bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between vascular ultrasound features and DNA sequencing in breast cancer: a preliminary study
Authors: Han Mi-Ryung , Park Ah Young , Seo Bo Kyoung , Bae Min Sun , Kim Jung Sun , Son Gil Soo , Lee Hye Yoon , Chang Young Woo , Cho Kyu Ran , Song Sung Eun , Woo Ok Hee , Ju Hye-Yeon , Oh Hyunseung
Published: April 2023

There are few radiogenomic studies to correlate ultrasound features of breast cancer with genomic changes. We investigated whether vascular ultrasound phenotypes are associated with breast cancer gene profiles for predicting angiogenesis and prognosis. We prospectively correlated quantitative and qualitative features of microvascular ultrasound (vascular index, vessel morphology, distribution, and penetrating vessel) and contrast-enhanced ultrasound (time–intensity curve parameters and enhancement pattern) with genomic characteristics in 31 breast cancers. DNA obtained from breast tumors and normal tissues were analyzed using targeted next-generation sequencing of 105 genes. The single-variant association test was used to identify correlations between vascular ultrasound features and genomic profiles. Chi-square analysis was used to detect single nucleotide polymorphisms (SNPs) associated with ultrasound features by estimating p values and odds ratios (ORs). Eight ultrasound features were significantly associated with 9 SNPs (p < 0.05). Among them, four ultrasound features were positively associated with 5 SNPs: high vascular index with rs1136201 in ERBB2 (p = 0.04, OR = 7.75); large area under the curve on contrast-enhanced ultrasound with rs35597368 in PDGFRA (p = 0.04, OR = 4.07); high peak intensity with rs35597368 in PDGFRA (p = 0.049, OR = 4.05) and rs2305948 in KDR (p = 0.04, OR = 5.10); and long mean transit time with rs2275237 in ARNT (p = 0.02, OR = 10.25) and rs755793 in FGFR2 (p = 0.02, OR = 10.25). We identified 198 non-silent SNPs in 71 various cancer-related genes. Vascular ultrasound features can reflect genomic changes associated with angiogenesis and prognosis in breast cancer.
Clinical utility of polygenic risk scores: a critical 2023 appraisal
Authors: Koch Sebastian , Schmidtke Jörg , Krawczak Michael , Caliebe Amke
Published: May 2023

Since their first appearance in the context of schizophrenia and bipolar disorder in 2009, polygenic risk scores (PRSs) have been described for a large number of common complex diseases. However, the clinical utility of PRSs in disease risk assessment or therapeutic decision making is likely limited because PRSs usually only account for the heritable component of a trait and ignore the etiological role of environment and lifestyle. We surveyed the current state of PRSs for various diseases, including breast cancer, diabetes, prostate cancer, coronary artery disease, and Parkinson disease, with an extra focus upon the potential improvement of clinical scores by their combination with PRSs. We observed that the diagnostic and prognostic performance of PRSs alone is consistently low, as expected. Moreover, combining a PRS with a clinical score at best led to moderate improvement of the power of either risk marker. Despite the large number of PRSs reported in the scientific literature, prospective studies of their clinical utility, particularly of the PRS-associated improvement of standard screening or therapeutic procedures, are still rare. In conclusion, the benefit to individual patients or the health care system in general of PRS-based extensions of existing diagnostic or treatment regimens is still difficult to judge.
LANTITE’s impact on teacher diversity: Unintended consequences of testing pre-service teachers
Authors: Hilton Alison L. , Saunders Rebecca
Published: April 2023

Australian schools are diverse, and support students from a wide range of racial, cultural, and linguistic backgrounds, as well as students with disability. Ironically, efforts to ensure equally diverse teacher workforces have been ineffective. Attempts to improve broader representation in teachers have been hampered by a homogenous approach to teacher recruitment and education. In 2016, Literacy and Numeracy Test for Initial Teacher Education (LANTITE) became a graduation requirement for teachers. The aim of this research is to explore the test-taking experiences of students (pre-service teachers) from diverse backgrounds, and the stakeholders who support them. A thematic analysis of data from a larger mixed methods study revealed additional tensions for students from diverse backgrounds including unintended consequences such as traumatic experiences and having to encounter additional hurdles to be successful. This study provides unique insights into additional pressures and hurdles students from diverse backgrounds experience when completing this high-stakes test.
Between Regional Recommendations and National Implementation: An Analysis of the East African Community Partner States’ Legislative Responses to TRIPS Obligations
Authors: Olatunji Olugbenga A.
Published: May 2023

With the access-to-medicines conundrum facing its populations, the East African Community has adopted a policy framework which promotes a collective approach to resolving the access gap in the region. To this end, crucial policy documents on the implementation of TRIPS obligations, harmonisation of drug regulation and boosting regional manufacturing capacity have been adopted. This paper is a case study of the regional policy on the implementation of TRIPS obligations, specifically examining the extent to which partner states’ implementation of TRIPS obligations mirrors the regional recommendations. The paper finds that, while many partner states follow the regional recommendations on implementing TRIPS obligations, coherence remains a big challenge. This, the paper concludes, may affect the overall usefulness of a regional approach to solving the access conundrum.
Multi-criteria comparative analysis of the pressure drop on coal gangue fly-ash slurry at different parts along an L-shaped pipeline
Authors: Wang Defeng , Jiao Dengwu , Cheng Zhanbo , Shi Qingwen , Mischo Helmut
Published: May 2023

Disposing of coal gangue and fly-ash on the surface is a risky method with tremendous potential catastrophic consequences for the environment. Backfill mining is a promising practice for turning those hazardous wastes into functional backfill materials. Unfortunately, how to efficiently deliver the slurry to the desired places remains under-researched. To address this issue, the computational fluid dynamics software Fluent was used in the current study in addition to a laboratory rheological test to simulate the impact of various parameters on the evolution of pressure at a particular section of the pipeline. Furthermore, the response surface method was employed to investigate how the various components and their corresponding influencing weights interact to affect the pressure drop. This study demonstrates that the pressure drop of the slurry is highly influenced by slurry concentration, speed, and pipe diameter. While conveying speed is the main component in the bend section, pipe diameter takes over in the horizontal and vertical pipe sections.
A simple note on the number-theoretic function $$\Omega (n)$$ and Dirichlet L-functions
Authors: Kohnen Winfried
Published: May 2023

We give a relation between the orders of potential non-trivial zeros of Dirichlet L-functions and analytic properties of certain Dirichlet series first introduced by Selberg.
Bregman dynamics, contact transformations and convex optimization
Authors: Bravetti Alessandro , Daza-Torres Maria L. , Flores-Arguedas Hugo , Betancourt Michael
Published: April 2023

Recent research on accelerated gradient methods of use in optimization has demonstrated that these methods can be derived as discretizations of dynamical systems. This, in turn, has provided a basis for more systematic investigations, especially into the geometric structure of those dynamical systems and their structure-preserving discretizations. In this work, we introduce dynamical systems defined through a contact geometry which are not only naturally suited to the optimization goal but also subsume all previous methods based on geometric dynamical systems. As a consequence, all the deterministic flows used in optimization share an extremely interesting geometric property: they are invariant under contact transformations. In our main result, we exploit this observation to show that the celebrated Bregman Hamiltonian system can always be transformed into an equivalent but separable Hamiltonian by means of a contact transformation. This in turn enables the development of fast and robust discretizations through geometric contact splitting integrators. As an illustration, we propose the Relativistic Bregman algorithm, and show in some paradigmatic examples that it compares favorably with respect to standard optimization algorithms such as classical momentum and Nesterov’s accelerated gradient.
Ultra-Trace Analysis of Fallout Plutonium Isotopes in Soil: Emerging Trends and Future Perspectives
Authors: Dowell Sophia M. , Humphrey Olivier S. , Blake William H. , Osano Odipo , Chenery Simon , Watts Michael J.
Published: May 2023

The measurement of isotopic abundances and ratio variations of plutonium can provide important information about the sources and behaviours of radiogenic isotopes in the environment. The detection of ultra-trace isotopes of plutonium is increasing interest in the scientific literature for the determination of soil erosion rates due to their long retention times in the environment. The characteristics of plutonium within the environment make it an ideal tracer for the determination of soil redistribution rates and its robustness presents the opportunity to replace more commonly used radioisotopes such as 137Cesium and 210Lead. However, ultra-trace analysis of plutonium (fg g−1) presents analytical challenges which must be overcome in a variety of soil types. Inductively Coupled Plasma Mass Spectrometry has proven valuable for detection of plutonium in a range of environmental samples. However, severe polyatomic interferences from uranium isotopes significantly limits its application. Due to the improvements in detection sensitivity and reaction cell technology, inductively coupled plasma tandem mass spectrometry, which is also commonly referred to as triple quadrupole inductively coupled plasma tandem mass spectrometry (ICP-MS/MS), has emerged as an exceptional tool for ultra-trace elemental analysis of plutonium isotopes in environmental samples overcoming the limitations of standard quadrupole ICP-MS such as limited sensitivity and cost of analysis. In this review, common methods reported in the literature for the separation and subsequent detection of plutonium isotopes are compared to recent advances in analysis using ICP-MS/MS technology.

Graphical Abstract
Application of the path-repairing technique and virus optimization algorithm for the dimensional synthesis of four-bar mechanisms
Authors: Grabski Jakub Krzysztof , Sopa Martyna , Mrozek Agata
Published: April 2023

This paper considers the synthesis of the four-bar mechanism. It is treated here as an optimization problem, in which an objective function is defined. To solve this problem, a metaheuristic called the virus optimization algorithm is employed. Furthermore, a new path-repairing technique recently published by Sleesongsom and Bureerat is applied instead of the very common technique related to the application of a penalty function. This makes the search by means of the metaheuristic more efficient. Furthermore, the obtained results are very accurate.
Properties, applications, and prospects of carbon nanotubes in the construction industry
Authors: Yang Shengdan
Published: May 2023

Nanotechnology and nanomaterials have offered sustainable design options for the built environment and enabled architects to design more flexible architectural forms. Carbon nanotubes have excellent mechanical, electrical, thermal, and chemical properties and are useful in a wide range of engineering applications. However, the role of carbon nanotube composites as a functional construction material has large potential and awaits further investigation and exploration. This paper gives an overview of the synthesis and fabrication methods of carbon nanotubes, carbon nanotube properties, different forms of carbon nanotube composites, and application of carbon nanotubes in the construction industry. To explore the prospects for construction use, the aesthetic, structural, and functional characteristics of several futuristic building projects are discussed. This overview proposes a promising material approach for the application of carbon nanotubes in construction and explains the related opportunities and challenges.
Indeterminacy in the World
Authors: Torza Alessandro
Published: May 2023

The way we represent the world in thought and language is shot through with indeterminacy: we speak of red apples and yellow apples without thereby committing to any sharp cutoff between the application of the predicate 'red' and of the predicate 'yellow'. But can reality itself be indeterminate? In other words, can indeterminacy originate in the mind-independent world, and not only in our representations? If so, can the phenomenon also arise at the microscopic scale of fundamental physics? Section 1 of this Element provides a brief overview of the question of indeterminacy. Section 2 discusses the thesis that the world is comprised of indeterminate objects, whereas Section 3 focuses on the thesis that there are indeterminate states of affairs. Finally, Section 4 is devoted to the case study of indeterminacy in quantum physics.
Secular Saints
Authors: Misemer Sarah
Published: May 2023

The sanctification of stardom.
Women farmers and climate change: Empirical evidence from Burkina Faso
Authors: Diendéré Achille Augustin , Ouédraogo Djibril
Published: May 2023

This study examines the factors influencing women farmers’ choice of adaptation strategies to reduce the negative impacts of climate change and the effects of these strategies on household income and food insecurity. A field survey was conducted among 426 women farmers in the Center-North region, which covers 7% of Burkina Faso territory. Descriptive statistics, a multinomial logit model, and a propensity score matching model were used to analyze the data collected. The results of the econometric analysis show that high domestic tasks, type of climate shocks experienced, membership in women’s group, and financial constraints are important determinants of adaptation decisions. Adaptation strategies are also found to have a positive impact on income and a negative impact on household food insecurity. These different findings highlight the need to prioritize flexible adaptation options to improve women farmers’ resilience to climate change, rather than generic solutions.
The effect of low temperature on the Raman spectra of calcium-rich sulfates on Mars
Authors: Huidobro Jennifer , Aramendia Julene , Arana Gorka , Hausrath Elisabeth M. , Madariaga Juan Manuel
Published: May 2023

Raman spectra (532 nm diode laser) of gypsum, syngenite and görgeyite powders were studied from 273 to 83 K every −10 K. Although it was found that not all the Raman peaks are temperature-sensitive, the effect of temperature on the Raman signal of some bands was modelled. It was observed that the main bands of the three sulfates shift toward higher wavenumbers as temperature decreases. The strengthening of the bonds causes an increase in energy and, consequently, higher wavenumbers. However, –OH bands shift depending on the crystal structure they acquire as the temperature decreases, so not all –OH bands behave in the same way. Finally, the gypsum –OH bands change to more ordered crystalline structures with decreasing temperature, so their bandwidths become narrower and sharper.
Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia
Authors: Parker Jessica , Hockney Sean , Blaschuk Orest W. , Pal Deepali
Published: May 2023

This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia–niche interactions. The tumour microenvironment plays an integral role in conferring treatment resistance to leukaemia cells, this poses as a key clinical challenge that hinders management of this disease. Here we focus on the role of the cell adhesion molecule N-cadherin (CDH2) within the malignant BM microenvironment and associated signalling pathways that may bear promise as therapeutic targets. Additionally, we discuss microenvironment-driven treatment resistance and relapse, and elaborate the role of CDH2-mediated cancer cell protection from chemotherapy. Finally, we review emerging therapeutic approaches that directly target CDH2-mediated adhesive interactions between the BM cells and leukaemia cells.
Demonic Assault, Providence, and the Search for Salvation in Early Modern Reformed English Protestant Theology
Authors: Walsh Brendan C.
Published: May 2023

During the late sixteenth and early seventeenth centuries—the height of European demonological interest—England experienced a series of demonic possession cases that gained substantial attention from the clergy and laypeople alike. Reported across sensationalist pamphlets and learned demonological treatises, these cases were presented as extraordinary tokens of God's providence intended to be interpreted and responded to by those involved. English Calvinists during this period were largely interested in demonic possession for three primary reasons: what providential meaning this spiritual affliction offered, what action God was compelling them to carry out, and, more importantly, what profit they could gain in fulfilling their godly duties. The profit cited by these Calvinists was a glimpse into their predestined fate. This article argues that demonic affliction was fashioned as an emblematic phenomenon by English Calvinist communities with dispossession (exorcism) cast as a definitive form of spiritual warfare designed to provide comfort for the faithful and guide them toward a blessed conclusion. In this context, possession functioned as a providential catalyst: a call to carry out dispossession that, once fulfilled, brought the entire act to completion. Examining four possession textual accounts in detail, with a particular focus on the exploits of the controversial Puritan exorcist John Darrell, this article examines the intellectual construction of spirit possession and exorcism within an aligned Calvinist providential and eschatological framework. These cases exemplify many of the prevailing interpretations of spirit possession in the early modern English context and illustrate how this affliction offered individuals a potential salve to the vexed nature of Calvinist predestination.
“An Oppressive Insensibility”: Disestablishment, Clerical Infirmity, and the Origins of the Manual Labor Movement
Authors: Stokum Christopher J.
Published: May 2023

In the contested spiritual economy of the early nineteenth century, recently disestablished American clergymen consolidated themselves in theological seminaries. Members of the dominant New England Congregationalist and Presbyterian ministries, these seminarians organized a defensive front against itinerant, populist rivals by intensifying their curricula, proscribing physical exertion as a distraction from study, and shielding clerical students from popular influence. Yet critical voices from within the seminaries soon reported that unrelenting study damaged students’ bodily health and alienated the clergy from a laity on whom their educational funding now depended. Accompanying such critiques were proposals for an alternative pedagogy that gained its fullest expression in the manual labor school, where physical vigor was enshrined as a complement to theological training and where barriers separating clergy from laity were minimized. By situating the infirmities that seminarians logged in memoirs and exposés alongside their efforts to reform the seminary system, this article argues that the graduate clergy mustered a coherent, forceful response to the crisis in spiritual leadership that disestablishment precipitated. The article presents clerical elites not as casualties of democratization or as agents of capital, but as self-aware and self-interested economic actors in the reordering of American religious authority after disestablishment.
Puritans, Padres, and Pentecostals: Perspectival and Pedagogical Shifts in Americana Church History
Authors: Ramírez Daniel
Published: May 2023

In this article, I invite the guild to rethink received paradigms and perspectives in the study and teaching of American church and religious history. The common additive approach of the last decades that folds in Latino/a experience usually reflects new themes of contemporary immigration and diversity, but rarely considers constitutive contributions to foundational stories or is conscious of perspectival constraints. In the spirit of previous ASCH presidential addresses, the proposed introspection weighs the cost of the refractions, redactions, and omissions. Through a reconsideration of seminality—whether agential or textual—in Spanish colonial expansion (Esteban of Azamor), in the Puritan colonial imaginary, and in Latino/Latin American Pentecostal growth, and of anachronistic geographical boundaries in the case of New Mexico curate Antonio José Martínez, this address calls for greater clarity in our understanding of the variegated contours of Americana church history.
Bank Influence at a Discount
Authors: Gersbach Hans , Papageorgiou Stylianos
Published: May 2023

In a general equilibrium framework, we show that banks may “buy” political influence at a discount: They offer disproportionately small campaign contributions compared to the influence they exert, thus generating abnormal returns. We distinguish between the direct effect of contributions which, as a cost, reduce bank returns, and the indirect effect of contributions which boost returns via inducing bank-favoring policies. Therefore, abnormal returns may or may not increase with the amount of contributions, depending on which effect dominates: Stricter capital requirements decrease contributions and abnormal returns. When politicians attach more weight to households’ welfare, contributions increase and abnormal returns decrease.
Elevation and cation exchange capacity determine diversity of ferns in a low-montane tropical rainforest in Ecuador
Authors: Michel Jennifer , Lehnert Marcus , Quandt Dietmar
Published: May 2023

Ferns (Polypodiophyta) are an abundant floral element of the tropics with high sensitivity to environmental conditions and good indicators of overall biodiversity. Here, we set out to identify which geochemical factors determine fern diversity in a low-montane tropical rainforest in Eastern Ecuador. We conducted a field survey of high-spatial resolution completing a comprehensive fern inventory across two elevational ranges, combined with biochemical characterisation of the underlying soils. While α-diversity was negatively correlated with cation exchange capacity (CEC) and with elevation, β-diversity increased with elevation and with geographic distance, as predicted. Our results confirm that ferns have a high sensitivity to both elevational and environmental gradients, where the latter in this study was derived from enhanced aluminium, iron and calcium contents in some of the studied soils. Further monitoring of fern communities could therefore help to better understand and predict how environmental change may impact biodiversity, with a particular focus on threats potentially arising from toxic elements being released in tropical soils through modified soil CEC.
Economic analyses of repugnant market transactions: a modest typology
Authors: Cserne Péter
Published: May 2023

Economic accounts of repugnance concern two broad questions: the rationalisation of sentiments of repugnance (do emotional and visceral reactions of repugnance track valid reasons for not engaging in or condemning certain (trans)actions?) and institutional design (how to institute, regulate, or restrict markets in response to reasonable objections). If repugnance expresses valid practical reasons for regulating or limiting markets, our institutions should acknowledge and express these. If attitudes of repugnance are not rationalisable in the sense of instrumental or moral values, we should disregard or eventually counteract or reduce them. Focusing on a special case of repugnance, when commodification, i.e., the sale of goods or services for money meets societal disapproval, this paper identifies three characteristic ways to combine conceptual, empirical, and normative arguments and map repugnance into a disciplinary ‘epistemic frame’ of economics: repugnance as taste; repugnance as proxy for market failures or moral reasons; repugnance as hypocrisy or contingent cultural fact. Correspondingly, economists advise to (1) work around; (2) make sense of; and (3) explain away people's sentiments of repugnance.
Co‐Located Wind and Temperature Observations at Mid‐Latitudes During Mesospheric Inversion Layer Events
Authors: Mariaccia A. , Keckhut P. , Hauchecorne A. , Khaykin S. , Ratynski M.
Published: May 2023

The mesospheric inversion layer (MIL) phenomenon is a temperature enhancement (10–50 K) in a vertical layer (∼10 km) lasting several days and spanning thousands of kilometers within the mesosphere. As MILs govern the mesospheric variability, their study is crucial for a better understanding of the middle‐atmosphere global circulation. MIL phenomenon is also important for applications in aeronautics as perturbations in the mesosphere are significant issues for the safe reentry of rockets, space shuttles, or missiles. However, the description of this phenomenon remains incomplete, since no observations of MIL's effects on winds exist, hampering an understanding of the mechanisms responsible for their formation. This study investigates simultaneous wind‐temperature observations in the altitude range of 30–90 km during MIL events. Strong winds deceleration occurred in the same altitude range as the temperature inversion, confirming the role of gravity waves in MIL's formation mechanisms.
New Late Cretaceous and CAMP Magmatic Sources off West Iberia, From High‐Resolution Magnetic Surveys on the Continental Shelf
Authors: Neres Marta , Terrinha Pedro , Noiva João , Brito Pedro , Rosa Marcos , Batista Luis , Ribeiro Carlos
Published: May 2023

Magma‐poor rifted margins can be affected by magmatic occurrences coeval with rifting and post‐rifting. Understanding the geological processes that originated these magmatic events requires determining their extent, type and size of magmatic bodies and tectonics. This work investigates the distribution and origin of two large magmatic events off SW Iberia, the Late Triassic Central Atlantic Magmatic Province (CAMP) and the West Iberia Late Cretaceous Alkaline Province (WILCAP). Marine magnetic data were densely acquired over ∼4,400 km2 and new magnetic maps reveal a complex heterogeneous anomaly field with different anomaly zones. A wide number and variety of magmatic bodies are interpreted, from km‐scale deeply intruded plutons to small plug‐like and dike‐like intrusions. Integration with bathymetry and seismic reflection data allows discussing the geometry, extent and age of the magmatic sources. The Cabo Raso complex is a densely intruded zone related to the WILCAP event. The Sines complex comprises the offshore prolongation of the on‐land Sines WILCAP magmatic rocks but also the newly mapped Côvo and Milfontes anomalies. Côvo is possibly the largest magmatic intrusion recognized in West Iberia. Milfontes intrudes the non‐rifted Paleozoic crust and is the first known evidence of a plutonic source of the CAMP in Iberia. The intrusion of magmatic bodies was mostly controlled by the crustal tectonic fabric inherited from the Paleozoic Variscan orogeny, which was re‐worked during the Mesozoic rifting and the Cenozoic Alpine collision.
Stormflow Response and “Effective” Hydraulic Conductivity of a Degraded Tropical Imperata Grassland Catchment as Evaluated With Two Infiltration Models
Authors: Cheng Zhuo , Zhang Jun , Yu Bofu , Chappell Nick A. , van Meerveld H. J. (Ilja) , Bruijnzeel L. Adrian
Published: May 2023

Predicting catchment stormflow responses after tropical deforestation remains difficult. We used 5‐min rainfall and storm runoff data for 30 events to calibrate the Green–Ampt (GA) and the Spatially Variable Infiltration (SVI) models and predict runoff responses for a small, degraded grassland catchment on Leyte Island (the Philippines), where infiltration‐excess overland flow (IOF) is considered the dominant runoff process. SVI replicated individual stormflow hydrographs better than GA, particularly for events with small runoff responses or multiple peaks. Calibrated parameter values of the SVI model (i.e., spatially averaged maximum infiltration capacity, Im and initial abstraction, F0) varied markedly between events, but were statistically significant and negatively correlated with (mid‐slope) soil moisture content at 10 cm (SWC10)—as did the “catchment‐wide effective” hydraulic conductivity (Ke) of the GA model. Using SWC10‐based estimates of F0 and Im in SVI yielded satisfactory to good simulations for 11 out of 17 events with runoff coefficients ≥15%, but failed to reproduce the hydrographs for events with very small runoff amounts (0.25–1 mm) and low runoff coefficients (3%–6%). The median field‐measured near‐surface Ksat (2 mm hr−1) was distinctly lower than the median Im (32 mm hr−1) and, to a lesser extent, Ke (∼8 mm hr−1), suggesting an underestimation of the spatially averaged Ksat by the field measurements. Application of SVI is expected to give the most realistic results for situations where IOF is dominant, that is, where surface conditions are degraded and rainfall intensities high.
Numerical Modeling and Data‐Worth Analysis for Characterizing the Architecture and Dissolution Rates of a Multicomponent DNAPL Source
Authors: Prieto‐Estrada Andres E. , Widdowson Mark A. , Stewart Lloyd D.
Published: May 2023

A numerical solute transport model was calibrated to a high‐resolution monitoring data set to characterize a multicomponent source of nonaqueous phase liquids (NAPLs) and evaluate the uncertainty of estimated parameters. The dissolution of NAPL mass was simulated using SEAM3D with parameter zones including adjustable NAPL saturations and mass transfer coefficients, representing the heterogenous architecture of the source zone. Source zone parameters were simultaneously estimated using PEST from aqueous‐phase concentrations measured in a multilevel monitoring transect and from mass recovery rates measured at extraction wells during a controlled field experiment. Data‐worth analyses, facilitated by PEST ancillary software, linked maximum aqueous‐phase concentrations of all compounds to reductions in the pre‐calibration uncertainty of mass transfer coefficients. In turn, decreasing concentrations of the most soluble NAPL fraction constrained the source mass estimation. The accurate estimation of model parameters was possible by removing concentrations measured during early NAPL dissolution stages, identified as drivers of model bias using the iterative ensemble smoother PESTPP‐iES. Although uncertainty analyses highlighted model limitations for representing sub‐grid‐scale heterogeneity of NAPL distribution and mass transfer rates, final stages of NAPL dissolution measured at multilevel ports eliminated parameter bias and produced long‐term projections of multi‐stage source zone depletion. Including mass discharge rates for model calibration further improved the accuracy of estimated residual source mass, complementing multilevel monitoring constraints on the saturation distribution and mass transfer coefficients.
The Increasing Role of Seasonal Rainfall in Western U.S. Summer Streamflow
Authors: Ban Zhaoxin , Li Dongyue , Lettenmaier Dennis P.
Published: May 2023

Summer streamflow variations strongly affect water supply reliability and ecological functioning of western U.S. (WUS) streams. Traditional snow‐based forecasts of summer streamflow are becoming less accurate with warming‐induced reductions in winter snow accumulation. This reflects a rising importance of competing runoff‐generating processes in controlling summer streamflow variations, primarily an increasing role of rainfall in contrast to snowmelt. Here, based on a snowmelt‐rainfall tracking algorithm applied to two hydrological models, we show that cool‐season rainfall provides an important volumetric contribution to summer streamflow for many WUS streams in the current climate, and this contribution will increase under climate warming, especially in years with warm snow droughts and abnormally dry summers. We also show that seasonal rainfall (warm‐/cool‐seasons) dominates the variability of summer streamflow across ∼70% area of WUS. We show that an increasing warm‐season rainfall contribution to summer streamflow (largely replacing snowmelt) results in reduced summer streamflow predictability.
mTOR inhibition suppresses Myc-driven polyposis by inducing immunogenic cell death
Authors: Leibowitz Brian J. , Zhao Guangyi , Xia Wenxin , Wang Yuhan , Ruan Hang , Zhang Lin , Yu Jian
Published: May 2023

Myc is a key driver of colorectal cancer initiation and progression, but remains a difficult drug target. In this study, we show that mTOR inhibition potently suppresses intestinal polyp formation, regresses established polyps, and prolongs lifespan of APCMin/+ mice. Everolimus in diet strongly reduces p-4EBP1, p-S6, and Myc levels, and induces apoptosis of cells with activated β-catenin (p-S552) in the polyps on day 3. The cell death is accompanied by ER stress, activation of the extrinsic apoptotic pathway, innate immune cell recruitment, and followed by T-cell infiltration on day 14 persisting for months thereafter. These effects are absent in normal intestinal crypts with physiologic levels of Myc and a high rate of proliferation. Using normal human colonic epithelial cells, EIF4E S209A knockin and BID knockout mice, we found that local inflammation and antitumor efficacy of Everolimus requires Myc-dependent induction of ER stress and apoptosis. These findings demonstrate mTOR and deregulated Myc as a selective vulnerability of mutant APC-driven intestinal tumorigenesis, whose inhibition disrupts metabolic and immune adaptation and reactivates immune surveillance necessary for long-term tumor control.
HNF1A binds and regulates the expression of SLC51B to facilitate the uptake of estrone sulfate in human renal proximal tubule epithelial cells
Authors: Chan Jun Wei , Neo Claire Wen Ying , Ghosh Soumita , Choi Hyungwon , Lim Su Chi , Tai E. Shyong , Teo Adrian Kee Keong
Published: May 2023

Renal defects in maturity onset diabetes of the young 3 (MODY3) patients and Hnf1a-/- mice suggest an involvement of HNF1A in kidney development and/or its function. Although numerous studies have leveraged on Hnf1α-/- mice to infer some transcriptional targets and function of HNF1A in mouse kidneys, species-specific differences obviate a straightforward extrapolation of findings to the human kidney. Additionally, genome-wide targets of HNF1A in human kidney cells have yet to be identified. Here, we leveraged on human in vitro kidney cell models to characterize the expression profile of HNF1A during renal differentiation and in adult kidney cells. We found HNF1A to be increasingly expressed during renal differentiation, with peak expression on day 28 in the proximal tubule cells. HNF1A ChIP-Sequencing (ChIP-Seq) performed on human pluripotent stem cell (hPSC)-derived kidney organoids identified its genome-wide putative targets. Together with a qPCR screen, we found HNF1A to activate the expression of SLC51B, CD24, and RNF186 genes. Importantly, HNF1A-depleted human renal proximal tubule epithelial cells (RPTECs) and MODY3 human induced pluripotent stem cell (hiPSC)-derived kidney organoids expressed lower levels of SLC51B. SLC51B-mediated estrone sulfate (E1S) uptake in proximal tubule cells was abrogated in these HNF1A-deficient cells. MODY3 patients also exhibit significantly higher excretion of urinary E1S. Overall, we report that SLC51B is a target of HNF1A responsible for E1S uptake in human proximal tubule cells. As E1S serves as the main storage form of nephroprotective estradiol in the human body, lowered E1S uptake and increased E1S excretion may reduce the availability of nephroprotective estradiol in the kidneys, contributing to the development of renal disease in MODY3 patients.
Selection-driven trait loss in independently evolved cavefish populations
Authors: Moran Rachel L. , Richards Emilie J. , Ornelas-García Claudia Patricia , Gross Joshua B. , Donny Alexandra , Wiese Jonathan , Keene Alex C. , Kowalko Johanna E. , Rohner Nicolas , McGaugh Suzanne E.
Published: May 2023

Laboratory studies have demonstrated that a single phenotype can be produced by many different genotypes; however, in natural systems, it is frequently found that phenotypic convergence is due to parallel genetic changes. This suggests a substantial role for constraint and determinism in evolution and indicates that certain mutations are more likely to contribute to phenotypic evolution. Here we use whole genome resequencing in the Mexican tetra, Astyanax mexicanus, to investigate how selection has shaped the repeated evolution of both trait loss and enhancement across independent cavefish lineages. We show that selection on standing genetic variation and de novo mutations both contribute substantially to repeated adaptation. Our findings provide empirical support for the hypothesis that genes with larger mutational targets are more likely to be the substrate of repeated evolution and indicate that features of the cave environment may impact the rate at which mutations occur.
Mid-infrared analogue polaritonic reversed Cherenkov radiation in natural anisotropic crystals
Authors: Guo Xiangdong , Wu Chenchen , Zhang Shu , Hu Debo , Zhang Shunping , Jiang Qiao , Dai Xiaokang , Duan Yu , Yang Xiaoxia , Sun Zhipei , Zhang Shuang , Xu Hongxing , Dai Qing
Published: May 2023

Cherenkov radiation (CR) excited by fast charges can serve as on-chip light sources with a nanoscale footprint and broad frequency range. The reversed CR, which usually occurs in media with the negative refractive index or negative group-velocity dispersion, is highly desired because it can effectively separate the radiated light from fast charges thanks to the obtuse radiation angle. However, reversed CR at the mid-infrared remains challenging due to the significant loss of conventional artificial structures. Here we observe mid-infrared analogue polaritonic reversed CR in a natural van der Waals (vdW) material (i.e., α-MoO3), whose hyperbolic phonon polaritons exhibit negative group velocity. Further, the real-space image results of analogue polaritonic reversed CR indicate that the radiation distributions and angles are closely related to the in-plane isofrequency contours of α-MoO3, which can be further tuned in the heterostructures based on α-MoO3. This work demonstrates that natural vdW heterostructures can be used as a promising platform of reversed CR to design on-chip mid-infrared nano-light sources.
Bacterial capsular polysaccharides with antibiofilm activity share common biophysical and electrokinetic properties
Authors: Bernal-Bayard Joaquín , Thiebaud Jérôme , Brossaud Marina , Beaussart Audrey , Caillet Céline , Waldvogel Yves , Travier Laetitia , Létoffé Sylvie , Fontaine Thierry , Rokbi Bachra , Talaga Philippe , Beloin Christophe , Mistretta Noëlle , Duval Jérôme F. L. , Ghigo Jean-Marc
Published: May 2023

Bacterial biofilms are surface-attached communities that are difficult to eradicate due to a high tolerance to antimicrobial agents. The use of non-biocidal surface-active compounds to prevent the initial adhesion and aggregation of bacterial pathogens is a promising alternative to antibiotic treatments and several antibiofilm compounds have been identified, including some capsular polysaccharides released by various bacteria. However, the lack of chemical and mechanistic understanding of the activity of these polymers limits their use to control biofilm formation. Here, we screen a collection of 31 purified capsular polysaccharides and first identify seven new compounds with non-biocidal activity against Escherichia coli and/or Staphylococcus aureus biofilms. We measure and theoretically interpret the electrophoretic mobility of a subset of 21 capsular polysaccharides under applied electric field conditions, and we show that active and inactive polysaccharide polymers display distinct electrokinetic properties and that all active macromolecules share high intrinsic viscosity features. Despite the lack of specific molecular motif associated with antibiofilm properties, the use of criteria including high density of electrostatic charges and permeability to fluid flow enables us to identify two additional capsular polysaccharides with broad-spectrum antibiofilm activity. Our study therefore provides insights into key biophysical properties discriminating active from inactive polysaccharides. The characterization of a distinct electrokinetic signature associated with antibiofilm activity opens new perspectives to identify or engineer non-biocidal surface-active macromolecules to control biofilm formation in medical and industrial settings.
Parabolic avalanche scaling in the synchronization of cortical cell assemblies
Authors: Capek Elliott , Ribeiro Tiago L. , Kells Patrick , Srinivasan Keshav , Miller Stephanie R. , Geist Elias , Victor Mitchell , Vakili Ali , Pajevic Sinisa , Chialvo Dante R. , Plenz Dietmar
Published: May 2023

Neurons in the cerebral cortex fire coincident action potentials during ongoing activity and in response to sensory inputs. These synchronized cell assemblies are fundamental to cortex function, yet basic dynamical aspects of their size and duration are largely unknown. Using 2-photon imaging of neurons in the superficial cortex of awake mice, we show that synchronized cell assemblies organize as scale-invariant avalanches that quadratically grow with duration. The quadratic avalanche scaling was only found for correlated neurons, required temporal coarse-graining to compensate for spatial subsampling of the imaged cortex, and suggested cortical dynamics to be critical as demonstrated in simulations of balanced E/I-networks. The corresponding time course of an inverted parabola with exponent of χ = 2 described cortical avalanches of coincident firing for up to 5 s duration over an area of 1 mm2. These parabolic avalanches maximized temporal complexity in the ongoing activity of prefrontal and somatosensory cortex and in visual responses of primary visual cortex. Our results identify a scale-invariant temporal order in the synchronization of highly diverse cortical cell assemblies in the form of parabolic avalanches.
Multidimensional cerebellar computations for flexible kinematic control of movements
Authors: Markanday Akshay , Hong Sungho , Inoue Junya , De Schutter Erik , Thier Peter
Published: May 2023

Both the environment and our body keep changing dynamically. Hence, ensuring movement precision requires adaptation to multiple demands occurring simultaneously. Here we show that the cerebellum performs the necessary multi-dimensional computations for the flexible control of different movement parameters depending on the prevailing context. This conclusion is based on the identification of a manifold-like activity in both mossy fibers (MFs, network input) and Purkinje cells (PCs, output), recorded from monkeys performing a saccade task. Unlike MFs, the PC manifolds developed selective representations of individual movement parameters. Error feedback-driven climbing fiber input modulated the PC manifolds to predict specific, error type-dependent changes in subsequent actions. Furthermore, a feed-forward network model that simulated MF-to-PC transformations revealed that amplification and restructuring of the lesser variability in the MF activity is a pivotal circuit mechanism. Therefore, the flexible control of movements by the cerebellum crucially depends on its capacity for multi-dimensional computations.
Unveiling an indole alkaloid diketopiperazine biosynthetic pathway that features a unique stereoisomerase and multifunctional methyltransferase
Authors: Deletti Garrett , Green Sajan D. , Weber Caleb , Patterson Kristen N. , Joshi Swapnil S. , Khopade Tushar M. , Coban Mathew , Veek-Wilson James , Caulfield Thomas R. , Viswanathan Rajesh , Lane Amy L.
Published: May 2023

The 2,5-diketopiperazines are a prominent class of bioactive molecules. The nocardioazines are actinomycete natural products that feature a pyrroloindoline diketopiperazine scaffold composed of two D-tryptophan residues functionalized by N- and C-methylation, prenylation, and diannulation. Here we identify and characterize the nocardioazine B biosynthetic pathway from marine Nocardiopsis sp. CMB-M0232 by using heterologous biotransformations, in vitro biochemical assays, and macromolecular modeling. Assembly of the cyclo-L-Trp-L-Trp diketopiperazine precursor is catalyzed by a cyclodipeptide synthase. A separate genomic locus encodes tailoring of this precursor and includes an aspartate/glutamate racemase homolog as an unusual D/L isomerase acting upon diketopiperazine substrates, a phytoene synthase-like prenyltransferase as the catalyst of indole alkaloid diketopiperazine prenylation, and a rare dual function methyltransferase as the catalyst of both N- and C-methylation as the final steps of nocardioazine B biosynthesis. The biosynthetic paradigms revealed herein showcase Nature’s molecular ingenuity and lay the foundation for diketopiperazine diversification via biocatalytic approaches.
Rhodium nanoparticles supported on silanol-rich zeolites beyond the homogeneous Wilkinson’s catalyst for hydroformylation of olefins
Authors: Liu Yifeng , Liu Zhiqiang , Hui Yu , Wang Liang , Zhang Jian , Yi Xianfeng , Chen Wei , Wang Chengtao , Wang Hai , Qin Yucai , Song Lijuan , Zheng Anmin , Xiao Feng-Shou
Published: May 2023

Hydroformylation is one of the largest industrially homogeneous processes that strongly relies on catalysts with phosphine ligands such as the Wilkinson’s catalyst (triphenylphosphine coordinated Rh). Heterogeneous catalysts for olefin hydroformylation are highly desired but suffer from poor activity compared with homogeneous catalysts. Herein, we demonstrate that rhodium nanoparticles supported on siliceous MFI zeolite with abundant silanol nests are very active for hydroformylation, giving a turnover frequency as high as ~50,000 h−1 that even outperforms the classical Wilkinson’s catalyst. Mechanism study reveals that the siliceous zeolite with silanol nests could efficiently enrich olefin molecules to adjacent rhodium nanoparticles, enhancing the hydroformylation reaction.