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Morphogenesis and differentiation are important stages in organ development and shape determination. However, how they are balanced and tuned during development is not fully understood. In the compound leaved tomato, an extended morphogenesis phase allows for the initiation of leaflets, resulting in the compound form. Maintaining a prolonged morphogenetic phase in early stages of compound-leaf development in tomato is dependent on delayed activity of several factors that promote differentiation, including the CIN-TCP transcription factor (TF) LA, the MYB TF CLAU and the plant hormone Gibberellin (GA), as well as on the morphogenesis-promoting activity of the plant hormone cytokinin (CK). Here, we investigated the genetic regulation of the morphogenesis-differentiation balance by studying the relationship between LA, CLAU, TKN2, CK and GA. Our genetic and molecular examination suggest that LA is expressed earlier and more broadly than CLAU and determines the developmental context of CLAU activity. Genetic interaction analysis indicates that LA and CLAU likely promote differentiation in parallel genetic pathways. These pathways converge downstream on tuning the balance between CK and GA. Comprehensive transcriptomic analyses support the genetic data and provide insights into the broader molecular basis of differentiation and morphogenesis processes in plants.

Social media data are transforming sustainability science. However, challenges from restrictions in data accessibility and ethical concerns regarding potential data misuse have threatened this nascent field. Here, we review the literature on the use of social media data in environmental and sustainability research. We find that they can play a novel and irreplaceable role in achieving the UN Sustainable Development Goals by allowing a nuanced understanding of human-nature interactions at scale, observing the dynamics of social-ecological change, and investigating the co-construction of nature values. We reveal threats to data access and highlight scientific responsibility to address trade-offs between research transparency and privacy protection, while promoting inclusivity. This contributes to a wider societal debate of social media data for sustainability science and for the common good.

Magnetic nulls are locations where the magnetic field vanishes. Nulls are the location of magnetic reconnection, and they determine to a large degree the magnetic connectivity in a system. We describe a novel approach to understanding movement, appearance, and disappearance of nulls in magnetic fields. This approach is based on the novel concept of isotropes, or lines where the field direction is constant. These lines are streamlines of a vector field whose flux is sourced by the topological indices of nulls, and can be conceptualized as corresponding "lines of force" between nulls. We show how this topological approach can be used to generate analytical expressions for the location of nulls in the presence of external fields for dipoles and for a field defined by the Hopf fibration.

Dusty plasmas are known to support a diverse range of instabilities, including both generalizations of standard plasma instabilities and ones caused by effects specific to dusty systems. It has been recently demonstrated that a novel broad class of streaming instabilities, termed resonant drag instabilities (RDIs), can be attributed to a particular resonance phenomenon, manifested by defective eigenvalues of the linearized dust/fluid system. In this work, it is demonstrated that this resonance phenomenon is not unique to RDIs and can be used as a framework to understand a wider range of instabilities, termed resonant instabilities. Particular attention is given to the filamentary ionization instability seen in laboratory dusty plasmas and to the two-stream instability. It is shown that, due to the commonalities in underlying physics between the dust-ion-acoustic two-stream instability and the acoustic RDI, these instabilities should be relevant in strongly overlapping regimes in astrophysical dusty plasmas. It is proposed that a similar overlap in the experimental accessibility of these modes (and of the filamentary instability) allows for the possibility of experimental investigation in the laboratory of complex and astrophysically relevant instability dynamics., Comment: 21 pages, 15 figures

The grey mullet is a catadromous species that spawns in the taurine-rich seawater environment, followed by the young fish generally migrating to less saline, low taurine waters during the larva-juvenile transition. Consequently, this study aimed to (1) determines whether there is a dietary taurine requirement in juvenile grey mullet for enhanced growth and (2) the potential for taurine biosynthesis. The experimental system consisted of sixteen 400-l V-tanks, where filtered, UV-treated ambient seawater (40 ‰) entered the bottom of the tanks at a rate of 7 tank exchanges/day. This allowed the testing of four 1 mm pelleted diets (0, 0.5, 1.0, and 2.0% taurine DW diet) in replicates of 4 tanks/treatment for 58 days. Grey mullet juveniles demonstrated (P<0.05) a specific requirement for a 0.5% taurine DW diet for improved growth. Fish fed the taurine diets displayed populations with a markedly (P < 0.05) higher average number of surviving fish (23.4±1.1) of moderately sized (10- 20 g) cohorts than smaller (< 10 g) individuals (12.5±1.1). In contrast, the fish fed the taurine control (0% taurine) exhibited similar average numbers of small and moderate sized fish (18.0±3.6-20.0±4.1). Dietary taurine accumulated highly (P<0.05) in the muscles in a dose dependent manner but less so (P<0.05) in eyes, and liver. The gene expression of liver cysteine sulfinic acid decarboxylase (CSD) exhibited an upregulation (P<0.05) with taurine diets from 0 to 1% but was down regulated (P<0.05) in fish fed the 2% taurine DW diet.

Online communities develop unique characteristics, establish social norms, and exhibit distinct dynamics among their members. Activity in online communities often results in concrete ``off-line'' actions with a broad societal impact (e.g., political street protests and norms related to sexual misconduct). While community dynamics, information diffusion, and online collaborations have been widely studied in the past two decades, quantitative studies that measure the effectiveness of online communities in promoting their agenda are scarce. In this work, we study the correspondence between the effectiveness of a community, measured by its success level in a competitive online campaign, and the underlying dynamics between its members. To this end, we define a novel task: predicting the success level of online communities in Reddit's r/place - a large-scale distributed experiment that required collaboration between community members. We consider an array of definitions for success level; each is geared toward different aspects of collaborative achievement. We experiment with several hybrid models, combining various types of features. Our models significantly outperform all baseline models over all definitions of `success level'. Analysis of the results and the factors that contribute to the success of coordinated campaigns can provide a better understanding of the resilience or the vulnerability of communities to online social threats such as election interference or anti-science trends. We make all data used for this study publicly available for further research., Comment: Accepted for publication at ICWSM 2024

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

The inference of genome rearrangement events has been extensively studied, as they play a major role in molecular evolution. However, probabilistic evolutionary models that explicitly imitate the evolutionary dynamics of such events, as well as methods to infer model parameters, are yet to be fully utilized. Here, we developed a probabilistic approach to infer genome rearrangement rate parameters using an Approximate Bayesian Computation (ABC) framework. We developed two genome rearrangement models, a basic model, which accounts for genomic changes in gene order, and a more sophisticated one which also accounts for changes in chromosome number. We characterized the ABC inference accuracy using simulations and applied our methodology to both prokaryotic and eukaryotic empirical datasets. Knowledge of genome-rearrangement rates can help elucidate their role in evolution as well as help simulate genomes with evolutionary dynamics that reflect empirical genomes.

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

We address the task of controlled generation of small molecules, which entails finding novel molecules with desired properties under certain constraints (e.g., similarity to a reference molecule). Here we introduce MolMIM, a probabilistic auto-encoder for small molecule drug discovery that learns an informative and clustered latent space. MolMIM is trained with Mutual Information Machine (MIM) learning, and provides a fixed length representation of variable length SMILES strings. Since encoder-decoder models can learn representations with ``holes'' of invalid samples, here we propose a novel extension to the training procedure which promotes a dense latent space, and allows the model to sample valid molecules from random perturbations of latent codes. We provide a thorough comparison of MolMIM to several variable-size and fixed-size encoder-decoder models, demonstrating MolMIM's superior generation as measured in terms of validity, uniqueness, and novelty. We then utilize CMA-ES, a naive black-box and gradient free search algorithm, over MolMIM's latent space for the task of property guided molecule optimization. We achieve state-of-the-art results in several constrained single property optimization tasks as well as in the challenging task of multi-objective optimization, improving over previous success rate SOTA by more than 5\% . We attribute the strong results to MolMIM's latent representation which clusters similar molecules in the latent space, whereas CMA-ES is often used as a baseline optimization method. We also demonstrate MolMIM to be favourable in a compute limited regime, making it an attractive model for such cases., Comment: Published at the MLDD workshop, ICLR 2023. version 2. 8 pages, 4 figures, 4 tables

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

Social platforms such as Gab and Parler, branded as `free-speech' networks, have seen a significant growth of their user base in recent years. This popularity is mainly attributed to the stricter moderation enforced by mainstream platforms such as Twitter, Facebook, and Reddit. In this work we provide the first large scale analysis of hate-speech on Parler. We experiment with an array of algorithms for hate-speech detection, demonstrating limitations of transfer learning in that domain, given the illusive and ever changing nature of the ways hate-speech is delivered. In order to improve classification accuracy we annotated 10K Parler posts, which we use to fine-tune a BERT classifier. Classification of individual posts is then leveraged for the classification of millions of users via label propagation over the social network. Classifying users by their propensity to disseminate hate, we find that hate mongers make 16.1\% of Parler active users, and that they have distinct characteristics comparing to other user groups. We find that hate mongers are more active, more central and express distinct levels of sentiment and convey a distinct array of emotions like anger and sadness. We further complement our analysis by comparing the trends discovered in Parler and those found in Gab. To the best of our knowledge, this is among the first works to analyze hate speech in Parler in a quantitative manner and on the user level, and the first annotated dataset to be made available to the community.

Understanding collective decision making at a large-scale, and elucidating how community organization and community dynamics shape collective behavior are at the heart of social science research. In this work we study the behavior of thousands of communities with millions of active members. We define a novel task: predicting which community will undertake an unexpected, large-scale, distributed campaign. To this end, we develop a hybrid model, combining textual cues, community meta-data, and structural properties. We show how this multi-faceted model can accurately predict large-scale collective decision-making in a distributed environment. We demonstrate the applicability of our model through Reddit's r/place - a large-scale online experiment in which millions of users, self-organized in thousands of communities, clashed and collaborated in an effort to realize their agenda. Our hybrid model achieves a high F1 prediction score of 0.826. We find that coarse meta-features are as important for prediction accuracy as fine-grained textual cues, while explicit structural features play a smaller role. Interpreting our model, we provide and support various social insights about the unique characteristics of the communities that participated in the \r/place experiment. Our results and analysis shed light on the complex social dynamics that drive collective behavior, and on the factors that propel user coordination. The scale and the unique conditions of the \rp~experiment suggest that our findings may apply in broader contexts, such as online activism, (countering) the spread of hate speech and reducing political polarization. The broader applicability of the model is demonstrated through an extensive analysis of the WallStreetBets community, their role in r/place and four years later, in the GameStop short squeeze campaign of 2021.

Asaf Israeli,1 Danna Gal,1 Autba Younis,2 Scott Ehrenberg,1 Ehud Rozner,3 Yoav Turgeman,1,3 Edmund Naami,4 Robert Naami,5 Ofir Koren1,3 1Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 2Internal Medicine E, Emek Medical Center, Afula, Israel; 3Heart Institute, Emek Medical Center, Afula, Israel; 4Department of Medicine, University of Illinois College of Medicine, Chicago, IL, USA; 5Department of Medicine, University Hospitals Cleveland Medical center, Case Western Reserve University School of Medicine, Cleveland, OH, USACorrespondence: Ofir Koren, Heart Institute, Emek Medical Center, 21 Rabin Boulevard, Afula, 1834111, Israel, Tel +972-04-6495585, Email Drkorenofir@gmail.comBackground: Studies analyze the degree to which gender-based differences are affected by age and comorbidities show mixed results.Methods: Using a retrospective cohort study, we analyzed 327 consecutive patients who presented to the emergency department (ED) due to Atrial Fibrillation (AF) from 2014 to 2017 with follow-up at one year.Results: Females with AF were older (p < 0.001), with higher Body Mass Indexes (BMI) (p < 0.001), and a higher rate of hypertension (p < 0.001), hyperlipidemia (p = 0.01), diabetes mellitus (p = 0.05), valvular heart disease (p = 0.05), and thyroid dysfunction (18.3% vs 1.8%, p < 0.001). AF males had higher rate of coronary artery disease (p < 0.001) and heart failure with reduced ejection fraction (p < 0.001). Females were managed with rate control medications more frequently than with antiarrhythmic (p < 0.001). After adjusting gender to age and comorbidities, females continued to have higher rates of heart failure hospitalization (Odds Ratio (OR) 2.73 95% Confidence Interval (CI) 1.04– 5.89, P-value < 0.001) and recurrent AF (OR 3.86, P-value=0.02). Thyroid dysfunction and the lack of antiarrhythmic treatments significantly increased the risk of AF (OR 5.95 95% CI 3.15– 9.73, OR 3.42, respec

This article investigates early Slavic exegesis and its influence on Slavic languages (and, more broadly, models for transferring Judeo-Christian thought onto the Slavic soil). The investigation is based on an example of a unique phenomenon related to the sacro-secular homonymy in the terminology defining the God of monotheistic religions. Out of all the languages of Christian civilization, only the languages belonging to Slavia Orthodoxa depart from this general pattern. The development of a dichotomy between the forms gospod’ (“lord”) and gospodin” (“master”) is connected with a particular translational exegesis unknown in other early ecclesiastical traditions. This therefore stands as a unique and, at any rate, independent Slavic innovation in the interpretation of the biblical text. This new Slavic dichotomy compensated for the ambiguous polysemy of the underlying Greek term, κύριος (kyrios), and restored a semantic distinction present in the original Biblical Hebrew text. This phenomenon represents one of the not yet completely elucidated and comprehended cases of independent Slavic exegetical thought, which at this early stage manifested itself not so much in the composition of biblical commentaries and theological works as in translational and editorial choices. It is also significant that certain processes in the allocation of meanings depending on the grammatical form, attested already in early Slavic biblical texts, are cognate with analogous processes in contemporary Slavic languages. Moreover, such semantic distinction between related and highly cognate forms has even enriched the modern Slavic languages connected to this tradition, thus creating means of artistic expression that remain impossible in most other languages of Christian civilization. DOI: 10.31168/2305-6754.2019.8.1.2, В статье рассматривается ранняя славянская экзегеза и ее влияние на славянские языки (и шире — модели перенесения иудео-христианского мышления на славянскую почву) на примере уникального феномена профанно-сакральной омонимии терминологии, определяющей Бога монотеистических религий, которая из всех языков христианской цивилизации снимается только в языках, принадлежащих к Slavia Orthodoxa. Развитие дихотомии форм господь и господинъ связано с переводческой экзегезой, неизвестной другим ранним церковным традициям и являющейся уникальной — и во всяком случае, самостоятельной — славянской инновацией в интерпретации библейского текста. Новая славянская дихотомия компенсировала многозначность стоящего за ней греческого термина κύριος и восстанавливала различение значений оригинального еврейского текста Библии. Это один из не вполне выявленных и осмысленных случаев самостоятельной славянской экзегетической мысли, на этом раннем этапе проявлявшейся не столько в сочинении библейских комментариев и богословских трудов, сколько в переводческом и редакторском выборе. Важно также, что некоторые процессы в распределении значений в зависимости от грамматической формы, зафиксированные в ранних славянских библейских текстах, сходны с аналогичными процессами в современных славянских языках. Кроме того, такое семантическое различение родственных и очень сходных форм обогатило и причастные к этой традиции современные славянские языки, создав средства художественного выражения, невозможные в большинстве других языков христианской цивилизации. DOI: 10.31168/2305-6754.2019.8.1.2

This article investigates early Slavic exegesis and its influence on Slavic languages (and, more broadly, models for transferring Judeo-Christian thought onto the Slavic soil). The investigation is based on an example of a unique phenomenon related to the sacro-secular homonymy in the terminology defining the God of monotheistic religions. Out of all the languages of Christian civilization, only the languages belonging to Slavia Orthodoxa depart from this general pattern. The development of a dichotomy between the forms gospod’ (“lord”) and gospodin” (“master”) is connected with a particular translational exegesis unknown in other early ecclesiastical traditions. This therefore stands as a unique and, at any rate, independent Slavic innovation in the interpretation of the biblical text. This new Slavic dichotomy compensated for the ambiguous polysemy of the underlying Greek term, κύριος (kyrios), and restored a semantic distinction present in the original Biblical Hebrew text. This phenomenon represents one of the not yet completely elucidated and comprehended cases of independent Slavic exegetical thought, which at this early stage manifested itself not so much in the composition of biblical commentaries and theological works as in translational and editorial choices. It is also significant that certain processes in the allocation of meanings depending on the grammatical form, attested already in early Slavic biblical texts, are cognate with analogous processes in contemporary Slavic languages. Moreover, such semantic distinction between related and highly cognate forms has even enriched the modern Slavic languages connected to this tradition, thus creating means of artistic expression that remain impossible in most other languages of Christian civilization. DOI: 10.31168/2305-6754.2019.8.1.2, В статье рассматривается ранняя славянская экзегеза и ее влияние на славянские языки (и шире — модели перенесения иудео-христианского мышления на славянскую почву) на примере уникального феномена профанно-сакральной омонимии терминологии, определяющей Бога монотеистических религий, которая из всех языков христианской цивилизации снимается только в языках, принадлежащих к Slavia Orthodoxa. Развитие дихотомии форм господь и господинъ связано с переводческой экзегезой, неизвестной другим ранним церковным традициям и являющейся уникальной — и во всяком случае, самостоятельной — славянской инновацией в интерпретации библейского текста. Новая славянская дихотомия компенсировала многозначность стоящего за ней греческого термина κύριος и восстанавливала различение значений оригинального еврейского текста Библии. Это один из не вполне выявленных и осмысленных случаев самостоятельной славянской экзегетической мысли, на этом раннем этапе проявлявшейся не столько в сочинении библейских комментариев и богословских трудов, сколько в переводческом и редакторском выборе. Важно также, что некоторые процессы в распределении значений в зависимости от грамматической формы, зафиксированные в ранних славянских библейских текстах, сходны с аналогичными процессами в современных славянских языках. Кроме того, такое семантическое различение родственных и очень сходных форм обогатило и причастные к этой традиции современные славянские языки, создав средства художественного выражения, невозможные в большинстве других языков христианской цивилизации. DOI: 10.31168/2305-6754.2019.8.1.2

Purpose: Previous research has repeatedly shown that people only search for files in a small minority of cases when they do not remember the file's location. The current study aimed to examine whether there is a group of hyper-searchers who search significantly more than others. Based on previous neurocognitive studies, this study aims to hypothesize that if such a group exists, they will have superior verbal memory and reduced visuospatial memory. Design/methodology/approach: In total, 65 participants completed a questionnaire estimating their search percentages, as well as reporting demographic data. Verbal memory was measured using the Wechsler logical memory test, and visuospatial memory was assessed using an online card memory game. Findings: Hyper-searchers were defined as participants with search percentage of over one standard deviation (SD) above the mean. The average search percentage of the seven participants who met this criterion was 51% (SD = 14%), over five times more than the other participants (M = 10%, SD = 9%). Similar results were obtained by re-analyzing data from four previous papers (N = 1,252). The results further confirmed the hypothesis that hyper-searchers have significantly better verbal memory than other participants, possibly making searching easier and more successful for them. Lastly, the search percentage was positively predicted by verbal memory scores and negatively predicted by visuospatial memory scores. Explanations and future research are discussed. Originality/value: This preliminary study is the first to introduce the concept of hyper-searchers, demonstrate its existence and study its causes.

Using the most recent data from various databases we have retrieved economic and health data from OECD member countries and analyzed it in regard to the Oxford COVID-19 Government Response Tracker, what we call Stringency index. We examine the effects on different economic variables such as GDP, exports, and unemployment, together with the health outcome variable excess mortality. In regard to our different countries' restriction strategies, that is their Stringency Index. The main method we employed is bivariate plots and regression analysis. The investigation and analysis are solely made for the first year of the pandemic, 2020. Our results reveal that all of our variables are significant in at least one regression. The adjusted R2 value shows that the dependent variables can be explained by our independent variables ranging from 27 to 75 percent. The variables we most often find significant are: Excess mortality per 100,000, GDP and Stringency index. A considerable effort was made when selecting, retrieving, and processing the data for our purposes and to make it comparable between the countries chosen. Other aspects that undeniably impact the outcomes are mentioned and discussed but due to the complexity we chose to limit this research to a few variables with complete and comparable data. Our results show how the different outcomes are significant for the measurements taken but also how the measurements impact the outcomes in a bilateral relationship. The insights derived are hopefully useful for economists, politicians, and the public in concerns to the management of the Pandemic during its first year.

Morphogenesis and differentiation are important stages in organ development and shape determination. However, how they are balanced and tuned during development is not fully understood. In the compound leaved tomato, an extended morphogenesis phase allows for the initiation of leaflets, resulting in the compound form. Maintaining a prolonged morphogenetic phase in early stages of compound-leaf development in tomato is dependent on delayed activity of several factors that promote differentiation, including the CIN-TCP transcription factor (TF) LA, the MYB TF CLAU and the plant hormone Gibberellin (GA), as well as on the morphogenesis-promoting activity of the plant hormone cytokinin (CK). Here, we investigated the genetic regulation of the morphogenesis-differentiation balance by studying the relationship between LA, CLAU, TKN2, CK and GA. Our genetic and molecular examination suggest that LA is expressed earlier and more broadly than CLAU and determines the developmental context of CLAU activity. Genetic interaction analysis indicates that LA and CLAU likely promote differentiation in parallel genetic pathways. These pathways converge downstream on tuning the balance between CK and GA. Comprehensive transcriptomic analyses support the genetic data and provide insights into the broader molecular basis of differentiation and morphogenesis processes in plants., identifier:1553-7404

Morphogenesis and differentiation are important stages in organ development and shape determination. However, how they are balanced and tuned during development is not fully understood. In the compound leaved tomato, an extended morphogenesis phase allows for the initiation of leaflets, resulting in the compound form. Maintaining a prolonged morphogenetic phase in early stages of compound-leaf development in tomato is dependent on delayed activity of several factors that promote differentiation, including the CIN-TCP transcription factor (TF) LA, the MYB TF CLAU and the plant hormone Gibberellin (GA), as well as on the morphogenesis-promoting activity of the plant hormone cytokinin (CK). Here, we investigated the genetic regulation of the morphogenesis-differentiation balance by studying the relationship between LA, CLAU, TKN2, CK and GA. Our genetic and molecular examination suggest that LA is expressed earlier and more broadly than CLAU and determines the developmental context of CLAU activity. Genetic interaction analysis indicates that LA and CLAU likely promote differentiation in parallel genetic pathways. These pathways converge downstream on tuning the balance between CK and GA. Comprehensive transcriptomic analyses support the genetic data and provide insights into the broader molecular basis of differentiation and morphogenesis processes in plants.

Morphogenesis and differentiation are important stages in organ development and shape determination. However, how they are balanced and tuned during development is not fully understood. In the compound leaved tomato, an extended morphogenesis phase allows for the initiation of leaflets, resulting in the compound form. Maintaining a prolonged morphogenetic phase in early stages of compound-leaf development in tomato is dependent on delayed activity of several factors that promote differentiation, including the CIN-TCP transcription factor (TF) LA, the MYB TF CLAU and the plant hormone Gibberellin (GA), as well as on the morphogenesis-promoting activity of the plant hormone cytokinin (CK). Here, we investigated the genetic regulation of the morphogenesis-differentiation balance by studying the relationship between LA, CLAU, TKN2, CK and GA. Our genetic and molecular examination suggest that LA is expressed earlier and more broadly than CLAU and determines the developmental context of CLAU activity. Genetic interaction analysis indicates that LA and CLAU likely promote differentiation in parallel genetic pathways. These pathways converge downstream on tuning the balance between CK and GA. Comprehensive transcriptomic analyses support the genetic data and provide insights into the broader molecular basis of differentiation and morphogenesis processes in plants., journal article

Background A Mediterranean diet is favourable for cardiometabolic risk. Objective To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk. Methods For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3–4 cups/day) and a Wolffia globosa (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state. Results Participants (n=294; age 51 years; body mass index 31.3 kg/m2; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean −6.2 kg; Mediterranean −5.4 kg) vs the HDG group −1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (−8.6 cm) than the Mediterranean (−6.8 cm; p=0.033) and HDG (−4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean −6.1 mg/dL (−3.7%), −2.3 (-0.8%), HDG −0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean −7.2 mm Hg, Mediterranean −5.2 mm Hg, HDG −3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean −0.77, Mediterranean −0.46, HDG −0.27; p=0.020 between extreme gr

Purpose: Previous research has repeatedly shown that people only search for files in a small minority of cases when they do not remember the file's location. The current study aimed to examine whether there is a group of hyper-searchers who search significantly more than others. Based on previous neurocognitive studies, this study aims to hypothesize that if such a group exists, they will have superior verbal memory and reduced visuospatial memory. Design/methodology/approach: In total, 65 participants completed a questionnaire estimating their search percentages, as well as reporting demographic data. Verbal memory was measured using the Wechsler logical memory test, and visuospatial memory was assessed using an online card memory game. Findings: Hyper-searchers were defined as participants with search percentage of over one standard deviation (SD) above the mean. The average search percentage of the seven participants who met this criterion was 51% (SD = 14%), over five times more than the other participants (M = 10%, SD = 9%). Similar results were obtained by re-analyzing data from four previous papers (N = 1,252). The results further confirmed the hypothesis that hyper-searchers have significantly better verbal memory than other participants, possibly making searching easier and more successful for them. Lastly, the search percentage was positively predicted by verbal memory scores and negatively predicted by visuospatial memory scores. Explanations and future research are discussed. Originality/value: This preliminary study is the first to introduce the concept of hyper-searchers, demonstrate its existence and study its causes.

Using the most recent data from various databases we have retrieved economic and health data from OECD member countries and analyzed it in regard to the Oxford COVID-19 Government Response Tracker, what we call Stringency index. We examine the effects on different economic variables such as GDP, exports, and unemployment, together with the health outcome variable excess mortality. In regard to our different countries' restriction strategies, that is their Stringency Index. The main method we employed is bivariate plots and regression analysis. The investigation and analysis are solely made for the first year of the pandemic, 2020. Our results reveal that all of our variables are significant in at least one regression. The adjusted R2 value shows that the dependent variables can be explained by our independent variables ranging from 27 to 75 percent. The variables we most often find significant are: Excess mortality per 100,000, GDP and Stringency index. A considerable effort was made when selecting, retrieving, and processing the data for our purposes and to make it comparable between the countries chosen. Other aspects that undeniably impact the outcomes are mentioned and discussed but due to the complexity we chose to limit this research to a few variables with complete and comparable data. Our results show how the different outcomes are significant for the measurements taken but also how the measurements impact the outcomes in a bilateral relationship. The insights derived are hopefully useful for economists, politicians, and the public in concerns to the management of the Pandemic during its first year.

Free nerve endings are key structures in sensory transduction of noxious stimuli. In spite of this, little is known about their functional organization. Transient receptor potential (TRP) channels have emerged as key molecular identities in the sensory transduction of pain-producing stimuli, yet the vast majority of our knowledge about sensory TRP channel function is limited to data obtained from in vitro models which do not necessarily reflect physiological conditions. In recent years, the development of novel optical methods such as genetically encoded calcium indicators and photo-modulation of ion channel activity by pharmacological tools has provided an invaluable opportunity to directly assess nociceptive TRP channel function at the nerve terminal.

Children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) overexpressing the CRLF2 gene (hiCRLF2) have poor prognosis. CRLF2 protein overexpression leads to activated JAK/STAT signaling and trials are underway using JAK inhibitors to overcome treatment failure. Pre-clinical studies indicated limited efficacy of single JAK inhibitors, thus additional pathways must be targeted in hiCRLF2 cells. To identify additional activated networks, we used single-cell mass cytometry to examine 15 BCP-ALL primary patient samples. We uncovered a coordinated signaling network downstream of CRLF2 characterized by co-activation of JAK/STAT, PI3K, and CREB pathways. This CRLF2-driven network could be more effectively disrupted by SRC/ABL inhibition than single-agent JAK or PI3K inhibition, and this could be demonstrated even in primary minimal residual disease (MRD) cells. Our study suggests SCR/ABL inhibition as effective in disrupting the cooperative functional networks present in hiCRLF2 BCP-ALL patients, supporting further investigation of this strategy in pre-clinical studies.

Children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) overexpressing the CRLF2 gene (hiCRLF2) have poor prognosis. CRLF2 protein overexpression leads to activated JAK/STAT signaling and trials are underway using JAK inhibitors to overcome treatment failure. Pre-clinical studies indicated limited efficacy of single JAK inhibitors, thus additional pathways must be targeted in hiCRLF2 cells. To identify additional activated networks, we used single-cell mass cytometry to examine 15 BCP-ALL primary patient samples. We uncovered a coordinated signaling network downstream of CRLF2 characterized by co-activation of JAK/STAT, PI3K, and CREB pathways. This CRLF2-driven network could be more effectively disrupted by SRC/ABL inhibition than single-agent JAK or PI3K inhibition, and this could be demonstrated even in primary minimal residual disease (MRD) cells. Our study suggests SCR/ABL inhibition as effective in disrupting the cooperative functional networks present in hiCRLF2 BCP-ALL patients, supporting further investigation of this strategy in pre-clinical studies.

The tragic failure of the global supply chain in the face of the current coronavirus outbreak has caused acute shortages of essential frontline medical devices and personal protective equipment, crushing fear among frontline health workers and causing fundamental concerns about the sustainability of the health system. Much more coordination, integration, and management of global supply chains will be needed to mitigate the impact of the pandemics. This article describes the pressing need to revisit the governance and resilience of the supply chains that amplified the crisis at pandemic scale. We propose a model that profiles critical stockpiles and improves production efficiency through new technologies such as advanced analytics and blockchain. A new governance system that supports intervention by public-health authorities during critical emergencies is central to our recommendation, both in the face of the current crisis and to be better prepared for potential future crises. These reinforcements offer the potential to minimize the compromise of our healthcare workers and health systems due to infection exposure and build capacity toward preparedness and action for a future outbreak.

The tragic failure of the global supply chain in the face of the current coronavirus outbreak has caused acute shortages of essential frontline medical devices and personal protective equipment, crushing fear among frontline health workers and causing fundamental concerns about the sustainability of the health system. Much more coordination, integration, and management of global supply chains will be needed to mitigate the impact of the pandemics. This article describes the pressing need to revisit the governance and resilience of the supply chains that amplified the crisis at pandemic scale. We propose a model that profiles critical stockpiles and improves production efficiency through new technologies such as advanced analytics and blockchain. A new governance system that supports intervention by public-health authorities during critical emergencies is central to our recommendation, both in the face of the current crisis and to be better prepared for potential future crises. These reinforcements offer the potential to minimize the compromise of our healthcare workers and health systems due to infection exposure and build capacity toward preparedness and action for a future outbreak.

Black holes in binary systems execute patterns of outburst activity where two characteristic X-ray states are associated with different behaviours observed at radio wavelengths. The hard state is associated with radio emission indicative of a continuously replenished, collimated, relativistic jet, whereas the soft state is rarely associated with radio emission, and never continuously, implying the absence of a quasi-steady jet. Here we report radio observations of the black hole transient MAXI J1820+070 during its 2018 outburst. As the black hole transitioned from the hard to soft state, we observed an isolated radio flare, which, using high-angular-resolution radio observations, we connect with the launch of bipolar relativistic ejecta. This flare occurs as the radio emission of the core jet is suppressed by a factor of over 800. We monitor the evolution of the ejecta over 200 days and to a maximum separation of 10″, during which period it remains detectable due to in situ particle acceleration. Using simultaneous radio observations sensitive to different angular scales, we calculate an accurate estimate of energy content of the approaching ejection. This energy estimate is far larger than that derived from the state transition radio flare, suggesting a systematic underestimate of jet energetics. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

The optimized superconducting stellarator device Wendelstein 7-X (with major radius , minor radius , and plasma volume) restarted operation after the assembly of a graphite heat shield and 10 inertially cooled island divertor modules. This paper reports on the results from the first high-performance plasma operation. Glow discharge conditioning and ECRH conditioning discharges in helium turned out to be important for density and edge radiation control. Plasma densities of with central electron temperatures were routinely achieved with hydrogen gas fueling, frequently terminated by a radiative collapse. In a first stage, plasma densities up to were reached with hydrogen pellet injection and helium gas fueling. Here, the ions are indirectly heated, and at a central density of a temperature of with was transiently accomplished, which corresponds to with a peak diamagnetic energy of and volume-averaged normalized plasma pressure . The routine access to high plasma densities was opened with boronization of the first wall. After boronization, the oxygen impurity content was reduced by a factor of 10, the carbon impurity content by a factor of 5. The reduced (edge) plasma radiation level gives routinely access to higher densities without radiation collapse, e.g. well above line integrated density and central temperatures at moderate ECRH power. Both X2 and O2 mode ECRH schemes were successfully applied. Core turbulence was measured with a phase contrast imaging diagnostic and suppression of turbulence during pellet injection was observed.

Contains fulltext : 205162.pdf (publisher's version ) (Open Access), BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged >/=50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial regist

The optimized superconducting stellarator device Wendelstein 7-X (with major radiusR = 5.5 m, minor radius a = 0.5 m, and 30 m3 plasma volume) restarted operation after the assembly of a graphite heat shield and 10 inertially cooled island divertor modules. This paper reports on the results from the first high-performance plasma operation. Glow discharge conditioning and ECRH conditioning discharges in helium turned out to be important for density and edge radiation control. Plasma densities of 1–4.5 × 1019 m−3 with central electron temperatures 5–10 keV were routinely achieved with hydrogen gas fueling, frequently terminated by a radiative collapse. In a first stage, plasma densities up to 1.4 × 1020 m−3 were reached with hydrogen pellet injection and helium gas fueling. Here, the ions are indirectly heated, and at a central density of 8 · 1019 m−3 a temperature of 3.4 keV with Te/Ti = 1 was transiently accomplished, which corresponds to nTi(0)τE = 6.4 × 1019 keV s m−3 with a peak diamagnetic energy of 1.1 MJ and volume-averaged normalized plasma pressure β = 1.2%. The routine access to high plasma densities was opened with boronization of the first wall. After boronization, the oxygen impurity content was reduced by a factor of 10, the carbon impurity content by a factor of 5. The reduced (edge) plasma radiation level gives routinely access to higher densities without radiation collapse, e.g. well above 1 × 1020 m−2 line integrated density and Te = Ti = 2 keV central temperatures at moderate ECRH power. Both X2 and O2 mode ECRH schemes were successfully applied. Core turbulence was measured with a phase contrast imaging diagnostic and suppression of turbulence during pellet injection was observed.

The performance of a highly granular calorimeter system for future collider experiments, consisting of a silicon-tungsten electromagnetic calorimeter and a plastic scintillator-based hadronic calorimeter and muon tracker, is studied using data collected in hadron beams. A reconstruction technique using software compensation methods has been developed, achieving an improvement of the energy resolution of the system by up to 30% compared to the standard energy measurement., Das Verhalten eines hochgranularen Kalorimetersystems für zukünftige Teilchenphysikexperimente, bestehend aus einem elektromagnetischen Silizium-Wolfram Kalorimeter sowie einem hadronischen Kalorimeter und Myonendetektor mit Plastikszintillatoren, wird mit Daten von Hadronstrahlen untersucht. Eine auf Software-Kompensation basierende Rekonstruktionstechnik wurde entwickelt. Diese erreicht eine Verbesserung der Energieauflösung um 30% im Vergleich zur regulären Energiemessung.

In breast cancer, the increased stiffness of the extracellular matrix is a key driver of malignancy. Yet little is known about the epigenomic changes that underlie the tumorigenic impact of extracellular matrix mechanics. Here, we show in a three-dimensional culture model of breast cancer that stiff extracellular matrix induces a tumorigenic phenotype through changes in chromatin state. We found that increased stiffness yielded cells with more wrinkled nuclei and with increased lamina-associated chromatin, that cells cultured in stiff matrices displayed more accessible chromatin sites, which exhibited footprints of Sp1 binding, and that this transcription factor acts along with the histone deacetylases 3 and 8 to regulate the induction of stiffness-mediated tumorigenicity. Just as cell culture on soft environments or in them rather than on tissue-culture plastic better recapitulates the acinar morphology observed in mammary epithelium in vivo, mammary epithelial cells cultured on soft microenvironments or in them also more closely replicate the in vivo chromatin state. Our results emphasize the importance of culture conditions for epigenomic studies, and reveal that chromatin state is a critical mediator of mechanotransduction.

In breast cancer, the increased stiffness of the extracellular matrix is a key driver of malignancy. Yet little is known about the epigenomic changes that underlie the tumorigenic impact of extracellular matrix mechanics. Here, we show in a three-dimensional culture model of breast cancer that stiff extracellular matrix induces a tumorigenic phenotype through changes in chromatin state. We found that increased stiffness yielded cells with more wrinkled nuclei and with increased lamina-associated chromatin, that cells cultured in stiff matrices displayed more accessible chromatin sites, which exhibited footprints of Sp1 binding, and that this transcription factor acts along with the histone deacetylases 3 and 8 to regulate the induction of stiffness-mediated tumorigenicity. Just as cell culture on soft environments or in them rather than on tissue-culture plastic better recapitulates the acinar morphology observed in mammary epithelium in vivo, mammary epithelial cells cultured on soft microenvironments or in them also more closely replicate the in vivo chromatin state. Our results emphasize the importance of culture conditions for epigenomic studies, and reveal that chromatin state is a critical mediator of mechanotransduction.

Contains fulltext : 205162.pdf (publisher's version ) (Open Access), BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged >/=50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial regist

Contains fulltext : 205162.pdf (publisher's version ) (Open Access), BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged >/=50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial regist

The performance of a highly granular calorimeter system for future collider experiments, consisting of a silicon-tungsten electromagnetic calorimeter and a plastic scintillator-based hadronic calorimeter and muon tracker, is studied using data collected in hadron beams. A reconstruction technique using software compensation methods has been developed, achieving an improvement of the energy resolution of the system by up to 30% compared to the standard energy measurement., Das Verhalten eines hochgranularen Kalorimetersystems für zukünftige Teilchenphysikexperimente, bestehend aus einem elektromagnetischen Silizium-Wolfram Kalorimeter sowie einem hadronischen Kalorimeter und Myonendetektor mit Plastikszintillatoren, wird mit Daten von Hadronstrahlen untersucht. Eine auf Software-Kompensation basierende Rekonstruktionstechnik wurde entwickelt. Diese erreicht eine Verbesserung der Energieauflösung um 30% im Vergleich zur regulären Energiemessung.

Background and Aims: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. Methods: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. Results: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P =.0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P =.0033) flat adenomas (P <.0001) and sessile serrated adenomas/polyps (P =.0026). Conclusion: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial regist

Genomic instability can be a hallmark of both human genetic disease and cancer. We identify a deleterious UBQLN4 mutation in families with an autosomal recessive syndrome reminiscent of genome instability disorders. UBQLN4 deficiency leads to increased sensitivity to genotoxic stress and delayed DNA double-strand break (DSB) repair. The proteasomal shuttle factor UBQLN4 is phosphorylated by ATM and interacts with ubiquitylated MRE11 to mediate early steps of homologous recombination-mediated DSB repair (HRR). Loss of UBQLN4 leads to chromatin retention of MRE11, promoting non-physiological HRR activity in vitro and in vivo. Conversely, UBQLN4 overexpression represses HRR and favors non-homologous end joining. Moreover, we find UBQLN4 overexpressed in aggressive tumors. In line with an HRR defect in these tumors, UBQLN4 overexpression is associated with PARP1 inhibitor sensitivity. UBQLN4 therefore curtails HRR activity through removal of MRE11 from damaged chromatin and thus offers a therapeutic window for PARP1 inhibitor treatment in UBQLN4-overexpressing tumors.Control of MRE11 association with chromatin by UBQLN4 during double-strand break repair influences repair pathway choice and can be dysregulated in tumorigenesis.

Tijekom posljednjih petnaest godina u Izraelu je došlo do znatnog porasta bavljenja brdskim biciklizmom, što je osobito vidljivo po značajnim ulaganjima u infrastrukturu na otvorenom i u šumama te po promjenama socioloških obilježja samih biciklista. Što se tiče trendova u različitim ruralnim područjima drugih zemalja postavlja se pitanje u kojoj mjeri biciklisti prihvaćaju obrasce „ozbiljnog slobodnog vremena“ i stupanj u kojem se sport, koji se obično poistovjećuje sa slobodnim aktivnostima, razvija kao cikloturizam ili biciklistički odmor. Ovaj rad temelji se na dva istraživanja biciklizma provedena u razmaku od osam godina što je omogućilo analizu karakteristika, percepcije i potreba biciklista, kao i usporedbu promjena u tim aspektima tijekom vremena. Rezultati pokazuju da, iako su mnoge pronađene karakteristike slične trendovima u drugim zemljama, postoje neke koje su specifične za malu zemlju i njenu društvenu strukturu., During the last fi fteen years, there has been an impressive increase in the scope of mountain biking in Israel, particularly evident in the significant investments in open spaces and forest infrastructures, and the sociological changes of the cyclists themselves. Regarding trends in different rural areas in other countries, issues have been raised concerning the degree to which cyclists adopt ‘serious leisure’ patterns, and the degree to which the sport, which is usually identified with leisure activity, is developing as cycling tourism or cycling holidays. This study was based on two cycling surveys with a time gap of eight years, so that it enabled analysis of the cyclists’ characteristics, perceptions, and needs, as well as comparison of changes in these aspects over time. The results indicate that although many characteristics found are similar to trends in other countries, there are some which are specific to a small country and to its social structure.