bluuebunny/crossref_metadata_2025 huggingface dataset:
Consistent pressure Poisson splitting methods for incompressible multi-phase flows: eliminating numerical boundary layers and inf-sup compatibility restrictions
Authors: Pacheco Douglas R. Q. , Schussnig Richard
Published: June 2022

For their simplicity and low computational cost, time-stepping schemes decoupling velocity and pressure are highly popular in incompressible flow simulations. When multiple fluids are present, the additional hyperbolic transport equation in the system makes it even more advantageous to compute different flow quantities separately. Most splitting methods, however, induce spurious pressure boundary layers or compatibility restrictions on how to discretise pressure and velocity. Pressure Poisson methods, on the other hand, overcome these issues by relying on a fully consistent problem to compute the pressure from the velocity field. Additionally, such pressure Poisson equations can be tailored so as to indirectly enforce incompressibility, without requiring solenoidal projections. Although these schemes have been extended to problems with variable viscosity, constant density is still a fundamental assumption in existing formulations. In this context, the main contribution of this work is to reformulate consistent splitting methods to allow for variable density, as arising in two-phase flows. We present a strong formulation and a consistent weak form allowing standard finite element spaces. For the temporal discretisation, backward differentiation formulas are used to decouple pressure, velocity and density, yielding iteration-free steps. The accuracy of our framework is showcased through a wide variety of numerical examples, considering manufactured and benchmark solutions, equal-order and mixed finite elements, first- and second-order stepping, as well as flows with one, two or three phases.
Evaluation of a sampling approach for computationally efficient uncertainty quantification in regression learning models
Authors: Freschi Valerio , Lattanzi Emanuele
Published: June 2022

The capability of effectively quantifying the uncertainty associated to a given prediction is an important task in many applications that range from drug design to autonomous driving, providing valuable information to many downstream decision-making processes. The increasing capacity of novel machine learning models, and the growing amount of data on which these systems are trained poses however significant issues to be addressed. Recent research advocated the need for evaluating learning systems not only according to traditional accuracy metrics but also according to the computational complexity required to design them, toward a perspective of sustainability and inclusivity. In this work, we present an empirical investigation aimed at assessing the impact of uniform sampling on the reduction in computational requirements, the quality of regression, and on its uncertainty quantification. We performed several experiments with recent state-of-the-art methods characterized by statistical guarantees whose performances have been measured according to different metrics for evaluating uncertainty quantification (i.e., coverage and length of prediction intervals) and regression (i.e., errors measures and correlation). Experimental results highlight possible interesting trade-offs between computation time, regression and uncertainty evaluation quality, thus confirming the viability of sampling-based approaches to overcome computational bottlenecks without significantly affecting the quality of predictions.
Relapsing subarachnoid hemorrhage as a clinical manifestation in microscopic polyangiitis: a case report and literature review
Authors: Xie Jingjing , Jia Ertao , Wang Suli , Yu Ye , Li Zhiling , Zhang Jianyong , Li Jia
Published: June 2022

Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) and predominantly causes kidney and pulmonary injuries. Subarachnoid hemorrhage, a life-threatening manifestation of the central nervous system (CNS), rarely occurs in patients with ANCA-associated vasculitis (AAV). We report the case of a young man with spontaneous SAH recurrence and active nephritis. The patient was treated with a glucocorticoid pulse and intravenous cyclophosphamide (CTX) in combination with decreasing cerebral perfusion pressure and analgesic therapy. All the patients’ symptoms except the proteinuria resolved. We reviewed the clinical characteristics of 34 previously reported cases of SAH with AAV, comprising six cases of MPA, eight cases of granulomatosis with polyangiitis (GPA), and 19 cases of eosinophilic granulomatosis with polyangiitis (EGPA), and one case of unclassified AAV. All the cases showed features of active vasculitis. Concomitant nephritis and peripheral neuropathy were found in the MPA and EGPA cases with SAH, respectively. Renal and pulmonary manifestations were predominant in the patients with GPA and SAH. Ten patients had aneurysmal abnormalities, and six patients had cardiac abnormalities. Thirty-one patients were treated with glucocorticoids, and 18 patients received concurrent immunosuppressants. Patients with SAH had a mortality rate of 38.2%. The presence of cerebrovascular events or cardiac involvement in patients with AAV and SAH is associated with increased mortality of 64.3%. Our study indicates that SAH should be cautioned as a disease occurring in patients with AAV. Early diagnosis with aggressive immunosuppressive therapy can help improve the prognosis of patients with SAH.
The Dark Side of Leader Narcissism: The Relationship Between Leaders’ Narcissistic Rivalry and Abusive Supervision
Authors: Gauglitz Iris K. , Schyns Birgit , Fehn Theresa , Schütz Astrid
Published: June 2022

Narcissists often attain leadership positions, but at the same time do not care for others and often engage in unethical behaviors. We therefore explored the role of leader narcissism as an antecedent of abusive supervision, a form of unethical leadership. We based our study on the narcissistic admiration and rivalry concept (NARC) and proposed a direct positive effect of leaders’ narcissistic rivalry—the maladaptive narcissism dimension—on abusive supervision. In line with trait activation and threatened egotism theory, we also proposed a moderated mediation assuming that leaders high in narcissistic rivalry would be particularly prone to showing abusive supervision in reaction to followers’ supervisor-directed deviance, as this form of follower behavior would threaten their self-esteem. We conducted a field study with leader–follower dyads (Study 1) and an experimental vignette study with leaders (Study 2). Leaders’ narcissistic rivalry was positively related to abusive supervision (intentions) in both studies. This effect was independent of followers’ supervisor-directed deviance and leaders’ perceived self-esteem threat. We discuss our findings in light of the NARC, as well as threatened egotism theory, and offer directions for future research. Finally, we make practical recommendations for organizations.
Who Has a Seat at the Table in Impact Investing? Addressing Inequality by Giving Voice
Authors: Casasnovas Guillermo , Jones Jessica
Published: June 2022

Despite recognizing the importance of impact investing in combating complex societal challenges, researchers have yet to examine the capacity of the field to address systemic inequality. While impact investments are intended to benefit vulnerable stakeholders, the voices of those stakeholders are generally overlooked in the design and implementation of such investments. To resolve this oversight, we theorize how the fields’ design—through its tools, organizations, and field-level bodies—influences its capacity to address inequality by focusing on the concept of giving voice, which we define as the inclusive participation of vulnerable stakeholders in decision-making processes. We build from stakeholder engagement research to show how the design of impact investing can address inequality using three illustrative cases: social impact bonds, impact investing funds, and national advisory boards. We conclude with a discussion of how the ethical decision of giving voice to vulnerable stakeholders will determine the capacity of the field to address inequality, as well as provide implications for future research and practice.
How to Undo (and Redo) Words with Facts: A Semio-enactivist Approach to Law, Space and Experience
Authors: Ricca Mario
Published: June 2022

In this essay both the facts/values and facticity/normativity divides are considered from the perspective of global semiotics and with specific regard to the relationships between legal meaning and spatial scope of law’s experience. Through an examination of the inner and genetic projective significance of categorization, I will analyze the semantic dynamics of the descriptive parts comprising legal sentences in order to show the intermingling of factual and axiological/teleological categorizations in the unfolding of legal experience. Subsequently, I will emphasize the translational and enactive cognitive disposition underlying the construction of the second premise of the so-called judiciary syllogism and thereby the untenability of the idea that ‘law makes its facts.’ Hence, I will try to bring to the fore the cultural pre-assumptions encapsulated in the positivistic and therefore also formalistic or analytical approaches to legal experience and the loss of their inner consistency when legal experience confronts the phases and major changes of global semiotics. Finally, I will strive to relativize the opposition between the positivist and non-positivistic theories of law in view of an understanding of legal experience focused not only, or at least not primarily, on what ‘law is’ but also on ‘how’ it unwinds through, andin spite of, environmental and semantic transformations.
Antagonistic Effect of Plant Growth-Promoting Fungi Against Fusarium Wilt Disease in Tomato: In vitro and In vivo Study
Authors: Attia Mohamed S. , El-Wakil Deiaa A. , Hashem Amr H. , Abdelaziz Amer M.
Published: June 2022

Fusarium wilt is considered one of the most destructive diseases for tomato plants. The novelty of this work was to investigate the antifungal and plant growth-promoting capabilities of some plant growth-promoting fungi (PGPF). Plant growth-promoting fungi (PGPF) improved the plant health and control plant infections. In this study, two fungal strains as PGPF were isolated and identified as Aspergillus fumigatus and Rhizopus oryzae using molecular method. The extracts of A. fumigatus and R. oryzae exhibited promising antifungal activity against F. oxysporum in vitro. Moreover, antagonistic effect of A. fumigatus and R. oryzae against F. oxysporum causing tomato wilt disease was evaluated in vivo. Disease severity and growth markers were recorded and in vitro antagonistic activity assay of the isolated A. fumigatus and R. oryzae against Fusarium oxysporum was measured. Physiological markers of defense in plant as response to stimulate systemic resistance (SR) were recorded. Our results indicated that A. fumigatus and R. oryzae decreased the percentage of disease severity by 12.5 and 37.5%, respectively. In addition, they exhibited relatively high protection percentage of 86.35 and 59.06% respectively. Fusarium wilt was declined the growth parameters, photosynthetic pigments, total soluble carbohydrate, and total soluble protein, whereas content of free proline, total phenols, and the activity of antioxidant enzymes activity increased under infection. Moreover, application of A. fumigatus and R. oryzae on infected plants successfully recovered the loss of morphological traits, photosynthetic pigment total carbohydrates, and total soluble proteins in comparison to infected control plants. PGPF strains in both non-infected and infected plants showed several responses in number and density of peroxidase (POD) and polyphenol oxidase (PPO) isozymes.
The Biochemical Effects of Silver Nanoparticles and Spirulina Extract on Experimentally Induced Prostatic Cancer in Rats
Authors: El-Magid Afaf D. Abd , AbdEl-Hamid Omnia M. , Younes M. A.
Published: June 2022

Prostate cancer (PCa) is the most diagnosed cancer in 112 countries and the second leading cause of death in men in 48 countries. We studied the outstanding agents silver nanoparticles (AgNPs) and Spirulina algae (Sp) for the management of PCa once as monotherapy or last as a combination. PCa in rats was induced using bicalutamide (Casodex®) and testosterone, followed by (7, 12-dimethylbenz[a]anthracene). Then, testosterone was injected s.c. for 3 months. Rats were divided into six groups, with 12 rats in each group. Group I was assigned as the control (co), group II as the PCa model, group III treated with AgNPs, group IV treated with Spirulina extract, group V treated with a combination of AgNPs plus Spirulina, and group VI treated with bicalutamide. The results show that AgNPs could normalize IL-6 levels and could overcome the hormonal disturbance induced in PCa rats along the hypothalamic–pituitary–testis axis. Spirulina revealed a significant reduction in the level of total and free prostatic specific antigen (PSA) to the same level as bicalutamide treatment, which was the same as the control group. Histopathological study revealed regression (75%) of the histological pattern of high-grade prostatic intraepithelial neoplasia (HGPIN) for Spirulina alone, and (50%) for bicalutamide. The best effect on IL-6 decline was reached with the AgNPs/Spirulina combination as well as bicalutamide treatment compared with the PCa group. Bicalutamide treatment significantly decreased the PSA concentration relative to the PCa group and reached the normal level. Adding Spirulina to AgNPs as a combination enhanced its effect on all mentioned drawbacks associated with PCa except hormonal imbalance that needs more adjustments.
How to approach clinically discordant FT4 results when changing testing platforms: real-world evidence
Authors: Giovanella Luca , Duntas Leonidas , D’Aurizio Federica , Kurka Hedwig , Ammer Tatjana , Rank Christopher M. , Visser W. Edward , van den Berg Sjoerd A. A.
Published: June 2022

Purpose

Measurement of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is important for assessing thyroid dysfunction. After changing assay manufacturer, high FT4 versus TSH levels were reported at Ente Ospedaliero Cantonale (EOC; Bellinzona, Switzerland).

Methods

Exploratory analysis used existing TSH and FT4 measurements taken at EOC during routine clinical practice (February 2018–April 2020) using Elecsys® TSH and Elecsys FT4 III immunoassays on cobas® 6000 and cobas 8000 analyzers (Roche Diagnostics). Reference intervals (RIs) were estimated using both direct and indirect (refineR algorithm) methods.

Results

In samples with normal TSH levels, 90.9% of FT4 measurements were within the normal range provided by Roche (12–22 pmol/L). For FT4 measurements, confidence intervals (CIs) for the lower end of the RI obtained using direct and indirect methods were lower than estimated values in the method sheet; the estimated value of the upper end of the RI (UEoRI) in the method sheet was within the CI for the UEoRI using the direct method but not the indirect method. CIs for the direct and indirect methods overlapped at both ends of the RI. The most common cause of increased FT4 with normal TSH was identified in a subset of patients as use of thyroxine therapy (72.6%).

Conclusions

It is important to verify RIs for FT4 in the laboratory population when changing testing platforms; indirect methods may constitute a convenient tool for this. Applying specific RIs for selected subpopulations should be considered to avoid misinterpretations and inappropriate clinical actions.
Uncovering dimensions of the impact of blockchain technology in supply chain management
Authors: Tokkozhina Ulpan , Lucia Martins Ana , Ferreira Joao C.
Published: June 2022

Supply chains around the globe are faced with difficulties and disruptions due to the worldwide pandemic situation and digital solutions are needed. There is significant research interest in the implementation of blockchain technology (BCT) for supply chain management (SCM). A challenge that remains is analyzing the interactions of BCT in different areas of SCM. This study aims to identify the influential dimensions of the impact of BCT adoption in SCM and to discuss the synergetic and counter-synergetic effects between these dimensions. Advantages, disadvantages, and constraints of adopting BCT in the SCM context are explored through a systematic literature review, which provides the foundation for identifying the dimensions of impact. The interactions between these dimensions are conceptually discussed. This study introduces three dimensions of the impact of implementing BCT in SCM: ‘operations and processes’, ‘supply chain relationships’, and ‘innovation and data access’. These dimensions are interrelated and have overlapping areas within them, which leads to synergetic and counter-synergetic effects. The overlaps and synergies of the three dimensions of impact are illustrated, and the virtuous and vicious cycles of BCT adoption in SCM cases are highlighted. This study assists scholars and practitioners by clarifying the synergetic relationships within the dimensions of the impact of BCT in SCM and by providing considerations to prevent undesirable effects and expand desired ones.
Single Track Geometry Prediction of Laser Metal Deposited 316L-Si Via Multi-Physics Modelling and Regression Analysis with Experimental Validation
Authors: Biyikli Merve , Karagoz Taner , Calli Metin , Muslim Talha , Ozalp A. Alper , Bayram Ali
Published: June 2022

Laser metal deposition (LMD) is an additive manufacturing process used in manufacturing freeform geometries, repair applications, coating and surface modification, fabrication of functionally graded materials. It has a broad range of applications in various industries, including aviation, space, defence, automotive, tooling, etc. In this work, a multi-physics model of the LMD process was developed to rapidly predict the geometrical characteristics of the single clad track using the commercial software package Flow-3D. The volume of fluid (VOF) method was integrated to differentiate the interface between the metallic and gaseous cells. To validate the numerical model single bead tracks were deposited, and cross-sections of the beads were analysed. Mathematical formulae to predict different aspects of the single clad track (height, width, and depth) were derived using regression analysis. The influence of the process parameters on the geometrical characteristics of the single clad track was analysed in detail using analysis of variance (ANOVA). Both multi-physics model and mathematical regression model results were compared to the experimental measurements. The results were in good agreement with the experimental results.

Graphical abstract
Design of IR zoom lens system for long-range detection in uncooled LWIR camera
Authors: Mowafy Khaled , EL-Dessouky Tawfik , Medhat Mohamed
Published: June 2022

A new compact optical zoom lens system with variable focal length 100–200 mm for uncooled LWIR (8–12 μm) camera is designed. It is used for long-range detection. The optimized IR zoom lens consists of four group elements. The F/# of the zoom system is F/1.4 at all zoom positions. Its performance reaches the diffraction limit at each focal length position. Moreover, optical design and image quality are calculated by ZEMAX optical software. The imaging quality performance is steady during zoom process. In addition to the above benefits, the optimized IR zoom lens is light and compact (200 mm) with 4 lenses and only one of them has diffractive surface to lower production cost. Upon applying anti-reflection coating, the total transmittance of the optical system is enhanced from 2 to 99% at λ = 10 µm.
Analysis of the global trade network using exponential random graph models
Authors: Setayesh Amin , Sourati Hassan Zadeh Zhivar , Bahrak Behnam
Published: June 2022

The global trade network has significant importance in analyzing countries’ economic exchanges. Therefore, studying the global trade network and the factors influencing its structure is helpful for both economists and political decision makers. Putting these in mind, we try to analyze the global trade network from various viewpoints. We use the backbone filtering methods to construct a network of essential trades between countries. We analyze the structural, economic, geographical, political, and cultural factors and their effect on the global trade network using exponential random graph models. Additionally, we analyze the global trade network evolution using the separable temporal exponential random models. Our results show multiple structural, economic, geographical, and political factors affect the global trade network structure.
Atomic Force Microscope with an Adjustable Probe Direction and Integrated Sensing and Actuation
Authors: Schaude Janik , Hausotte Tino
Published: June 2022

This article presents the application and evaluation of a cantilever with integrated sensing and actuation as part of an atomic force microscope (AFM) with an adjustable probe direction, which is integrated into a nano measuring machine (NMM-1). The AFM, which is operated in closed-loop intermittent contact mode, is based on two rotational axes that enable the adjustment of the probe direction to cover a complete hemisphere. The axes greatly enlarge the metrology frame of the measuring system by materials with a comparatively high coefficient of thermal expansion, which ultimately limits the achievable measurement uncertainty of the measuring system. Thus, to reduce the thermal sensitivity of the system, the redesign of the rotational kinematics is mandatory. However, in this article, some preliminary investigations on the application of a self-sensing cantilever with an integrated micro heater for its stimulation will be presented. In previous investigations, a piezoelectric actuator has been applied to stimulate the cantilever. However, the removal of the piezoelectric actuator, which is enabled by the application of a cantilever with an integrated micro heater, promises an essential simplification of the sensor holder. Thus, in the future it might be possible to use materials with a low coefficient of thermal expansion, which are often difficult to machine and therefore only allow for rather simple geometries. Furthermore, because of the creepage of piezoelectric actuators, their removal from the metrology frame might lead to improved metrological characteristics. As will be shown, there are no significant differences between the two modes of actuation. Therefore, the redesigned rotational system will be based on the cantilever with integrated sensing and actuation.
Erectile Dysfunction in Multiple Sclerosis: A Prevalence Meta-Analysis and Systematic Review
Authors: Wu Xu , Zhang Yuyang , Zhang Wei , Liu Guodong , Jiang Hui , Huang Houbao , Zhang Xiansheng
Published: June 2022

Background

A connection between multiple sclerosis (MS) and erectile dysfunction (ED) has been debatable.

Aim

To assess the pooled prevalence of ED among men with MS and whether MS was a risk factor for ED.

Methods

A systematic review of the literature was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library to find relevant English-language studies published up to February 2022 that assessed the prevalence of ED in MS patients. Two authors independently evaluated the full text of the enrolled studies to determine eligibility, and if there was disagreement, the decision was made by a third author after discussion. Assessment tools adapted for prevalence studies were used to evaluate the quality of cross-sectional studies, and the quality of case-control studies was assessed by Newcastle-Ottawa scale. The relative risk (RR) and its 95% confidence interval (CI) were used to assess the strength of association between MS and the risk of ED. The sources of heterogeneity were investigated by subgroup analysis. Sensitivity analysis was conducted to evaluate the stability of the results.

Outcomes

The pooled prevalence of ED in MS patients as well as 95% CIs were estimated, and the RR and its 95% CI were used to assess the strength of association between MS and the risk of ED.

Results

Sixteen studies included collectively gave information about ED in 2,760 MS men, resulting in a pooled prevalence of 49% (95% CI = 42–56%) for ED with a large heterogeneity. Synthesis of results revealed that MS was significantly associated with an increased risk of ED (RR = 3.17, 95% CI = 2.31–4.36, P < .001; heterogeneity: I2 = 0.0%, P = .716). The pooled prevalence estimates of ED were 55, 63, and 57% in the age >40, IIEF diagnostic tool, and mean disease duration >10 years subgroups, respectively.

Clinical Implications

The present meta-analysis indicates that MS patients had a significantly increased risk of ED, which should raise awareness of the potential association between MS and ED by clinicians.

Strengths & Limitations

This is the first meta-analysis to provide the global prevalence of ED in MS patients and to demonstrate that MS is a risk factor for ED. However, all enrolled studies were observational in design, which may reduce the robustness of this evidence.

Conclusion

Results of this meta-analysis showed that ED was highly prevalent in adult men with MS and MS was a potential risk factor for ED development.
Dispute Settlement Reports 2006
Authors: World Trade Organization
Published: June 2022

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. These are the WTO authorized and paginated reports in English. An essential addition to the library of all practising and academic trade lawyers, and needed by students worldwide taking courses in international economic or trade law. DSR 2006: XII reports on United States – Final Dumping Determination on Softwood Lumber from Canada, European Communities - Customs Classification of Frozen Boneless Chicken Cuts, Chile – Price Band System and Safeguard Measures Relating to Certain Agricultural Products and United States - Measures Affecting the Cross-Border Supply of Gambling and Betting Services.
Bidirectional Exchange of Biogenic Volatile Organic Compounds in Subarctic Heath Mesocosms During Autumn Climate Scenarios
Authors: Baggesen Nanna S. , Davie‐Martin Cleo L. , Seco Roger , Holst Thomas , Rinnan Riikka
Published: June 2022

Biogenic volatile organic compound (BVOC) flux dynamics during the subarctic autumn are largely unexplored and have been considered insignificant due to the relatively low biological activity expected during autumn. Here, we exposed subarctic heath ecosystems to predicted future autumn climate scenarios (ambient, warming, and colder, dark conditions), changes in light availability, and flooding, to mimic the more extreme rainfall or snowmelt events expected in the future. We used climate chambers to measure the net ecosystem fluxes and bidirectional exchange of BVOCs from intact heath mesocosms using a dynamic enclosure technique coupled to a proton‐transfer‐reaction time‐of‐flight mass spectrometer (PTR–ToF–MS). We focused on six BVOCs (methanol, acetic acid, acetaldehyde, acetone, isoprene, and monoterpenes) that were among the most dominant and that were previously identified in arctic tundra ecosystems. Warming increased ecosystem respiration and resulted in either net BVOC release or increased uptake compared to the ambient scenario. None of the targeted BVOCs showed net release in the cold and dark scenario. Acetic acid exhibited significantly lower net uptake in the cold and dark scenario than in the ambient scenario, which suggests reduced microbial activity. Flooding was characterized by net uptake of the targeted BVOCs and overruled any temperature effects conferred by the climate scenarios. Monoterpenes were mainly taken up by the mesocosms and their fluxes were not affected by the climate scenarios or flooding. This study shows that although autumn BVOC fluxes on a subarctic heath are generally low, changes in future climate may strongly modify them.
Why Did Sunspots Disappear for 70 Years? Nearby Star Holds Clues
Authors: Cartier Kimberly
Published: June 2022

Five decades of data revealed a star undergoing a pause in magnetic activity similar to what the Sun experienced almost 400 years ago.
Loss of Ocean Memory Has Implications from Forecasting to Conservation
Authors: Loomis Ilima
Published: June 2022

New research indicates climate change may thin the mixed layer and contribute to a reduction of sea surface temperature anomalies.
Wind‐Modulated Western Maine Coastal Current and Its Connectivity With the Eastern Maine Coastal Current
Authors: Li Denghui , Wang Zhengui , Xue Huijie , Thomas Andrew C. , Etter Ron J.
Published: June 2022

Using a high‐resolution circulation model and an offline particle tracking model, we investigated variations of the Western Maine Coastal Current (WMCC) and its connectivity with the Eastern Maine Coastal Current (EMCC). The models showed that the weak, broad, and sinuous WMCC is generally southwestward with an offshore and a nearshore core, fed by the extension of the EMCC and runoff from the Penobscot and Kennebec–Androscoggin Rivers, respectively. A sea‐level dome can form offshore of Casco Bay in late fall and early winter as the northeastward alongshore wind sets up a seaward sea‐level gradient from the coast to meet the shoreward sea‐level gradient from Wilkinson Basin. Consequently, northeastward flows (i.e., the counter‐WMCC) emerge on the inshore side of the dome. Both the circulation and particle tracking models suggested that the connectivity generally peaks twice annually, highest in winter and then secondarily in late spring or early summer. The former is concurrent with the most southwest offshore veering of the EMCC, while the latter is concurrent with the strongest EMCC. Moreover, the counter‐WMCC can reduce the connectivity and result in year‐to‐year variations.
A New Approach to Skillful Seasonal Prediction of Southeast Asia Tropical Cyclone Occurrence
Authors: Feng Xiangbo , Hodges Kevin I. , Hoang Lam , Pura Alvin G. , Yang Gui‐Ying , Luu Huyen , David Shirley J. , Duran Ger Anne M. W. , Guo Yi‐Peng
Published: June 2022

Predicting the peak‐season (July–September) tropical cyclones (TCs) in Southeast Asia (SEA) several months ahead remains challenging, related to limited understanding and prediction of the dynamics affecting the variability of SEA TC activity. Here, we introduce a new statistical approach to sequentially identify mutually independent predictors for the occurrence frequency of peak‐season TCs in the South China Sea (SCS) and east of the Philippines (PHL). These predictors, which are identified from the preseason (April‐June) environmental fields, can capture the interannual variability of different clusters of peak‐season TCs, through a cross‐season effect on large‐scale environment that governs TC genesis and track. The physically oriented approach provides a skillful seasonal prediction in the 41‐year period (1979–2019), with r = 0.73 and 0.54 for SCS and PHL TC frequency, respectively. The lower performance for PHL TCs is likely related to the nonstationarity of the cross‐season TC‐environment relationship. We further develop the statistical approach to a hybrid method using the predictors derived from dynamical seasonal forecasts. The hybrid prediction shows a significant skill for both SCS and PHL TCs, for lead times up to four or 5 months ahead, related to the good performance of models for the sea surface temperatures and low‐level winds in the tropics. The statistical and hybrid predictions outperform the dynamical predictions, showing the potential for operational use.
Revisiting the Pan Evaporation Trend in China During 1988–2017
Authors: Shen Jiaju , Yang Hanbo , Li Sien , Liu Ziwei , Cao Yongqiang , Yang Dawen
Published: June 2022

Pan evaporation decrease has been reported worldwide over the past decades. A recent increasing pan evaporation trend has been found globally. Remarkably, most studies on Chinese pan evaporation change were based on simulations involving meteorological variables, including temperature, radiation (sunshine duration [SSD]), wind speed, and relative humidity (RH), due to the pan evaporation observation inconsistency caused by the micro‐pan (D20) replacement with large pan (E601) around 2002. In addition, a large‐scale humidity sensor replacement across China occurred since the 2000s can cause an inconsistency of RH and in turn lead to that of simulated pan evaporation. Therefore, the recent pan evaporation trends independent of the observed RH in China should be revisited. In this study, we (a) generate merged D20 pan evaporation from 1988 to 2017 according to E601 observations under the constant conversion coefficient assumption between the evaporation observations of these pans in the same month of every year at each station, and (b) propose a framework based on the PenPan‐D20 model to attribute pan evaporation change into specific humidity (instead of RH or vapor pressure deficit in previous studies), SSD, air temperature, and wind speed, since RH and vapor pressure deficit are not independent from air temperature. The results show a significant 2.68 mm/a/a upward pan evaporation trend (p < 0.05) across China from 1988 to 2017, which was primarily driven by the rising air temperature. Humidity sensor replacement causes an ∼2.2% inconsistency in RH, which produces nonnegligible errors in simulated pan evaporation trend.
CircRFWD3 promotes HNSCC metastasis by modulating miR-27a/b/PPARγ signaling
Authors: Wei Zihao , Wang Ying , Peng Jiakuan , Li Honglin , Gu Junjie , Ji Ning , Li Taiwei , Zhou Xikun , Zeng Xin , Li Jing , Chen Qianming
Published: June 2022

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, the 5-year survival rate of patients with HNSCC is still about 50% due to frequent metastasis and recurrence. Circular RNAs (circRNAs) have been characterized as key regulators of gene expression in numerous malignancies. However, the role of circRNA in HNSCC metastasis remains largely unknown. Here, we demonstrated that the circRFWD3 was significantly upregulated in HNSCC tissues and cell lines by circRNA microarray analysis and qPCR. Notably, high expression of circRFWD3 is related to highly aggressive HNSCC cell lines and lymph node metastasis in HNSCC patients. After that, Sanger sequencing, RNase R, and actinomycin D assay were performed to verify the ring structure of circRFWD3. Then functional experiments found it could promote the metastasis of HNSCC cells both in vitro and in vivo. Mechanistically, a dual-luciferase reporter assay, FISH, RIP, RNA pull-down, RNA-seq, and western blot experiments were employed and found that circRFWD3 served as a miRNAs sponge for miR-27a/27b, leading to the upregulation of PPARγ, and then promoted HNSCC metastasis via NF-κB/MMP13 pathway. Finally, ISH and IHC were carried out to determine the expression levels and clinical significances of circRFWD3 and PPARγ in clinical cohorts of HNSCC. According to the analysis results from two independent HNSCC cohorts, upregulated expression of circRFWD3 and PPARγ were positively associated with worse survival in patients with HNSCC. Overall, our results uncover that circRFWD3 acts a critical role in promoting the aggressiveness of HNSCC cells and is a prognostic marker for the disease, indicating that circRFWD3 may act as a potential therapeutic target in HNSCC.
Caspase-2 is a mediator of apoptotic signaling in response to gemtuzumab ozogamicin in acute myeloid leukemia
Authors: Hååg Petra , Olsson Magnus , Forsberg Jeremy , Lindberg Marita Lagergren , Stenerlöw Bo , Zong Dali , Kanter Lena , Lewensohn Rolf , Viktorsson Kristina , Zhivotovsky Boris , Stenke Leif
Published: June 2022

The antibody conjugate gemtuzumab ozogamicin (GO; Mylotarg®) provides targeted therapy of acute myeloid leukemia (AML), with recent approvals for patients with CD33-positive disease at diagnosis or relapse, as monotherapy or combined with chemotherapeutics. While its clinical efficacy is well documented, the molecular routes by which GO induces AML cell death warrant further analyses. We have earlier reported that this process is initiated via mitochondria-mediated caspase activation. Here we provide additional data, focusing on the involvement of caspase-2 in this mechanism. We show that this enzyme plays an important role in triggering apoptotic death of human AML cells after exposure to GO or its active moiety calicheamicin. Accordingly, the caspase-2 inhibitor z-VDVAD-fmk reduced GO-induced caspase-3 activation. This finding was validated with shRNA and siRNA targeting caspase-2, resulting in reduced caspase-3 activation and cleavage of poly [ADP-ribose] polymerase 1 (PARP-1). We previously demonstrated that GO-induced apoptosis included a conformational change of Bax into a pro-apoptotic state. Present data reveal that GO-treatment also induced Bid cleavage, which was partially reduced by caspase-2 specific inhibition while the effect on GO-induced Bax conformational change remained unaltered. In mononuclear cells isolated from AML patients that responded to GO treatment in vitro, processing of caspase-2 was evident, whereas in cells from an AML patient refractory to treatment no such processing was seen. When assessing diagnostic samples from 22 AML patients, who all entered complete remission (CR) following anthracycline-based induction therapy, and comparing patients with long versus those with short CR duration no significant differences in baseline caspase-2 or caspase-3 full-length protein expression levels were found. In summary, we demonstrate that GO triggers caspase-2 cleavage in human AML cells and that the subsequent apoptosis of these cells in part relies on caspase-2. These findings may have future clinical implications.
The combination of hydroxychloroquine and 2-deoxyglucose enhances apoptosis in breast cancer cells by blocking protective autophagy and sustaining endoplasmic reticulum stress
Authors: Zhou Ning , Liu Qingyun , Wang Xiao , He Lixin , Zhang Tao , Zhou Han , Zhu Xinying , Zhou Tianhong , Deng Ganzhen , Qiu Changwei
Published: June 2022

2-Deoxyglucose (2-DG) can be used in antitumour research by inhibiting glycolysis and promoting the endoplasmic reticulum stress (ERS) pathway, but its clinical application is restricted due to dose-limiting side effects and survival chance for cancer cells by protective autophagy. Therefore, our research explored whether the combination of hydroxychloroquine (HCQ), an FDA-approved autophagy inhibiting drug, and 2-DG is a promising therapeutic strategy. Here, we report that HCQ combined with 2-DG can further inhibit the viability and migration and induce apoptosis of breast tumour cells compared with other individual drugs. The combination of 2-DG and HCQ can significantly reduce transplanted tumour size and tumour cell metastasis of the lung and liver in vivo. At the cellular level, HCQ suppressed autolysosome formation and terminated the autophagy process induced by 2-DG-mediated ERS, resulting in the continuous accumulation of misfolded proteins in the endoplasmic reticulum, which generated sustained ERS through the PERK-eIF2α-ATF-4-CHOP axis and triggered the transformation from a survival process to cell death. Our research reinforced the research interest of metabolic disruptors in triple-negative breast cancer and emphasized the potential of the combination of 2-DG and HCQ as an anticancerous treatment.
Photon-free (s)CMOS camera characterization for artifact reduction in high- and super-resolution microscopy
Authors: Diekmann Robin , Deschamps Joran , Li Yiming , Deguchi Takahiro , Tschanz Aline , Kahnwald Maurice , Matti Ulf , Ries Jonas
Published: June 2022

Modern implementations of widefield fluorescence microscopy often rely on sCMOS cameras, but this camera architecture inherently features pixel-to-pixel variations. Such variations lead to image artifacts and render quantitative image interpretation difficult. Although a variety of algorithmic corrections exists, they require a thorough characterization of the camera, which typically is not easy to access or perform. Here, we developed a fully automated pipeline for camera characterization based solely on thermally generated signal, and implemented it in the popular open-source software Micro-Manager and ImageJ/Fiji. Besides supplying the conventional camera maps of noise, offset and gain, our pipeline also gives access to dark current and thermal noise as functions of the exposure time. This allowed us to avoid structural bias in single-molecule localization microscopy (SMLM), which without correction is substantial even for scientific-grade, cooled cameras. In addition, our approach enables high-quality 3D super-resolution as well as live-cell time-lapse microscopy with cheap, industry-grade cameras. As our approach for camera characterization does not require any user interventions or additional hardware implementations, numerous correction algorithms that rely on camera characterization become easily applicable.
High critical current density and high-tolerance superconductivity in high-entropy alloy thin films
Authors: Jung Soon-Gil , Han Yoonseok , Kim Jin Hee , Hidayati Rahmatul , Rhyee Jong-Soo , Lee Jung Min , Kang Won Nam , Choi Woo Seok , Jeon Hye-Ran , Suk Jaekwon , Park Tuson
Published: June 2022

High-entropy alloy (HEA) superconductors—a new class of functional materials—can be utilized stably under extreme conditions, such as in space environments, owing to their high mechanical hardness and excellent irradiation tolerance. However, the feasibility of practical applications of HEA superconductors has not yet been demonstrated because the critical current density (Jc) for HEA superconductors has not yet been adequately characterized. Here, we report the fabrication of high-quality superconducting (SC) thin films of Ta–Nb–Hf–Zr–Ti HEAs via a pulsed laser deposition. The thin films exhibit a large Jc of >1 MA cm−2 at 4.2 K and are therefore favorable for SC devices as well as large-scale applications. In addition, they show extremely robust superconductivity to irradiation-induced disorder controlled by the dose of Kr-ion irradiation. The superconductivity of the HEA films is more than 1000 times more resistant to displacement damage than that of other promising superconductors with technological applications, such as MgB2, Nb3Sn, Fe-based superconductors, and high-Tc cuprate superconductors. These results demonstrate that HEA superconductors have considerable potential for use under extreme conditions, such as in aerospace applications, nuclear fusion reactors, and high-field SC magnets.
Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight
Authors: Bertaux François , Sosa-Carrillo Sebastián , Gross Viktoriia , Fraisse Achille , Aditya Chetan , Furstenheim Mariela , Batt Gregory
Published: June 2022

Small-scale, low-cost bioreactors provide exquisite control of environmental parameters of microbial cultures over long durations. Their use is gaining popularity in quantitative systems and synthetic biology. However, existing setups are limited in their measurement capabilities. Here, we present ReacSight, a strategy to enhance bioreactor arrays for automated measurements and reactive experiment control. ReacSight leverages low-cost pipetting robots for sample collection, handling and loading, and provides a flexible instrument control architecture. We showcase ReacSight capabilities on three applications in yeast. First, we demonstrate real-time optogenetic control of gene expression. Second, we explore the impact of nutrient scarcity on fitness and cellular stress using competition assays. Third, we perform dynamic control of the composition of a two-strain consortium. We combine custom or chi.bio reactors with automated cytometry. To further illustrate ReacSight’s genericity, we use it to enhance plate-readers with pipetting capabilities and perform repeated antibiotic treatments on a bacterial clinical isolate.
Antigen glycosylation regulates efficacy of CAR T cells targeting CD19
Authors: Heard Amanda , Landmann Jack H. , Hansen Ava R. , Papadopolou Alkmini , Hsu Yu-Sung , Selli Mehmet Emrah , Warrington John M. , Lattin John , Chang Jufang , Ha Helen , Haug-Kroeper Martina , Doray Balraj , Gill Saar , Ruella Marco , Hayer Katharina E. , Weitzman Matthew D. , Green Abby M. , Fluhrer Regina , Singh Nathan
Published: June 2022

While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most patients treated will not achieve durable remission. Identification of the mechanisms leading to failure is essential to broadening the efficacy of this promising platform. Several studies have demonstrated that disruption of CD19 genes and transcripts can lead to disease relapse after initial response; however, few other tumor-intrinsic drivers of CAR T cell failure have been reported. Here we identify expression of the Golgi-resident intramembrane protease Signal peptide peptidase-like 3 (SPPL3) in malignant B cells as a potent regulator of resistance to CAR therapy. Loss of SPPL3 results in hyperglycosylation of CD19, an alteration that directly inhibits CAR T cell effector function and suppresses anti-tumor cytotoxicity. Alternatively, over-expression of SPPL3 drives loss of CD19 protein, also enabling resistance. In this pre-clinical model these findings identify post-translational modification of CD19 as a mechanism of antigen escape from CAR T cell therapy.
Impact of extra-anatomical bypass on coarctation fluid dynamics using patient-specific lumped parameter and Lattice Boltzmann modeling
Authors: Sadeghi Reza , Tomka Benjamin , Khodaei Seyedvahid , Daeian MohammadAli , Gandhi Krishna , Garcia Julio , Keshavarz-Motamed Zahra
Published: June 2022

Accurate hemodynamic analysis is not only crucial for successful diagnosis of coarctation of the aorta (COA), but intervention decisions also rely on the hemodynamics assessment in both pre and post intervention states to minimize patient risks. Despite ongoing advances in surgical techniques for COA treatments, the impacts of extra-anatomic bypass grafting, a surgical technique to treat COA, on the aorta are not always benign. Our objective was to investigate the impact of bypass grafting on aortic hemodynamics. We investigated the impact of bypass grafting on aortic hemodynamics using a patient-specific computational-mechanics framework in three patients with COA who underwent bypass grafting. Our results describe that bypass grafting improved some hemodynamic metrics while worsened the others: (1) Doppler pressure gradient improved (decreased) in all patients; (2) Bypass graft did not reduce the flow rate substantially through the COA; (3) Systemic arterial compliance increased in patients #1 and 3 and didn’t change (improve) in patient 3; (4) Hypertension got worse in all patients; (5) The flow velocity magnitude improved (reduced) in patient 2 and 3 but did not improve significantly in patient 1; (6) There were elevated velocity magnitude, persistence of vortical flow structure, elevated turbulence characteristics, and elevated wall shear stress at the bypass graft junctions in all patients. We concluded that bypass graft may lead to pseudoaneurysm formation and potential aortic rupture as well as intimal hyperplasia due to the persistent abnormal and irregular aortic hemodynamics in some patients. Moreover, post-intervention, exposures of endothelial cells to high shear stress may lead to arterial remodeling, aneurysm, and rupture.