bluuebunny/crossref_metadata_2025 huggingface dataset:
Conjugation curvature for Cayley graphs
Authors: Bar-Natan Assaf , Duchin Moon , Kropholler Robert
Published: October 2020

We introduce a notion of Ricci curvature for Cayley graphs that can be thought of as “medium-scale” because it is neither infinitesimal nor asymptotic, but based on a chosen finite radius parameter. We argue that it gives the foundation for a definition of Ricci curvature well adapted to geometric group theory, beginning by observing that the sign can easily be characterized in terms of conjugation in the group. With this conjugation curvature [Formula: see text], abelian groups are identically flat, and in the other direction we show that [Formula: see text] implies the group is virtually abelian. Beyond that, [Formula: see text] captures known curvature phenomena in right-angled Artin groups (including free groups) and nilpotent groups, and has a strong relationship to other group-theoretic notions like growth rate and dead ends. We study dependence on generators and behavior under embeddings, and close with directions for further development and study.
Q-Series and quantum spin networks
Authors: Elhamdadi Mohamed , Hajij Mustafa , Levitt Jesse S. F.
Published: October 2020

The tail of a quantum spin network in the two-sphere is a q-series associated to the network. We study the existence of the head and tail functions of quantum spin networks colored by 2n. We compute the q-series for an infinite family of quantum spin networks and give the relation between the tail of these networks and the tail of the colored Jones polynomial. Finally, we show that the family of quantum spin networks under study satisfies a natural product structure.
High-Level Synthesis of Key-Obfuscated RTL IP with Design Lockout and Camouflaging
Authors: Islam Sheikh Ariful , Sah Love Kumar , Katkoori Srinivas
Published: October 2020

We propose three orthogonal techniques to secure Register-Transfer-Level (RTL) Intellectual Property (IP). In the first technique, the key-based RTL obfuscation scheme is proposed at an early design phase during High-Level Synthesis (HLS). Given a control-dataflow graph, we identify operations on non-critical paths and leverage synthesis information during and after HLS to insert obfuscation logic. In the second approach, we propose a robust design lockout mechanism for a key-obfuscated RTL IP when an incorrect key is applied more than the allowed number of attempts. We embed comparators on obfuscation logic output to check if the applied key is correct or not and a finite-state machine checker to enforce design lockout. Once locked out, only an authorized user (designer) can unlock the locked IP. In the third technique, we design four variants of the obfuscating module to camouflage the RTL design. We analyze the security properties of obfuscation, design lockout, and camouflaging. We demonstrate the feasibility on four datapath-intensive IPs and one crypto core for 32-, 64-, and 128-bit key lengths under three design corners (best, typical, and worst) with reasonable area, power, and delay overheads on both ASIC and FPGA platforms.
Robust Multi-Target Sample Preparation on MEDA Biochips Obviating Waste Production
Authors: Poddar Sudip , Banerjee Tapalina , Wille Robert , Bhattacharya Bhargab B.
Published: October 2020

Digital microfluidic biochips have fueled a paradigm shift in implementing bench-top laboratory experiments on a single tiny chip, thus replacing costly and bulky equipment. However, because of imprecise fluidic functions, several volumetric split errors may occur during the execution of bioassays. Earlier approaches to error-correcting sample preparation addressed this problem by using a cyberphysical system yielding several drawbacks such as increased sample preparation cost and time, and uncertainty in assay completion time. In addition, error correction for only a single-target sample has been considered so far, although many assays require the production of multi-target samples. In this work, we present an error-free dilution technique that guarantees the correctness of the resulting concentration factor of a sample without performing any additional roll-back or roll-forward action. To the best of our knowledge, we are the first to present a solution strategy for tackling dispensing errors during sample preparation. We use micro-electrode-dot-array biochips that offer the advantages of manipulating fractional volumes of droplets (aliquots) for navigation, as well as mix-split operations. Instead of performing traditional mix-and-split steps with integral-volume droplets, we execute only an aliquoting-and-mix sequence using differential-size aliquots. Thus, all split operations, which are the main source of errors in conventional digital microfluidic biochips, are completely eliminated, and hence neither sensing nor any correcting action is needed, and further, no management of intermediate waste droplets is needed. Additionally, the procedure can be fully parallelized for accurately producing multiple dilutions of a sample. Experimental results corroborate the superiority of the proposed method in terms of error management, as well as sample preparation cost and time.
How Instructors Learn to Teach Online: Considering the past to plan for the future
Authors: Schmidt Steven , Hodge Elizabeth M. , Tschida Christina M.
Published: October 2020

The onset of the COVID-19 Pandemic had major effects on all aspects of higher education, including the way in which courses were taught. Literally, overnight, courses that were taught face-to-face were moved online, and face-to-face instructors of those courses became online educators. Now, several months into the pandemic, it has become clear that instructors at colleges and universities today must be able to teach both online and face-to-face, and they must be able to move from one medium to the other as circumstances dictate. However, that is not easy to do, as learning to teach online takes time, and involves a good deal of effort. Several years ago, we conducted a research study on how university faculty members learned to teach online. What we learned in that research may be helpful to instructors learning to teach online today.
Experimental Verification of Current Conduction Mechanism for a Lithium Niobate Based Memristor
Authors: Zaman Ayesha , Subramanyam Guru , Shin Eunsung , Yakopcic Chris , Taha Tarek M. , Islam Ahmad Ehteshamul , Ganguli Sabyasachi , Dorsey Donald , Roy Ajit
Published: October 2020

This work presents electrical characterization and analysis of the dominant charge transport mechanism suggesting inhomogeneous, filamentary conduction for a lithium niobate switching layer based memristor for use in neuromorphic computing. Memristor conductivity has been investigated both for the high and low resistance states. It is suggested that when the device is in a high resistance state, deep trap energy level within the switching layer initiate the device conduction process. The elastic trap assisted tunneling mechanism with a simple steady state approach agrees with the experimental measurements in the high resistance state. This work considers existence of inhomogeneously distributed positively charged oxygen ions/vacancies (within the oxygen deficient switching layer) as the deep trap energy level, required for electron tunneling from memristor electrode. Alternatively, ohmic conduction was found to be the main mechanism for the memristor on state conductivity at room temperature. Existence of intermediate resistive states in the memristor’s high resistive region was experimentally investigated and the elastic trap assisted tunneling mechanism for such phenomena was validated through simulation.
Design of a Silicon Carbide Chemical Vapor Deposition Reactor Cleaning Process Using Chlorine Trifluoride Gas Accounting for Exothermic Reaction Heat
Authors: Hayashi Masaya , Mamyouda Takumi , Habuka Hitoshi , Ishiguro Akio , Ishii Shigeaki , Daigo Yoshiaki , Ito Hideki , Mizushima Ichiro , Takahashi Yoshinao
Published: October 2020

A silicon carbide chemical vapor deposition reactor cleaning process was designed by managing and utilizing the temperature increase due to the exothermic reaction heat produced by the chemical reaction between chlorine trifluoride gas and a particle-type polycrystalline silicon carbide layer. The main issues were (i) the initial susceptor temperature, (ii) the exothermic reaction heat, and (iii) the heat transport from the susceptor surface for reducing the peeling of the susceptor coating film. The important parameter was the initial susceptor temperature for performing the moderate etching of the silicon carbide layer and the local etching at the contact point between the silicon carbide particles and the susceptor surface. The 30-μm-thick particle-type polycrystalline silicon carbide layer could be detached and cleaned in two minutes.
Evaluating the Validity of Risk Scoring in Predicting Pacemaker Rates following Transcatheter Aortic Valve Replacement
Authors: Spring Alexander M. , Catalano Michael A. , Prasad Vikram , Rutkin Bruce , Koss Elana , Hartman Alan , Yu Pey-Jen
Published: October 2020

Introduction. Requirement of permanent pacemaker (PPM) implantation is a known and common postoperative consequence of transcatheter aortic valve replacement (TAVR). The Emory risk score has been recently developed to help risk stratify the need for PPM insertion in patients undergoing TAVR with SAPIEN 3 valves. Our aim was to assess the validity of this risk score in our patient population, as well as its applicability to patients receiving self-expanding valves. Methods. We conducted a retrospective review of 479 TAVR patients without preoperative pacemakers from November 2016 through December 2018. Preoperative risk factors included in the Emory risk score were collected for each patient: preoperative QRS, preoperative right bundle branch block (RBBB), preoperative syncope, and degree of valve oversizing. Multivariable analysis of the individual variables within the scoring system to identify predictors of PPM placement was performed. The predictive discrimination of the risk score for the risk of PPM placement after TAVR was assessed with the area under the receiver operating characteristic curve (AUC). Results. Our results demonstrated that, of the 479 patients analyzed, 236 (49.3%) received balloon-expandable valves and 243 (50.7%) received self-expanding valves. Pacemaker rates were higher in patients receiving self-expanding valves than those receiving balloon-expandable valves (25.1% versus 16.1%,

p
=
0.018

). The Emory risk score showed a moderate correlation with pacemaker requirement in patients receiving each valve type, with AUC for balloon-expandable and self-expanding valves of 0.657 and 0.645, respectively. Of the four risk score components, preoperative RBBB was the only predictor of pacemaker requirement with an AUC of 0.615 for both balloon-expandable and self-expanding valves. Conclusion. In our cohort, the Emory risk score had modest predictive utility for PPM insertion after balloon-expandable and self-expanding TAVR. The risk score did not offer better discriminatory utility than that of preoperative RBBB alone. Understanding the determinants of PPM insertion after TAVR can better guide patient education and postoperative management.
Prognostic Value and Clinicopathological Features of MicroRNA‐206 in Various Cancers: A Meta‐Analysis
Authors: Liu Rongqiang , Zheng Shiyang , Peng Shengjia , Yu Yajie , Fang Jianwen , Tan Siwen , Yao Fan , Guo Zhihua , Shao Yi
Published: October 2020

It has been reported that microRNA‐206(miR‐206) plays an important role in cancers and could be used as a prognostic biomarker. However, the results are controversial. Therefore, we summarize all available evidence and present a meta‐analysis to estimate the prognostic value of miR‐206 in various cancers. The relevant studies were collected by searching PubMed, EMBASE, and Web of Science databases until August 21, 2020. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were applied to explore the association between miR‐206 and survival results and clinicopathologic features. Sources of heterogeneity were investigated by subgroup analysis and sensitivity analysis. Publication bias was evaluated using Egger’s test. Twenty articles involving 2095 patients were included in the meta‐analysis. The pooled HR showed that low miR‐206 expression was significantly associated with unfavourable overall survival (OS) (HR = 2.03, 95 CI%: 1.53‐2.70, P < 0.01). In addition, we found that low miR‐206 expression predicted significantly negative association with tumor stage (III‐IV VS. I‐II) (OR = 4.20, 95% CI: 2.17‐8.13, P < 0.01), lymph node status (yes VS. no) (OR = 3.58, 95%: 1.51‐8.44, P = 0.004), distant metastasis (yes VS. no) (OR = 3.19, 95%: 1.07‐9.50, P = 0.038), and invasion depth (T3 + T4 vs. T2 + T1) (OR = 2.43, 95%: 1.70‐3.49, P < 0.01). miR‐206 can be used as an effective prognostic indicator in various cancers. Further investigations are warranted to validate the present results.
Study of the Permanent Deformation of Soil Used in Flexible Pavement Design
Authors: Cabral Wendel S. , Barroso Suelly H. A. , Torquato Samuel A.
Published: October 2020

The decreasing supply of soils with geotechnical parameters suitable for pavement designs is a visible problem in our environment. In order to establish more efficient designs and adequate construction criteria, it is essential to understand the performance of materials. This is a study of the permanent deformation (PD) of soil used in pavement layers, obtaining prediction models through the technique of artificial neural networks, in addition to the design of pavement structures using mechanistic‐empirical and empirical methods. The multistage repeated load triaxial (RLT) test, as well as numerical analyses of stresses and displacements using the CAP3D program, was used. The results showed that both the test procedure and the prediction models performed satisfactorily in obtaining PD behavior. Moreover, designs using the methods adopted resulted in distinct structures, that is, thickness different from the granular pavement layers. It was concluded that the model and test procedure exhibit significant potential for characterizing and modeling the PD of granular materials.
Aliskiren Reduces the Adrenal Zona Glomerulosa Apoptosis and Autophagy in Wistar Rats with 2K1C Hypertension
Authors: de Matos Veronica S. , do Nascimento Ana L. R. , Pereira Priscila G. , Rabelo Kíssila , Andrade Cherley B. V. , Moraes Alan C. N. , Salata Camila , Araújo Victor H. V. de O. , Ciambarella Bianca Torres , Bonfim Vieira Aline , Alves Luciana Lontro , da Silva Jemima F. R. , de Carvalho Jorge J.
Published: October 2020

Hypertension is a disease classified as primary or secondary, manifested not only by elevation of blood pressure but also involved in structural and functional changes of target organs. Renal artery stenosis is a leading factor of secondary hypertension, and its progress is associated with overactivation of the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a renin inhibiting drug that suppresses RAAS and culminates in decreased renin release, plasma angiotensin II concentration, and inhibition of aldosterone secretion. In this sense, the aim of the present study was to analyze the structural and ultrastructural morphophysiology of the adrenal glomerular zone, after treatment with aliskiren in Wistar rats with 2K1C hypertension. Parameters as structure and ultrastructure of the adrenal glomerular zone, cellular apoptosis, nuclear cell proliferation, and AT1 receptor expression were analyzed by immunostaining and electron microscopy. Our results showed that the hypertensive animals treated with aliskiren presented a reestablishment of AT1 receptor expression and decrease in apoptosis and autophagy. In addition, treatment with aliskiren improves the cell aspects in the adrenal glomerular zone, evidenced by ultrastructural analysis through preserved nuclei and well-developed mitochondria. Therefore, our evidence suggests that aliskiren has a beneficial effect on the adrenal glomerular zone remodeling in animals with renovascular hypertension.
Ultrasonography of the Kidneys in Healthy and Diseased Camels (Camelus dromedarius)
Authors: Tharwat Mohamed
Published: October 2020

This review article is written to describe the results of ultrasonography of the kidneys in healthy camels as well as camels with some renal disorders. In the dromedary camel, the physiology of the kidney is of interest in view of the specialization of the camel to hot dry deserts and to prolonged periods without water. It plays an important role in water conservation through the production of highly concentrated urine that may predispose animal to varieties of renal disorders. Examples of kidney affections in dromedary camels are renal capsular pigmentation, medullary hyperemia, subcapsular calcification, cortical and medullar discoloration, hemorrhage in renal pelvis, nephrolithiasis, and hydatidosis. Congestion, hemorrhage, hydronephrosis, acute glomerulonephritis, subacute glomerulonephritis, chronic glomerulonephritis, diffuse interstitial nephritis, focal interstitial nephritis, renal cyst, hyaline degeneration, renal amyloidosis, tubular nephrosis, pyelonephritis, hemosiderosis, and renal toxicity. When the kidney is examined by ultrasonography, the clinician can get sufficient information about the size, position, and echo patterns of the renal cortex and medulla and renal pelvis and outlines of the renal blood vessels. In recent years, ultrasonography has been used in camels for scanning of the healthy status as well as evaluation and determining the diagnosis and prognosis of diseased cases. Examples of diseases evaluated by ultrasonography are paratuberculosis, trypanosomiasis, pneumonia, pleurisy, gastrointestinal neoplasms, chronic peritonitis, splenic abscessation, and hepatic disorders. Of the renal disorders assessed by ultrasonography are nephrolithiasis, hydronephrosis, pyelonephritis, renal abscessation, and renal neoplasms. Ultrasound guidance in biopsy of renal specimens has also been reported in dromedary camels.
Superparamagnetic Behaviour and Surface Analysis of Fe3O4/PPY/CNT Nanocomposites
Authors: Rajagukguk Juniastel , Simamora Pintor , Saragih C. S. , Abdullah Hairus , Gultom Noto Susanto , Imaduddin Agung
Published: October 2020

The superparamagnetic property of nanomaterials such as Fe3O4 has been considered to be promising for various applications. In this paper, Fe3O4/PPY/CNT nanocomposites were synthesized with utilizing natural iron sand by a coprecipitation method. The as-precipitated Fe3O4 NPs were combined with carbon nanotubes (CNTs) using conductive polypyrrole (PPY) as linking agents. The Fe3O4/PPY/CNT nanocomposites were systematically characterized by FE-SEM, EDS, XRD, BET, and FTIR. Furthermore, the effects of CNTs on magnetic and thermal properties of nanocomposites were investigated by VSM and thermal gravimetric analysis (TGA), respectively. The composites exhibited significant decrease of coercivity value with the content of CNTs increasing. The VSM result confirmed that Fe3O4/PPY/CNT nanocomposites were superparamagnetic. It was found that by increasing the amounts of CNTs, the magnetization of Fe3O4/PPY/CNT nanocomposites gradually decreased. The addition of CNTs is intended to improve the mesoporous property as proved by BET analysis which has the potential application as a nanocatalyst.
An Approach of Spectra Standardization and Qualitative Identification for Biomedical Materials Based on Terahertz Spectroscopy
Authors: Shi Chenjun , Zhu Ji , Xu Mingqian , Wu Xu , Peng Yan
Published: October 2020

Terahertz time-domain spectroscopy (THz-TDS) systems are widely used to obtain fingerprint spectra of many different biomedical substances, and thus the identification of different biological materials, medicines, or dangerous chemicals can be realized. However, the spectral data for the same substance obtained from different THz-TDS systems may have distinct differences because of differences in system errors and data processing methods, which leads to misclassification and errors in identification. To realize the exact and fast identification of substances, spectral standardization is the key issue. In this paper, we present detailed disposal methods and execution processes for the spectral standardization and substance identification, including feature extracting, database searching, and fingerprint spectrum matching of unknown substances. Here, we take twelve biomedical compounds including different biological materials, medicines, or dangerous chemicals as examples. These compounds were analyzed by two different THz-TDS systems, one of which is a commercial product and the other is our verification platform. The original spectra from two systems showed obvious differences in their curve shapes and amplitudes. After wavelet transform, cubic spline interpolation, and support vector machine (SVM) classification with an appropriate kernel function, the spectra from two systems can be standardized, and the recognition rate of qualitative identification can be up to 99.17%.
Acoustic Emission Characteristics and Failure Prediction of the Granite with Orthogonal Cracks under Compressive Loading
Authors: Ju Yizhong , Wu Xu
Published: October 2020

Natural joints existing in rock significantly affect the stability of long‐term served subsurface engineering. In this paper, granite specimens with two orthogonal cracks were made for uniaxial compressive tests. The acoustic emission monitoring (AE) and digital image correlation techniques were employed to record the acoustic events and cracking of rock. The stress, ring‐down count, and cumulative ring‐down count of AE during the tests were obtained. The b‐value of AE was calculated based on the magnitude and number of AE events. The relationship between the b‐value and rock cracking for the specimens with orthogonal cracks was discussed. Further, the effects of orthogonal cracks distribution on the b‐value and rock cracking were investigated. Experimental results show that the specimens with orthogonal cracks would undergo multiple cycles of energy accumulation‐release‐reaccumulation‐rerelease under the uniaxial compression. For the specimens with orthogonal cracks, the b‐value of AE was volatile but generally decreased until complete failure. Every cracking event during the loading made the b‐value drop and then the reaccumulation of energy made the b‐value increase or stable. The specimen with orthogonal cracks was more prone to initial cracking than the intact rock. The orientation of cracks had effects on the b‐value evolution and crack patterns. The b‐value reaching about 1.5 can be used as the failure precursor of specimens with orthogonal cracks.
Cross-Border E-Commerce Personalized Recommendation Based on Fuzzy Association Specifications Combined with Complex Preference Model
Authors: Xiang Dan , Zhang Zhijie
Published: October 2020

Since cross-border e-commerce involves the export and import of commodities, it is affected by many policies and regulations, resulting in some special requirements for the recommendation system, which makes the traditional collaborative filtering recommendation algorithm less effective for the cross-border e-commerce recommendation system. To address this issue, a simple yet effective cross-border e-commerce personalized recommendation is proposed in this paper, which integrates fuzzy association rule and complex preference into a recommendation model. Under the constraint of fuzzy association rules, a hybrid recommendation model based on user complex preference features is constructed to mine user preference features, and personalized commodities recommendation is realized according to user behavior preference. Compared with the traditional recommendation algorithm, the improved algorithm reduces the impact of data sparsity. The experiment also verifies that the improved fuzzy association rule algorithm has a better recommendation effect than the existing state-of-the-art recommendation models. The recommendation system proposed in this paper has better generalization and has the performance to be applied to real-life scenarios.
Betaine Modulates Rumen Archaeal Community and Functioning during Heat and Osmotic Stress Conditions In Vitro
Authors: Mahmood Mubarik , Khiaosa-ard Ratchaneewan , Zebeli Qendrim , Petri Renée M.
Published: October 2020

Rumen archaea play an important role in scavenging ruminal hydrogen (H2) and thus facilitate rumen fermentation. They require optimum temperature and osmolality for their growth and metabolism; however, a number of external factors may put archaea under heat and osmotic stress. Betaine is an osmolyte, molecular chaperone, and antioxidant; therefore, it bears potential to combat against these stressors. In this in vitro study, three betaine levels, namely, 0 (control), 51 (low), and 286 (high) ppm, were used. Each of these was subjected to two temperatures (39.5 and 42°C) and two osmolality conditions (295 and 420 mOsmol kg-1) with

n
=
6

per treatment. Sequencing analyses of the solid phase (which use solid materials containing primarily fibrous materials of low-density feed particles) and the liquid phase (rumen fermenter liquid) using 16S rRNA revealed that more than 99.8% of the ruminal archaea in fermenters belong to the phylum Euryarchaeota. At the genus level, Methanobrevibacter was the most prevalent in both phases, and Methanosaeta was only detected in the liquid phase. The genera Methanobrevibacter and Methanobacterium both showed a positive correlation with methane (CH4) formation in the liquid and solid phases, respectively (

P
<
0.05

). Heat stress increased the relative abundance of genus Methanimicrococcus at the expense of candidate archaeal genus Vadin CA11 (

P
<
0.05

). In the solid phase, osmotic stress significantly reduced the Shannon and Simpson indices of diversity, and relative abundance was higher for Methanobrevibacter at the expense of Methanimicrococcus. In the liquid phase, osmotic stress increased not only the abundance-based coverage estimator (ACE) and singles parameters of diversity but also the relative abundances of Methanosphaera and Methanobacterium. The overall decrease in all gas parameters and estimated metabolic hydrogen ([2H]) utilization was observed during osmotic stress conditions (

P
<
0.05

). Betaine enhanced the diversity of solid phase archaea as indicated by the increase in ACE and singles during heat stress, and only a high dose improved all diversity parameters in the liquid phase during osmotic stress (

P
<
0.05

). Thus, betaine alleviates the effects of heat stress and osmotic stress on the archaea community.
Influence of Shape and Size of Foundation on Vibration Reduction of High-Speed Punching Press Based on Multidomain Modeling
Authors: Xu Teng , Xia Qinxiang , Long Xiaobin , Ran Jiaqi , Gong Feng
Published: October 2020

With the aid of multidomain modeling method, the vibration of a high-speed punching press was modeled and predicted, and the influence of the installation of foundation, as well as the shape and size parameters of the foundation on the vibration of the punching press, is discussed. The rectangular foundation size with the best effect of vibration reduction under the premise of saving the installation area was obtained. The validity of the multidomain model of the high-speed punching press with the foundation for vibration reduction is verified, by comparing the simulation results with the experimental results.
Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion
Authors: Yuan Zhao-Di , Zhu Wei-Ning , Liu Ke-Zhi , Huang Zhan-Peng , Han Yan-Chuang
Published: October 2020

Although innovative technologies for somatic cell reprogramming and transdifferentiation provide new strategies for the research of translational medicine, including disease modeling, drug screening, artificial organ development, and cell therapy, recipient safety remains a concern due to the use of exogenous transcription factors during induction. To resolve this problem, new induction approaches containing clinically applicable small molecules have been explored. Small molecule epigenetic modulators such as DNA methylation writer inhibitors, histone methylation writer inhibitors, histone acylation reader inhibitors, and histone acetylation eraser inhibitors could overcome epigenetic barriers during cell fate conversion. In the past few years, significant progress has been made in reprogramming and transdifferentiation of somatic cells with small molecule approaches. In the present review, we systematically discuss recent achievements of pure chemical reprogramming and transdifferentiation.
Wide Anterior Maxillary Reconstruction with Equine Bone Xenograft: A Case Report of 24-Month Follow-Up
Authors: De Cicco Davide , Colella Giuseppe , Tartaro Gianpaolo , Zerbinati Nicola , Fragola Romolo , Rauso Raffaele
Published: October 2020

Introduction. Orofacial reconstruction plays an important role in the treatment of patients affected by oral and maxillofacial cancers. Improvements in technologies and studies of biomaterials have widely expanded surgical possibilities to achieve good functional and aesthetic outcomes. By the way, xenografting procedures gained great consensus in the last decades, because of their documented reliability and efficacy. We present a case of anterior maxillary chondrosarcoma (CHS) that has undergone surgical ablation followed by reconstruction with an equine-derived bone xenograft. Case Presentation. A 68-year-old woman affected by CHS of the premaxilla underwent surgical ablation involving the four incisors followed by reconstruction using an equine-derived bone substitute. Bony reconstruction was planned to achieve implant and dental prosthetic rehabilitation at a second surgical time. Primary surgery was carried out without complications. Good integration of the graft was confirmed by radiological examination. At 12-month follow-up, the patient refused the implant placement and spontaneously adopted a mobile prosthesis. One year later, plates and screws were removed, because of the exposure of a titanium plate. The graft was finally rejected within 3 weeks. Discussion. Nonantigenic equine-derived biomaterials have shown reliability and a good safety profile. In the presented case, implant insertion should have been performed 12 months after the primary surgery. During the follow-up, until dental mobile prosthesis was applied, clinical and instrumental examinations demonstrated a good integration of the graft. We suppose that a chronic inflammation of the mucosa led to the exposure of the plate, perhaps due to pressure, minimal movements, or imperfect fitting of the mobile prosthesis. Removal of fixation means was performed to prevent grafting failure, without success. On the other hand, missing load could induce the graft to act just like a prosthesis, without a real process of integration. Safety and reliability of equine-derived bone xenografts cannot be currently confirmed if not followed by implant insertion and dental rehabilitation.
Stakeholder‐Associated Risks and Their Interactions in PPP Projects: Social Network Analysis of a Water Purification and Sewage Treatment Project in China
Authors: Yang Mingzhu , Chen Haitao , Xu Yongshun
Published: October 2020

As a result of complex contractual relationships, multiple stakeholders with different interests are involved in public‐private partnership (PPP) projects. Compared to traditional models, PPP projects have more uncertainty. This study integrated stakeholders and risk factors in PPP projects from a network perspective to better determine how to control risks. Using social network analysis (SNA), a case study was conducted to identify the critical risk factors, and mitigation actions are proposed. The results indicated that, compared to other stakeholders, local governments play the most important role in PPP projects. Managers should therefore pay more attention to political and legal risk factors and develop reasonable risk‐sharing plans. This study expands PPP risk research from the individual level to the network level and provides a visualized, innovative research paradigm for PPP risk analysis. The results can also be used by project managers for decision‐making, risk management, and other processes, thus helping to achieve the sustainable management of PPP projects.
Using the Functional Resonance Analysis Method (FRAM) in Aviation Safety: A Systematic Review
Authors: Tian Wulin , Caponecchia Carlo
Published: October 2020

The functional resonance analysis method (FRAM) is a system-based method to understand highly complex sociotechnical systems. Besides learning from safety occurrences or undesirable states, FRAM can be used to understand how things go well in a system, by identifying gaps between “work as imagined” (WAI) and “work as done” (WAD). FRAM is increasingly used in many domains and can enhance our understanding of a complex system and proposes strategies to refine the work design. This systematic review identified 108 FRAM research papers from 2006–2019. Most of these papers were conducted by European researchers and employed qualitative methods such as document analysis, interviews, and focus groups with subject matter experts (SMEs) and observations to develop WAI and WAD. Despite being used in healthcare, construction, and maritime sectors among others, aviation was the most commonly explored domain in FRAM studies. The 26 FRAM studies in aviation explored many aspects of the aviation industry, including Air Traffic Control (ATC) systems, cockpit operation, ground handling, maintenance, and a range of past safety incidents, like runway incursions. This paper also characterises the FRAM studies focused on aviation in terms of the common methods and steps used to build FRAM and the available software tools to build FRAM nets. Current FRAM illustrates its advantages in capturing the dynamic and nonlinear nature of complex systems and facilitates our understanding and continual improvement of complex systems. However, there are some critical issues in FRAM use and interpretation, such as the consistency of methods and complexity and reliability of data collection methods, which should be considered by researchers and FRAM users in industry.
Antioxidant Function and Metabolomics Study in Mice after Dietary Supplementation with Methionine
Authors: Yu Manrong , Chen Hui , Liu Pan , Yang Mei , Zou Leqin , Xiao Dingfu
Published: October 2020

The antioxidant function and metabolic profiles in mice after dietary supplementation with methionine were investigated. The results showed that methionine supplementation enhanced liver GSH‐Px activity and upregulated Gpx1 expression in the liver and SOD1 and Gpx4 expressions in the jejunum. Nrf2/Keap1 is involved in oxidative stress, and the western blotting data exhibited that dietary methionine markedly increased Keap1 abundance, while failed to influence the Nrf2 signal. Metabolomics investigation showed that methionine administration increased 2‐hydroxypyridine, salicin, and asparagine and reduced D‐Talose, maltose, aminoisobutyric acid, and inosine 5’‐monophosphate in the liver, which are widely reported to involve in oxidative stress, lipid metabolism, and nucleotides generation. In conclusion, our study provides insights into antioxidant function and liver metabolic profiles in response to dietary supplementation with methionine.
Autofluorescence Imaging of 3D Tumor–Macrophage Microscale Cultures Resolves Spatial and Temporal Dynamics of Macrophage Metabolism
Authors: Heaster Tiffany M. , Humayun Mouhita , Yu Jiaquan , Beebe David J. , Skala Melissa C.
Published: October 2020

Macrophages within the tumor microenvironment (TME) exhibit a spectrum of protumor and antitumor functions, yet it is unclear how the TME regulates this macrophage heterogeneity. Standard methods to measure macrophage heterogeneity require destructive processing, limiting spatiotemporal studies of function within the live, intact 3D TME. Here, we demonstrate two-photon autofluorescence imaging of NAD(P)H and FAD to nondestructively resolve spatiotemporal metabolic heterogeneity of individual macrophages within 3D microscale TME models. Fluorescence lifetimes and intensities of NAD(P)H and FAD were acquired at 24, 48, and 72 hours poststimulation for mouse macrophages (RAW264.7) stimulated with IFNγ or IL4 plus IL13 in 2D culture, confirming that autofluorescence measurements capture known metabolic phenotypes. To quantify metabolic dynamics of macrophages within the TME, mouse macrophages or human monocytes (RAW264.7 or THP-1) were cultured alone or with breast cancer cells (mouse polyoma-middle T virus or primary human IDC) in 3D microfluidic platforms. Human monocytes and mouse macrophages in tumor cocultures exhibited significantly different FAD mean lifetimes and greater migration than monocultures at 24, 48, and 72 hours postseeding. In cocultures with primary human cancer cells, actively migrating monocyte-derived macrophages had greater redox ratios [NAD(P)H/FAD intensity] compared with passively migrating monocytes at 24 and 48 hours postseeding, reflecting metabolic heterogeneity in this subpopulation of monocytes. Genetic analyses further confirmed this metabolic heterogeneity. These results establish label-free autofluorescence imaging to quantify dynamic metabolism, polarization, and migration of macrophages at single-cell resolution within 3D microscale models. This combined culture and imaging system provides unique insights into spatiotemporal tumor–immune cross-talk within the 3D TME.

Significance:

Label-free metabolic imaging and microscale culture technologies enable monitoring of single-cell macrophage metabolism, migration, and function in the 3D tumor microenvironment.
Determinants of Guideline-Discordant Breast Cancer Care
Authors: McDougall Jean A. , Cook Linda S. , Tang Mei-Tzu C. , Linden Hannah M. , Thompson Beti , Li Christopher I.
Published: October 2020

Background:

Evidence-based breast cancer treatment guidelines recommend the most appropriate course of therapy based on tumor characteristics and extent of disease. Evaluating the multilevel factors associated with guideline discordance is critical to identifying strategies to eliminate breast cancer survival disparities.

Methods:

We identified females diagnosed with a first primary, stage I–III breast cancer between the ages of 20–69 years of age from the population-based Seattle-Puget Sound Surveillance, Epidemiology, and End Results registry. Participants completed a survey about social support, utilization of patient support services, hypothesized barriers to care, and initiation of breast cancer treatment. We used logistic regression to estimate odds ratios and 95% confidence intervals (CI).

Results:

Among 1,390 participants, 10% reported guideline-discordant care. In analyses adjusted for patient-level sociodemographic factors, individuals who did not have someone to go with them to appointments or drive them home (OR 1.96; 95% CI, 1.09–3.59) and those who had problems talking to their doctors or their staff (OR 2.03; 95% CI, 1.13–3.64) were more likely to be guideline discordant than those with social support or without such problems, respectively. Use of patient support services was associated with a 43% lower odds of guideline discordance (OR 0.57; 95% CI, 0.36–0.88).

Conclusions:

Although guideline discordance in this cohort of early-stage breast cancer survivors diagnosed <70 years of age was low, instrumental social support, patient support services, and communication with doctors and their staff emerged as potential multilevel intervention targets for improving breast cancer care delivery.

Impact:

This study supports extending the reach of interventions designed to improve guideline concordance.
Activin A Promotes Regulatory T-cell–Mediated Immunosuppression in Irradiated Breast Cancer
Authors: De Martino Mara , Daviaud Camille , Diamond Julie M. , Kraynak Jeffrey , Alard Amandine , Formenti Silvia C. , Miller Lance D. , Demaria Sandra , Vanpouille-Box Claire
Published: October 2020

Increased regulatory T cells (Treg) after radiotherapy have been reported, but the mechanisms of their induction remain incompletely understood. TGFβ is known to foster Treg differentiation within tumors and is activated following radiotherapy. Thus, we hypothesized that TGFβ blockade would result in decreased Tregs within the irradiated tumor microenvironment. We found increased Tregs in the tumors of mice treated with focal radiotherapy and TGFβ blockade. This increase was mediated by upregulation of another TGFβ family member, activin A. In vitro, activin A secretion was increased following irradiation of mouse and human breast cancer cells, and its expression was further enhanced upon TGFβ blockade. In vivo, dual blockade of activin A and TGFβ was required to decrease intratumoral Tregs in the context of radiotherapy. This resulted in an increase in CD8+ T-cell priming and was associated with a reduced tumor recurrence rate. Combination of immune checkpoint inhibitors with the dual blockade of activin A and TGFβ led to the development of tumor-specific memory responses in irradiated breast cancer. Supporting the translational value of activin A targeting to reduce Treg-mediated immunosuppression, retrospective analysis of a public dataset of patients with breast cancer revealed a positive correlation between activin A gene expression and Treg abundance. Overall, these results shed light on an immune escape mechanism driven by activin A and suggest that dual targeting of activin A and TGFβ may be required to optimally unleash radiation-induced antitumor immunity against breast cancer.
The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma
Authors: Wang Xiuli , Huynh Christian , Urak Ryan , Weng Lihong , Walter Miriam , Lim Laura , Vyas Vibhuti , Chang Wen-Chung , Aguilar Brenda , Brito Alfonso , Sarkissian Aniee , Bandara N. Achini , Yang Lu , Wang Jinhui , Wu Xiwei , Zhang Jianying , Priceman Saul J. , Qin Hong , Kwak Larry W. , Budde Lihua E. , Thomas Sandra H. , Clark Mary C. , Popplewell Leslie , Siddiqi Tanya , Brown Christine E. , Forman Stephen J.
Published: October 2020

Lymphomas with central nervous system (CNS) involvement confer a worse prognosis than those without CNS involvement, and patients currently have limited treatment options. T cells genetically engineered with CD19-targeted chimeric antigen receptors (CAR) are effective against B-cell malignancies and show tremendous potential in the treatment of systemic lymphoma. We aimed to leverage this strategy toward a more effective therapy for patients with lymphoma with CNS disease. NOD-scid IL2Rgammanull (NSG) mice with CNS and/or systemic lymphoma were treated with CD19-CAR T cells via intracerebroventricular (ICV) or intravenous (IV) injection. CAR T cells isolated after treatment were rigorously examined for phenotype, gene expression, and function. We observed that CAR T cells infused ICV, but not IV, completely and durably eradicated both CNS and systemic lymphoma. CAR T cells delivered ICV migrated efficiently to the periphery, homed to systemic tumors, and expanded in vivo, leading to complete elimination of disease and resistance to tumor rechallenge. Mechanistic studies indicated that ICV-delivered CAR T cells are conditioned by exposure to cerebrospinal fluid in the ICV environment for superior antilymphoma activity and memory function compared with IV-delivered CAR T cells. Further analysis suggested that manipulating cellular metabolism or preactivating therapeutic CAR T cells with antigen ex vivo may improve the efficacy of CAR T cells in vivo. Our demonstration that ICV-delivered CD19-CAR T cells had activity against CNS and systemic lymphoma could offer a valuable new strategy for treatment of B-cell malignancies with CNS involvement.
Multi-SimLex: A Large-Scale Evaluation of Multilingual and Crosslingual Lexical Semantic Similarity
Authors: Vulić Ivan , Baker Simon , Ponti Edoardo Maria , Petti Ulla , Leviant Ira , Wing Kelly , Majewska Olga , Bar Eden , Malone Matt , Poibeau Thierry , Reichart Roi , Korhonen Anna
Published: October 2020

We introduce Multi-SimLex, a large-scale lexical resource and evaluation benchmark covering data sets for 12 typologically diverse languages, including major languages (e.g., Mandarin Chinese, Spanish, Russian) as well as less-resourced ones (e.g., Welsh, Kiswahili). Each language data set is annotated for the lexical relation of semantic similarity and contains 1,888 semantically aligned concept pairs, providing a representative coverage of word classes (nouns, verbs, adjectives, adverbs), frequency ranks, similarity intervals, lexical fields, and concreteness levels. Additionally, owing to the alignment of concepts across languages, we provide a suite of 66 crosslingual semantic similarity data sets. Because of its extensive size and language coverage, Multi-SimLex provides entirely novel opportunities for experimental evaluation and analysis. On its monolingual and crosslingual benchmarks, we evaluate and analyze a wide array of recent state-of-the-art monolingual and crosslingual representation models, including static and contextualized word embeddings (such as fastText, monolingual and multilingual BERT, XLM), externally informed lexical representations, as well as fully unsupervised and (weakly) supervised crosslingual word embeddings. We also present a step-by-step data set creation protocol for creating consistent, Multi-Simlex–style resources for additional languages. We make these contributions—the public release of Multi-SimLex data sets, their creation protocol, strong baseline results, and in-depth analyses which can be helpful in guiding future developments in multilingual lexical semantics and representation learning—available via a Web site that will encourage community effort in further expansion of Multi-Simlex to many more languages. Such a large-scale semantic resource could inspire significant further advances in NLP across languages.
What Should/Do/Can LSTMs Learn When Parsing Auxiliary Verb Constructions?
Authors: de Lhoneux Miryam , Stymne Sara , Nivre Joakim
Published: October 2020

There is a growing interest in investigating what neural NLP models learn about language. A prominent open question is the question of whether or not it is necessary to model hierarchical structure. We present a linguistic investigation of a neural parser adding insights to this question. We look at transitivity and agreement information of auxiliary verb constructions (AVCs) in comparison to finite main verbs (FMVs). This comparison is motivated by theoretical work in dependency grammar and in particular the work of Tesnière ( 1959 ), where AVCs and FMVs are both instances of a nucleus, the basic unit of syntax. An AVC is a dissociated nucleus; it consists of at least two words, and an FMV is its non-dissociated counterpart, consisting of exactly one word. We suggest that the representation of AVCs and FMVs should capture similar information. We use diagnostic classifiers to probe agreement and transitivity information in vectors learned by a transition-based neural parser in four typologically different languages. We find that the parser learns different information about AVCs and FMVs if only sequential models (BiLSTMs) are used in the architecture but similar information when a recursive layer is used. We find explanations for why this is the case by looking closely at how information is learned in the network and looking at what happens with different dependency representations of AVCs. We conclude that there may be benefits to using a recursive layer in dependency parsing and that we have not yet found the best way to integrate it in our parsers.