bluuebunny/crossref_metadata_2025 huggingface dataset:
Facet‐Selective Deposition of Ultrathin Al2O3 on Copper Nanocrystals for Highly Stable CO2 Electroreduction to Ethylene
Authors: Li Hui , Yu Peiping , Lei Renbo , Yang Feipeng , Wen Peng , Ma Xiao , Zeng Guosong , Guo Jinghua , Toma Francesca M. , Qiu Yejun , Geyer Scott M. , Wang Xinwei , Cheng Tao , Drisdell Walter S.
Published: September 2021

Catalysts based on Cu nanocrystals (NCs) for electrochemical CO2‐to‐C2+ conversion with high activity have been a subject of considerable interest, but poor stability and low selectivity for a single C2+ product remain obstacles for realizing sustainable carbon‐neutral cycles. Here, we used the facet‐selective atomic layer deposition (FS‐ALD) technique to selectively cover the (111) surface of Cu NCs with ultrathin Al2O3 to increase the exposed facet ratio of (100)/(111), resulting in a faradaic efficiency ratio of C2H4/CH4 for overcoated Cu NCs 22 times higher than that for pure Cu NCs. Peak performance of the overcoated catalyst (Cu NCs/Al2O3‐10C) reaches a C2H4 faradaic efficiency of 60.4 % at a current density of 300 mA cm−2 in 5 M KOH electrolyte, when using a gas diffusion electrode flow cell. Moreover, the Al2O3 overcoating effectively suppresses the dynamic mobility and the aggregation of Cu NCs, which explains the negligible activity loss and selectivity degradations of Cu NCs/Al2O3‐10C shown in stability tests.
Thermoplastic polyurethanes for biomedical application: A synthetic, mechanical, antibacterial, and cytotoxic study
Authors: Al Nakib Rana , Toncheva Antoniya , Fontaine Veronique , Vanheuverzwijn Jérôme , Raquez Jean‐Marie , Meyer Franck
Published: September 2021

Thermoplastic polyurethanes (TPUs) bear tunable chemistry offering the possibility to develop a rich palette of physio‐mechanical properties, making the materials suitable for various fields of application. The great variety in TPUs properties comes from the choices of the monomers and the reaction conditions. Herein, the mechanical properties of the developed TPUs are tailored, while fine‐tuning the hard and soft segment molar ratio, as well as the reaction conditions. TPUs are synthesized from 4,4′‐methylenebis(phenyl isocyanate), poly(tetrahydrofuran), and 1,4‐butanediol, and their thermal and mechanical properties are fully characterized. The sample with the most appropriate mechanical properties that are suitable for catheter fabrication, is selected for the biomedical application. Quaternary ammonium salt is synthesized, and 0.5 mol% is incorporated in the TPU to confer antibacterial properties to the material while preserving its mechanical strength. The microbiological tests reveal the antibacterial effect of the developed materials against Staphylococcus aureus and Pseudomonas aeruginosa, as well as 80% SiHa cell viability, after 72 h of exposure, as part of the performed cytotoxicity studies. Finally, TPUs catheter prototypes fabrication is also proposed, applying an extrusion or injection molding approach for the production of biomedical devices with desirable mechanical properties.
Effects of solid lubricants on the tribological behavior of steel‐backed UHMWPE fabric composites
Authors: Lin Yudong , Guo Zhiwei , Yuan Chengqing
Published: September 2021

Aboard ship, the use of lubricating oil in mechanical equipment is sometimes difficult to achieve and applied oil can easily leak. The use of self‐lubricating materials can largely solve this problem. In this study, three kinds of solid lubricant‐enhanced 304 stainless steel‐backed ultrahigh molecular weight polyethylene (UHMWPE) fabric composites were fabricated with the addition of graphite, molybdenum (IV) disulfide, or polytetrafluoroethylene (PTFE). They were tested under various rotating speeds and compared with pure steel‐backed UHMWPE fabric composites. The tribological performance of these composites was evaluated by analysis of friction coefficient, wear rate, and worn face morphology. The results showed that PTFE‐enhanced composites exhibited the best friction reduction performance under all test conditions, better antiwear ability at rotating speeds under 200 rpm, and optimized wear surface morphology, thus indicating better synergy between PTFE and UHMWPE fabric.
Functional clustering methods for resistance spot welding process data in the automotive industry
Authors: Capezza Christian , Centofanti Fabio , Lepore Antonio , Palumbo Biagio
Published: September 2021

In the automotive industry, quality assessment of resistance spot welding (RSW) joints of metal sheets is typically based on costly and lengthy offline tests, which are unfeasible in the full‐scale production on a large scale. However, the massive industrial digitalization triggered by the Industry 4.0 framework makes online measurements of RSW process parameters available for every joint produced. Among these, the so‐called dynamic resistance curve (DRC) is recognized as the full technological signature of the spot welds. Motivated by this context, this article intends to show the potentiality and practical applicability of clustering methods to data represented by curves, and, in general, to functional data. In this way, the task of separating DRCs into homogeneous groups pertaining to spot welds with common mechanical and metallurgical properties can be performed without the need for arbitrary and problem‐specific feature extraction. We provide a hands‐on overview of the most promising functional clustering methods, and apply them to DRCs collected during RSW lab tests at Centro Ricerche Fiat. The identified groups of DRCs emerge to be strictly linked with the wear status of the electrodes, which, in turn, is conjectured to impact the RSW joint final quality. The analysis code, developed in the software environment , accompanied by an essential tutorial and the ICOSAF project data set containing DRC measurements, are openly available online at
https://github.com/unina‐sfere/funclustRSW/.
A validated stability‐indicating reversed‐phase‐HPLC method for dipyridamole in the presence of degradation products and its process‐related impurities in pharmaceutical dosage forms
Authors: Mallavarapu Ravindra , Katari Naresh Kumar , Dongala Thirupathi , Rekulapally Vijay Kumar , Marisetti Vishnu Murthy , Vyas Govind
Published: September 2021

In this study, we developed and validated a method to determine dipyridamole‐related impurities in pharmaceutical dosage forms using the reversed‐phase‐HPLC technique. All impurities were separated on a YMC pack C8 (150 mm × 4.6 mm, 3.0 μm) analytical column using a suitable mobile phase. Mobile phase A was 10 mM concentration of phosphate buffer (pH adjusted to 4.7 by adding diluted orthophosphoric acid) and mobile phase B was buffer:acetonitrile:methanol (at the ratio of 30:40:30 v/v). The optimized chromatographic conditions used in the experiment were as follows: flow rate, 1.0 mL/min; injection volume, 10 μL and column temperature, 35°C. Chromatographic detection was performed at 295 nm. The stressed samples were analyzed for degradation under acidic, basic, peroxide, water hydrolysis, and physical degradation conditions. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines, and found to be specific, linear, accurate and have a robust stability‐indicating nature. The method showed excellent linearity from limit of quantification (LOQ) to 150% level of concentrations for all impurities. The correlation coefficient (r2) for all impurities was between 0.995 and 0.999. The recovery study was performed from LOQ to 150% level concentrations, with mean recovery values between 92.9% and 103.2%, respectively. The developed method can be used to determine dipyridamole and its relative impurities. The degradation and validated study results indicate its stability‐indicating nature. Therefore, the method can be used in pharmaceutical research and development and quality control departments.
Four‐year HbA1c and LDL‐cholesterol trajectories among individuals with mental disorders and newly developed type 2 diabetes
Authors: Kristensen Frederik P. , Rohde Christopher , Østergaard Søren D. , Thomsen Reimar W.
Published: September 2021

The impact of different types of mental disorders on long‐term glycemic and lipid trajectories following newly diagnosed type 2 diabetes (T2D) remains unknown. We used real‐world clinical data in a population‐based cohort to fill this knowledge gap. We found that individuals with new T2D and preexisting personality, anxiety, unipolar depression, or psychotic disorder had higher mean HbA1c levels over 4 years following the onset of T2D, whereas no differences were found regarding LDL‐C levels. This knowledge should be considered in the management of T2D in these vulnerable groups.
Mirror Symmetry Breaking and Network Formation in Achiral Polycatenars with Thioether Tail
Authors: Alaasar Mohamed , Darweesh Ahmed F. , Cai Xiaoqian , Liu Feng , Tschierske Carsten
Published: September 2021

Mirror symmetry breaking in systems composed of achiral molecules is of importance for the design of functional materials for technological applications as well as for the understanding of the mechanisms of spontaneous emergence of chirality. Herein, we report the design and molecular self‐assembly of two series of rod‐like achiral polycatenar molecules derived from a π‐conjugated 5,5’‐diphenyl‐2,2’‐bithiophene core with a fork‐like triple alkoxylated end and a variable single alkylthio chain at the other end. In both series of liquid crystalline materials, differing in the chain length at the trialkoxylated end, helical self‐assembly of the π‐conjugated rods in networks occurs, leading to wide temperature ranges (>200 K) of bicontinuous cubic network phases, in some cases being stable even around ambient temperatures. The achiral bicontinuous cubic Ia
d phase (gyroid) is replaced upon alkylthio chain elongation by a spontaneous mirror symmetry broken bicontinuous cubic phase (I23) and a chiral isotropic liquid phase (Iso1[*]). Further chain elongation results in removing the I23 phase and the re‐appearance of the Ia
d phase with different pitch lengths. In the second series an additional tetragonal phase separates the two cubic phase types.
Synthesis of Polycyclic Aromatic Hydrocarbons Decorated by Fluorinated Carbon Acids/Carbanions
Authors: Hoshikawa Shoki , Yanai Hikaru , Martín‐Mejías Irene , Lázaro‐Milla Carlos , Aragoncillo Cristina , Almendros Pedro , Matsumoto Takashi
Published: September 2021

The carboarylation reaction of biphenyl‐alkynes was successfully triggered by electrophilic attack of 1,1‐bis(triflyl)ethylene on the alkyne moiety to give polycyclic aromatic hydrocarbons (PAHs) decorated by superacidic carbon acid functionality. Neutralisation of thus obtained acids with NaHCO3 yielded the corresponding sodium salts, which showed improved solubility in both aqueous and organic solvents.
Coupling Long‐Range Raman with X‐Ray Photoelectron Spectroscopy for Complementary Bulk and Surface Characterization of Battery Materials
Authors: Radtke Mariusz , Kopp Karl , Hess Christian
Published: September 2021

For the combined surface and bulk characterization of functional powder materials, we report on the direct coupling of Raman spectroscopy with X‐ray photoelectron spectroscopy (XPS) within one setup, avoiding the influence of different sample states and measurement environments. Our approach is based on the Raman integration into the XPS analysis chamber, employing a long‐range camera objective connected to a portable 532 nm Raman spectrometer. For optimization of the measurement geometry, a (400) single crystal (SC), chemical vaper deposition (CVD)‐grown diamond was employed. The applicability of the combined XPS‐Raman spectroscopy approach was first validated by measurements on powder V2O5, used as a commercial standard, and then demonstrated on lithium ion battery materials, that is, LixV2O5 lithium pentoxides. The transferability to other XPS systems is strongly facilitated by the long‐range Raman‐spectroscopic approach, which allowed for Raman analysis over a distance of 320 mm for the CVD‐grown (400) single crystal diamond and 285 mm for LixV2O5. Our results demonstrate the inexpensive and straightforward implementation of coupled XPS‐Raman spectroscopy for combined surface/bulk analysis.
Identification of hub genes in bladder cancer based on weighted gene co‐expression network analysis from TCGA database
Authors: Wang Lei , Liu Xudong , Yue Miao , Liu Zhe , Zhang Yu , Ma Ying , Luo Jia , Li Wuling , Bai Jiangshan , Yao Hongmei , Chen Yuxuan , Li Xiaofeng , Feng Dayun , Song Xinqiang
Published: September 2021

Background

Muscular invasive bladder cancer (MIBC) is a common malignant tumor in the world. Because of their heterogeneity in prognosis and response to treatment, biomarkers that can predict survival or help make treatment decisions in patients with MIBC are essential for individualized treatment.

Aim

We aimed to integrate bioinformatics research methods to identify a set of effective biomarkers capable of predicting, diagnosing, and treating MIBC. To provide a new theoretical basis for the diagnosis and treatment of bladder cancer.

Methods and results

Gene expression profiles and clinical data of MIBC were obtained by downloading from the Cancer Genome Atlas database. A dataset of 129 MIBC cases and controls was included. 2084 up‐regulated genes and 2961 down‐regulated genes were identified by differentially expressed gene (DEG) analysis. Then, gene ontology analysis was performed to explore the biological functions of DEGs, respectively. The up‐regulated DEGs are mainly enriched in epidermal cell differentiation, mitotic nuclear division, and so forth. They are also involved in the cell cycle, p53 signaling pathway, PPAR signaling pathway, and so forth. The weighted gene co‐expression network analysis yielded five modules related to pathological stages and grading, of which blue and turquoise were the most relevant modules for MIBC. Next, Using Kaplan–Meier survival analysis to identify further hub genes, the screening criteria at p ≤ .05, we found CNKSR1, HIP1R, CFL2, TPM1, CSRP1, SYNM, POPDC2, PJA2, and RBBP8NL genes associated with the progression and prognosis of MIBC patients. Finally, immunohistochemistry experiments further confirmed that CNKSR1 plays a vital role in the tumorigenic context of MIBC.

Conclusion

The research suggests that CNKSR1, POPDC2, and PJA2 may be novel biomarkers as therapeutic targets for MIBC, especially we used immunohistochemical further to validate CNKSR1 as a therapeutic target for MIBC which may help to improve the prognosis for MIBC.
Lymphocyte Profile and Immune Checkpoint Expression in Drug‐Induced Liver Injury: An Immunophenotyping Study
Authors: Cueto‐Sanchez Alejandro , Niu Hao , Del Campo‐Herrera Enrique , Robles‐Díaz Mercedes , Sanabria‐Cabrera Judith , Ortega‐Alonso Aida , Garcia‐Cortes Miren , Gonzalez‐Grande Rocio , Jimenez‐Perez Miguel , Ruiz‐Cabello Francisco , Andrade Raúl J. , Lucena M. Isabel , Stephens Camilla
Published: September 2021

The identification of specific HLA risk alleles in drug‐induced liver injury (DILI) points toward an important role of the adaptive immune system in DILI development. In this study, we aimed to corroborate the role of an adaptive immune response in DILI through immunophenotyping of leukocyte populations and immune checkpoint expressions. Blood samples were collected from adjudicated DILI (n = 12), acute viral hepatitis (VH; n = 13), acute autoimmune hepatitis (AIH; n = 9), and acute liver injury of unknown etiology (n = 15) at day 1 (recognition), day 7, and day >30. Blood samples from patients with nonalcoholic fatty liver disease (NAFLD; n = 20) and healthy liver controls (HLCs; n = 54) were extracted at one time point. Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA‐4 that was determined intracellularly, using flow cytometry. At recognition, DILI demonstrated significantly higher levels of activated helper T‐cell (P < 0.0001), activated cytotoxic T‐cells (P = 0.0003), Th1 (P = 0.0358), intracellular CTLA‐4 level in helper T‐cells (P = 0.0192), and PD‐L1 presenting monocytes (P = 0.0452) than HLC. These levels approached those of HLC over time. No significant differences were found between DILI and VH. However, DILI presented higher level of activated helper T‐cells and CTLA‐4 than NAFLD and lower PD‐L1 level than AIH. Our findings suggest that an adaptive immune response is involved in DILI in which activated CD4+ and CD8+ play an important role. Increased expression of negative immune checkpoints is likely the effect of peripheral tolerance regulation.
Evaluation of In Vivo Toxicity of Biological Nanoparticles
Authors: Driscoll Julia , Yan Irene K. , Angom Ramcharan Singh , Moirangthem Anuradha , Patel Tushar
Published: September 2021

Biologically derived nanoparticles such as extracellular vesicles are promising candidates for therapeutic applications. In vivo toxicity of biological nanoparticles can result in tissue or organ damage, immunological perturbations, or developmental effects but cannot be readily predicted from in vitro studies. Therefore, an essential component of the preclinical assessment of these particles for their use as therapeutics requires screening for adverse effects and detailed characterization of their toxicity in vivo. However, there are no standardized, comprehensive methods to evaluate the toxicity profile of nanoparticle treatment in a preclinical model. Here, we first describe a method to prepare bovine milk‐derived nanovesicles (MNVs). These MNVs are inexpensive to isolate, have a scalable production platform, and can be modified to achieve a desired biological effect. We also describe two vertebrate animal models, mice and zebrafish, that can be employed to evaluate the toxicity profile of biologically derived nanoparticles, using MNVs as an example. Treatment‐induced organ toxicity and immunological effects can be assessed in mice receiving systemic injections of MNVs, and developmental toxicity can be assessed in zebrafish embryos exposed to MNVs in embryo water. Utilizing these animal models provides opportunities to analyze the toxicity profiles of therapeutic extracellular vesicles in vivo. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Preparation of milk‐derived nanovesicles

Basic Protocol 2: In vivo screening for organ toxicity and immune cell profiling using mice

Basic Protocol 3: In vivo developmental toxicity screening using zebrafish
A secured authentication and DSM‐KL ascertained performance optimization of a hybrid block chain‐enabled framework for a multiple WSN
Authors: Baskaran Guruprakash , Kannaiah Sathish Kumar , Ramanujam Sukumar
Published: September 2021

Block chain is extensively seen as a potential alternative in the safety and efficiency problems of the vast internet of things (IoT) data to allow safe and successful data storage/processing/sharing. In this manuscript, a secured authentication and deep slime mould optimized kernel learning (DSM‐KL) ascertained performance optimization of a hybrid block chain‐enabled framework for a multiple wireless sensor network (WSN) is proposed to recover data security performance and efficiency. To reflect the reality of the multi‐WSN network better, local block chain and public block chain are deployed, and a hybrid block chain model is created as per the various capabilities and energy of different nodes. A multi‐WSN network model is intended. It has numerous nodes on IoT. Based on dissimilar functions of nodes, the IoT nodes are divided into base stations, cluster heads and ordinary nodes based on its capabilities that facilitate management and cooperation of nodes. A DSM‐KL algorithm for dynamically selecting/adjusting block producer, consensus algorithm, block size and block interval to recover efficiency to handle both dynamic and broad dimensional properties of IoT systems is designed. The simulation process is executed in the MATLAB platform. The proposed DSM‐KL attains lower drop 27.53%, higher delivery ratio 28.56%, lower drop 28.64%, lower energy depletion rate 38.63%, higher network active time 38.47%, lower overhead 26.47% and higher throughput 27.67%, and the performances are compared with the existing methods such as deep reinforcement learning (DRL) and block chain and reinforcement learning (RLBC), respectively.
Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?
Authors: Czornyj Liliana , Auzmendi Jerónimo , Lazarowski Alberto
Published: September 2021

The multidrug‐resistance (MDR) phenotype is typically observed in patients with refractory epilepsy (RE) whose seizures are not controlled despite receiving several combinations of more than two antiseizure medications (ASMs) directed against different ion channels or neurotransmitter receptors. Since the use of bromide in 1860, more than 20 ASMs have been developed; however, historically ~30% of cases of RE with MDR phenotype remains unchanged. Irrespective of metabolic biotransformation, the biodistribution of ASMs and their metabolites depends on the functional expression of some ATP‐binding cassette transporters (ABC‐t) in different organs, such as the blood‐brain barrier (BBB), bowel, liver, and kidney, among others. ABC‐t, such as P‐glycoprotein (P‐gp), multidrug resistance–associated protein (MRP‐1), and breast cancer–resistance protein (BCRP), are mainly expressed in excretory organs and play a critical role in the pharmacokinetics (PK) of all drugs. The transporter hypothesis can explain pharmacoresistance to a broad spectrum of ASMs, even when administered simultaneously. Since ABC‐t expression can be induced by hypoxia, inflammation, or seizures, a high frequency of uncontrolled seizures increases the risk of RE. These stimuli can induce ABC‐t expression in excretory organs and in previously non‐expressing (electrically responsive) cells, such as neurons or cardiomyocytes. In this regard, an alternative mechanism to the classical pumping function of P‐gp indicates that P‐gp activity can also produce a significant reduction in resting membrane potential (ΔΨ0 = −60 to −10 mV). P‐gp expression in neurons and cardiomyocytes can produce membrane depolarization and participate in epileptogenesis, heart failure, and sudden unexpected death in epilepsy. On this basis, ABC‐t play a peripheral role in controlling the PK of ASMs and their access to the brain and act at a central level, favoring neuronal depolarization by mechanisms independent of ion channels or neurotransmitters that current ASMs cannot control.
Chimpanzees (Pan troglodytes) in savanna landscapes
Authors: Lindshield Stacy , Hernandez‐Aguilar R. Adriana , Korstjens Amanda H. , Marchant Linda F. , Narat Victor , Ndiaye Papa Ibnou , Ogawa Hideshi , Piel Alex K. , Pruetz Jill D. , Stewart Fiona A. , van Leeuwen Kelly L. , Wessling Erin G. , Yoshikawa Midori
Published: September 2021

Chimpanzees (Pan troglodytes) are the only great apes that inhabit hot, dry, and open savannas. We review the environmental pressures of savannas on chimpanzees, such as food and water scarcity, and the evidence for chimpanzees' behavioral responses to these landscapes. In our analysis, savannas were generally associated with low chimpanzee population densities and large home ranges. In addition, thermoregulatory behaviors that likely reduce hyperthermia risk, such as cave use, were frequently observed in the hottest and driest savanna landscapes. We hypothesize that such responses are evidence of a “savanna landscape effect” in chimpanzees and offer pathways for future research to understand its evolutionary processes and mechanisms. We conclude by discussing the significance of research on savanna chimpanzees to modeling the evolution of early hominin traits and informing conservation programs for these endangered apes.
Development and assessment of an intrusive polynomial chaos expansion‐based continuous adjoint method for shape optimization under uncertainties
Authors: Papageorgiou Anastasios K. , Papoutsis‐Kiachagias Evangelos M. , Giannakoglou Kyriakos C.
Published: September 2021

This article contributes to the development of methods for shape optimization under uncertainties, associated with the flow conditions, based on intrusive Polynomial Chaos Expansion (iPCE) and continuous adjoint. The iPCE to the Navier–Stokes equations for laminar flows of incompressible fluids is developed to compute statistical moments of the Quantity of Interest which are, then, compared with those obtained through the Monte Carlo method. The optimization is carried out using a continuous adjoint‐enabled, gradient‐based loop. Two different formulations for the continuous adjoint to the iPCE PDEs are derived, programmed, and verified. Intrusive PCE methods for the computation of the statistical moments require mathematical development, derivation of a new system of governing equations and their numerical solution. The development is presented for a chaos order of two and two uncertain variables and can be used as a guide to those willing to extend this development to a different set of uncertain variables or chaos order. The developed method and software, programmed in OpenFOAM, is applied to two optimization problems pertaining to the flow around isolated airfoils with uncertain farfield conditions.
Genomic evolution and the impact of SLIT2 mutation in relapsed intrahepatic cholangiocarcinoma
Authors: Zhou Shao‐Lai , Luo Chu‐Bin , Song Cheng‐Li , Zhou Zheng‐Jun , Xin Hao‐Yang , Hu Zhi‐Qiang , Sun Rong‐Qi , Fan Jia , Zhou Jian
Published: September 2021

Background and Aims

Intrahepatic cholangiocarcinoma (ICC) is aggressive and has high rates of relapse, conferring poor long‐term survival after curative resection. Little is known about the genomic evolution that occurs during ICC relapse.

Approach and Results

We conducted whole‐exome sequencing of 30 paired primary and relapsed tumors from 10 patients with ICC who received curative resection. We sought to identify frequently altered genes, infer tumor subclonal architectures, and track genomic evolution from primary to relapsed tumors. We examined functional effects and the mechanism of action of SLIT2, a gene specifically mutated in relapsed tumors, on tumor growth and metastasis and the tumor microenvironment. Our results indicated that relapsed ICCs were genetically derived from intrahepatic dissemination of primary tumors. However, they acquired additional mutations while maintaining most drivers, such as TP53 and IDH1. Multiregion sequencing suggested polyclonal seeding of ICC dissemination. Four of 10 relapsed ICCs acquired SLIT2 mutations that were not present in the corresponding primary tumors. Validation in an expanded sample revealed SLIT2 mutations in 2.3% (1/44) of primary ICCs and 29.5% (13/44) of relapsed ICCs. Biofunctional investigations revealed that inactivating mutation of SLIT2 resulted in activation of PI3K–Akt signaling in ICC cells, directly enhanced neutrophil chemotaxis, mediated tumor‐associated neutrophil infiltration, and contributed to ICC growth and metastasis.

Conclusions

We characterized genomic evolution during ICC relapse and identified SLIT2 as a driver of tumor dissemination and tumor‐associated neutrophil infiltration.
Persistent biliary hypoxia and lack of regeneration are key mechanisms in the pathogenesis of posttransplant nonanastomotic strictures
Authors: de Jong Iris E. M. , Overi Diletta , Carpino Guido , Gouw Annette S. H. , van den Heuvel Marius C. , van Kempen Léon C. , Mancone Carmine , Onori Paolo , Cardinale Vincenzo , Casadei Luca , Alvaro Domenico , Porte Robert J. , Gaudio Eugenio
Published: September 2021

Background and Aims

Nonanastomotic biliary strictures (NAS) are a major cause of morbidity after orthotopic liver transplantation (OLT). Although ischemic injury of peribiliary glands (PBGs) and peribiliary vascular plexus during OLT has been associated with the later development of NAS, the exact underlying mechanisms remain unclear. We hypothesized that bile ducts of patients with NAS suffer from ongoing biliary hypoxia and lack of regeneration from PBG stem/progenitor cells.

Approach and Results

Forty‐two patients, requiring retransplantation for either NAS (n = 18), hepatic artery thrombosis (HAT; n = 13), or nonbiliary graft failure (controls; n = 11), were included in this study. Histomorphological analysis of perihilar bile ducts was performed to assess differences in markers of cell proliferation and differentiation in PBGs, microvascular density (MVD), and hypoxia. In addition, isolated human biliary tree stem cells (hBTSCs) were used to examine exo‐metabolomics during in vitro differentiation toward mature cholangiocytes.

Bile ducts of patients with NAS or HAT had significantly reduced indices of PBG mass, cellular proliferation and differentiation (mucus production, secretin receptor expression, and primary cilia), reduced MVD, and increased PBG apoptosis and hypoxia marker expression, compared to controls. Metabolomics of hBTSCs during in vitro differentiation toward cholangiocytes revealed a switch from a glycolytic to oxidative metabolism, indicating the need for oxygen.

Conclusions

NAS are characterized by a microscopic phenotype of chronic biliary hypoxia attributed to loss of microvasculature, resulting in reduced proliferation and differentiation of PBG stem/progenitor cells into mature cholangiocytes. These findings suggest that persistent biliary hypoxia is a key mechanism underlying the development of NAS after OLT.
Cassis and Green Tea: Spontaneous Release of Natural Aroma Compounds from β‐Alkylthioalkanones
Authors: Bättig Sarah , Egger Timothy , Gey Olga , Bochet Christian G. , Flachsmann Felix
Published: September 2021

In depth headspace analysis of the slow degradation of β‐alkylthioalkanones in ambient air led to the discovery of a novel δ‐cleavage pathway, by which β‐mercaptoketones are released. Since β‐mercaptoketones are potent natural aroma compounds occurring in many fruits, herbs and flowers, the discovery of an enzyme‐independent molecular precursor for this class of high‐impact molecules is of practical importance. Moreover, the formation of β‐diketones and aldehydes by concomitant oxidation at the α‐sulfur‐position enhances the versatility of this class of aroma precursors. A mechanistic model is proposed which suggests that the oxidative degradation occurs through a novel Pummerer‐type rearrangement of initially formed persulfoxides.
Is CAD A Good Paradigm for MBSE?
Authors: Henderson Kaitlin , Salado Alejandro
Published: September 2021

Those looking to advocate for Model‐Based Systems Engineering (MBSE) in the Systems Engineering field often turn to more established fields that have made a similar transition to models to assure others it will be beneficial. One practice that is often compared to MBSE is Computer‐Aided Design (CAD) from the field of mechanical engineering. However, the adequacy of this comparison is challenged upon a side‐by‐side examination of what MBSE and CAD are. Based on the established definitions, it is evident that while CAD can be considered a method of mechanical drawing, MBSE cannot be described as only a method. MBSE is more than installing and utilizing software, it is a process in and of itself. Comparing MBSE to CAD runs the risk of oversimplifying MBSE and setting up expectations that may not be met. Therefore, while CAD may represent a similar paradigm shift as MBSE in terms of digitalization, it may not serve as an adequate paradigm in terms of adoption and benefits. In this paper, we characterize and compare CAD and MBSE and identify the similarities and differences between them. We use the resulting insights to level the expectations of adopting and using MBSE.
Security in the Future of Systems Engineering (FuSE), a Roadmap of Foundation Concepts
Authors: Dove Rick , Willett Keith , McDermott Tom , Dunlap Holly , MacNamara Delia Pembrey , Ocker Cory
Published: September 2021

The Future of Systems Engineering (FuSE) is an INCOSE‐led multiorganizational collaborative initiative pursuing INCOSE's Vision 2025 and beyond. To accomplish this the FuSE initiative encompasses a number of topic areas with active projects to shape the future of systems engineering. This paper addresses the FuSE Security topic area and provides a roadmap of eleven foundational concepts for building the security vision. The purpose of this paper is to instigate and inspire thinking and involvement in the development and practice of the foundational concepts.
STPA‐Sec Analysis for DevSecOps Reference Design
Authors: Reule Ryyan T , Feighery Brynn , Winstead Mark W. , Hild Daryl R. , Barnum Will , Span Martin
Published: September 2021

This work describes a top down systems security requirements analysis approach for understanding and eliciting general security requirements for securing Software Factories (SF). More specifically, the System‐Theoretic Process Analysis approach for Security (STPA‐Sec) is used to understand and elicit systems security requirements for SFs. The effort employs STPA‐Sec on the DoD Enterprise DevSecOps Reference Design to detail a conceptual approach to analyze SFs. The intent is to develop functional‐level security requirements, design‐level engineering considerations, and architectural‐level security specification criteria early in the system life cycle. The aim is to secure the SFs themselves, enhancing the security of resulting software generated from the SF. These details were elaborated during a summer collaborative research effort by two United States Air Force Academy Systems Engineering cadets, working with a MITRE team of subject matter expertise (SME's), and guided by their instructor. This work provides insight into a viable systems security requirements analysis approach which results in traceable security, safety, and resiliency requirements that can be designed‐for, built‐to, and verified with confidence.
Unlocking the power of big data within the early design phase of the new product development process
Authors: Ali Haytham B. , Helgesen Fredrik H. , Falk Kristin
Published: September 2021

This study investigates how to exploit big data to increase knowledge in the early design phase within new product development through an industrial application. There are limited research and a scarcity of empirical studies that show the use of big data within new product development in manufacturing industries. Shorter design cycle demand, rapid decision‐making, and the need for data‐driven methodology are evident. An increase of knowledge through big data analytics, closing the loop with a knowledge base, has become a critical success criterion within the various industries.

This paper reviews the state‐of‐the‐art in academic literature and investigates a case company. The case uncovered a gap of limited feedback into the early design phase. We developed a generic agile approach to extract value through analyzing big data. To fill in the identified gap, we tested our approach on a sample of big data, including both internal and external user data. Positive feedback from a survey complemented by interviews indicates that our method can aid decision‐making within the early design phase by acquiring a more data‐driven methodology.
Application of A3 Architecture Overviews in Subsea Front‐End Engineering Studies: A Case Study
Authors: Haugland Remi , Engen Siv
Published: September 2021

This research investigates the application of A3 Architecture Overviews (A3AOs) in subsea front‐end engineering studies. A3AO is a valuable method to support multi‐disciplinary communication and share architectural knowledge in complex engineering domains. The method captures key information of an overall system and displays the system overview in a standard A3 format. In this paper, we investigate the beneficial impact a global subsea supplier can gain by applying A3AO as part of their concept evaluation process in the early phase study. Through interviews and a survey, we identified company's main challenges in concept evaluation of tie‐in and connection system. We then applied the A3AO method to investigate its mitigating effect in early phase concept evaluation. We found that the company resources found the A3AO to provide a holistic system overview and support knowledge sharing. Overall, our research supports the use of A3AO as a method to promote common understanding.
Verification and Validation of SysML Models
Authors: Hecht Myron , Chen Jaron
Published: September 2021

Model Based Systems Engineering depends on correct models. However, thus far, relatively little attention has been paid to ensuring their correctness. This paper describes a methodology for performing verification and validation on models written in SysML. The methodology relies on a catalog of candidate requirements that can be tailored for a specific project. Both manual and automated methods are used to verify and validate these requirements. Manual methods are necessary where knowledge of the domain and other extrinsic characteristics are necessary. Automated methods can be used where the requirements cover the use of SysML. Examples from a public domain SysML model of a satellite are presented to demonstrate application of automated requirements verification.
Developing a Model Based Systems Engineering Architecture for Defense Wearable Technology
Authors: Sarathi Tara , Cyr Jillian , DeLaura Rich , Balcius James , Collins Paula , Shatz Michael
Published: September 2021

The rapid advancement of commercial wearable sensing technologies provides an unprecedented opportunity to gather information that improves warfighter performance during military activities and to detect the onset of illness (such as COVID‐19) through surveillance. However, the promise of improved performance and illness prevention through these technologies remains unfulfilled because of the complexity of guaranteeing that technology development outside of the standard military acquisition cycle will meet military requirements. The key to meeting this challenge is to facilitate coordination among R&D efforts, commercially developed products, and military acquisition strategies. To address this, we developed an MBSE architecture and methodology for validating independently developed wearable system designs against military end‐user needs. This methodology includes developing a conceptual framework, a model library, and a capability needs matrix that maps defense mission characteristics to physiological states and product design implementations. This architecture allows military stakeholders to determine where capability gaps or opportunities for wider application of commercial technologies exist, thus providing a bridge between externally developed wearable sensing technologies and military acquisition strategies.
Challenges in Detecting Emergent Behavior in System Testing
Authors: Kjeldaas Kent Aleksander , Haugen Rune André , Syverud Elisabet
Published: September 2021

System integration testing in the defense and aerospace industry is becoming increasingly complex. The long lifetime of the system drives the need for sub‐system modifications throughout the system life cycle. The manufacturer must verify that these modifications do not negatively affect the system's behavior. Hence, an extensive test regime is required to ensure reliability and robustness of the system. System behaviors that emerge from the interaction of sub‐systems can be difficult to pre‐define and capture in a test setup using acceptance criteria. Typical challenges with current test practice include late detection of unwanted system behavior, high cost of repetitive manual processes, and risk of release delays because of late error detection.

This paper reviews the state of practice at a case company in the defense and aerospace industry. We use an industry‐as‐laboratory approach to explore the situation in the company. The research identifies the challenges and attempts to quantify the potential gain from improving the current practice. We find that the current dependency on manual analysis generates resources ‐and scheduling constraints and communication issues that hinder efficient detection of system emergent behavior. We explore two approaches to automate anomaly detection of system behavior from test data. The first approach looks at anomaly detection in a top‐down approach to give an indication of the system integrity. The second approach uses anomaly detection on system parts, resulting in the ability to localize the root causes. The work lays the foundation for further research of automated anomaly detection in system testing.
A State‐of‐Practice Survey of the Automotive and Space Industry Product Development Strategies
Authors: Moore James “Tony” , Adams Jim , Sega Ronald M.
Published: September 2021

Product Development is a process employed by all industries to support creating new opportunities. The approach to product development by the automotive industry is vastly different than the space industry. As disruptive technologies flow into the market, the space industry is in the midst of an evolutionary change. The methods of design, management and architecture are the topics reviewed in this work. From the background of the methods the analysis of each of these industries suggest that there may be an opportunity for further review. As the space industry continues to push into a new frontier of lower cost and quicker turnaround solutions, there can be great benefits to employing parts of the methods honed by the automotive industry. The possibilities of gaining knowledge from the automotive industry could in the future lead toward advancements in product development management and product development architecture methods that could continue fueling the evolutionary changes in the space industry.
Model of Models Methodology: Reuse Your Architectural Data
Authors: Jackson Aleczander , Palmer Barrion , Cobb Daniel , McCreless Joseph
Published: September 2021

One of the primary and underutilized benefits of Model Based Systems Engineering is reuse. Most users of Model Based Systems Engineering lack the understanding of the process involved to develop a project tree that enables use of projects in other projects to facilitate that multi‐dimensional reuse. Although the benefits speak for themselves, few practitioners fully grasp the modeling techniques and rigor necessary to facilitate a model that is fully traced, modular, and reusable. The Model of Models Methodology satisfies these needs, accomplishing the Digital Engineering needs on the project as well as enabling significant time and cost savings.
Overview of the Revised Standard on Architecture Description – ISO/IEC 42010
Authors: Martin James N
Published: September 2021

An updated version of the international standard for Architecture Description is expected to be published in 2021 as the new version of ISO/IEC/IEEE 42010. This paper provides an overview of the key concepts defined by this standard and the rationale for them. In particular, it describes the key new concepts such as aspects and perspectives that were incorporated to bring this into alignment with current architecting and MBSE practices. These concepts are used as the basis for architecture description templates and guidelines contained in methodology documents and in architecture modeling tools.
Individual forecaster perceptions of the persistence of shocks to GDP
Authors: Clements Michael P.
Published: September 2021

We analyse individual professional forecasters' beliefs concerning the persistence of GDP shocks. Despite substantial apparent heterogeneity in perceptions, with around one half of the sample of professional forecasters believing shocks do not have permanent effects, we show that these apparent differences may be largely due to short samples and survey respondents being active at different times. When we control for these effects, using a bootstrap, we formally do not reject the null that individuals' long‐horizon expectations are interchangeable at a given point in time. When we apply the same bootstrap approach to their medium‐term expectations, we do reject the null. We explore this difference between long and medium‐horizon forecasts by decomposing revisions in forecasts into permanent and transitory components.
Osteoblast-Specific Wnt Secretion Is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice
Authors: Lawson Lisa Y. , Brodt Michael D. , Migotsky Nicole , Chermside-Scabbo Christopher J. , Palaniappan Ramya , Silva Matthew J.
Published: September 2021

Wnt signaling is critical to many aspects of skeletal regulation, but the importance of Wnt ligands in the bone anabolic response to mechanical loading is not well established. Recent transcriptome profiling studies by our laboratory and others show that mechanical loading potently induces genes encoding Wnt ligands, including Wnt1 and Wnt7b. Based on these findings, we hypothesized that mechanical loading stimulates adult bone formation by inducing Wnt ligand expression. To test this hypothesis, we inhibited Wnt ligand secretion in adult (5 months old) mice using a systemic (drug) and a bone-targeted (conditional gene knockout) approach, and subjected them to axial tibial loading to induce lamellar bone formation. Mice treated with the Wnt secretion inhibitor WNT974 exhibited a decrease in bone formation in non-loaded bones as well as a 54% decline in the periosteal bone formation response to tibial loading. Next, osteoblast-specific Wnt secretion was inhibited by dosing 5-month-old Osx-CreERT2; WlsF/F mice with tamoxifen. Within 1 to 2 weeks of Wls deletion, skeletal homeostasis was altered with decreased bone formation and increased resorption, and the anabolic response to loading was reduced 65% compared to control (WlsF/F). Together, these findings show that Wnt ligand secretion is required for adult bone homeostasis, and furthermore establish a role for osteoblast-derived Wnts in mediating the bone anabolic response to tibial loading. © 2021 American Society for Bone and Mineral Research (ASBMR).
Effects of different surfactants on the degradation of petroleum hydrocarbons by mixed‐bacteria
Authors: Cui Jia‐Qi , Li Ya‐Qi , He Qing‐Sheng , Li Bing‐Zhi , Yuan Ying‐Jin , Wen Jian‐Ping
Published: September 2021

BACKGROUND

Surfactant‐enhanced remediation (SER) has been widely applied to remove petroleum hydrocarbon (PH) pollutants, but there are few studies on the mechanism through which surfactants affect the hydrocarbon metabolite ability of microorganism.

RESULTS

In this work, combination bacteria and surfactant were selected to remove PH, and the degradation bottleneck concentration of single‐bacteria was 10 g L–1 according to the PH degradation rate. However, the degradation efficient of mixed‐bacteria was further increased after adding surfactants. Among them, the PH degradation rate of Kocuria rosea + Bacillus odyssey and Microbacterium. sp + B. odyssey at the bottleneck concentration had been respectively reached to 81.58 ± 6.29% with tween‐80 and 88.35 ± 7.58% with rhamnolipid. Compared with no surfactant, the relative abundance of global overmaps, amino acid metabolism, and carbohydrate metabolism was increased in adding tween‐80 condition. However, when rhamnolipid was added, the relative abundance of ABC transporters, two‐component system, and bacteria chemotaxis was clearly increased, indicating an improvement of transportation, absorption, and degradation of PH. Additionally, the gene abundance of alkB and nah was also significantly increased with above condition. Meanwhile, the gene abundance of alkB and nah was also significantly enhanced by above condition.

CONCLUSION

This study offers new insights into the functional changes of mixed‐bacteria during PH degradation in different surfactant‐enhanced systems. © 2021 Society of Chemical Industry (SCI).