mild and non‐fibrotic controls. The expansion of CK19+ cells, coupled with a severely fibrotic environment, are phenomena found within patients suffering from a variety of congenital liver disorders of the biliary tract. Thus, the model presented here can be utilized as a novel in vitro testing platform to test drugs and identify new targets that could benefit pediatric patients that suffer from the biliary dysgenesis associated with a multitude of congenital liver diseases.
A method to improve quantitative radiotracing‐based analysis of the in vivo biodistribution of drug carriers
Authors: Roki Nikša , Solomon Melani , Casta Lou , Bowers Jessica , Getts Robert C. , Muro Silvia
Published: December 2020

Biodistribution studies are essential in drug carrier design and translation, and radiotracing provides a sensitive quantitation for this purpose. Yet, for biodegradable formulations, small amounts of free‐label signal may arise prior to or immediately after injection in animal models, causing potentially confounding biodistribution results. In this study, we refined a method to overcome this obstacle. First, we verified free signal generation in animal samples and then, mimicking it in a controllable setting, we injected mice intravenously with a radiolabeled drug carrier formulation (125I‐antibody/3DNA) containing a known amount of free radiolabel (125I), or free 125I alone as a control. Corrected biodistribution data were obtained by separating the free radiolabel from blood and organs postmortem, using trichloroacetic acid precipitation, and subtracting the confounding signal from each tissue measurement. Control free 125I‐radiolabel was detected at ≥85% accuracy in blood and tissues, validating the method. It biodistributed very heterogeneously among organs (0.6–39 %ID/g), indicating that any free 125I generated in the body or present in an injected formulation cannot be simply corrected to the free‐label fraction in the original preparation, but the free label must be empirically measured in each organ. Application of this method to the biodistribution of 125I‐antibody/3DNA, including formulations directed to endothelial target ICAM‐1, showed accurate classification of free 125I species in blood and tissues. In addition, this technique rendered data on the in vivo degradation of the traced agents over time. Thus, this is a valuable technique to obtain accurate measurements of biodistribution using 125I and possibly other radiotracers.
A practical nomogram and risk stratification system predicting the cancer‐specific survival for patients with early hepatocellular carcinoma
Authors: Yan Bing , Su Bing‐Bing , Bai Dou‐Sheng , Qian Jian‐Jun , Zhang Chi , Jin Sheng‐Jie , Jiang Guo‐Qing
Published: December 2020

Background

Our purpose was to establish and validate a nomogram model in early hepatocellular carcinoma (HCC) patients for predicting the cancer‐specific survival (CSS).

Methods

We extracted eligible data of relevant patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Further, we divided all patients into two groups (training and validation cohorts) at random (7:3). Nomogram was established using effective risk factors based on univariate and multivariate analysis. The effective performance of nomogram was evaluated using concordance index (C‐index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic curve (ROC).

Results

We selected 3620 patients with early HCC including the training cohort (70%, 2536) and the validation cohort (30%, 1084). The nomogram‐related C‐indexes were 0.755 (95% CI: 0.739–0.771) and 0.737 (95% CI: 0.712–0.762), in the training and validation cohorts, respectively. The calibration plots showed good consistency of 3‐and 5‐year CSS between the actual observation and the nomogram prediction. The 3‐, 5‐year DCA curves also indicated that the nomogram has excellent clinical utility. The 3‐, 5‐year area under curve (AUC) of ROC in the training cohort were 0.783, 0.779, respectively, and 0.767, 0.766 in the validation cohort, respectively. With the establishment of nomogram, a risk stratification system was also established that could divide all patients into three risk groups, and the CSS in different groups (i.e., low risk, intermediate risk, and high risk) had a good regional division.

Conclusions

We developed a practical nomogram in early HCC patients for predicting the CSS, and a risk stratification system follow arisen, which provided an applicable tool for clinical management.
Lidocaine inhibits the metastatic potential of ovarian cancer by blocking NaV1.5‐mediated EMT and FAK/Paxillin signaling pathway
Authors: Liu Chang , Yu Ming , Li Yi , Wang Hao , Xu Chuanya , Zhang Xiaoqing , Li Min , Guo Hongyan , Ma Daqing , Guo Xiangyang
Published: December 2020

Lidocaine, one of the most commonly used local anesthetics during surgery, has been reported to suppress cancer cell growth via blocking voltage‐gated sodium channels (VGSCs). VGSC 1.5 (NaV1.5) is highly expressed in invasive cancers including ovarian cancer. This study aims to investigate whether lidocaine inhibits the malignancy of ovarian cancer through NaV1.5 blockage. Human ovarian cancer, its metastatic cancer and normal ovarian tissues were probed with anti‐NaV1.5 antibody in situ. Human ovarian cancer A2780 and SKOV3 cells were cultured and their growth, epithelial‐mesenchymal transition (EMT), migration, and invasion in the presence or absence of lidocaine together with underlying molecular mechanisms were assessed. Murine syngeneic ovarian cancer (ID8) model was also used to determine the chemotherapeutic efficiency of cisplatin in combination with lidocaine. The high level of NaV1.5 expression was found in human ovarian cancer and even higher in its metastatic cancer but not in normal ovarian tissues. Lidocaine decreased the growth, EMT, migration, and invasion of human ovarian cancer A2780 and SKOV3 cells. Lidocaine enhanced the chemotherapeutic efficiency of cisplatin in both ovarian cancer cell cultures and a murine ovarian metastatic model. Furthermore, a downregulation of NaV1.5 by siRNA transfection, or FAK inhibitor application, inhibited the malignant properties of SKOV3 cells through inactivating FAK/Paxillin signaling pathway. Our data may indicate that lidocaine suppresses the metastasis of ovarian cancer and sensitizes cisplatin through blocking NaV1.5‐mediated EMT and FAK/paxillin signaling pathway. The translational value of lidocaine local application as an ovarian cancer adjuvant treatment warrants further study.
HELLS, a chromatin remodeler is highly expressed in pancreatic cancer and downregulation of it impairs tumor growth and sensitizes to cisplatin by reexpressing the tumor suppressor TGFBR3
Authors: Hou Xuyang , Yang Leping , Wang Kunpeng , Zhou Yan , Li Qinglong , Kong Fanhua , Liu Xi , He Jun
Published: December 2020

Pancreatic cancer (PC) is the most malignant cancer type in the digestive system with a poor prognosis. Chemotherapy such as cisplatin is the last chance for PC patients diagnosed with advanced or metastatic disease. Obtaining a deep understanding of the molecular mechanism underlying PC tumorigenesis and identifying optimal biomarkers to estimate chemotherapy sensitivity are essential for PC treatment. The chromatin remodeler HELLS was found to regulate various tumor suppressors through an epigenetic pathway in several cancers. We analyzed HELLS expression in clinical samples by Western blotting and immunohistochemical staining. Next, we identified the variation in tumor growth and cisplatin sensitivity after knockdown of HELLS and explored the downstream mediators of HELLS in PC via RNA‐seq, chromatin immunoprecipitation, and gain‐ and loss‐of‐function assays. We found that HELLS is upregulated in PC tissues and correlates with advanced clinical stage and a poor prognosis, and the knockdown of HELLS leads to tumor growth arrest and increased sensitivity to cisplatin. Mechanistically, the tumor suppressor TGFBR3 is markedly reexpressed after HELLS knockdown; conversely, compromising TGFBR3 rescues HELLS knockdown‐mediated effects in PC cells. Thus, our data provide evidence that HELLS can serve as a potential oncogene and suitable biomarker to evaluate chemotherapy sensitivity via epigenetically silencing the tumor suppressor TGFBR3 in PC.
Styrene hydrogenation in inclined packed‐bed bubble reactors: A reaction‐transport model for the catalytic hydrogenation of pyrolysis gasoline on‐board floating reactors
Authors: Iliuta Ion , Larachi Faïçal
Published: December 2020

Two‐phase upflow/downflow and styrene hydrogenation were explored numerically in vertical and inclined packed‐bed bubble reactors using a dynamic three‐dimensional model which integrates the hydrodynamics via macroscopic volume‐averaged continuity and momentum balance equations, energy and mass conservative equations in liquid/gas phases, and simultaneous diffusion and chemical reaction inside Pd/Al2O3 catalyst particles. Packed‐bed bubble reactors non‐verticality divert the liquid phase from its normally expected axial trajectory and generate an excessive axial symmetry distortion because of amplified secondary liquid flow associated with a larger liquid holdup and because of liquid reversal flow (two‐phase upflow). The significant liquid maldistribution over the packed beds (especially in deeper beds) substantially reduces the performance of the styrene hydrogenation process in inclined packed‐bed bubble reactors, more than in inclined trickle‐bed reactors. This drop in hydrogenation performance is more noticeable in downflow packed‐bed bubble reactors, particularly at higher packed bed inclinations, because of the reduction of catalyst wetting efficiency and overall effectiveness factor of the catalyst particles. Increasing the height and diameter of packed bed is recommended to compensate for reduction in hydrogenation performance in inclined packed‐bed bubble reactors. However, the ratio between the reactor height and diameter should be limited to a maximum value to avoid the excessive liquid maldistribution in deeper beds with a significant bypassing in the vicinity of the bottom of the packed bed.
Simulation of a moving bed chemical looping system for electricity production from coal via chemical looping water splitting
Authors: Kong Fanhe , Tene Youmbi Darryl , Tong Andrew , Fan Liang‐Shih
Published: December 2020

Coal is a crucial energy source for modern industry and society. Because coal is one of the most CO2‐intensive carbonaceous fuels, the combustion of coal with CO2 capture is of great environmental relevance. However, the conventional coal‐based power generation processes, including the pulverized coal (PC) boiler process and the integrated gasification combined cycle (IGCC) process, suffer a significant efficiency loss when integrated with conventional CO2 capture methods. Chemical looping technology is a promising alternative pathway for coal‐based power generation with intrinsic CO2 separation and capture. Process simulation of chemical looping processes can provide an overview on the viability of the processes, thereby quantifying their advantages over conventional processes. This study presents the process simulation of a chemical looping water splitting combined cycle (CLWS‐CC) system for electricity generation. The CLWS‐CC process directly uses coal as the feedstock to produce H2, which is subsequently combusted in a combined cycle to generate electricity. The oxygen carriers used in the chemical looping process are optimized in their composition. Autothermal operation is established within the chemical looping system. Four CLWS‐CC cases that operate at different pressures are considered. In two of the four cases, an unequal pressure operating strategy is adopted to minimize the compression power consumption in order to enhance the overall process energy efficiency. The process simulation shows that the CLWS‐CC process is able to achieve an 18% increase in net plant efficiency over the conventional IGCC process.
Influence of zeta potential of ZrO2 and Al2O3 nanoparticles on removal of metal ions by hybrid electrospun polyamide 6 membrane: Kinetics of adsorption and fouling mechanisms
Authors: Mosayebi Ali , Esfahani Hamid , Hoor Mehrnoosh
Published: December 2020

Electrostatic charging of the adsorbent is a critical method for the selective removal of metal ions fromacidic wastewater. In this study, electrospun polyamide 6 (PA6) membranes were separately incorporated with Al2O3 and ZrO2 nanoparticles (NPs), and their ability in the removal of cations (eg, Al3+ and Fe3+) were evaluated by static adsorption and filtration methods. The impact of various parameters, namely microstructure, surface porosity, functional molecular groups, and hydrophobicity of membranes on the removal process, was investigated. By evaluating the zeta (ζ) potential of oxide ceramic NPs, it was found that the Al2O3 and ZrO2 NPs had positive and negative electrostatic charges inacidic solution, respectively. The results showed that the incorporation of negatively charged ZrO2 NPs improved both the static adsorption and filtration removal capability of the PA6 membrane. The maximum adsorption efficiency of Al3+ and Fe3+ cations was 52.43% and 54.11%, and the highest filtration efficiency of the mentioned cations obtained by electrospun hybrid ZrO2 incorporated PA6 membrane was 98.6% and 99.3%, respectively. It was also found that the adsorption of both Al3+ and Fe3+ cations correlated well with the pseudo‐second‐order kinetic model. The results also demonstrated that the dominant blocking models were switched with the increase in the initial concentration of metal ions from 5 ppm‐70 ppm.
Behaviour of agglomerates formed by liquid injection in fluidized beds
Authors: Briens Cedric , Bhatti Muhammad O. I. , Sanchez Francisco J. , Berruti Franco , McMillan Jennifer
Published: December 2020

Formation of agglomerates in fluidized beds can cause operating problems, such as excessive stripper shed fouling, which can lead to premature unit shut down. The focus of this study is to reach a better understanding of how agglomerates move through a fluidized bed to improve the Fluid Cokers and minimize the risk of agglomerates reaching regions where they cause problems. Two experimental methods were used: first, a Gum Arabic binder solution was injected into a two‐dimensional (2D) fluidized bed under conditions that simulate agglomerate formation in Fluid Cokers, and the mass and density of recovered agglomerates were measured; second, a new 2D radioactive particle tracking (RPT) method was developed to track the motion of model agglomerates. The fluidized bed had a steel wall, resulting in significant and non‐uniform radiation absorption. The 2D RPT system was, thus, calibrated by placing the source at 290 locations in the bed, for each fluidization velocity. Since bubble flow patterns greatly affect agglomerate motion and segregation, a tribo‐electric method was used to determine bubble flow distribution in the fluidized bed. The RPT and liquid injection methods gave similar vertical distributions of agglomerates. The main results were that increasing the fluidization velocity reduced segregation, and larger agglomerates were more likely to segregate. There was a strong correlation between the bubbles and agglomerates flow patterns: establishing an asymmetric flow pattern by injecting more fluidization gas in one side of the bed greatly reduced agglomerate segregation.
Modular Click Chemistry Library: Searching for Better Functions
Authors: Zhang Jiong , Dong Jiajia
Published: December 2020

High throughput screening towards chemical libraries is the primary way to discover lead compounds in developing innovative drugs, especially new molecular entities. Accordingly, the preparation of chemical libraries is the key step for drug development. Now, conventional small molecule chemical libraries and DNA‐encoded chemical libraries are the main models of chemical libraries for high‐throughput screening. Recently, a new model of chemical library, called modular click chemistry library, was proposed, which gives us an alternative choice to construct chemical libraries for high throughput screening and exhibits broad prospects to accelerate drug development. Herein, this article mainly focuses on the strategy to prepare the modular click chemistry library.
Phospho‐regulation of mitotic spindle assembly
Authors: Ong Joseph Y. , Bradley Michelle C. , Torres Jorge Z.
Published: December 2020

The assembly of the bipolar mitotic spindle requires the careful orchestration of a myriad of enzyme activities like protein posttranslational modifications. Among these, phosphorylation has arisen as the principle mode for spatially and temporally activating the proteins involved in early mitotic spindle assembly processes. Here, we review key kinases, phosphatases, and phosphorylation events that regulate critical aspects of these processes. We highlight key phosphorylation substrates that are important for ensuring the fidelity of centriole duplication, centrosome maturation, and the establishment of the bipolar spindle. We also highlight techniques used to understand kinase–substrate relationships and to study phosphorylation events. We conclude with perspectives on the field of posttranslational modifications in early mitotic spindle assembly.
Regulatory Safety Learning Driven by the Mechanism of Action: The Case of TNF‐α Inhibitors
Authors: Minnema Lotte A. , Giezen Thijs J. , Hoekman Jarno , Egberts Toine C.G. , Leufkens Hubert G.M. , Gardarsdottir Helga
Published: December 2020

The summary of product characteristics (SmPCs) is an important information source that includes the adverse drug reactions (ADRs) associated with the drug. Drugs with the same mechanism of action are expected to have a similar ADR profile and thus a substantial overlap of the described ADRs in the SmPC. The objective of this study is to assess this overlap. We extracted all ADRs (excluding hypersensitivity and administration site reactions) that were described in the first and all subsequent versions of the SmPCs of all approved TNF‐α inhibitors in the European Union. The Medical Dictionary for Regulatory Activities was used to characterize the ADRs. At the end of follow‐up, 293 unique ADRs (at high level term level) were described in the SmPCs of the 5 TNF‐α inhibitors. There was substantial variation in the number of ADRs described in the SmPC among the TNF‐α inhibitors. Of the 293 ADRs, 133 (45%) were described in the SmPC of one TNF‐α inhibitor and 39 (13%) in the SmPCs of all 5 TNF‐α inhibitors. Serious ADRs and ADRs classified as important risks were described approximately four times more often in a second SmPC than ADRs not classified as such. In conclusion, the ADRs described in the SmPCs of the TNF‐α inhibitors differ considerably in number and type. In order to adequately inform prescribers and patients, acquired knowledge of the safety profile of drugs with the same mechanism of action should increasingly be taken into account in the assessment of all drugs within the class.
Experimental Medicine Study to Measure Immune Checkpoint Receptors PD‐1 and GITR Turnover Rates In Vivo in Humans
Authors: Lassman Michael E. , Chappell Derek L. , McAvoy Thomas , Cheng Amy , de Alwis Dinesh P. , Pruitt Scott K. , Laterza Omar F. , Li Claire , Stoch Aubrey , Mayawala Kapil
Published: December 2020

Development of monoclonal antibodies (mAbs) targeting immune‐checkpoint receptors (IMRs) for the treatment of cancer is one of the most active areas of investment in the biopharmaceutical industry. A key decision in the clinical development of anti‐IMR mAbs is dose selection. Dose selection can be challenging because the traditional oncology paradigm of administering the maximum tolerated dose is not applicable to anti‐IMR mAbs. Instead, dose selection should be informed by the pharmacology of immune signaling. Engaging an IMR is a key initial step to triggering pharmacologic effects, and turnover (i.e., the rate of protein synthesis) of the IMR is a key property to determining the dose level needed to engage the IMR. Here, we applied the stable isotope labeling mass spectrometry technique using 13C6‐leucine to measure the in vivo turnover rates of IMRs in humans. The 13C6‐leucine was administered to 10 study participants over 15 hours to measure 13C6‐leucine enrichment kinetics in 2 IMR targets that have been clinically pursued in oncology: GITR and PD‐1. We report the first measurements of GITR and PD‐1 median half‐lives associated with turnover to be 55.6 and ≥ 49.5 hours, respectively. The approach outlined here can be applied to other IMRs and, more generally, to protein targets.
Characterizing Effects of Antidiabetic Drugs on Heart Rate, Systolic and Diastolic Blood Pressure
Authors: Maringwa John , Sardu Maria Luisa , Hang Yaming , Czerniak Richard , Vishnubhotla Manasa , Vakilynejad Majid , Pfister Marc
Published: December 2020

A model‐based meta‐analysis was performed with reported data from obese subjects and patients with type 2 diabetes (T2DM) to characterize the effects of dipeptidyl peptidase 4 (DPP4) inhibitors, gastric inhibitory polypeptides (GIPs), glucagon‐like peptide‐1 (GLP1), and dual GIP/GLP1 agonists, or a combination of these antidiabetic drugs (ADs) on heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP). A systematic literature search and review after the Cochrane method identified sources for investigational and approved ADs resulted in a comprehensive database with data from 178 clinical studies in obese subjects and patients with T2DM. Results indicated that there were AD class‐dependent effects on HR and SBP, whereas no clear AD‐related effects on DBP were found. All AD classes, except for DPP4 inhibitors, increased HR. The largest increase of 12 bpm was seen with GLP1 receptor agonists. All AD classes appeared to decrease SBP. DPP4 inhibitors were associated with a marginal decrease of ~ 1 mmHg, whereas GLP1 and GIP/GLP1 dual agonists exhibited the largest decrease of ~ 3 mmHg in SBP. AD‐related effects were similar in obese subjects and patients with T2DM. In conclusion, there are clinically relevant AD‐related effects on both HR and SBP, but not on DBP. DPP4 inhibitors are associated with the smallest (if at all) effects on HR and SBP, whereas GLP1 inhibitors exhibited the largest effects on these two cardiovascular end points. Additional studies are warranted to further investigate how AD‐related SBP decreases combined with HR increases affect long‐term cardiovascular mortality.
Fishing, environment, and the erosion of a population portfolio
Authors: Stier Adrian C. , Olaf Shelton Andrew , Samhouri Jameal F. , Feist Blake E. , Levin Phillip S.
Published: December 2020

Many organisms exhibit tremendous fluctuations in population abundance and experience unexpected collapse. Conservationists seeking to minimize region‐wide variability in resources and reduce extinction risk often seek to preserve a metapopulation portfolio of spatially asynchronous subpopulations connected by dispersal. However, portfolio properties are not necessarily static, and the erosion of a portfolio can fundamentally alter the population dynamics and services a species provides. In the Northeast Pacific, a portfolio of spatially asynchronous herring populations has historically provided regional reliability of herring to mobile predators and commercial fishermen as well as local subsistence and ceremonial harvest. Here, we fit a mechanistic time‐series model to herring spawn and catch records from 1950 to 2015 to quantify how population growth, climate, and fishing have contributed to a major shift in the herring portfolio over time. We document the erosion of the herring portfolio and a severe decline in herring population growth. Commercial harvest historically played a key role in herring dynamics, hovering around typical annual exploitation rates (15%) at the archipelago scale, but local harvest rates were much higher when fishing occurred (as high as 65%). Additionally, the Pacific Decadal Oscillation and population growth had equally strong effects on local and regional herring population dynamics. Our results highlight how spatially structured populations can undergo major shifts following disturbance and emphasize how ecological systems do not always rapidly recover and provide services following disturbance. Developing herring management strategies at a finer scale may ensure greater regional resource reliability by recovering previous levels of spatial population asynchrony. However, doing so may require higher implementation and monitoring costs in order to yield higher ecological, social, and economic benefits. Such place‐based solutions that match the spatial scale of governance to the spatial scale of ecological dynamics have the potential to improve future management and conservation in an increasingly dynamic world.
Isotopic niche breadth of a generalist mesopredator increases with habitat heterogeneity across its range
Authors: Walsh Lisa L. , Tucker Priscilla K.
Published: December 2020

Although generalists are becoming increasingly abundant and widespread, little is known about their response to ecological variation they encounter across their range. For example, the generalist’s flexible diet is cited to help explain recent range expansions, but no study has directly examined this claim. Here, we use stable isotope values of the Virginia opossum (Didelphis virginiana), a true generalist, to examine an extension of MacArthur’s habitat heterogeneity hypothesis for a single generalist species. If a generalist’s diet reflects local food abundance, then more heterogeneous landscapes should result in broader niches. We used stable isotope analysis, landcover indices, and WorldClim data to further evaluate how the opossum’s use of its environment varies across ancestral regions, expansion fronts, and regions of human‐facilitated introductions. Niche breadth varied across its range, especially between expansion fronts. We found a positive relationship between landcover diversity and isotopic niche breadth. WorldClim variables linked to aridity and C4 plant abundance were most strongly associated with nitrogen (δ15N) and carbon (δ13C) values, respectively. Our results reveal that a generalist’s stable isotope signature reflects its local environment, demonstrating their flexible diet is captured with stable isotopes and supporting the generalist habitat heterogeneity hypothesis.