bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractFor 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

AbstractBackgroundMuscular 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.AimWe 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 resultsGene 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.ConclusionThe 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

AbstractBiologically 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 nanovesiclesBasic Protocol 2: In vivo screening for organ toxicity and immune cell profiling using miceBasic 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

SummaryBlock 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

AbstractThe 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

AbstractChimpanzees (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

AbstractThis 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

Abstract

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

Abstract

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

AbstractIn 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

AbstractThose 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

AbstractThe 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

AbstractThis 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.