bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Shrinkage, Coarse‐Grained Tantalum–Alumina Refractory Composites via Cold Isostatic Pressing
Authors: Endler Dirk , Zienert Tilo , Roungos Vasileios , Hubálková Jana , Gehre Patrick , Aneziris Christos G.
Published: July 2022

Alumina–tantalum composites are produced in a two‐step synthesis via cold isostatic pressing (CIP) from commercially available raw materials without any addition of organic additives. The highest densification for fine‐grained composites is found with a maximum pressure of 150 MPa, whereby a cyclic pressure increase or at maximum pressure showed no measurable influence. The increase of the sintering temperature from 1600 to 1700 °C led to a higher densification up to a relative density of . Aggregates received by jawbreaking show a blocky morphology, rounded corners, and edges with porosities of . The formation of tantalum carbide and the incorporation of oxygen into the tantalum lattice are verified during sintering. The coarse‐grained composites produced from these aggregates show open porosities of and shrinkage . Determined splitting tensile strenghts are in the range between 8.4 and 9.1 MPa.
Large‐Area Low‐Cost Multiscale‐Hierarchical Metasurfaces for Multispectral Compatible Camouflage of Dual‐Band Lasers, Infrared and Microwave
Authors: Feng Xingdong , Pu Mingbo , Zhang Fei , Pan Rui , Wang Si , Gong Jintao , Zhang Renyan , Guo Yinghui , Li Xiong , Ma Xiaoliang , Luo Xiangang
Published: July 2022

Multispectral complementary detection technologies have made single‐band camouflage materials ineffective, creating strong demand for multispectral compatible camouflage materials. Here, multiscale‐hierarchical metasurfaces (MHM) compatible with large‐area low‐cost fabrication are proposed for the first time to realize multispectral camouflage of dual‐band lasers, infrared and microwave. The MHM consists of an all‐metallic metasurface array (AMMA) and a microwave absorber. The AMMA hinders dual‐band lasers and thermal infrared detection, while the microwave absorber beneath the AMMA is applied as a defence against microwave detection. As a proof‐of‐concept, a MHM sample with an area of 30 × 30 cm2 and a minimum linewidth of 1.8 µm is fabricated based on nanoimprint lithography. The excellent multispectral camouflage performance is verified in experiments, showing low reflectance (<0.2) in 0.9–1.2 µm and 9–12 µm, low infrared emissivity (<0.2), and high absorption efficiency of over 90% 2.7–26 GHz. Wide‐angle and polarization‐independent characteristics are also demonstrated. This work offers a promising opportunity for the engineering application of metasurfaces in the multispectral camouflage field. Moreover, this methodology can be easily extended to other electromagnetic spectrum, providing significant guidance for the design and fabrication of multispectral devices.
Efficient Radiolabeling of Block Copolymer Micelles through Radiometal Salt Precipitation for Theranostic Applications
Authors: Liu Huanhuan , de Kruijff Robin M. , Laan Adrianus C. , Beekman Freek J. , van den Heuvel Eline , Ramakers Ruud M. , Eelkema Rienk , Denkova Antonia G.
Published: July 2022

A variety of polymer micelles are designed for the delivery of chemotherapeutic drugs to tumors. Although the promise of these nanocarriers is very high, in the clinic the effectivity is rather limited. Determining the in vivo fate of the micelles can greatly help to improve this treatment. Here, a simple and fast chelator‐free method for radiolabeling of polymer micelles composed of different block copolymers is presented, which can allow evaluating the behavior of the nanocarriers in vivo using noninvasive nuclear imaging techniques (e.g., single photon computed tomography, SPECT). The radiolabeling method consists of adding the radioisotope ions, i.e., 111In(III), resulting in a high radiolabeling efficiencies up to 90%. The results suggest that the radiolabeling efficiency depends on two important factors: the properties of the hydrophobic block in the block copolymer composing the micelle core, and the speciation of the radiometal salts. The formation of metal hydroxides and their precipitation in the core of the micelles appears to be a key factor for high stability. Moreover, the method can be applied to radiolabel the micelles in the presence of chemotherapeutic drugs. Finally, a SPECT study shows that the radiolabeled samples are stable in vivo without any evident loss of 111In(III).
Phenotypic characterization of seven individuals with Marbach–Schaaf neurodevelopmental syndrome
Authors: Marbach Felix , Lipska‐Ziętkiewicz Beata S. , Knurowska Agata , Michaud Vincent , Margot Henri , Lespinasse James , Tran Mau Them Frédéric , Coubes Christine , Park Joohyun , Grosch Sarah , Roggia Cristiana , Grasshoff Ute , Kalsner Louisa , Denommé‐Pichon Anne‐Sophie , Afenjar Alexandra , Héron Bénédicte , Keren Boris , Caro Pilar , Schaaf Christian P.
Published: July 2022

We present the phenotypes of seven previously unreported patients with Marbach–Schaaf neurodevelopmental syndrome, all carrying the same recurrent heterozygous missense variant c.1003C>T (p.Arg335Trp) in PRKAR1B. Clinical features of this cohort include global developmental delay and reduced sensitivity to pain, as well as behavioral anomalies. Only one of the seven patients reported here was formally diagnosed with autism spectrum disorder (ASD), while ASD‐like features were described in others, overall indicating a lower prevalence of ASD in Marbach–Schaaf neurodevelopmental syndrome than previously assumed. The clinical spectrum of the current cohort is similar to that reported in the initial publication, delineating a complex developmental disorder with behavioral and neurologic features. PRKAR1B encodes the regulatory subunit R1β of the protein kinase A complex (PKA), and is expressed in the adult and embryonal central nervous system in humans. PKA is crucial to a plethora of cellular signaling pathways, and its composition of different regulatory and catalytic subunits is cell‐type specific. We discuss potential molecular disease mechanisms underlying the patients' phenotypes with respect to the different known functions of PKA in neurons, and the phenotypes of existing R1β‐deficient animal models.
Peripartum management of tuberous sclerosis complex complicated by massive angiomyolipomas
Authors: Knapp C. , Ince M. , Zacharzewski A.
Published: July 2022

Tuberous sclerosis complex is a genetic disease that can affect multiple organs, commonly the renal, central nervous, cardiac and respiratory systems. Here, we present the peripartum management of a woman with a new diagnosis of tuberous sclerosis complex associated with massive renal angiomyolipomas. There was significant risk of catastrophic haemorrhage from the angiomyolipomas during pregnancy. This created a challenging scenario for the anaesthetists, obstetricians, urologists and interventional radiologists involved in their care, necessitating collaborative working, numerous investigations and honest patient‐centred discussions. Evidence for the management of tuberous sclerosis and angiomyolipomas in pregnancy does not appear to have been previously reported. After much consideration, arterial embolisation of the most vascular area of the angiomyolipoma was completed at 28 weeks gestation under remifentanil sedation. An elective caesarean section under combined spinal epidural anaesthesia was completed at 37 + 3 weeks gestation. Central nervous system involvement must always be considered; benign tumours within the brain and spinal cord may contraindicate neuraxial techniques. Early multidisciplinary involvement is essential due to the diverse and complex nature of tuberous sclerosis. Individuals differ in their presentation and disease severity; therefore, they must be assessed on an individual basis with management tailored accordingly.
Biodiesel from high‐acid‐value grease trap waste: process optimization and purification using bio‐based adsorbent
Authors: Jariah Nurhani Fatihah , Roslan Ahmad Muhaimin , Hassan Mohd Ali , Taufiq‐Yap Yun Hin
Published: July 2022

Material with negative value such as grease trap waste appears to be a cost‐effective feedstock for biodiesel production since it can be collected at little to no charge. Owing to its high lipid content, fatty acid methyl ester can be produced from grease trap waste via a two‐step production process with methanol, using potassium hydroxide as the catalyst. However, there are several process parameters that could affect the yield of the fatty acid methyl ester produced. In this study, the optimum conditions for biodiesel production were 6:1 methanol‐to‐oil molar ratio, 1.5 wt% potassium hydroxide loadings, a 40 °C reaction temperature and a 2 h reaction time, resulting in a fatty acid methyl ester yield of 87%. Further purification using 0.05 g L−1 of biobased adsorbent from woodchip biomass for a 1 h residence time at 25 °C yielded the highest removal of free fatty acid and soap at 98.2 and 67.9%, respectively. This study not only demonstrates the potential of grease trap waste as a bioresource for the production of biodiesel, but also proves an interesting and additional use of bio‐based adsorbent from woodchip biomass as an effective tool in biodiesel purification since the quality of biodiesel produced within the standard EN14214. © 2022 Society of Chemical Industry and John Wiley & Sons, Ltd.
Reevaluation of the topographical anatomy of the mid‐thigh: A magnetic resonance and ultrasound imaging study
Authors: Torun Bilge Ipek , Balaban Mehtap , Hatipoglu Sukru Cem
Published: July 2022

Adductor canal (AC) and sciatic nerve (SN) blockades are commonly used during total knee arthroplasties for postoperative pain control. Medical professionals have begun to utilize single injection combined regional anesthesia methods due to increased patient comfort. In this study, we examined the topographical anatomy of the mid‐thigh, which is recommended as the appropriate intervention level for combined AC and SN blockades, in order to provide a safe approach for clinicians. We examined 184 thigh magnetic resonance images (MRI) from 98 patients. We measured the diameter of the mid‐thigh, anterior thigh muscle thickness, subcutaneous adipose tissue thickness, and SN depth on the MRIs. We obtained ultrasound (US) images of the vastoadductor membranes (VAM) of 26 volunteers, and measured the vertical distances between the greater trochanter and the adductor tubercle (A) and the greater trochanter and the upper edge of the VAM (B). We then proportioned B to A in order to determine in which part of the thigh the AC was located. The AC was in the distal third of the thigh, and the SN's depth was located in the third quarter of the thigh's diameter. Only the adductor magnus, and no neurovascular structure, was at risk of injury between the AC and the SN. The upper edge of the VAM was 6.5 cm below the mid‐thigh, therefore it is not appropriate to suggest performing an AC blockade at mid‐thigh. We think that it is safe to perform a combined AC and SN blockade in a single injection in selected patients.
Flavonoid extract Kushenol a exhibits anti‐proliferative activity in breast cancer cells via suppression of PI3K/AKT/mTOR pathway
Authors: Liu Tao , Gong Jinhua , Lai Guobin , Yang Yichao , Wu Xiaoan , Wu Xiuping
Published: July 2022

Background

Kushenol A is natural flavonoid extract discovered in recent years, with potential anti‐tumor activity. Its role in breast cancer is poorly understood.

Methods

To investigate biological function of Kushenol A in breast cancer (BC), Cell Counting Kit‐8 assay, colony formation assay, flow cytometry, western blotting, qPCR analysis, and xenograft mouse model were performed.

Results

We found that Kushenol A treatment reduced proliferative capability and induced G0/G1 phase cell cycle arrest and apoptosis of BC cells in a concentration‐dependent manner. Besides, Kushenol A treatment contributed to the upregulation of apoptosis‐related and cell cycle‐associated genes. In nude mice, Kushenol A administration repressed BC xenograft tumor growth. Mechanistically, phosphorylation levels of AKT and mTOR were markedly attenuated in Kushenol A‐treated BC cells; however, there were no significant differences in total AKT and mTOR expressions. Moreover, PI3K inhibitor combined with Kushenol A exhibited synergistic inhibitory activity on cell proliferation.

Conclusions

Taken together, our findings suggested that Kushenol A suppressed BC cell proliferation by modulating PI3K/AKT/mTOR signaling pathway. Kushenol A may be a promising therapeutic drug for treating BC.
Sterically Controlled Late‐Stage Functionalization of Bulky Phosphines
Authors: Deng Hao , Bengsch Marco , Tchorz Nico , Neumann Constanze N.
Published: July 2022

The fine‐tuning of metal‐phosphine‐catalyzed reactions relies largely on accessing ever more precisely tuned phosphine ligands by de‐novo synthesis. Late‐stage C−H functionalization and diversification of commercial phosphines offers rapid access to entire libraries of derivatives based on privileged scaffolds. But existing routes, relying on phosphorus‐directed transformations, only yield functionalization of C
−H bonds in a specific position relative to phosphorus. In contrast to phosphorus‐directed strategies, herein we disclose an orthogonal functionalization strategy capable of introducing a range of substituents into previously inaccessible positions on arylphosphines. The strongly coordinating phosphine group acts solely as a bystander in the sterically controlled borylation of bulky phosphines, and the resulting borylated phosphines serve as the supporting ligands for palladium during diversification through phosphine self‐assisted Suzuki‐Miyaura reactions.
Responsiveness and interpretation of the PROMIS Cancer Function Brief 3D Profile
Authors: Smith Sean R. , Vargo Mary , Zucker David S. , Shahpar Samman , Gerber Lynn H. , Henderson Maryanne , Jay Gina , Cheville Andrea L.
Published: July 2022

Background

Measuring function with valid and responsive tools in patients with cancer is essential for driving clinical decision‐making and for the end points of clinical trials. Current patient‐reported outcome measurements of function fall short for many reasons. This study evaluates the responsiveness of the Patient‐Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile, a novel measure of function across multiple domains.

Methods

Two hundred nine participants across five geographically distinct tertiary care centers completed the assessment and pain rating at two outpatient cancer rehabilitation clinic visits. Patients and providers completed a global rating of change measure at the second visit to indicate whether the patient was improving or worsening in function. Multiple response indices and linear models measured whether the measure was responsive to self‐reported and clinician‐rated changes over time. Correlations between changes in function and changes in anchors (pain rating and performance status) were also calculated.

Results

Function as measured by the PROMIS Cancer Function Brief 3D Profile changed appropriately as both patients and clinicians rated change. Small to moderate effect sizes supported the tool's responsiveness. Function was moderately correlated with pain and more strongly correlated with performance status, and changes in function corresponded with changes in anchor variables. No floor/ceiling effect was found.

Conclusions

The PROMIS Cancer Function Brief 3D Profile is sensitive to changes over time in patients with cancer. The measure may be useful in clinical practice and as an end point in clinical trials.

Lay summary

We gave patients a questionnaire by which they told their physicians how well they were functioning, including how fatigued they were.

This study tested that questionnaire to see whether the scores would change if patients got better or worse.
Toxicity and outcomes after external beam irradiation for prostate cancer in patients with prior holmium laser enucleation of the prostate: Early experience
Authors: Laughlin Brady S. , Narang Gopi L. , Cheney Scott M. , Humphreys Mitchell R. , Vargas Carlos E. , Keole Sameer R. , Rwigema Jean‐Claude M. , Schild Steven E. , Wong William W.
Published: July 2022

Purpose/Objectives

Holmium laser enucleation of the prostate (HoLEP) is commonly performed in patients with significant bladder outlet obstruction. However, there are few reports on the toxicity of external beam irradiation (RT) for prostate cancer in patients after prior HoLEP. In this study, we evaluate the side effects and treatment outcomes of RT after HoLEP.

Materials/Methods

Eighteen patients who had HoLEP and subsequently received RT for prostate cancer were included. Data collected included patient and disease characteristics, urinary function, and radiation dose. Acute and late urinary (GU) and gastrointestinal (GI) side effects were evaluated. Disease control and survival rates were calculated using Kaplan–Meier method.

Results

Median follow‐up was 18 months (range: 4–46 months). Median prostate volume was 107 ml before HoLEP and 24 ml after HoLEP. Median International Prostate Symptom Score (IPSS) was 17 (range: 5–32) before HoLEP. Median decline in IPSS score after HoLEP was 7 (range: −2–21). On uroflow study, peak flow rate, and post‐void residual were significantly improved after HoLEP. After radiation, peak flow rate and average flow rate showed a decline but remained significantly improved compared to pre‐HoLEP measurements. Maximum acute Common Terminology Criteria for Adverse Events (CTCAE) adverse events were 12 grade 1 and 3 grade 2 for GU, and 3 grade 1 for GI, respectively. Maximum late adverse events were 13 grade 1 and 2 grade 2 for GU, and all grade 0 for GI, respectively. At last follow‐up, there were 8 grade 1 and 1 grade 2 late GU, and 3 grade 1 late GI adverse events, respectively. There was no significant increase in urinary incontinence after RT compared to before RT. The 18‐month biochemical control, local control, distant control rates were 78%, 94%, and 80%, respectively.

Conclusions

Patients who received RT as definitive treatment for prostate cancer after prior HoLEP had low risk of serious acute and late side effects. HoLEP can be safely performed and should be considered in patients with significant bladder outlet obstruction and large prostate volume before RT.
Heterogeneous graph prompt for Community Question Answering
Authors: Liu Huanghai , Qin Ying
Published: July 2022

Compared with general question answering, Community Question Answering (CQA), which has been widely used in various scenarios like E‐commerce and is well welcomed. In order to answer the user's question precisely, many CQA models resort to external knowledge sources such as Wikipedia. The main challenge of the task is knowledge extraction and utilization. Different from the traditional method of designing task‐specific knowledge modules, we propose a graph prompt‐based learning method that directly steers the pretrained language model to solve CQA tasks. Multiple information sources are organized as graph prompts to guide the generation of the model, naturally leveraging the knowledge learned in the pretrained step. Based on the pretrained bidirectional and autoregressive transformers, a large‐scale language model, a comparable performance is achieved with less than 10% of the full‐finetuning time by only optimizing the graph prompt parameters. Experiments on two standard CQA datasets show that compared with traditional sequential initialized prompts, graph prompt achieves 20.47% and 14.89% increments in terms of BLEU and ROUGE‐L scores on quick finetuning and outperforms in few‐shot learning.
Interlayer Expansion in a Layered Metal‐Organic Framework Enhances CO2Capture and CO2/N2Separation
Authors: Wang Maohuai , Wei Shuxian , Liu Siyuan , Wang Zhaojie , Lu Xiaoqing
Published: July 2022

Developing efficient CO2adsorbent materials and technologies is significant to reduce the increasing greenhouse gases concentration in the atmosphere. Herein, a layered MOF with a porous kagomé lattice (kgm), which owned three phases (kgm‐1, kgm‐2, and kgm‐3) via interlayer expansion, was evaluated as a promising CO2capture and separation material by using grand canonical Monte Carlo simulations. Results showed that the interlayer expansion provided additional pore volume, which played a considerable role in CO2adsorption and separation. The CO2adsorption capacity and CO2/N2selectivity followed the sequence kgm‐3>kgm‐2>kgm‐1, and kgm‐3 exhibited an excellent CO2adsorption capacity of 8.7 mmol g−1at 1 bar with a CO2/N2selectivity of 130.3 at 20 bar and 298 K. Gas distribution analysis showed that CO2and N2are adsorbed only in the channels in kgm‐1, whereas they could be adsorbed between layers in kgm‐2 and kgm‐3 due to the interlayer expansion. The adsorption heat and interactions between CO2and frameworks were analyzed to elucidate the effect of interlayer expansion. Results of this work highlighted that appropriate interlayer expansion can be an effective approach for framework adsorbents to improve CO2capture ability and separation performance at the same time.
Combining stereo‐video monitoring and physiological trials to estimate reef fish metabolic demands in the wild
Authors: Schiettekatte Nina M. D. , Conte Francesca , French Beverly , Brandl Simon J. , Fulton Christopher J. , Mercière Alexandre , Norin Tommy , Villéger Sébastien , Parravicini Valeriano
Published: July 2022

Organismal metabolic rates (MRs) are the basis of energy and nutrient fluxes through ecosystems. In the marine realm, fishes are some of the most prominent consumers. However, their metabolic demand in the wild (field MR [FMR]) is poorly documented, because it is challenging to measure directly. Here, we introduce a novel approach to estimating the component of FMR associated with voluntary activity (i.e., the field active MR [). Our approach combines laboratory‐based respirometry, swimming speeds, and field‐based stereo‐video systems to estimate the activity of individuals. We exemplify our approach by focusing on six coral reef fish species, for which we quantified standard MR and maximum MR (SMR and MMR, respectively) in the laboratory, and body sizes and swimming speeds in the field. Based on the relationships between MR, body size, and swimming speeds, we estimate that the activity scope (i.e., the ratio between and SMR) varies from 1.2 to 3.2 across species and body sizes. Furthermore, we illustrate that the scaling exponent for varies across species and can substantially exceed the widely assumed value of 0.75 for SMR. Finally, by scaling organismal estimates to the assemblage level, we show the potential effect of this variability on community metabolic demand. Our approach may improve our ability to estimate elemental fluxes mediated by a critically important group of aquatic animals through a non‐destructive, widely applicable technique.
Beyond the cubic law: A finite volume method for convective and transient fracture flow
Authors: Gee Bruce , Gracie Robert
Published: July 2022

The reduced dimension fracture flow model (referred to as the GG22 model) is a recently derived extension of the cubic law model for flow through fractures of variable aperture with fluid inertia effects. Novel numerical methods are required to solve the nonlinear partial differential equations governing the GG22 model, as it is more complex than the cubic law. The GG22 model is derived from Navier–Stokes, which allows the adoption of similar numerical methods to the Navier–Stokes equations, but the model contains its own idiosyncrasies which must be addressed. This article presents the first numerical methods to solve the GG22 model. An explicit multi‐step finite volume method is developed and verified. The method is based on deriving a Poisson equation for pressure with an additional continuity correction to overcome numerical instabilities. The critical timestep is derived and shown to be a function of the fundamental frequency of the fracture‐fluid system and the maximum fluid velocity. The results show excellent agreement with analytical solutions, and the method demonstrates a first‐order rate of fluid flux convergence in time and a second‐order rate of pressure convergence in space. The model is applied to a traveling aperture wave which shows that higher pressures are required to generate lower average fluxes than predicted by the cubic law.
Solar Tariff Battle Triggers Domestic Production Act
Authors: Cartwright Echo D.
Published: July 2022

The Biden Administration's clean energy agenda has taken a few hits in recent months due to several factors—high inflation, the ongoing conflict between Russia and Ukraine destabilizing global natural gas markets, and supply chain issues resulting from the COVID‐19 pandemic and the war, to name a few. The latest controversy surrounding solar tariffs has impacted US progress toward meeting large‐scale solar energy targets in the wake of an investigation by the US Department of Commerce (DOC). In March 2022, the DOC announced it would launch an investigation into whether Southeast Asian solar cell manufacturers are using parts made in China that would normally be subject to a solar tariff—specifically from Malaysia, Thailand, Vietnam, and Cambodia. The investigation was launched following an anti‐circumvention petition by a single company (San Jose‐based Auxin Solar, which represents less than 3 percent of the US module market) that was filed alleging unfair trade practices by Chinese suppliers.
What Got Us Here Will Not Get Us There
Authors: DeCotis Paul A.
Published: July 2022

Hats off to the US and selected states, and countries across the globe for successfully advancing energy efficiency and demand response initiatives to reduce energy use and costs. And as a result, reducing the harmful pollutant and greenhouse gas (GHG) emissions associated with fossil fuel use. Thanks in large part to efficiency investments in buildings and industry, appliances, lighting and transportation, US energy use is about the same today as it was in 2000, despite economic growth of approximately 30 percent. This represents a significant improvement in energy productivity.
Very Small Entities (VSEs): Outsourcing Risk to the Supply Chain Is Placing Systems Security Engineering on a Clay Foundation, but Playing Games May Help
Authors: Georgsen Roar E. , Køien Geir M.
Published: July 2022

This article addresses the inherent risk in a supply chain that comprises primarily Very Small Entities (VSE) with little to no security proficiency and limited resources and incentive to prioritize system security. In a globalized economy based on outsourcing and risk‐sharing, most engineering activities occur in the smallest companies, even for large and complex projects. The Future of Systems Engineering initiative (FuSE) appropriately has agility at the core of its Systems Security Engineering (SSE) foundation concepts, and VSEs are by their very nature agile. However, the line between agility and chaos may be thin, and engineers at VSEs must often accept a level of restraint and rigidity beyond their comfort level to achieve functional agility. The primary challenge in VSEs is adding structure without the necessary resources to enforce compliance manually. We propose that VSE focus their initial efforts on FuSE SSE Foundation Concepts that play into their nature and strengths as dynamic human social activity systems. Improvements in security proficiency and stakeholder alignment do not necessarily require much formal structure, and digital tools combined with social strategies can add structure to a resource‐constrained environment. Games can be excellent low‐cost tools to provide structure while minimizing resistance, and Agile Model‐Based Systems Engineering (AMBSE) using digital models can support automated enforcement. Here we use the card gameElevation of Privilege(EoP) as an example. Within the context of a SysML Threat Model integrated into a larger System Model, players naturally treat security requirements as traceable functional requirements. Automated model validation, re‐usable components and patterns enforce a Zero‐Trust architecture, a sufficiently formal trust model to provide evidence‐based assurance, yet achievable for small companies with limited resources.
Framework for Operational Resilience in Engineering and System Test (FOREST) Part II: Case Study – Responding to “Security as a Functional Requirement”
Authors: McDermott Tom , Clifford Megan M. , Sherburne Tim , Horowitz Barry , Beling Peter A.
Published: July 2022

Silverfish is a case study of a fictional system of systems of medium complexity. It evaluates the FOREST methodologies referenced in part I of this article series in the contexts of system design, system test and evaluation, and training. The Silverfish case study illustrates implementation of the FOREST meta‐process model and the Mission Aware metamodel described in part I. The case study demonstrates how to accomplish the modeling of functional behaviors and associated derivation of requirements for a realistic system. This article begins with a short description of Silverfish, then describes the outcome of cyber tabletop exercises captured into modeling artifacts, the outcome of a resilience analysis, and a full derivation of cyber resilience functional and performance requirements from the modeling and analysis.
Analyzing System Security Architecture in Concept Phase Using UAF Domains
Authors: López García Juan José , Pereira Daniel Patrick
Published: July 2022

This paper presents combining MBSE (Model‐Based System Engineering) and STPA (Systems‐Theoretic Process Analysis) to mitigate security risks at an early stage of system development and to increase agility when developing or modifying architectures. The MBSE approach states that the systems development process should have a system model or a set of models as the unique source of truth. From the system model or a set of models, systems engineers of different specialties should be able to extract the information needed to perform their job. However, some specialties usually create their artefact apart from the model to perform the analysis, breaking the premises of MBSE to have a unique source of truth leading to out‐of‐date artefacts. This article proposes extending the Unified Architecture Framework (UAF) Profile (UAFP) to enable safety and security systems engineers to perform their analysis from the early stage of a system development process.
Gratitude and internalizing/externalizing symptoms among adolescents after the Wenchuan earthquake: Mediating roles of social support and resilience
Authors: Wang Dongfang , Chen Xiao‐Yan , Zhai Shuyi , Fan Fang
Published: July 2022

Introduction

Adolescents are susceptible to exhibiting internalizing and externalizing symptoms following natural disasters. However, little is known regarding factors that may influence these symptoms from the perspective of positive psychology. The current study examined whether and how social support and resilience mediated the association between gratitude and adolescents' internalizing and externalizing symptoms.

Method

The participants were 765 Chinese adolescents exposed to the Wenchuan earthquake (41.8% male, mean age 17.46 years), who were enrolled in a three‐wave longitudinal study with data spanning 1 year. All adolescents completed self‐report questionnaires on gratitude at 18 months postearthquake (T18m), social support and resilience at 24 months (T24m), and internalizing and externalizing symptoms at 18 months (T18m) and 30 months (T30m).

Results

The results showed that social support (T24m) and resilience (T24m) serially mediate the relationship between gratitude (T18m) and internalizing (β = −.003, 95% confidence interval [CI]= −0.006, −0.001) or externalizing (T30m) symptoms (β = −.004, 95% CI= −0.004, −0.001). Social support (T24m) acts as a mediator only between gratitude (T18m) and internalizing symptoms (T30m) (β = −.021, 95% CI = −0.044, −0.004), while not being a significant predictor for externalizing symptoms (T30m).

Conclusion

By highlighting the mechanisms by which gratitude longitudinally attenuates adolescents' internalizing, externalizing, and total symptoms, our findings may provide clinical practitioners with important information regarding intervention design.
Inside Cover
Authors: Liu Hanzi , Wu Xiaoyan , Liu Guodong , Ren Hongliang , R. V. Vinu , Chen Ziyang , Pu Jixiong
Published: July 2022

By adopting the polarization phase shifting and space division multiplexing in digital holographic microscopy, a reflectance quantitative phase microscopy system capable of dynamic quantitative phase imaging and depth‐resolved imaging is developed. The compact design of on‐axis near common‐path Fizeau polarization interferometry offers a single‐shot microscopy system with robust phase stability in comparison to other techniques. The proposed system has the advantages of label‐free, singleshot, and depth‐selective imaging features, which will be a prospective tool in the quantified investigations in medical diagnosis and in vivo imaging in optical phase microscopy.

Further details can be found in the article by Hanzi Liu, Xiaoyan Wu, Guodong Liu, Hongliang Ren, Vinu R. V., Ziyang Chen, and Jixiong Pu (e202100400)

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Protein palmitoylation regulates extracellular vesicle production and function in sepsis
Authors: Yang Xiaoyuan , Zheng Ethan , Chatterjee Victor , Ma Yonggang , Reynolds Amanda , Villalba Nuria , Wu Mack H. , Yuan Sarah Y.
Published: July 2022

Extracellular vesicles (EVs) are bioactive membrane‐encapsulated particles generated by a series of events involving membrane budding, fission and fusion. Palmitoylation, mediated by DHHC palmitoyl acyltransferases, is a lipidation reaction that increases protein lipophilicity and membrane localization. Here, we report palmitoylation as a novel regulator of EV formation and function during sepsis. Our results showed significantly decreased circulating EVs in mice with DHHC21 functional deficiency (Zdhhc21dep/dep), compared to wild‐type (WT) mice 24 h after septic injury. Furthermore, WT and Zdhhc21dep/dep EVs displayed distinct palmitoyl‐proteomic profiles. Ingenuity pathway analysis indicated that sepsis altered several inflammation related pathways expressed in EVs, among which the most significantly activated was the complement pathway; however, this sepsis‐induced complement enrichment in EVs was greatly blunted in Zdhhc21dep/dep EVs. Functionally, EVs isolated from WT mice with sepsis promoted neutrophil adhesion, transmigration, and neutrophil extracellular trap production; these effects were significantly attenuated by DHHC21 loss‐of‐function. Furthermore, Zdhhc21dep/dep mice displayed reduced neutrophil infiltration in lungs and improved survival after CLP challenges. These findings indicate that blocking palmitoylation via DHHC21 functional deficiency can reduce sepsis‐stimulated production of complement‐enriched EVs and attenuates their effects on neutrophil activity.
Impact of photoperiod on uterine redox/inflammatory and metabolic status of golden hamster, Mesocricetus auratus
Authors: Pal Sriparna , Haldar Chandana , Verma Rakesh
Published: July 2022

Photoperiod modulates reproductive physiology at multiple levels in seasonally breeding animals. Golden hamsters are long‐day breeders that diminish their fertility during the short days. Photoperiod is known to regulate hormonal milieu and uterus is a hormone‐sensitive dynamic tissue. However, there is lack of molecular insight regarding the impact of photoperiod on uterine physiology with respect to redox and metabolic status in Mesocricetus auratus. We evaluated the impact of photoperiod on circulatory hormonal parameters (triiodothyronine [T3], thyroxin [T4], estradiol [E2], progesterone [P4], melatonin, and insulin), their receptor expressions and key markers associated with redox (SIRT‐1/FOXO‐1), inflammatory (NFĸB/COX‐2) and metabolic (IR/GLUT4) status in uterus. Adult female golden hamsters were exposed to different photoperiodic regimes, that is, short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. SP drastically decreased peripheral hormone profiles (T3, T4, E2, and P4) and compromised uterine histoarchitecture when compared with LP‐exposed hamsters. Further, SP markedly decreased thyroid hormone receptor‐α (TRα), insulin receptor, and glucose uptake transporter‐4 (GLUT‐4) expressions in uterus. We noted enhanced uterine oxidative (increased MDA and decreased SOD/CAT levels), SIRT‐1/FOXO‐1 expression and inflammatory (NFĸB/COX‐2) load in SP condition. Further, elevated levels of circulatory insulin, melatonin, and its receptor (MT‐1) expression in uterus was noted under SP condition. Thus, we may suggest that photoperiod might regulate uterine seasonality through modulation of local hormonal and redox/metabolic homeostasis thereby may restrict offspring bearing capacity under short days.
農薬によりエチレングリコール中毒を来した1例(A case of ethylene glycol intoxication caused by the pesticides)
Authors: (Kyohei Maeno) 前野 恭平 , (Kasumi Satoh) 佐藤 佳澄 , (Manabu Okuyama) 奥山 学 , (Nobuhisa Hirasawa) 平澤 暢史 , (Kenji Yoshida) 吉田 健二 , (Hajime Nakae) 中永 士師明
Published: July 2022

本邦におけるエチレングリコール中毒は比較的稀であり，農薬によってエチレングリコール中毒を来した症例報告はない。本症例は70歳代の女性。除草剤「バッチリ® フロアブル」を450mL飲用し当院に救急搬送された。来院時はJapan coma scale I–1，酸塩基平衡は保たれ，浸透圧ギャップの上昇はなかった。除草剤の外装にはイマゾスルフロン，ピラクロニル，ブロモブチド水和剤と表記されており，当初はこれらによる影響の経過観察目的に集中治療室に入室した。第2病日，急性腎障害のため持続的血液濾過透析（CHDF）を開始した。中毒情報センターからの情報を参考に除草剤によるエチレングリコール中毒と考えられた。腎機能は速やかに改善し第4病日にCHDを離脱，第5病日に精神科病棟へ転棟転出した。これまで農薬によってエチレングリコール中毒を来した報告はなく，本例が本邦で初である。農薬摂取者においてもエチレングリコール中毒の可能性を想定し早期に診断することで，特異的治療につなげることができる可能性がある。
COVID–19流行下における自殺企図患者の推移(Changes in suicide attempt patients during the COVID–19 pandemic)
Authors: (Akihiro Kato) 加藤 明裕 , (Hiroyuki Kayata) 茅田 洋之 , (Shino Beika) 米花 紫乃 , (Hideaki Yakushiji) 藥師寺 秀明 , (Masanori Morita) 森田 正則 , (Yasuki Nakata) 中田 康城 , (Asako Matsushima) 松嶋 麻子
Published: July 2022

【目的】COVID–19流行下において救急搬送された自殺企図患者の特徴を調査し，パンデミックが自殺に与える影響を検討する。【対象】2020年1月から12月をCOVID–19流行期，2018年1月から2019年12月までの2年間をCOVID–19非流行期として，当院救命救急センターに搬送された自殺企図および自殺既遂患者の年齢，性別，精神科通院歴，自殺手段を調査した。2020年と2019年については自殺企図者の同居家族，経済問題，就労，精神科診断についても調査した。さらに流行期については，20歳ごとの年代別，月別患者数を調査して，COVID–19新規患者数と比較した。【結果】2020年の自殺企図患者数は20代以下が39%を占めており，COVID–19非流行期の27%と比較して若年者の割合が増加していた。2020年の月別患者数の変化では，年代に関係なく，COVID–19新規感染者数が増加している時期には自殺企図患者は少なく，新規感染者数が減少した時期に自殺企図患者数の増加がみられた。自殺既遂についても同様の傾向がみられた。【結語】COVID–19の流行期では，若年者の自殺企図が増加した。また，流行期における自殺企図者数はCOVID–19新規感染者数の増減と逆の変動を示した。今後，パンデミックが自殺企図に与える影響をさらに解析する必要がある。
重症COVID–19におけるデルタ株流行の影響と予後：単施設後方視研究(Prognostic impact of delta variant in COVID–19 patients requiring mechanical ventilation in comparison with other variants: a single center retrospective analysis)
Authors: (Fumito Kato) 加藤 史人 , (Keigo Sekihara) 関原 圭吾 , (Tatsuya Okamoto) 岡本 竜哉 , (Reo Iguma) 井熊　 玲央 , (Tomohiro Kojimahara) 小島原 知大 , (Tatsuki Uemura) 植村 樹 , (Akio Kimura) 木村 昭夫
Published: July 2022

【背景】COVID–19は変異株ごとに感染性や毒性が異なる。デルタ株による第5波では重症者，死者数が増加した。第5波における重症患者の臨床的特徴と治療成績を明らかにすることを目的とした。【方法】2020年2月から2021年9月までに当院でCOVID–19による呼吸不全で人工呼吸器を使用した53例を対象とした。2020年2月から2021年6月までの第1～4波と2021年7月から10月までの第5波の2群に分け，後方視的に全生存期間を比較した。観察期間中央値は90日。【結果】第1～4波は40例，第5波は13例，全例ワクチン未接種であった。第1～4波ではL452R変異は検出されず，第5波では10例（77%）だった。年齢中央値は68歳vs. 56歳（第1～4波vs. 第5波，P<0.01），BMIは27 vs. 30（P=0.02），P/F比は136 vs. 80（P<0.01），入院までの日数は6日vs. 8日（P=0.03）と有意差を認めた。全生存期間では90日生存率が71% vs. 37%（P<0.01）と第5波が予後不良であった。多変量解析では第1～4波に対して第5波は生存率悪化に影響を及ぼしていた（HR 6.35，95%CI 1.96–20.6）。【結語】第1～4波に比べ第5波の重症COVID–19患者は若年にも関わらず，救命率が低かった。デルタ株の影響，搬送困難による治療の遅れが示唆された。
Analysis of potential biomarkers of response to IL-12 therapy
Authors: Schwarz Emily , Carson William E
Published: July 2022

IL-12 is a proinflammatory cytokine capable of inducing a wide range of effects on both innate and adaptive immune responses. Its stimulatory effects on T cells and NK cells have led to its classification as a potential inducer of antitumor immunity. Clinical trials have been attempting to harness its immune-stimulating capacity since the 1990s and have had much success despite notable toxicity issues early on. Several methods of IL-12 delivery have been employed including i.v., s.c., and local administrations as well as plasmid and gene therapies. However, despite differing methods, dosages, and cancer types utilized in these clinical trials, there are still many patients who do not respond to IL-12 therapy. This creates an opportunity for further investigation into the immunologic differences between responding and nonresponding patients in order to better understand the variable efficacy of IL-12 therapy. This review focuses on a limited collection of IL-12 clinical trials, which further analyzed these individual subsets and detected biologic variables correlating with differential patient responses. A comprehensive review of these potential biomarkers identified 7 analytes that correlated with beneficial patient responses in 3 or more clinical trials. These were increased levels of IFN-γ, IP-10, TNF-α, MIP-1α, MIG, and CD4+ and CD8+ T cells, with a decrease in VEGF, bFGF, FoxP3+ T regulatory cells, and M2 macrophages. These potential biomarkers highlight the possibility of identifying immunologic determinants of patient response to IL-12 therapy to conserve valuable resources and benefit patients.
Evolution of a proglacial lake in the Izborsko‐Malskaya Valley, Russia, in the Late Glacial
Authors: Karpukhina Natalia V. , Karevskaya Inessa A. , Borisova Olga K. , Konstantinov Evgeny A. , Kurbanov Redzhep N. , Zakharov Andrey L. , Filippova Ksenia G. , Zazovskaya Elya P.
Published: July 2022

A proglacial lake system formed during the Late Valdai (Weichselian) Ice Sheet recession on the East European Plain. Poor knowledge about chronology, levels and the drainage pathways of ice‐dammed lakes does not allow us to fully evaluate their palaeogeographic significance. This study focuses on the Izborsko‐Malskaya Valley where fingerprints of a glaciolacustrine environment were found. Based on litho‐, biostratigraphic and geochronological data, it is estimated that the proglacial lake in the Izborsko‐Malskaya Valley existed from ~14.3 ka cal. BP (the Vashinogorskaya Valley from ~14.9 ka (optically stimulated luminescence)) to 13.2 ka cal. BP. The maximum level was ~72 m a.s.l. (above sea level) and the minimum was ~53 m a.s.l. Sedimentation proceeded mostly in deepwater conditions. The ice‐dammed lake in the Izborsko‐Malskaya and nearest valleys could have been part of a huge lake on the Pskov lowland which formed after ~15.7 ka cal. BP. The lake level dropped rapidly when the proglacial Lake Pskovsko‐Chudskoe (Peipsi) connected with the Baltic Ice Lake. A lacustrine regime was preserved only in the southern portion of the Izborsko‐Malskaya Valley after drainage and still exists in the modern lakes. The presented approaches to the ice‐dammed lake reconstruction could be useful for the verification of other lakes which existed on the East European Plain.
Seasonal space use and habitat selection in magpie geese: implications for reducing human‐wildlife conflicts
Authors: Corriveau Amélie , Klaassen Marcel , Garnett Stephen T. , Kaestli Mirjam , Christian Keith , Crewe Tara L. , Loewensteiner David A. , Campbell Hamish A.
Published: July 2022

Negative interactions between waterbirds and people are increasing. Waterbirds feeding on agricultural crops cause significant losses to farmers worldwide, but so far most research to address these conflicts has been conducted on migratory species in the temperate northern hemisphere. We investigated the space use and habitat selection of the magpie goose (Anseranas semipalmata), a taxonomically distinct waterbird endemic to Australia and southern Papua New Guinea. In tropical northern Australia, magpie geese are protected but are increasingly persecuted by farmers to protect crops during the late dry–early wet season (~Sep–Jan), a bottleneck of natural resources for waterbirds in the monsoonal tropics. Using satellite telemetry of 38 geese spread across 3 seasons (2016–2017, 2017–2018, 2018–2019), we evaluated daily and seasonal space use, individual site fidelity, and habitat selection to determine the extent of use of agricultural fields by geese, and the spatiotemporal scales at which management should be undertaken. Geese used relatively small daily areas (x̄ = 8.2 km2) consistently throughout the late dry–early wet season, and repeatedly used agricultural fields, forested bushlands, and local wetlands. Geese used comparatively large seasonal areas (x̄ = 219.5 km2) encompassing several agricultural areas, and had a low mean overlap between successive weekly core activity areas, indicating that site fidelity rapidly weakened over time. These results suggest that farm‐scale (<30 ha) management of geese is unlikely to be effective because hazed individuals are likely to be replaced soon afterwards. Instead, our findings suggest that goose management should be coordinated strategically at the local (~1,000 ha), or regional (~100,000 ha) scale. Farm‐level management would likely be more effective if implemented in conjunction with the creation of regional sanctuaries where geese could rest and potentially feed undisturbed away from farms. Our findings can be used by wildlife managers for optimizing the location of such sanctuaries and highlight the necessity for management to be adaptive given the opportunistic nature of the species.
Diagnosing molecular subtypes of breast cancer by means of Raman spectroscopy
Authors: Melitto Alexandre S. , Arias Victor E. A. , Shida Jorge Y. , Gebrim Luiz H. , Silveira Landulfo
Published: July 2022

Objectives

Raman spectroscopy has been used to discriminate human breast cancer and its different tumor molecular subtypes (luminal A, luminal B, HER2, and triple‐negative) from normal tissue in surgical specimens.

Materials and Methods

Breast cancer and normal tissue samples from 31 patients were obtained by surgical resection and submitted for histopathology. Before anatomopathological processing, the samples had been submitted to Raman spectroscopy (830 nm, 25 mW excitation laser parameters). In total, 424 Raman spectra were obtained. Principal component analysis (PCA) was used in an exploratory analysis to unveil the compositional differences between the tumors and normal tissues. Discriminant models were developed to distinguish the different cancer subtypes by means of partial least squares (PLS) regression.

Results

PCA vectors showed spectral features referred to the biochemical constitution of breast tissues, such as lipids, proteins, amino acids, and carotenoids, where lipids were decreased and proteins were increased in breast tumors. Despite the small spectral differences between the different subtypes of tumor and normal tissues, the discriminant model based on PLS was able to discriminate the spectra of the breast tumors from normal tissues with an accuracy of 97.3%, between luminal and nonluminal subtypes with an accuracy of 89.9%, between nontriple‐negative and triple‐negative with an accuracy of 94.7%, and each molecular subtype with an accuracy of 73.0%.

Conclusion

PCA could reveal the compositional difference between tumors and normal tissues, and PLS could discriminate the Raman spectra of breast tissues regarding the molecular subtypes of cancer, being a useful tool for cancer diagnosis.