bluuebunny/crossref_metadata_2025 huggingface dataset:
GANT61/BI-847325 combination: a new hope in lung cancer treatment
Authors: El-Kishky Abdel Halim M. , Moussa Nermine , Helmy Maged W. , Haroun Medhat
Published: July 2022

Despite the huge efforts employed to implement novel chemotherapeutic paradigms for lung cancer, the disease still remains a major concern worldwide. Targeting molecular pathways as Hedgehog (Hh) and Mitogen-activated protein kinase (MAPK) represent a new hope in lung cancer treatment. This work was undertaken to evaluate the antitumor effects of GANT61 (5 μM), BI-847325(30 μM), and GANT61 (5 μM)/BI-847325(30 μM) combination on A549 adenocarcinoma lung cancer cell line. The growth inhibition 50 (GI50) for both drugs was performed using MTT. The protein levels of Caspase-3, Bcl-2-associated X protein (Bax), Myeloid cell leukemia sequence 1 (MCL-1), cyclin D1, vascular endothelial growth factor (VEGF), extracellular signal-regulated kinases (ERK), p-Akt, and phosphohistone H3 (pHH3) were measured using ELISA. Glioma-associated oncogene homolog 1(Gli1) gene expression was assessed by quantitative real-time PCR. The GI50 for GANT61 and BI-8473255 were 5 µM and 30 µM, respectively. Caspase-3 and Bax protein levels were significantly elevated while MCL-1, cyclin D1, VEGF, ERK 1/2, p-Akt, and pHH3 levels were significantly reduced by both drugs and their combination relative to the control group. Gli1 gene expression was down-regulated in all groups relative to the control group. GANT61, BI-847325 and their combination inhibited proliferation and angiogenesis but activated the apoptotic pathway. Both drugs conferred a profound negative impact on the crosstalk between each of Hh and MAPK pathways and Phosphoinositide 3 -kinases (PI3K)/Akt/Mammalian target of Rapamycin (mTOR). To the best of our knowledge, the antitumor effects of BI-847325/GANT61 combination have not been tested before. Further in-vitro and in-vivo studies are warranted to support the findings.
Blocking Kripke’s Argument Against the Type-Identity Theory of Mind
Authors: Gozzano Simone
Published: July 2022

In this paper, I present a two-pronged argument devoted to defending the type-identity theory of mind against the argument presented by Kripke inNaming and Necessity. In the first part, the interpersonal case, I show that since it is not possible to establish the metaphysical conditions for phenomenal identity, it is not possible to argue that there can be physical differences between two subjects despite their phenomenal identity. In the second part, the intrapersonal case, I consider the possibility of imagining one and the same individual having the same phenomenal state while counterfactually being in very different physical states. I argue that this case should respect Kripke’s implicit theory of personal identity—but this proves to be a very difficult task to accomplish, thus preventing the argument from getting off the ground. Therefore, I maintain, that the type-identity theory is still the better option to solve the mind–body problem.
Glass-Ceramics from Trachyte Rock- Limestone or Magnesite
Authors: Abd El-Shakour Zeinab A. , Abd El Ghaffar Nahla I. , El-Bassyouni Gehan T. , Hamzawy Esmat M. A.
Published: July 2022

Inexpensive sintered glass-ceramic glaze was prepared from a mixture of Egyptian trachyte with either limestone or magnesite. A represented trachyte rock was pulverized to powder (<0.083 mm) and also both limestone and magnesite. The well mixed batches were melted near 1450 °C/3 h temperature then the glass melt was quenched in water, dried, pulverized to powder and finally shaped in moulds. The sintering process of the pre-shaped glasses, within 1000-1100 °C range, gave augite and olivine in case of trachyte-magnesite whereas wollastonite and Ca-olivine in case of trachyte-limestone. However, cristobalite was developed in both cases. The microstructures in both cases showed glassy matrix scattered with submicron and nano-size crystals either in irregular shape in case of trachyte-limestone or clear crystals in case of trachyte-magnesite. The densities of the sintered samples were in the range of 2.36 and 2.57 g/cm3 in case of the trachyte-limestone and 2.36 and 2.64 g/cm3 in case of the trachyte-magnesite. The coefficient of thermal expansion (CTE) and the hardness of the sintered glass-ceramic were in the range of 6.2-8.5 × 10−6 °C−1 and 440-563 GPa respectively. However, the CTE values decreased in case of trachyte-limestone whereas the hardness values were high in case of trachyte-magnesite. The present glass-ceramic samples had porcelain nature and could be used in cladding of wall and floor.
Evaluating molecular diagnostic techniques for seed detection of Pseudomonas savastanoi pv. phaseolicola, causal agent of halo blight disease in mungbean (Vigna radiata)
Authors: Noble Thomas J. , Williams Brett , Douglas Colin A. , Giblot-Ducray Daniele , Mundree Sagadevan , Young Anthony J.
Published: July 2022

Halo blight of mungbean (Vigna radiata var. radiata) is caused by the bacterium Pseudomonas savastanoi pv. phaseolicola. This pathogen is transmitted via infected seed, facilitating the spread of the disease into new cultivated areas. Prospective mungbean seed crops are currently subjected to visual inspection as a means of determining disease status, however, this is a poor method that relies on visible symptoms and does not account for latent infections. A range of molecular diagnostics targeting P. savastanoi pv. phaseolicola have been developed, but these have not been deployed on seeds. Quantitative PCR (qPCR) SYBR assay, hydrolysis probe, and conventional PCR, using the same primers were optimised against a plate-truthed dilution series of P. savastanoi pv. phaseolicola. The detection limit of the conventional PCR assay was approximately 9,000 CFU µl-1, while both qPCR assays could detect 9 CFU µl-1. These tests were then used to screen DNA extracted from 200 g allotments of 38 seed lots comprising six mungbean cultivars representing the primary Australian production area, and two seed lots of known infection status. Of these, the pathogen was detected in six seed lots by conventional PCR. The SYBR assay and hydrolysis probe methods detected 20 and 24 infected seed lots respectively. This shows that the hydrolysis probe method was the most effective at diagnosing the presence of P. savastanoi pv. phaseolicola in mungbean seed, providing a valuable molecular diagnostic to aid in integrated disease management and seed certification, substantially mitigating losses to halo blight disease.
A new design for market power monitoring in the electricity market. A simulation for Italy
Authors: Bigerna Simona , Bollino Carlo Andrea , D’Errico Maria Chiara , Polinori Paolo
Published: July 2022

The liberalization of electricity markets has been dominated by conditions of oligopoly and market power, as shown in numerous studies in empirical literature on the supply side. However, regulators have used statistical measurements to monitor the extent of market power, making little reference to founded theoretical approaches. This paper provides a new contribution to the literature on the electricity market by presenting a theoretical and empirical model to construct competitive equilibrium, and estimating market power on both the supply and demand side of the day-ahead electricity market. We implement an accurate measurement of the welfare loss associated with non-competitive market conditions, based on ex-ante demand and supply behavior.This model provides a useful analytical tool for regulators and policy-makers in order to implement pro-competitive regulation. We perform an empirical simulation to show the effects of non-competitive equilibria on the Italian hourly markets over the period 2013–2014. In an ideal competitive market, prices would be lower than historical prices by about 2–5% and quantities would be higher by about 0.5–1%.
Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae Findings in Children During COVID-19 Pandemic in Finland
Authors: Kuitunen Ilari
Published: July 2022

Social restrictions effectively interrupted the typical respiratory virus circulation. The aim of this report is to describe how atypical pneumonia bacteria detections have changed during the COVID-19 pandemic in Finnish children. Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae findings were gathered from the National Infectious Diseases Register from 2015 to 2021 and stratified into three age groups (0–4, 5–9, and 10–14 years). Incidences per 100,000 children were calculated and 2020 and 2021 was compared to the mean incidence of reference years (2015–2019) by incidence rate ratios. B. pertussis incidence was 32% lower in 2020 and 88% lower in 2021 compared to reference years. C. pneumoniae detections decreased rapidly in 2020 and not a single detection of C. pneumoniae was reported to the register in 2021. M. pneumoniae incidence was 72% lower in 2020 and 89% lower in 2021 than in the reference years. All these findings were seen in all age groups. As the incidences of B. pertussis, C. pneumoniae, and M. pneumoniae detections have been low throughout the pandemic, it seems that the social restrictions have been effective in preventing the spreading of these respiratory bacteria in children.
The production of actinides in neutron star mergers
Authors: Wu Meng-Ru , Banerjee Projjwal
Published: July 2022

Although the multimessenger detection of the neutron star merger event GW170817 confirmed that mergers are promising sites producing the majority of nature’s heavy elements via the rapid neutron-capture process (r-process), a number of issues related to the production of translead nuclei—the actinides—remain to be answered. In this short review paper, we summarize the general requirements for actinide production in r-process and the impact of nuclear physics inputs. We also discuss recent efforts addressing the actinide production in neutron star mergers from different perspectives, including signatures that may be probed by future kilonova and γ-ray observations, the abundance scattering in metal-poor stars, and constraints put by the presence of short-lived radioactive actinides in the Solar system.
The Cultural Value of Work
Authors: Griffith David
Published: July 2022

Traditional wage labor has experienced a significant decline in industrialized countries over the past few decades. The spread of temporary work, the proliferation of subcontracting arrangements, the use of artificial intelligence (AI), the shipment of manufacturing jobs overseas, and the employment of foreign contract workers are among the key factors driving this decline. The result is a rise of labor insecurity and fragmentation among increasingly diverse forms of flexible labor arrangements. This book examines this important transformation by considering the impact of foreign contract labor on temporary migrant workers in their places of employment and home communities. It assesses work as a source of value in capitalist, reproductive, domestic, and cultural economics, and argues for a new, work-centric field of economics. Rich in examples, it is a sophisticated anthropological appreciation of the many forms that work can take and what these forms mean for the creation of value in people's lives.
Case–case–control study of risk factors for carbapenem-resistant Enterobacterales infections among hospitalized patients
Authors: Stuever David M. , Ferketich Amy K. , Lee Jiyoung , Stevenson Kurt B. , Wittum Thomas E.
Published: July 2022

Objective:

To identify important risk factors for carbapenem-resistant Enterobacterales (CRE) infections among hospitalized patients.

Design:

We utilized a case–case–control design that compared patients with CRE infections to patients with carbapenem-susceptible Enterobacterales (CSE) infections and randomly selected controls during the period from January 2011 through December 2016.

Setting:

The study population was selected from patients at a large metropolitan tertiary-care and instructional medical center.

Patients:

Cases of CRE were defined as initial admission of adults diagnosed with a bacterial infection of an Enterobacterales species resistant clinically or through sensitivity testing to carbapenems 48 hours or more after admission. Cases of CSE were selected from the same patient population as the CRE cases within a 30-day window for admission, with diagnostic pathogens identified as susceptible to carbapenems. Controls were defined as adult patients admitted to any service within a 30-day window from a CRE case for >48 hours who did not meet either of the above case definitions during that admission.

Results:

Antibiotic exposure within 90 days prior to admission and length of hospital stay were both associated with increased odds of CRE and CSE infections compared to controls. Patients with CRE infections had >18 times greater odds of prior antibiotic exposure compared to patients with CSE infections.

Conclusions:

Antibiotic exposure and increased length of hospital stay may result in increased patient risk of developing an infection resistant to carbapenems and other β-lactams.
Human–machine collaboration using artificial intelligence to enhance the safety of donning and doffing personal protective equipment (PPE)
Authors: Segal Reny , Bradley William Pierre , Williams Daryl Lindsay , Lee Keat , Krieser Roni Benjamin , Mezzavia Paul Mario , Correa de Araujo Nunes Rommie , Ng Irene
Published: July 2022

Objectives:

To compare the accuracy of monitoring personal protective equipment (PPE) donning and doffing process between an artificial intelligent (AI) machine collaborated with remote human buddy support system and an onsite buddy, and to determine the degree of AI autonomy at the current development stage.

Design and setting:

We conducted a pilot simulation study with 30 procedural scenarios (15 donning and 15 doffing, performed by one individual) incorporating random errors in 55 steps. In total, 195 steps were assessed.

Methods:

The human–AI machine system and the onsite buddy assessed the procedures independently. The human–AI machine system performed the assessment via a tablet device, which was positioned to allow full-body visualization of the donning and doffing person.

Results:

The overall accuracy of PPE monitoring using the human–AI machine system was 100% and the overall accuracy of the onsite buddy was 99%. There was a very good agreement between the 2 methods (κ coefficient, 0.97). The current version of the AI technology was able to perform autonomously, without the remote human buddy’s rectification in 173 (89%) of 195 steps. It identified 67.3% of all the errors independently.

Conclusions:

This study provides preliminary evidence suggesting that a human–AI machine system may be able to serve as a substitute or enhancement to an onsite buddy performing the PPE monitoring task. It provides practical assistance using a combination of a computer mirror, visual prompts, and verbal commands. However, further studies are required to examine its clinical efficacy with a diverse range of individuals performing the donning and doffing procedures.
Afterword to Persianate Pasts, National Presents: Persian Literary and Cultural Production in the Twentieth Century
Authors: Gould Rebecca Ruth
Published: July 2022

What is the relevance of the Persianate as a category of analysis in a world wherein even world literature continues to be framed as the literary history of discrete nations? First coined by historian Marshall Hodgson in 1974, Persianate initially referred to cultures such as Georgian, Armenian, Chaghatay, Urdu, and Ottoman, which were heavily influenced lexically and culturally by Persian without themselves being related to Persian linguistically. Gradually, an additional meaning was grafted onto “Persianate,” which referenced cultures such as Judeo-Persian that were linguistically Persian but culturally diverse, bearing multiple alphabets, religions, and identities. These two meanings—the first grounded in cultural affinity and the second in linguistic origins—complement each other and ensure that the concept of the Persianate is reducible neither to language nor to identity.
Subharmonic eigenvalue orbits in the spectrum of pulsating Poiseuille flow
Authors: Kern J.S. , Hanifi A. , Henningson D.S.
Published: July 2022

Spectral degeneracies where eigenvalues and eigenvectors simultaneously coalesce, also known as exceptional points, are a natural consequence of the strong non-normality of the Orr–Sommerfeld operator describing the evolution of infinitesimal disturbances in parallel shear flows. While the resonances associated with these points give rise to algebraic growth, the development of non-modal stability theory exploiting specific perturbation structures with much larger potential for transient energy growth has led to waning interest in spectral degeneracies. The appearance of subharmonic eigenvalue orbits, recently discovered in the periodic spectrum of pulsating Poiseuille flow, can be traced back to the coalescence of eigenvalues at exceptional points. We present a thorough analysis of the spectral properties of the linear operator to identify exceptional points and accurately map the prevalence of subharmonic eigenvalue orbits for a large range of pulsation amplitudes and frequencies. This information is then combined with solutions of the linear initial value problem to analyse the impact of the appearance of these orbits on the temporal evolution of linear disturbances in pulsating Poiseuille flow. The periodic amplification phases are shown to be heralded by repeated non-normal growth bursts that are intensified by the formation of subharmonic orbits involving the leading eigenvalues. These bursts are associated with the change of alignment of the perturbation from the decaying towards the amplified branch of the subharmonic eigenvalue orbits in a so-called branch transition process.
The Philosophical Retreat to the Here and Now: Notes on Living in Time
Authors: Moran Richard
Published: July 2022

The ordinary human concerns with the past and the future can be seen both as forms of suffering (anxiety toward the future, regret toward the past, etc.) and as illusory because they involve the failure to appreciate the primary reality of the present. In this lecture I argue that while there are certainly ways of being occupied with past or future times that we have reason to criticize, such criticism cannot base itself on any metaphysical claim to the singular or exclusive reality of the present. The task of developing useful forms of describing and assessing the different ways we can go wrong in temporalizing our lives is hindered rather than helped by the suggestion that our concerns with the past and with the future are as such forms of attachment to the Unreal.
Twenty-year associations between disordered eating behaviors and sociodemographic features in a multiple cross-sectional sample
Authors: Santana Danilo Dias , Mitchison Deborah , Mannan Haider , Griffiths Scott , Appolinario Jose Carlos , da Veiga Gloria Valeria , Touyz Stephen , Hay Phillipa
Published: July 2022

Background

Disordered eating behaviors (DEB) impact on health and wellbeing worldwide. This study aimed to examine sociodemographic trends in the prevalence of DEB over 20 years in the Australian general population.

Methods

Data were derived from five sequential cross-sectional surveys (1998, 2008, 2009, 2016 and 2017) with population-representative samples of adults and adolescents residing in South Australia (N= 15 075). DEBs investigated were objective binge eating (OBE), strict dieting/fasting, and purging. Sociodemographic data included gender, age, educational level, work and marital status, and residence.

Results

OBE prevalence increased significantly. Strict dieting/fasting also increased from 1998 to 2008/9 but remained stable between 2008/9 and 2016/7. Purging prevalence did not change significantly over time. All survey years were associated with a significantly higher odds of OBE, and strict diet/fasting compared to 1998. Lower age, a higher Accessibility Remoteness Index of Australia (ARIA) score, higher body mass index (BMI), higher educational attainment, and not being in a married orde factorelationship were independently associated with greater adjusted odds for endorsing OBE. Younger age, female gender, and higher BMI were also independently associated with greater adjusted odds for endorsing strict dieting/fasting.

Conclusions

The increased prevalence of DEBs in various strata of Australian society has both public health and clinical implications. The results refute the stereotype that eating disorders (EDs) predominantly affect young women. They build impetus for future research on EDs among men and older individuals, with a view to developing tailored public health and clinical interventions for these populations.
Real-time monitoring of increases in restlessness to assess idiographic risk of recurrence of depressive symptoms
Authors: Smit Arnout C. , Snippe Evelien
Published: July 2022

Background

This confirmatory study aimed to examine whether we can foresee recurrence of depressive symptoms using personalized modeling of rises in restlessness.

Methods

Participants were formerly depressed patients (N = 41) in remission who (gradually) discontinued antidepressants. Participants completed five smartphone-based Ecological Momentary Assessments (EMA) a day, for a period of 4 months, yielding a total of 21 180 observations. Statistical Process Control by means of Exponentially Weighted Moving Average (EWMA) control charts was used to detect rises in the EMA item ‘I feel restless’, for each individual separately.

Results

An increase in restlessness was detected in 68.3% of the participants with recurring depressive symptoms, and in 26.3% of those who stayed in remission (Fisher's exact test p = 0.01, sensitivity was 68.3%, specificity was 73.7%). In the participants with a recurrence and an increase in restlessness, this increase could be detected in the prodromal phase of depression in 93.3% of the cases and at least a month before the onset of the core symptoms of depression in 66.7% of the cases.

Conclusions

Restlessness is a common prodromal symptom of depression. The sensitivity and specificity of the EWMA charts was at least as good as prognostic models based on cross-sectional patient characteristics. An advantage of the current idiographic method is that the EWMA charts provide real-time personalized insight in a within-person increase in early signs of depression, which is key to alert the right patient at the right time.
Where to put them? Burial location in middle Hellenistic to late Roman Sagalassos, southwest Anatolia
Authors: Cleymans Sam , Beaujean Bas
Published: July 2022

In classical archaeology the spatial aspects of deathscapes and associated funerary phenomena are often taken at face value. Beginning from a relational understanding of space, this article examines the necropoleis of middle Hellenistic to late Roman Sagalassos (second century BC to fifth century AD) within the wider context of the city. To facilitate this methodologically, four spatial aspects are investigated for the Hellenistic, Roman Imperial and late Roman periods: the relations between the spaces of the living and dead, landscaping practices, visibility and accessibility. These four aspects offer insight into the funerary and non-funerary relations from which the necropoleis emerged, developed, expanded and eventually disappeared. A whole range of funerary phenomena are included, ranging from cinerary urns, rectangular and vase-shaped ostothekai, aediculae, naiskoi, arcosolia and sarcophagi to larger sepulchral structures like temple tombs. In addition to being compared with urban developments, the observed patterns are further evaluated within the larger framework of Asia Minor. Ultimately, the enunciated archaeological patterns facilitate multicausal answers to where the Sagalassians placed their dead, if and how this changed and became more varied, and why these developments occurred in particular (re)configurations of time-space.
From commons to resilience grabbing: Insights from historically-oriented social anthropological research on African peasants
Authors: Haller Tobias
Published: July 2022

This paper aims to show the relevance that institutions governing common-pool resources (CPRs) play in peasant resilience. It outlines nine variables for resilience taken from socio-economic and ecological anthropological theories focusing on subsistence and minimax strategies and used for the comparative historical analysis of African case studies. These include drylands (Morocco, Ghana), semi-arid areas (Sierra Leone, Malawi, Tanzania) and wetlands (Cameroon, Kenya, Zambia). The variables could be found under pre-colonial common property but were no longer operating during colonial and postcolonial institutional change from common to state property and privatisation via land grabbing, leading to commons and resilience grabbing.
Acute interstitial pneumonia and the biology of 3-methylindole in feedlot cattle
Authors: Haydock Luke A. J. , Fenton R. Kent , Sergejewich Lauren , Squires E. James , Caswell Jeff L.
Published: July 2022

Acute interstitial pneumonia (AIP) of cattle has been recognized for many decades. While the pathogenesis and risk factors for this condition in pastured cattle are relatively well characterized, there remains a poor understanding of the disease as it occurs in intensively fed cattle such as in beef feedlots. Specifically, in pastured cattle, AIP results from excessive ruminal production of the pneumotoxicant 3-methylindole (3-MI). In feedlot cattle, the evidence to substantiate the role of 3-MI is comparatively deficient and further investigations into the cause, pathogenesis, and control are sorely needed. This review highlights our current understanding of AIP with a focus on the disease as it occurs in feedlot cattle. Additionally, it illustrates the need for further work in understanding the specific animal factors (e.g. the ruminal microbiome, and the role of concurrent diseases), management factors (e.g. animal stocking and vaccination protocols), and dietary factors (e.g. dietary supplements) that may impact the development of AIP and which are relatively unique to the feedlot setting. All stakeholders in the beef industry stand to benefit from a greater understanding of what remains a pressing yet poorly understood issue in beef production.
Building Information Modeling Using Constraint Logic Programming
Authors: ARIAS JOAQUÍN , TÖRMÄ SEPPO , CARRO MANUEL , GUPTA GOPAL
Published: July 2022

Building Information Modeling (BIM) produces three-dimensional object-oriented models of buildings combining the geometrical information with a wide range of properties about materials, products, safety, to name just a few. BIM is slowly but inevitably revolutionizing the architecture, engineering, and construction industry. Buildings need to be compliant with regulations about stability, safety, and environmental impact. Manual compliance checking is tedious and error-prone, and amending flaws discovered only at construction time causes huge additional costs and delays. Several tools can check BIM models for conformance with rules/guidelines. For example, Singapore’s CORENET e-Submission System checks fire safety. But since the current BIM exchange format only contains basic information about building objects, a separate, ad-hoc model pre-processing is required to determine, for example, evacuation routes. Moreover, they face difficulties in adapting existing built-in rules and/or adding new ones (to cater for building regulations, that can vary not only among countries but also among parts of the same city), if at all possible. We propose the use of logic-based executable formalisms (CLP and Constraint ASP) to couple BIM models with advanced knowledge representation and reasoning capabilities. Previous experience shows that such formalisms can be used to uniformly capture and reason with knowledge (including ambiguity) in a large variety of domains. Additionally, incorporating checking within design tools makes it possible to ensure that models are rule-compliant at every step. This also prevents erroneous designs from having to be (partially) redone, which is also costly and burdensome. To validate our proposal, we implemented a preliminary reasoner under CLP(Q/R) and ASP with constraints and evaluated it with several BIM models.
Mit Kind zur Konferenz? Ein Positionspapier zur Erweiterung Familienfreundlicher Maßnahmen auf Fachgruppentagungen
Authors: Pohl Anna , Werthmann Jessica , Cwik Jan C. , Richter Jan , Dawans Bernadette von , Pané-Farré Christiane A. , Renner Fritz , Hunger-Schoppe Christina
Published: July 2022

Zusammenfassung. Die Vereinbarkeit von Wissenschaft und Familie ist für Eltern im Allgemeinen und Frauen im Besonderen eine große Herausforderung. Tagungsteilnahmen sind wichtige Karrierebausteine und eine organisatorische Herausforderung für Eltern. In diesem Positionspapier wird ein Stimmungsbild zu familienfreundlicheren Kongressgestaltung in der Fachgruppe (FG) Klinische Psychologie und Psychotherapie der Deutschen Gesellschaft für Psychologie (DGPs) erfragt. 147 FG-Mitglieder (Rücklaufquote: 18.36 %) beantworteten Fragen zur Demographie, sowie Einstellungen gegenüber der FG-Tagung, Betreuungsmöglichkeiten und familienfreundlichen Maßnahmen. Von den Teilnehmenden waren 66 % Eltern, 45 % sagten wegen familiärer Verpflichtungen die FG-Tagung ab. Zusätzliche Kosten durch familiäre Verpflichtungen wurden als hoch eingeschätzt und familienfreundlichere Maßnahmen von vielen Teilnehmenden gewünscht. Familienfreundliche Konferenzen können ein klares Signal der Inklusion und Solidarität setzen und für die Aufrechterhaltung und Nachhaltigkeit wissenschaftlicher Kompetenz sorgen. Konkrete Empfehlungen für eine familienfreundliche Konferenzgestaltung werden als Checkliste im elektronischen Anhang zur Verfügung gestellt.
Emotional Reactivity, Emotion Regulation, and Social Emotions in Affective Disorders
Authors: Förster Katharina , Kurtz Marcel , Konrad Annika , Kanske Philipp
Published: July 2022

Abstract. Affective disorders, specifically Major Depressive Disorder and Bipolar Disorders, show high prevalence, relapse rates, and a high likelihood to develop a chronic course. For the past two decades, research has investigated the neural correlates of emotion processing and emotion regulation in patients with affective disorders. Putative underlying causal mechanisms of dysregulated affect have been informed by knowledge from the intersection of neuroimaging and clinical psychology. More recent investigations also consider processing the role of mostly negative, self-blaming social emotions, which have been linked to treatment resistance and, hence, provide a prolific target for intervention. Several psychotherapeutic treatment approaches already focus on emotion, and here specific knowledge about the mechanisms underlying persistent changes in affect bears the potential to improve the treatment of affective disorders. In this narrative review, we delineate why and how our insights into the neural correlates of emotion processing and regulation can be applied to the treatment of patients with affective disorders.
Psychometric Properties and Measurement Invariance of a Short Form of	the Unified Multidimensional Calling Scale (UMCS)
Authors: Gerdel Sophie , Dalla Rosa Anna , Vianello Michelangelo
Published: July 2022

Abstract: This paper reports on the development of a unidimensional short scale for measuring career calling (UMCS-7). The scale has been developed drawing from the theoretical model behind the Unified Multidimensional Calling Scale (UMCS; Vianello et al., 2018 ), according to which calling is composed of Passion, Prosociality, Purpose, Pervasiveness, Sacrifice, Transcendent Summons, and Identity. The UMCS-7 integrates classical and modern conceptualizations of career calling and can be used when time constraints prevent using the UMCS. The UMCS-7 has been validated in a sample of Italian workers ( N = 1,246) using exploratory and confirmatory factor analysis. A sample of US employees ( N = 165) was used to estimate measurement invariance across languages, establishing the equivalence of factor loadings, all but two intercepts, and all error variances. The UMCS-7 demonstrated nearly perfect convergent validity with the UMCS ( r = .97), excellent internal consistency (αItaly = .86; αUS = .87), and satisfactory concurrent validity with job satisfaction, life satisfaction, and turnover intentions.
High Spatial and Temporal Resolution Studies of Thermospheric Vector Wind Fields Derived From a Ground‐Based Network of All‐Sky Fabry‐Perot Interferometers
Authors: Elliott J. , Conde M. G.
Published: July 2022

Simple scaling analysis of terms in the Navier‐Stokes momentum equation for Earth's atmosphere suggests that winds at heights above 120 km should be smooth and laminar, with little spatial variation over horizontal scale lengths smaller than several hundred kilometers. However, there is increasing evidence that this traditional understanding may fail to account for several important processes, including both waves and small‐scale ion‐neutral momentum coupling. Here, we examine the thermospheric neutral wind field over Alaska in unprecedented detail using observations from an array of four ground‐based all‐sky imaging Fabry‐Perot interferometers, processed using a new geophysical inverse algorithm, to derive high‐resolution maps of all three wind components, with a temporal cadence of 30 seconds. The reconstructed high‐resolution neutral winds showed synoptic‐scale agreement with prior observations and previously validated techniques, with all results exhibiting behavior in agreement with basic physics. However, stacked time‐series plots of vector wind components reveal significantly more spatial and temporal structure than previously reported. In particular, the observed responses included complex wave‐like behavior and highly geographically variable vertical winds. Local flow features were observed at spatial scales as small as 100 km at times, with temporal scales as short as a few tens of minutes. Instances of close spatial and temporal correlations were observed between the wind fields reconstructed from green‐line spectra and ionospheric flows observed independently by SuperDARN.
Effects of Mesoscale Dynamics on the Path of Fast‐Sinking Particles to the Deep Ocean: A Modeling Study
Authors: Wang Lu , Gula Jonathan , Collin Jérémy , Mémery Laurent
Published: July 2022

The gravitational sinking of organic particles is a vital component of the biological carbon pump. This sinking process is strongly modulated by the spatiotemporally varying eddy field, complicating the interpretation of particle flux measured by deep‐moored sediment traps. By backtracking particles to 200 m depth based on the outputs of a realistic eddy‐resolving simulation, we characterize the origins of particles collected at a long‐term observatory site in the Northeast Atlantic and focus on the impact of mesoscale dynamics on particle transport. Our results show that mesoscale dynamics between 200 and 1,000 m control the statistical funnel. Over the long term, the horizontal sampling scales of traps are estimated as hundreds of kilometers, with containment radius ranging from 90 to 490 km, depending on sinking velocities. Particle travel time suggests that overall vertical flow acts to facilitate the export, with estimated deviations up to 1 ± 2 days for particles sinking at 50 m d−1 to 1,000 m. Statistical analyses of horizontal displacements reveal that mesoscale eddies at the site confine particle sources in a more local area. On average, particles in anticyclonic eddies sink faster to depth than expected from purely gravitational sinking, contrary to their counterparts in cyclonic eddies. The results highlight the critical role of mesoscale dynamics in determining particle transport in a typical open ocean region with moderate eddy kinetic energy. This study provides implications for the sampling design of particle flux measurements during cruises and the interpretation of deep‐ocean mooring observations.
RBM47 inhibits hepatocellular carcinoma progression by targeting UPF1 as a DNA/RNA regulator
Authors: Guo Tao , You Ke , Chen Xi , Sun Yuqi , Wu Ying , Wu Ping , Jiang Yingying
Published: July 2022

The mechanisms by which the tumor behaviors of hepatocellular carcinoma (HCC) support growth and metastasis remain largely unknown, and it has become increasingly apparent that molecular dysregulation is of considerable importance for cellular signaling pathways. Recently, RNA-binding motif protein 47 (RBM47) has been suggested to function as a tumor regulator by acting as an RNA binding protein (RBP), but its role in HCC remains ambiguous. Here, in HCC, we identified that RBM47 had an inhibitory influence on tumor behaviors in vitro and accordingly suppressed the growth and metastasis of xenograft tumors in vivo. Additionally, RBM47 was verified to positively regulate Upframeshift 1 (UPF1), which is a crucial protein involved in the nonsense-mediated RNA decay (NMD) process and was previously determined to be an HCC suppressor. Mechanistically, the stability of UPF1 mRNA was demonstrated to be enhanced with its 3’UTR bound by RBM47, which acted as an RNA binding protein. Meanwhile, RBM47 was also proven to promote the transcription of UPF1 as a transcription factor. Taken together, we concluded that RBM47 functioned as a tumor suppressor by upregulating UPF1, acting as a DNA/RNA binding protein at the transcriptional and posttranscriptional levels.
Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application
Authors: Guesdon-Vennerie Alban , Couvreur Patrick , Ali Fatoumia , Pouzoulet Frédéric , Roulin Christophe , Martínez-Rovira Immaculada , Bernadat Guillaume , Legrand François-Xavier , Bourgaux Claudie , Mazars Cyril Lucien , Marco Sergio , Trépout Sylvain , Mura Simona , Mériaux Sébastien , Bort Guillaume
Published: July 2022

Electromagnetic radiation-triggered therapeutic effect has attracted a great interest over the last 50 years. However, translation to clinical applications of photoactive molecular systems developed to date is dramatically limited, mainly because their activation requires excitation by low-energy photons from the ultraviolet to near infra-red range, preventing any activation deeper than few millimetres under the skin. Herein we conceive a strategy for photosensitive-system activation potentially adapted to biological tissues without any restriction in depth. High-energy stimuli, such as those employed for radiotherapy, are used to carry energy while molecular activation is provided by local energy conversion. This concept is applied to azobenzene, one of the most established photoswitches, to build a radioswitch. The radiation-responsive molecular system developed is used to trigger cytotoxic effect on cancer cells upon gamma-ray irradiation. This breakthrough activation concept is expected to expand the scope of applications of photosensitive systems and paves the way towards the development of original therapeutic approaches.
Contrasting suitability and ambition in regional carbon mitigation
Authors: Liu Yu , Du Mingxi , Cui Qi , Lin Jintai , Liu Yawen , Liu Qiuyu , Tong Dan , Feng Kuishuang , Hubacek Klaus
Published: July 2022

Substantially enhancing carbon mitigation ambition is a crucial step towards achieving the Paris climate goal. Yet this attempt is hampered by poor knowledge on the potential cost and benefit of emission mitigation for each emitter. Here we use a global economic model to assess the mitigation costs for 27 major emitting countries and regions, and further contrast the costs against the potential benefits of mitigation valued as avoided social cost of carbon and the mitigation ambition of each region. We find a strong negative spatial correlation between cost and benefit of mitigating each ton of carbon dioxide. Meanwhile, the relative suitability of carbon mitigation, defined as the ratio of normalized benefit to normalized cost, also shows a considerable geographical mismatch with the mitigation ambition of emitters indicated in their first submitted nationally determined contributions. Our work provides important information to improve concerted climate action and formulate more efficient carbon mitigation strategies.
Structures of β1-adrenergic receptor in complex with Gs and ligands of different efficacies
Authors: Su Minfei , Paknejad Navid , Zhu Lan , Wang Jinan , Do Hung Nguyen , Miao Yinglong , Liu Wei , Hite Richard K. , Huang Xin-Yun
Published: July 2022

G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of β1-adrenergic receptor (β1-AR) in complex with Gs (GαsGβ1Gγ2) and a partial agonist or a very weak partial agonist, and compare them to the β1-AR–Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutations of β1-AR residues show effects on the cellular signaling from β1-AR to the cAMP response initiated by the three different ligands, with residue-specific functional differences. Biochemical investigations uncover that the intermediate state complex comprising β1-AR and nucleotide-free Gs is more stable when binding a full agonist than a partial agonist. Molecular dynamics simulations support the local conformational flexibilities and different stabilities among the three complexes. These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins.
Topology mediates transport of nanoparticles in macromolecular networks
Authors: Dai Xiaobin , Zhang Xuanyu , Gao Lijuan , Xu Ziyang , Yan Li-Tang
Published: July 2022

Diffusion transport of nanoparticles in confined environments of macromolecular networks is common in diverse physical systems and regulates many biological responses. Macromolecular networks possess various topologies, featured by different numbers of degrees and genera. Although the network topologies can be manipulated from a molecular level, how the topology impacts the transport of nanoparticles in macromolecular networks remains unexplored. Here, we develop theoretical approaches combined with simulations to study nanoparticle transport in a model system consisting of network cells with defined topologies. We find that the topology of network cells has a profound effect on the free energy landscape experienced by a nanoparticle in the network cells, exhibiting various scaling laws dictated by the topology. Furthermore, the examination of the impact of cell topology on the detailed behavior of nanoparticle dynamics leads to different dynamical regimes that go beyond the particulars regarding the local network loop. The results might alter the conventional picture of the physical origin of transport in networks.
Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis
Authors: Kar Siddhartha P. , Quiros Pedro M. , Gu Muxin , Jiang Tao , Mitchell Jonathan , Langdon Ryan , Iyer Vivek , Barcena Clea , Vijayabaskar M. S. , Fabre Margarete A. , Carter Paul , Petrovski Slavé , Burgess Stephen , Vassiliou George S.
Published: July 2022

Clonal hematopoiesis (CH), the clonal expansion of a blood stem cell and its progeny driven by somatic driver mutations, affects over a third of people, yet remains poorly understood. Here we analyze genetic data from 200,453 UK Biobank participants to map the landscape of inherited predisposition to CH, increasing the number of germline associations with CH in European-ancestry populations from 4 to 14. Genes at new loci implicate DNA damage repair (PARP1, ATM, CHEK2), hematopoietic stem cell migration/homing (CD164) and myeloid oncogenesis (SETBP1). Several associations were CH-subtype-specific including variants at TCL1A and CD164 that had opposite associations with DNMT3A- versus TET2-mutant CH, the two most common CH subtypes, proposing key roles for these two loci in CH development. Mendelian randomization analyses showed that smoking and longer leukocyte telomere length are causal risk factors for CH and that genetic predisposition to CH increases risks of myeloproliferative neoplasia, nonhematological malignancies, atrial fibrillation and blood epigenetic ageing.
Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate
Authors: McCorvie Thomas J. , Loria Paula M. , Tu Meihua , Han Seungil , Shrestha Leela , Froese D. Sean , Ferreira Igor M. , Berg Allison P. , Yue Wyatt W.
Published: July 2022

Glycogen synthase (GYS1) is the central enzyme in muscle glycogen biosynthesis. GYS1 activity is inhibited by phosphorylation of its amino (N) and carboxyl (C) termini, which is relieved by allosteric activation of glucose-6-phosphate (Glc6P). We present cryo-EM structures at 3.0–4.0 Å resolution of phosphorylated human GYS1, in complex with a minimal interacting region of glycogenin, in the inhibited, activated and catalytically competent states. Phosphorylations of specific terminal residues are sensed by different arginine clusters, locking the GYS1 tetramer in an inhibited state via intersubunit interactions. The Glc6P activator promotes conformational change by disrupting these interactions and increases the flexibility of GYS1, such that it is poised to adopt a catalytically competent state when the sugar donor UDP-glucose (UDP-glc) binds. We also identify an inhibited-like conformation that has not transitioned into the activated state, in which the locking interaction of phosphorylation with the arginine cluster impedes subsequent conformational changes due to Glc6P binding. Our results address longstanding questions regarding the mechanism of human GYS1 regulation.
Diagnosis of colonic dysmotility associated with autonomic dysfunction in patients with chronic refractory constipation
Authors: Liu Lijun , Milkova Natalija , Nirmalathasan Sharjana , Ali M. Khawar , Sharma Kartik , Huizinga Jan D. , Chen Ji-Hong
Published: July 2022

We report the first study assessing human colon manometric features and their correlations with changes in autonomic functioning in patients with refractory chronic constipation prior to consideration of surgical intervention. High-resolution colonic manometry (HRCM) with simultaneous heart rate variability (HRV) was performed in 14 patients, and the resulting features were compared to healthy subjects. Patients were categorized into three groups that had normal, weak, or no high amplitude propagating pressure waves (HAPWs) to any intervention. We found mild vagal pathway impairment presented as lower HAPW amplitude in the proximal colon in response to proximal colon balloon distention. Left colon dysmotility was observed in 71% of patients, with features of (1) less left colon HAPWs, (2) lower left colon HAPW amplitudes (69.8 vs 102.3 mmHg), (3) impaired coloanal coordination, (4) left colon hypertonicity in patients with coccyx injury. Patients showed the following autonomic dysfunction: (1) high sympathetic tone at baseline, (2) high sympathetic reactivity to active standing and meal, (3) correlation of low parasympathetic reactivity to the meal with absence of the coloanal reflex, (4) lower parasympathetic and higher sympathetic activity during occurrence of HAPWs. In conclusion, left colon dysmotility and high sympathetic tone and reactivity, more so than vagal pathway impairment, play important roles in refractory chronic constipation and suggests sacral neuromodulation as a possible treatment.