julilili42/papers huggingface dataset:
Universal and nonuniversal probability laws in Markovian open quantum dynamics subject to generalized reset processes
2024-04-11

We consider quantum-jump trajectories of Markovian open quantum systems subject to stochastic in time resets of their state to an initial configuration. The reset events provide a partitioning of quantum trajectories into consecutive time intervals, defining sequences of random variables from the values of a trajectory observable within each of the intervals. For observables related to functions of the quantum state, we show that the probability of certain orderings in the sequences obeys a universal law. This law does not depend on the chosen observable and, in the case of Poissonian reset processes, not even on the details of the dynamics. When considering (discrete) observables associated with the counting of quantum jumps, the probabilities in general lose their universal character. Universality is only recovered in cases when the probability of observing equal outcomes in the same sequence is vanishingly small, which we can achieve in a weak-reset-rate limit. Our results extend previous findings on classical stochastic processes [N. R. Smith et al., Europhys. Lett. 142, 51002 (2023)0295-507510.1209/0295-5075/acd79e] to the quantum domain and to state-dependent reset processes, shedding light on relevant aspects for the emergence of universal probability laws.
Ancient mitogenomes from Pre-Pottery Neolithic Central Anatolia and the effects of a Late Neolithic bottleneck in sheep ( Ovis aries )
2024-04-12

Occupied between ~10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Aşıklı Höyük in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Aşıklı Höyük which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Aşıklı Höyük’s occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations.
Memory enhancement for emotional words is attributed to both valence and arousal
2024-04-12

We do not memorize items in our surroundings with equal priority. Previous literature has widely shown that emotional stimuli are better remembered than neutral stimuli. However, given emotional stimuli and neutral stimuli often differ in both valence and arousal dimensions, it remains unclear whether the enhancement effects can be attributed to valence, or just to arousal. Importantly, most prior studies relied on a relatively small number of stimuli and non-emotional factors such as word length, imageability and other confounds were hard to control. To address these challenges, we analyzed multiple large databases of recognition memory and free recall tasks from previous research by items with many lexical and semantic covariates included, examining the effects of valence or arousal when controlling for each other. Our results showed a U-shaped relationship between valence and memory performance for both recognition and free recall, and a linear relationship between arousal and memory performance for both tasks. These findings showed that the memory enhancement effects can be attributed to both valence and arousal. We demonstrated these effects with generalizability across many stimuli and controlled for non-emotional factors. Together, these findings disentangle the contribution of valence and arousal in emotional memory enhancement effects and provide insights for current major theories of emotional memory.
Rare‐Earth‐Metal Alkyl and Aryl Compounds in Organic Synthesis
2024-04-12

Abstract Rare‐earth‐metal (Ln) alkyl and aryl compounds feature highly reactive, thermally labile [Ln−C] σ‐bonds which result in rapid and violent decomposition in the presence of air and moisture. Nevertheless, such [Ln−C] moieties display important intermediate species in numerous organic transformations. Reagents containing [Ln−C] bonds are deliberately generated in situ like Imamoto‐type reagents Ln(III)Cl 3 /RLi (routinely at low temperatures) or “heavy” lanthanide‐Grignard compounds RLnX. Samarium(III)‐alkyl species are supposed intermediates of SmI 2 ‐promoted Barbier‐type carbon–carbon coupling reactions. Alkyl/aryl ligand exchange at Ln(III) centers has been identified as the crucial step of lanthanide–halogen‐exchange reactions. In the meantime, several such mixed alkyl/halogenido complexes, devoid of an ancillary ligand, could be isolated and scrutinized with regard to structure and reactivity. More recently, Ln(III)‐alkylidene complexes could be accessed, structurally authenticated and successfully employed in Tebbe‐like olefination reactions of ketones.
The base-rate and longer-term relevance of year-to-year change in personality traits
2024-04-12

Personality traits are assumed to change slowly and incrementally. Recent intervention studies apparently challenge this assumption, showing that personality traits can also change quickly and substantially. However, how frequently do such quick changes manifest in the general population? This study sought to determine (1) a base rate of year-to-year changes in the general population and (2) the extent to which these shifts are related to longer-term change patterns. We examined year-to-year change in Big Five traits with nationally representative data from 7005 German participants, annually tracked for up to six years. Year-to-year patterns exhibited stability and change (e.g., ≥ 1 SD year-to-year change in ≈ 20%). Across participants, year-to-year trait score increases and decreases occurred in equal proportions, suggesting that in a given sample, year-to-year changes in different directions average out. Within participants, however, in all domains but agreeableness, year-to-year changes reliably propagated to longer-term trajectories. While much of the year-to-year change faded away in subsequent years, lasting shifts in individuals’ trait levels remained, particularly upon pronounced year-to-year decreases. Overall, (pronounced) year-to-year changes were relatively common, largely reversible, and yet predictive of individuals’ longer-term trajectories. We discuss how the results bridge set-point assumptions with assumptions of incremental trait change.
The Affective Responses to Moderate Physical Activity: A Further Study to Prove the Convergent and the Discriminant Validity for the German Versions of the Feeling Scale and the Felt Arousal Scale
2024-04-12

The present study proves the construct validity of the German versions of the Feeling Scale (FS) and the Felt Arousal Scale (FAS) for measuring the affective responses (affective valence and arousal) for a moderate-intensity jogging (JG) exercise. In previous studies, both scales were validated for a high-intensity bicycle ergometer exercise and for relaxation techniques. In the present study, 194 participants performed the JG exercise for 45 min and completed the FS and the FAS, as well as the Self-Assessment Manikin (SAM), for a self–other comparison in a pre-test-intervention-post-test design. The results of the correlation analyses replicated the previous findings for the high-intensity bicycle ergometer exercise and the relaxation techniques, revealing significant positive correlations for the valence dimension between the FS and the SAM-Pleasure subscale (r = 0.50) and for the arousal dimension between the FAS and the SAM-Arousal subscale (r = 0.16). These findings suggest that the German versions of the FS and the FAS are also suitable for exercises of moderate intensity.
Genetic redundancy in the naphthalene-degradation pathway of Cycloclasticus pugetii strain PS-1 enables response to varying substrate concentrations
2024-04-12

Abstract Polycyclic aromatic hydrocarbon (PAH) contamination in marine environments range from low-diffusive inputs to high loads. The influence of PAH concentration on the expression of functional genes [e.g. those encoding ring-hydroxylating dioxygenases (RHDs)] has been overlooked in PAH biodegradation studies. However, understanding marker-gene expression under different PAH loads can help to monitor and predict bioremediation efficiency. Here, we followed the expression (via RNA sequencing) of Cycloclasticus pugetii strain PS-1 in cell suspension experiments under different naphthalene (100 and 30 mg L−1) concentrations. We identified genes encoding previously uncharacterized RHD subunits, termed rhdPS1α and rhdPS1β, that were highly transcribed in response to naphthalene-degradation activity. Additionally, we identified six RHD subunit-encoding genes that responded to naphthalene exposure. By contrast, four RHD subunit genes were PAH-independently expressed and three other RHD subunit genes responded to naphthalene starvation. Cycloclasticus spp. could, therefore, use genetic redundancy in key PAH-degradation genes to react to varying PAH loads. This genetic redundancy may restrict the monitoring of environmental hydrocarbon-degradation activity using single-gene expression. For Cycloclasticus pugetii strain PS-1, however, the newly identified rhdPS1α and rhdPS1β genes might be potential target genes to monitor its environmental naphthalene-degradation activity.
Structural insights in the GTP-driven monomerization and activation of a bacterial LRRK2 homologue using allosteric nanobodies
2024-04-12

Abstract The Roco proteins are a family of GTPases, characterized by the conserved presence of a Roc-COR tandem domain. These proteins entered the limelight after mutations in human LRRK2 were identified as a major cause of familial Parkinson’s disease. LRRK2 is a large and complex protein combining a GTPase and protein kinase activity, and disease mutations increase the kinase activity, while presumably decreasing the GTPase activity. Although a cross-communication between both catalytic activities has been suggested, the underlying mechanisms and the regulatory role of the GTPase domain remain unknown. Recently, several structures of LRRK2 have been reported, but so far structures of Roco proteins in their activated GTP-bound state are lacking. Here, we use single particle cryo-EM to solve the structure of a simpler bacterial Roco protein (CtRoco) in its GTP-bound state, aided by the use of two conformation-specific nanobodies: NbRoco1 and NbRoco2. This structure presents CtRoco in an active monomeric state, featuring very significant conformational changes compared to the previously solved nucleotide-free dimer structure. In particular, the structure shows a very large GTP-induced conformational change of the LRR domain, unleashing it from the Roc-COR domains, using the LRR-Roc linker as a hinge. Furthermore, this structure shows how NbRoco1 and NbRoco2 collaborate to activate CtRoco in an allosteric way. Altogether, our data provide important new insights in the activation mechanism of Roco proteins, with relevance to LRRK2 regulation, and suggest new routes for the allosteric modulation of their GTPase activity.
Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know
2024-04-12

Abstract Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.
To their Credit: The Aristocracy and Commercial Credit in Europe, c.1750–1820
2024-04-13

The aristocracy and their use of commercial credit are seldom explored in the European comparative context despite important studies of the French aristocracy and their credit relations with shopkeepers, tradesmen and fashion merchants. This article studies the aristocracy and commercial credit in England, Germany and Sweden, by drawing on the normative literature and the account books, receipted bills, correspondence and diaries of several families occupying different echelons of the nobility. We examine the extent and nature of aristocratic engagement with shop credit, the ways in which they manipulated and managed this credit, and their motivations for doing so. We argue that the aristocracy was involved in a modern commercial credit economy and that this was central to their position in society and way of life. Our analysis of the ideals communicated through conduct books and parental advice and the actual credit practices of the aristocracy show that they took their credit arrangements seriously. They had to abide by the rules of commercial credit and settle their accounts: sometimes promptly, most often in a timely manner and only occasionally after considerable delay. The article offers a comparative framework for further and broader studies on the aristocracy within economic history.
Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach
2024-04-13

Abstract Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1–neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.
The role of FraI in cell-cell communication and differentiation in the hormogonia-forming cyanobacterium Nostoc punctiforme
2024-04-13

Abstract Multicellular cyanobacteria, like Nostoc punctiforme , rely on septal junctions for cell-cell communication, which is crucial for coordinating various physiological processes including differentiation of N 2 -fixing heterocysts, spore-like akinetes and hormogonia - short, motile filaments important for dispersal. In this study we functionally characterize a protein, encoded by gene NpF4142 , which in a random mutagenesis approach, initially showed a motility-related function. The reconstructed NpF4142 knockout mutant exhibits further distinct phenotypic traits, including altered hormogonia formation with significant reduced motility, inability to differentiate heterocysts and filament fragmentation. For that reason, we named the protein FraI (fragmentation phenotype). The mutant displays severely impaired cell-cell communication, due to almost complete absence of the nanopore array in the septal cell wall, which is an essential part of the septal junctions. Despite lack of communication, hormogonia in the Δ fraI mutant maintain motility and phototactic behaviour, even though less pronounced than the wild type. This suggests an alternative mechanism for coordinated movement beyond septal junctions. Our study underscores the significance of FraI in nanopore formation and cell differentiation and provides additional evidence for the importance of septal junction formation and communication in various differentiation traits of cyanobacteria. The findings contribute to a deeper understanding of the regulatory networks governing multicellular cyanobacterial behaviour, with implications for broader insights into microbial multicellularity. Importance The filament-forming cyanobacterium Nostoc punctiforme serves as a valuable model for studying cell differentiation, including the formation of nitrogen-fixing heterocysts and hormogonia. Hormogonia filaments play a crucial role in dispersal and plant colonization, providing a nitrogen source through atmospheric nitrogen fixation, thus holding promise for fertilizer-free agriculture. The coordination among the hormogonia cells enabling uniform movement towards the positive signal remains poorly understood. This study investigates the role of septal junction-mediated communication in hormogonia differentiation and motility, by studying a Δ fraI mutant with significantly impaired communication. Surprisingly, impaired communication does not abolish synchronized filament movement, suggesting an alternative coordination mechanism. These findings deepen our understanding of cyanobacterial biology and have broader implications for multicellular behavior in prokaryotes.
PARP1 expression predicts PARP inhibitor sensitivity and correlates with metastatic potential and overall survival in melanoma
2024-04-15

Abstract Metastatic melanoma is still a difficult‐to‐treat cancer type owing to its frequent resistance mechanisms to targeted and immunotherapy. Therefore, we aimed to unravel novel therapeutic strategies for melanoma patients. Preclinical and clinical studies show that melanoma patients may benefit from a treatment with poly (ADP‐ribose) polymerase (PARP) inhibitors (PARPi). In this study, we focus on PARP1 as a potential biomarker to predict the response of melanoma cells to PARPi therapy. We found that melanoma cells with high basal PARP1 expression exhibit significantly increased cell death after PARPi treatment owing to higher PARP1 trapping compared with melanoma cells with low PARP1 expression. In addition, we could demonstrate that PARP1 expression levels are low in nonmalignant skin cells, and metastatic melanomas show considerably higher PARP1 levels compared with primary melanomas. Most strikingly, we found that high PARP1 levels correlate with worse overall survival of late stage metastasized melanoma patients. In conclusion, we show that PARP1 might act as a biomarker to predict the response to PARPi therapy, and that in particular the late stage metastasized melanoma patients are especially sensitive to PARPi therapy owing to elevated PARP1 expression. Our data suggest that the PARPi cytotoxicity primarily will affect the high PARP1 expressing melanoma cells, rather than the low PARP1 expressing nonmalignant skin cells resulting in only low side effects.
AAV-Mediated CAG-Targeting Selectively Reduces Polyglutamine-Expanded Protein and Attenuates Disease Phenotypes in a Spinocerebellar Ataxia Mouse Model
2024-04-15

Polyglutamine (polyQ)-encoding CAG repeat expansions represent a common disease-causing mutation responsible for several dominant spinocerebellar ataxias (SCAs). PolyQ-expanded SCA proteins are toxic for cerebellar neurons, with Purkinje cells (PCs) being the most vulnerable. RNA interference (RNAi) reagents targeting transcripts with expanded CAG reduce the level of various mutant SCA proteins in an allele-selective manner in vitro and represent promising universal tools for treating multiple CAG/polyQ SCAs. However, it remains unclear whether the therapeutic targeting of CAG expansion can be achieved in vivo and if it can ameliorate cerebellar functions. Here, using a mouse model of SCA7 expressing a mutant Atxn7 allele with 140 CAGs, we examined the efficacy of short hairpin RNAs (shRNAs) targeting CAG repeats expressed from PHP.eB adeno-associated virus vectors (AAVs), which were introduced into the brain via intravascular injection. We demonstrated that shRNAs carrying various mismatches with the CAG target sequence reduced the level of polyQ-expanded ATXN7 in the cerebellum, albeit with varying degrees of allele selectivity and safety profile. An shRNA named A4 potently reduced the level of polyQ-expanded ATXN7, with no effect on normal ATXN7 levels and no adverse side effects. Furthermore, A4 shRNA treatment improved a range of motor and behavioral parameters 23 weeks after AAV injection and attenuated the disease burden of PCs by preventing the downregulation of several PC-type-specific genes. Our results show the feasibility of the selective targeting of CAG expansion in the cerebellum using a blood–brain barrier-permeable vector to attenuate the disease phenotype in an SCA mouse model. Our study represents a significant advancement in developing CAG-targeting strategies as a potential therapy for SCA7 and possibly other CAG/polyQ SCAs.
Resequencing the complete SNCA locus in Indian patients with Parkinson’s disease
2024-04-15

Abstract The genetic loci implicated in familial Parkinson’s disease (PD) have limited generalizability to the Indian PD population. We tested mutations and the frequency of known mutations in the SNCA gene in a PD cohort from India. We selected 298 PD cases and 301 age-matched controls for targeted resequencing (before QC), along with 363 PD genomes of Indian ancestry and 1029 publicly available whole genomes from India as healthy controls (IndiGenomes), to determine the frequency of monogenic SNCA mutations. The raw sequence reads were analyzed using an in-house analysis pipeline, allowing the detection of small variants and structural variants using Manta. The in-depth analysis of the SNCA locus did not identify missense or structural variants, including previously identified SNCA mutations, in the Indian population. The familial forms of SNCA gene variants do not play a major role in the Indian PD population and this warrants further research in the under-represented population.