bluuebunny/crossref_metadata_2025 huggingface dataset:
Bidimensional self-esteem and sexual functioning among young adults: A systematic review
Authors: Kong Li Voon , Ting Rachel Sing Kiat , Chung Ker Rou , Hidayat Wajihah , Ooi Wee Liam , Goh Pei Hwa
Published: May 2023

Sexual difficulties marked by poor sexual functioning is often reported by young adults, where young adulthood is an important period for the formation of intimacy in relationships. There has been increasing research showing the relationship between global self-esteem and sexual functioning, but this association is seldom examined through the bidimensional framework of self-esteem that includes domains of self-liking and self-competence. Thus, the purpose of this systematic review was to examine the empirical evidence on self-esteem domains and sexual functioning among young adults. Six databases (PsycINFO, Ovid MEDLINE, Scopus, PubMed, Web of Science, and CINAHL Plus) were searched for peer-reviewed journal articles published from inception to June 2022. Articles were included in this review if they measured at least one domain of self-esteem, one domain of sexual functioning, reported the association between self-esteem and sexual functioning, and involved young adults from 18–30 years old. Of the 6020 records retrieved, 17 articles were included in this review. Data were extracted and synthesised, and a quality assessment tool for observational cohort and cross-sectional studies was used to appraise the quality of articles ranging from poor to good. Most studies found positive associations between self-esteem elements and sexual functioning, particularly for global self-esteem and sexual self-esteem. However, these findings cannot be generalised due to the heterogeneity in measures of self-esteem constructs. This review reveals a gap in the literature as self-liking and self-competence have not been studied together in relation to sexual functioning, where most studies have focused on sexual satisfaction.
Coexpression of natural killer cell antigens by T-cell large granular lymphocytes in hydroa vacciniforme lymphoproliferative disorder and the involvement of Vδ1 + epithelial-type γδT cells
Authors: Hirai Yoji , Iwatsuki Keiji , Takahashi Takahide , Miyake Tomoko , Nakagawa Yuki , Tanimoto Shogo , Kawakami Yoshio , Morizane Shin
Published: May 2023

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) is a cutaneous variant of chronic active Epstein–Barr virus disease. We examined the coexpression of T- and natural killer (NK)-cell antigens in five patients with classic HV (cHV) and five with systemic HV (sHV). T-cell receptor (TCR) repertoire analysis was performed with high‑throughput sequencing. All five cHV patients had increased γδT cells (> 5%), whereas five sHV patients showed γδT- and αβT-cell dominance in two patients each, and a mixture of abnormal γδT and αβT cells in one. Circulating CD3 + T cells expressed CD16/CD56 at 7.8–42.3% and 1.1–9.7% in sHV and cHV, respectively. The percentage of CD16/CD56 + T cells was higher in the large granular lymphocyte or atypical T-cell fractions in sHV, but no TCR Vα24 invariant chain characteristic of NKT cells was detected. Considerable numbers of CD3 + cells expressing CD56 were observed in sHV skin infiltrates. Of the circulating γδT cells tested, TCR Vδ1 + cells characteristic of the epithelial type of γδT cells were dominant in two sHV cases. Thus, atypical αβT and γδT cells in HV-LPD can express NK-cell antigens, such as CD16 and CD56, and Vδ1 + epithelial-type γδT cells are a major cell type in some HV-LPD cases.
Immunotherapy for metastatic melanoma—from little benefit to first-line treatment
Authors: Mutz-Rabl Christiane G. , Koelblinger Peter , Koch Lukas
Published: May 2023

At the turn of the past century, unresectable metastatic melanoma was primarily treated with different chemotherapeutic agents, such as dacarbazine, with only poor efficacy. Immunotherapeutic agents, such as interleukin‑2 or adjuvant interferon alpha, were used with modest results but frequent side effects. In the last 10 years, modern immunotherapy using checkpoint inhibition has dramatically changed the treatment landscape of metastatic melanoma and is now considered the first-line treatment for stage IV melanoma. Consequently, median overall survival has increased from 9.1 months with dacarbazine to up to 72.1 months using the current gold standard ipilimumab + nivolumab first-line. In 2023, in Europe, the anti-PD1 antibodies nivolumab and pembrolizumab are licensed in the adjuvant and metastatic setting and the combination therapies ipilimumab + nivolumab and relatlimab + nivolumab are approved in the metastatic setting. Nevertheless, despite tremendous progress in the last two decades, at least 50% of our patients with stage IV melanoma still die. Currently, research focuses on combining checkpoint inhibition with other drugs such as cancer vaccines, BRAF/MEK inhibition, other tyrosine kinase inhibitors or histone deacetylase inhibitors.
Clinical features and prognosis of double primary malignant neoplasms in patients with non-hodgkin lymphoma
Authors: Zhan Zhumei , Guo Wei , Li Jia , Wan Xin , Guo Jing , Bai Ou
Published: May 2023

To investigate the clinical features, survival, and prognostic factors of patients with double primary malignant neoplasms (DPMNs) comprising non-Hodgkin lymphoma (NHL) and malignant solid tumors. Of the 2352 patients diagnosed with NHL, 105 (4.46%) patients were diagnosed with DPMNs, 42 (40.0%) had NHL first (the NHL-first group) and 63 (60.0%) had solid tumor first (the ST-first group). Females were more frequent in the ST-first group, and the interval time between the two tumors was longer. More NHLs in early stages and originating from extranodal sites were observed in the NHL-first group. Male, age ≥ 55 years at diagnosis of the first tumor, interval time <60 months, NHL diagnosed first, NHL arising from an extranodal site, DPMNs without breast cancer, and no surgery for the first primary tumor were associated with poorer overall survival (OS). Interval time <60 months and NHL diagnosed first were independent risk factors that affected the prognosis of patients with DPMNs. Therefore, careful monitoring and follow-up are especially important for these patients. 50.5% (53/105) of patients with DPMNs did not receive chemotherapy or radiotherapy prior to the diagnosis of the second tumor. We further compared the baseline characteristics of diffuse large B-cell lymphoma(DLBCL) patients with and without solid tumors, the former had a higher proportion of extranodal DLBCL, suggesting that extranodal DLBCL is more likely to develop solid tumors than nodal DLBCL.
Neurobehavioral, biochemical and histological assessment of the effects of resveratrol on cuprizone-induced demyelination in mice: role of autophagy modulation
Authors: Samy Doaa M. , Zaki Eiman I. , Hassaan Passainte S. , Abdelmonsif Doaa A. , Mohamed Dalia Y. , Saleh Samar R.
Published: May 2023

Resveratrol is known to exhibit neuroprotective effects in many neurological disorders via autophagy modulation. However, controversial results have been reported about the therapeutic potential of resveratrol and the implication of autophagy in demyelinating diseases. This study aimed to evaluate the autophagic changes in cuprizone-intoxicated C57Bl/6 mice and explore the effect of autophagy activation by resveratrol on the demyelination and remyelination processes. Mice were fed with chow containing 0.2% cuprizone for 5 weeks, followed by a cuprizone-free diet for 2 weeks. Resveratrol (250 mg/kg/day) and/or chloroquine (an autophagy inhibitor; 10 mg/kg/day) were given for 5 weeks starting from the third week. At the end of the experiment, animals were tested on rotarod and then sacrificed for biochemical assessment, luxol fast blue (LFB) staining, and transmission electron microscopy (TEM) imaging of the corpus callosum. We observed that cuprizone-induced demyelination was associated with impaired degradation of autophagic cargo, induction of apoptosis, and manifest neurobehavioral disturbances. Oral treatment with resveratrol promoted motor coordination and improved remyelination with regular compacted myelin in most axons without a significant impact on myelin basic protein (MBP) mRNA expression. These effects are mediated, at least in part, via activating autophagic pathways that may involve SIRT1/FoxO1 activation. This study verified that resveratrol dampens cuprizone-induced demyelination, and partially enhances myelin repair through modulation of the autophagic flux, since interruption of the autophagic machinery by chloroquine reversed the therapeutic potential of resveratrol.
Evaluating Principals’ Satisfaction with Selection Processes in Second Chance Schools: A Multicriteria Approach
Authors: Zervoudakis Konstantinos , Mastrothanasis Konstantinos , Tsafarakis Stelios , Krassadaki Evangelia , Kyriakidis Anastasios
Published: May 2023

Research indicates that the importance the social validity of an appropriate principal-selection method may have, as well as the importance of the parameters that affect it, is directly related to the acceptance or reaction of the candidates to it and their job satisfaction. The aim of this quantitative research is to examine and present the candidate satisfaction in the selection of principals / assistant-principals of the Second Chance Schools in a major European country. The survey involved 184 candidates (77.97% of the total population) who responded to a valid and reliable evaluation scale of the qualitative characteristics of the selection procedures. The MUSA (multicriteria satisfaction analysis) method was used for analyzing the satisfaction of candidates with respect to satisfaction criteria, associated with four dimensions. The results indicate that candidates are overall satisfied, although only a small portion of their expectations is fulfilled. Moreover, it was found that interpersonal relationships and communication play a crucial role in the recruitment and selection process. Finally, ways of satisfaction improvement are provided, according to each factor.
Liars and Trolls and Bots Online: The Problem of Fake Persons
Authors: Harris Keith Raymond
Published: May 2023

This paper describes the ways in which trolls and bots impede the acquisition of knowledge online. I distinguish between three ways in which trolls and bots can impede knowledge acquisition, namely, by deceiving, by encouraging misplaced skepticism, and by interfering with the acquisition of warrant concerning persons and content encountered online. I argue that these threats are difficult to resist simultaneously. I argue, further, that the threat that trolls and bots pose to knowledge acquisition goes beyond the mere threat of online misinformation, or the more familiar threat posed by liars offline. Trolls and bots are, in effect, fake persons. Consequently, trolls and bots can systemically interfere with knowledge acquisition by manipulating the signals whereby individuals acquire knowledge from one another online. I conclude with a brief discussion of some possible remedies for the problem of fake persons.
Towards computational awareness in autonomous robots: an empirical study of computational kernels
Authors: Sifat Ashrarul H. , Bharmal Burhanuddin , Zeng Haibo , Huang Jia-Bin , Jung Changhee , Williams Ryan K.
Published: May 2023

The potential impact of autonomous robots on everyday life is evident in emerging applications such as precision agriculture, search and rescue, and infrastructure inspection. However, such applications necessitate operation in unknown and unstructured environments with a broad and sophisticated set of objectives, all under strict computation and power limitations. We therefore argue that the computational kernels enabling robotic autonomy must be scheduled and optimized to guarantee timely and correct behavior, while allowing for reconfiguration of scheduling parameters at runtime. In this paper, we consider a necessary first step towards this goal of computational awareness in autonomous robots: an empirical study of a base set of computational kernels from the resource management perspective. Specifically, we conduct a data-driven study of the timing, power, and memory performance of kernels for localization and mapping, path planning, task allocation, depth estimation, and optical flow, across three embedded computing platforms. We profile and analyze these kernels to provide insight into scheduling and dynamic resource management for computation-aware autonomous robots. Notably, our results show that there is a correlation of kernel performance with a robot’s operational environment, justifying the notion of computation-aware robots and why our work is a crucial step towards this goal.
Investigation of Microstructure and Mechanical Properties of AlSi7Mg0.3Cu0.5 Alloy with Addition of Zr, Ti and Sr
Authors: Bolibruchová Dana , Matejka Marek , Brůna Marek , Kuriš Michal , Michalcová Alena
Published: May 2023

The main objective of this paper is to investigate the effect of Zr and its synergistic effect together with the addition of an inoculant (Ti) and a modifier (Sr) in terms of structural analysis and mechanical characteristics of AlSi7Mg0.3Cu0.5 alloy. In accordance with the objectives of the paper, in the experimental part, eight material variants were cast by the investment casting method. The presence of Zr in the experimental alloys was manifested by the crystallization of phases with different chemical compositions mainly (AlSi)3(TiZr) and (AlSi)2(TiZr). The graded addition of Ti in the alloys resulted in a higher number of nucleation grains of Zr-rich phases, and alloys with a combination of Zr and Sr were characterized by the formation of (AlSi)2(TiZr) phases. Various types of precipitates based on Zr (Al3(ZrTi)) and Cu (Al2Cu) were observed in the substructure of the alloys. The addition of Zr and its synergistic effect with Ti and Sr led to an increase in the conventional yield strength, hardness and partly tensile strength with reduced elongation of the experimental alloys.
A national survey of antimicrobial stewardship content in Canadian entry-to-practice pharmacy programs
Authors: Sauve Jenna M. , Dresser Linda D. , Rocchi Marie A. , So Miranda
Published: May 2023

Objective:

To describe the current landscape of antimicrobial stewardship (AMS) instruction in Canadian entry-to-practice pharmacy programs and the perceived barriers and facilitators to optimizing teaching and learning.

Design:

Electronic survey.

Participants:

Faculty representatives from the 10 Canadian entry-to-practice pharmacy programs, including content experts and faculty leadership.

Methods:

A review of international literature pertaining to AMS in pharmacy curricula informed a 24-item survey, which was open for completion from March to May of 2021. Curriculum content questions were developed using AMS topics recommended by pharmacy educators in the United States, and professional roles described by the Association of Faculties of Pharmacy of Canada.

Results:

All 10 Canadian faculties returned a completed survey. All programs reported teaching AMS principles in their core curricula. Content coverage varied, with programs teaching, on average, 68% of the recommended AMS topics from the United States. Potential gaps were identified within the professional roles of “communicator” and “collaborator.” Didactic methods of content delivery and student assessment, such as lectures and multiple-choice questions, were most frequently used. Three programs offered additional AMS content in their elective curricula. Experiential rotations in AMS were commonly offered, though teaching AMS in formalized interprofessional settings was rare. Curricular time constraints were identified by all programs as a barrier to enhancing AMS instruction. A course to teach AMS, a curriculum framework, and prioritization by the faculty’s curriculum committee were perceived as facilitators.

Conclusions:

Our findings highlight potential gaps and areas of opportunity within Canadian pharmacy AMS instruction.
Ability of presepsin concentrations to predict mortality in adult patients with sepsis
Authors: Aliu-Bejta Ajete , Kurshumliu Mentor , Namani Sadie , Dreshaj Shemsedin , Baršić Bruno
Published: May 2023

Background:

Early diagnosis of sepsis is essential for a favorable disease outcome. The aim of this study was to evaluate the association of initial and subsequent presepsin concentrations with sepsis outcomes.

Methods:

One hundred sepsis patients were enrolled in the study from two different university centers. Four times during study, concentrations of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) were measured, and Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) score were calculated. Patients were grouped into survivors and nonsurvivors. A sandwich ELISA kit was used to measure presepsin concentrations. To test the changes in biomarkers concentrations and SOFA score and APACHE II score during the disease course and to estimate the differences between outcome groups, generalized linear mixed effects model was used. Receiver operating characteristic curve analysis was performed to determine the prognostic value of presepsin concentrations.

Results:

Initial values of presepsin, SOFA score, and APACHE II score were significantly higher in nonsurvivors compared to survivors. Concentrations of PCT and CRP did not differ significantly between outcome groups. ROC curve analyses show a greater predictive ability of initial presepsin concentrations for predicting mortality compared to subsequent measurements of presepsin concentrations.

Conclusions:

Presepsin has a good ability to predict mortality. Initial presepsin concentrations better reflects poor disease outcome compared to presepsin concentrations 24 and 72 hours after admission.
Age Inequalities in Political Representation: A Review Article
Authors: Stockemer Daniel , Sundström Aksel
Published: May 2023

People in political decision-making across the globe tend to be much older than the average voter. As such, parliaments and cabinets are unrepresentative of the larger population. This has consequences: it risks favouring policies geared towards the interests of older cohorts, it might alienate youth from voting and could push parties to appeal (even more) to older voters. In this review, we synthesize the growing literature on youth representation. We do so by: (1) delineating the group of young politicians, (2) discussing why youth ought to be present in politics, (3) empirically depicting the state of youth representation, and (4) illustrating the factors that help or harm youth to enter politics. This synthesis shows the degree to which young people are absent from decision-making bodies across the national, subnational and supra-national levels and attempts to make sense of the reasons why there is such a dearth of youth as candidates and representatives. We conclude by discussing gaps in research and suggesting several avenues for future work.
Transient deformation of a viscoelastic capsule in a cross-slot microchannel: effects of inertia and membrane viscosity
Authors: Lu R.X. , Guo Z.Y. , Yu P. , Sui Y.
Published: May 2023

With an immersed-boundary lattice-Boltzmann method, we consider the transit of a three-dimensional initially spherical capsule with a viscoelastic membrane through a cross-slot microchannel. The capsule is released with a small initial off-centre distance in the feeding channel, to mimic experiments where capsules or cells are not perfectly aligned with the centreline. Our main objective is to establish the phase diagram of the capsule's deformation modes as a function of the flow inertia and capsule membrane viscosity. We mainly find three deformation modes in the channel cross-slot. For a capsule with low membrane viscosity, a quasi-steady mode occurs at low Reynolds numbers (

$Re$

), in which the capsule can reach and maintain a steady ellipsoidal shape near the stagnation point, for a considerable time period. With

$Re$

increasing to 20, an overshoot–retract mode is observed. The capsule deformation oscillates on an inertial–elastic time scale, suggesting that the dynamics is mainly driven by the balance of the inertial and membrane elastic forces. The membrane viscosity slows down the capsule deformation and suppresses the overshoot–retract mode. A capsule with high membrane viscosity undergoes a continuous-elongation mode, in which its deformation keeps increasing during most of its journey in the channel cross-slot. We summarise the results in phase diagrams, and propose a scaling model which can predict the deformation modes of a viscoelastic capsule in the inertial flow regime. We also discuss implications of the present findings for practical experiments for mechanical characterisation of capsules or cells.
A learning perspective on the emergence of abstractions: the curious case of phone(me)s
Authors: Milin Petar , Tucker Benjamin V. , Divjak Dagmar
Published: May 2023

In this study, we propose an operationalization of the concept ofemergencewhich plays a crucial role in usage-based theories of language. The abstractions linguists operate with are assumed to emerge through a process of generalization over the data language users are exposed to. Here, we use two types of computational learning algorithms that differ in how they formalize and execute generalization and, consequently, abstraction, to probe whether a type of language knowledge that resembles linguistic abstractions could emerge from exposure to raw data only. More specifically, we investigated whether a phone, undisputedly the simplest of all linguistic abstractions, could emerge from exposure to speech sounds using two computational learning processes: memory-based learning and error-correction learning (ECL). Both models were presented with a significant amount of pre-processed speech produced by one speaker. We assessed (1) the consistency or stability of what these simple models learn and (2) their ability to approximate abstract categories. Both types of models fare differently regarding these tests. We show that only ECL models can learn abstractions and that at least part of the phone inventory and its grouping into traditional types can be reliably identified from the input.
Public Disclosure and Consumer Financial Protection
Authors: Dou Yiwei , Roh Yongoh
Published: May 2023

The U.S. Consumer Financial Protection Bureau has released a database of consumer complaints about banks’ financial products to the public since 2013. We find a greater reduction in mortgage applications to banks that receive more mortgage complaints in local markets after the disclosures. The effect is stronger in areas with more sophisticated consumers and higher credit competition, and for banks receiving more severe complaints. The number of monthly mortgage complaints per bank exhibits faster mean reversion after the publication of the database. These findings suggest that the public disclosure of mortgage complaints enhances product market discipline and consumer financial protection.
From British Menageries and Hippodromes to the Olympic Circus in the Grand Duchy of Posen: The Origins of the Use of Ostriches in European Sport and Entertainment
Authors: Rozmiarek Mateusz , Włodarczyk Arkadiusz
Published: May 2023

Throughout history, animals have been involved in human life in various ways. People have attributed a special role to birds of prey or exotic birds, including ostriches, whose involvement in entertainment and sports began in the first half of the nineteenth century. This article discusses the origins, development and reception of the ostrich entertainment industry in two areas of nineteenth-century Europe that had significantly different social, political and economic circumstances: the United Kingdom of Great Britain and Ireland (as it was then known) and partitioned Poland (the example of the Grand Duchy of Posen). The first uses of ostriches for entertainment purposes in Europe consisted of bird exhibitions in travelling menageries, hippodromes and in circus shows. Among the pioneers of this kind of entertainment in the British Isles was William Batty, and in the culturally excluded territories of partitioned Poland it was Ernst Renz, whose Olympic circus, thanks to its diverse programme of shows and performances, provided important entertainment and educational opportunities for Poles under occupation.
The Limits of Antiatheist Prejudice
Authors: Rabinovitch Aleksandra , Cantarero Katarzyna , Szocik Konrad
Published: May 2023

Abstract: People tend to perceive atheists as being immoral. We tested whether this perception also applies to moral transgressions against animals. Study 1 ( N = 288) and Study 2 ( N = 306, pre-registered) utilized a conjunction fallacy paradigm to show that people attributed harming animals most frequently to criminals, then to God-believers, and least often to nonbelievers. Study 3 ( N = 248, pre-registered) used a job-choice paradigm and found that people choose a God-believer over an atheist for a job involving animal harm because the God-believer was supposed to hold a more hierarchical view of the relationship between humans and animals than the atheist. Consequently, we discuss the limits of antiatheist prejudice in the domain of human–animal interactions.
Mesospheric and Upper Stratospheric Temperatures From OMPS‐LP
Authors: Chen Zhong , Schwartz Michael J. , Bhartia Pawan K. , Schoeberl Mark , Kramarova Natalya , Jaross Glen , DeLand Matthew
Published: May 2023

We report the development of a temperature profile data set from the Ozone Mapping and Profiler Suite Limb Profiler (OMPS‐LP) instrument on the Suomi NPP satellite. The data set covers a roughly 10 year period from 2012 to 2022, and temperatures are provided in the altitude range between 35 and 70 km. The algorithm uses daytime Rayleigh scattered radiation near 350 nm to estimate atmospheric density profiles, which are vertically integrated using the hydrostatic equation to estimate atmospheric pressure. Temperature profiles are then derived using the ideal gas law. Spectral structures in the OMPS‐LP radiances are a source of systematic errors that limit the absolute accuracy to ±2 K. However, since the systematic errors do not change significantly over time, the relative accuracy is better than ±1 K. Our temperature data set has been designed to supplement global temperature maps produced by assimilation of data from traditional meteorological sensors, including GNSS radio occultation sensors, that provide high quality atmospheric temperature profiles up to 40–55 km. We show comparisons to other co‐located temperature datasets to validate our product.
Time‐Variability of Flow Recession Dynamics: Application of Machine Learning and Learning From the Machine
Authors: Kim Minseok , Bauser Hannes H. , Beven Keith , Troch Peter A.
Published: May 2023

Flow recession analysis, relating discharge Q and its time rate of change −dQ/dt, has been widely used to understand catchment scale flow dynamics. However, data points in the recession plot, the plot of −dQ/dt versus Q, typically form a wide point cloud due to noise and hysteresis in the storage‐discharge relationship, and it is still unclear what information we can extract from the plot and how to understand the information. There seem to be two contrasting approaches to interpret the plot. One emphasizes the importance of the ensemble characteristics of many recessions (i.e., the lower envelope or a measure of central tendency), and the other highlights the importance of the event scale analysis and questions the meaning of the ensemble characteristics. We examine if those approaches can be reconciled. We utilize a machine learning tool to capture the point cloud using the past trajectory of daily discharge. Our model results for a catchment show that most of the data points can be captured using 5 days of past discharge. We show that we can learn the catchment scale flow recession dynamics from what the machine learned. We analyze patterns learned by the machine and explain and hypothesize why the machine learned those characteristics. The hysteresis in the plot mainly occurs during the early time dynamics, and the flow recession dynamics eventually converge to an attractor in the plot, which represents the master recession curve. We also illustrate that a hysteretic storage‐discharge relationship can be estimated based on the attractor.
The Severity of the 2014–2015 Snow Drought in the Oregon Cascades in a Multicentury Context
Authors: Dye Laura A. , Coulthard Bethany L. , Hatchett Benjamin J. , Homfeld Inga K. , Salazar Taylor N. , Littell Jeremy S. , Anchukaitis Kevin J.
Published: May 2023

The western United States (US) is a hotspot for snow drought. The Oregon Cascade Range is highly sensitive to warming and as a result has experienced the largest mountain snowpack losses in the western US since the mid‐20th century, including a record‐breaking snow drought in 2014–2015 that culminated in a state of emergency. While Oregon Cascade snowpacks serve as the state's primary water supply, short instrumental records limit water managers' ability to fully constrain long‐term natural snowpack variability prior to the influence of ongoing and projected anthropogenic climate change. Here, we use annually‐resolved tree‐ring records to develop the first multi‐century reconstruction of Oregon Cascade April 1st Snow Water Equivalent (SWE). The model explains 58% of observed snowpack variability and extends back to 1688 AD, nearly quintupling the length of the existing snowpack record. Our reconstruction suggests that only one other multiyear event in the last three centuries was as severe as the 2014–2015 snow drought. The 2015 event alone was more severe than nearly any other year in over three centuries. Extreme low‐to‐high snowpack “whiplash” transitions are a consistent feature throughout the reconstructed record. Multi‐decadal intervals of persistent below‐the‐mean peak SWE are prominent features of pre‐instrumental snowpack variability, but are generally absent from the instrumental period and likely not fully accounted for in modern water management. In the face of projected snow drought intensification and warming, our findings motivate adaptive management strategies that address declining snowpack and increasingly variable precipitation regimes.
Using Cave Formations to Investigate Ancient Wildfires
Authors: Campbell Micheline , McDonough Liza , Treble Pauline , Baker Andy
Published: May 2023

From sediment cores to speleothems, environmental archives are helping us to understand the history of wildfires.
Stratospheric Gas‐Phase Production Alone Cannot Explain Observations of Atmospheric Perchlorate on Earth
Authors: Chan Yuk‐Chun , Jaeglé Lyatt , Campuzano‐Jost Pedro , Catling David C. , Cole‐Dai Jihong , Furdui Vasile I. , Jackson W. Andrew , Jimenez Jose L. , Kim Dongwook , Wedum Alanna E. , Alexander Becky
Published: May 2023

Perchlorate has been observed in many environments on Earth and Mars but its sources remain poorly quantified. In this study, we use a global three‐dimensional chemical transport model to simulate perchlorate's gas‐phase photochemical production, atmospheric transport, and deposition on Earth's surface. Model predictions are compared to newly compiled observations of atmospheric concentrations, deposition flux, and oxygen isotopic composition of perchlorate. We find that the modeled gas‐phase production of perchlorate is consistent with reported stratospheric observations. Nevertheless, we show that this mechanism alone cannot explain the high levels of perchlorate observed at many near‐surface sites (aerosol concentrations >0.1 ng m−3 and deposition fluxes >10 g km−2 yr−1) or the low 17O‐excess observed in perchlorate sampled from pristine environments (<+18.4‰). We discuss four hypotheses to explain the model‐observation discrepancies and recommend laboratory and field observations to address key uncertainties in atmospheric sources of perchlorate.
G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders
Authors: Wong Thian-Sze , Li Guangzhi , Li Shiliang , Gao Wei , Chen Geng , Gan Shiyi , Zhang Manzhan , Li Honglin , Wu Song , Du Yang
Published: May 2023

Neuropsychiatric disorders are multifactorial disorders with diverse aetiological factors. Identifying treatment targets is challenging because the diseases are resulting from heterogeneous biological, genetic, and environmental factors. Nevertheless, the increasing understanding of G protein-coupled receptor (GPCR) opens a new possibility in drug discovery. Harnessing our knowledge of molecular mechanisms and structural information of GPCRs will be advantageous for developing effective drugs. This review provides an overview of the role of GPCRs in various neurodegenerative and psychiatric diseases. Besides, we highlight the emerging opportunities of novel GPCR targets and address recent progress in GPCR drug development.
Optical neural network via loose neuron array and functional learning
Authors: Huo Yuchi , Bao Hujun , Peng Yifan , Gao Chen , Hua Wei , Yang Qing , Li Haifeng , Wang Rui , Yoon Sung-Eui
Published: May 2023

This research proposes a deep-learning paradigm, termed functional learning (FL), to physically train a loose neuron array, a group of non-handcrafted, non-differentiable, and loosely connected physical neurons whose connections and gradients are beyond explicit expression. The paradigm targets training non-differentiable hardware, and therefore solves many interdisciplinary challenges at once: the precise modeling and control of high-dimensional systems, the on-site calibration of multimodal hardware imperfectness, and the end-to-end training of non-differentiable and modeless physical neurons through implicit gradient propagation. It offers a methodology to build hardware without handcrafted design, strict fabrication, and precise assembling, thus forging paths for hardware design, chip manufacturing, physical neuron training, and system control. In addition, the functional learning paradigm is numerically and physically verified with an original light field neural network (LFNN). It realizes a programmable incoherent optical neural network, a well-known challenge that delivers light-speed, high-bandwidth, and power-efficient neural network inference via processing parallel visible light signals in the free space. As a promising supplement to existing power- and bandwidth-constrained digital neural networks, light field neural network has various potential applications: brain-inspired optical computation, high-bandwidth power-efficient neural network inference, and light-speed programmable lens/displays/detectors that operate in visible light.
Non-Hertz-Millis scaling of the antiferromagnetic quantum critical metal via scalable Hybrid Monte Carlo
Authors: Lunts Peter , Albergo Michael S. , Lindsey Michael
Published: May 2023

A key component of the phase diagram of many iron-based superconductors and electron-doped cuprates is believed to be a quantum critical point (QCP), delineating the onset of antiferromagnetic spin-density wave order in a quasi-two-dimensional metal. The universality class of this QCP is believed to play a fundamental role in the description of the proximate non-Fermi liquid behavior and superconducting phase. A minimal model for this transition is the O(3) spin-fermion model. Despite many efforts, a definitive characterization of its universal properties is still lacking. Here, we numerically study the O(3) spin-fermion model and extract the scaling exponents and functional form of the static and zero-momentum dynamical spin susceptibility. We do this using a Hybrid Monte Carlo (HMC) algorithm with a novel auto-tuning procedure, which allows us to study unprecedentedly large systems of 80 × 80 sites. We find a strong violation of the Hertz-Millis form, contrary to all previous numerical results. Furthermore, the form that we do observe provides good evidence that the universal scaling is actually governed by the analytically tractable fixed point discovered near perfect “hot-spot’" nesting, even for a larger nesting window. Our predictions can be directly tested with neutron scattering. Additionally, the HMC method we introduce is generic and can be used to study other fermionic models of quantum criticality, where there is a strong need to simulate large systems.
A blueprint for a synthetic genetic feedback optimizer
Authors: Gyorgy Andras , Menezes Amor , Arcak Murat
Published: May 2023

Biomolecular control enables leveraging cells as biomanufacturing factories. Despite recent advancements, we currently lack genetically encoded modules that can be deployed to dynamically fine-tune and optimize cellular performance. Here, we address this shortcoming by presenting the blueprint of a genetic feedback module to optimize a broadly defined performance metric by adjusting the production and decay rate of a (set of) regulator species. We demonstrate that the optimizer can be implemented by combining available synthetic biology parts and components, and that it can be readily integrated with existing pathways and genetically encoded biosensors to ensure its successful deployment in a variety of settings. We further illustrate that the optimizer successfully locates and tracks the optimum in diverse contexts when relying on mass action kinetics-based dynamics and parameter values typical in Escherichia coli.
Identification of biomarkers for glycaemic deterioration in type 2 diabetes
Authors: Slieker Roderick C. , Donnelly Louise A. , Akalestou Elina , Lopez-Noriega Livia , Melhem Rana , Güneş Ayşim , Abou Azar Frederic , Efanov Alexander , Georgiadou Eleni , Muniangi-Muhitu Hermine , Sheikh Mahsa , Giordano Giuseppe N. , Åkerlund Mikael , Ahlqvist Emma , Ali Ashfaq , Banasik Karina , Brunak Søren , Barovic Marko , Bouland Gerard A. , Burdet Frédéric , Canouil Mickaël , Dragan Iulian , Elders Petra J. M. , Fernandez Celine , Festa Andreas , Fitipaldi Hugo , Froguel Phillippe , Gudmundsdottir Valborg , Gudnason Vilmundur , Gerl Mathias J. , van der Heijden Amber A. , Jennings Lori L. , Hansen Michael K. , Kim Min , Leclerc Isabelle , Klose Christian , Kuznetsov Dmitry , Mansour Aly Dina , Mehl Florence , Marek Diana , Melander Olle , Niknejad Anne , Ottosson Filip , Pavo Imre , Duffin Kevin , Syed Samreen K. , Shaw Janice L. , Cabrera Over , Pullen Timothy J. , Simons Kai , Solimena Michele , Suvitaival Tommi , Wretlind Asger , Rossing Peter , Lyssenko Valeriya , Legido Quigley Cristina , Groop Leif , Thorens Bernard , Franks Paul W. , Lim Gareth E. , Estall Jennifer , Ibberson Mark , Beulens Joline W. J. , ’t Hart Leen M , Pearson Ewan R. , Rutter Guy A.
Published: May 2023

We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
Dispersion-engineered metasurfaces reaching broadband 90% relative diffraction efficiency
Authors: Chen Wei Ting , Park Joon-Suh , Marchioni Justin , Millay Sophia , Yousef Kerolos M. A. , Capasso Federico
Published: May 2023

Dispersion results from the variation of index of refraction as well as electric field confinement in sub-wavelength structures. It usually results in efficiency decrease in metasurface components leading to troublesome scattering into unwanted directions. In this letter, by dispersion engineering, we report a set of eight nanostructures whose dispersion properties are nearly identical to each other while being capable of providing 0 to 2π full-phase coverage. Our nanostructure set enables broadband and polarization-insensitive metasurface components reaching 90% relative diffraction efficiency (normalized to the power of transmitted light) from 450 nm to 700 nm in wavelength. Relative diffraction efficiency is important at a system level – in addition to diffraction efficiency (normalized to the power of incident light) – as it considers only the transmitted optical power that can affect the signal to noise ratio. We first illustrate our design principle by a chromatic dispersion-engineered metasurface grating, then show that other metasurface components such as chromatic metalenses can also be implemented by the same set of nanostructures with significantly improved relative diffraction efficiency.
Molecular architecture of the Gαi-bound TRPC5 ion channel
Authors: Won Jongdae , Kim Jinsung , Jeong Hyeongseop , Kim Jinhyeong , Feng Shasha , Jeong Byeongseok , Kwak Misun , Ko Juyeon , Im Wonpil , So Insuk , Lee Hyung Ho
Published: May 2023

G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Gα). However, no complete structural evidence supporting the direct interaction between Gα and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Gαi3complexes with a 4:4 stoichiometry in lipid nanodiscs. Remarkably, Gαi3binds to the ankyrin repeat edge of TRPC5 ~ 50 Å away from the cell membrane. Electrophysiological analysis shows that Gαi3increases the sensitivity of TRPC5 to phosphatidylinositol 4,5-bisphosphate (PIP2), thereby rendering TRPC5 more easily opened in the cell membrane, where the concentration of PIP2is physiologically regulated. Our results demonstrate that ion channels are one of the direct effector molecules of Gα proteins triggered by GPCR activation–providing a structural framework for unraveling the crosstalk between two major classes of transmembrane proteins: GPCRs and ion channels.
Experimental electronic structure of the electrically switchable antiferromagnet CuMnAs
Authors: Linn A. Garrison , Hao Peipei , Gordon Kyle N. , Narayan Dushyant , Berggren Bryan S. , Speiser Nathaniel , Reimers Sonka , Campion Richard P. , Novák Vít , Dhesi Sarnjeet S. , Kim Timur K. , Cacho Cephise , Šmejkal Libor , Jungwirth Tomáš , Denlinger Jonathan D. , Wadley Peter , Dessau Daniel S.
Published: May 2023

Tetragonal CuMnAs is a room temperature antiferromagnet with an electrically reorientable Néel vector and a Dirac semimetal candidate. Direct measurements of the electronic structure of single-crystalline thin films of tetragonal CuMnAs using angle-resolved photoemission spectroscopy (ARPES) are reported, including Fermi surfaces (FS) and energy-wavevector dispersions. After correcting for a chemical potential shift of ≈− 390 meV (hole doping), there is excellent agreement of FS, orbital character of bands, and Fermi velocities between the experiment and density functional theory calculations. In addition, 2×1 surface reconstructions are found in the low energy electron diffraction (LEED) and ARPES. This work underscores the need to control the chemical potential in tetragonal CuMnAs to enable the exploration and exploitation of the Dirac fermions with tunable masses, which are predicted to be above the chemical potential in the present samples.
Ligand and G-protein selectivity in the κ-opioid receptor
Authors: Han Jianming , Zhang Jingying , Nazarova Antonina L. , Bernhard Sarah M. , Krumm Brian E. , Zhao Lei , Lam Jordy Homing , Rangari Vipin A. , Majumdar Susruta , Nichols David E. , Katritch Vsevolod , Yuan Peng , Fay Jonathan F. , Che Tao
Published: May 2023

The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders1. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects2. The initiation of KOR signalling requires the Gi/o-family proteins including the conventional (Gi1, Gi2, Gi3, GoA and GoB) and nonconventional (Gz and Gg) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers—Gi1, GoA, Gz and Gg—using cryo-electron microscopy. The KOR–G-protein complexes are bound to hallucinogenic salvinorins or highly selective KOR agonists. Comparisons of these structures reveal molecular determinants critical for KOR–G-protein interactions as well as key elements governing Gi/o-family subtype selectivity and KOR ligand selectivity. Furthermore, the four G-protein subtypes display an intrinsically different binding affinity and allosteric activity on agonist binding at KOR. These results provide insights into the actions of opioids and G-protein-coupling specificity at KOR and establish a foundation to examine the therapeutic potential of pathway-selective agonists of KOR.
Glioblastoma remodelling of human neural circuits decreases survival
Authors: Krishna Saritha , Choudhury Abrar , Keough Michael B. , Seo Kyounghee , Ni Lijun , Kakaizada Sofia , Lee Anthony , Aabedi Alexander , Popova Galina , Lipkin Benjamin , Cao Caroline , Nava Gonzales Cesar , Sudharshan Rasika , Egladyous Andrew , Almeida Nyle , Zhang Yalan , Molinaro Annette M. , Venkatesh Humsa S. , Daniel Andy G. S. , Shamardani Kiarash , Hyer Jeanette , Chang Edward F. , Findlay Anne , Phillips Joanna J. , Nagarajan Srikantan , Raleigh David R. , Brang David , Monje Michelle , Hervey-Jumper Shawn L.
Published: May 2023

Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1–4 and gliomas increasing neuronal excitability2,5–8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron–glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.