julilili42/papers huggingface dataset:
What Is the Maximum Likelihood Estimate When the Initial Solution to the Optimization Problem Is Inadmissible? The Case of Negatively Estimated Variances
2022-06-30

The default procedures of the software programs Mplus and lavaan tend to yield an inadmissible solution (also called a Heywood case) when the sample is small or the parameter is close to the boundary of the parameter space. In factor models, a negatively estimated variance does often occur. One strategy to deal with this is fixing the variance to zero and then estimating the model again in order to obtain the estimates of the remaining model parameters. In the present article, we present one possible approach for justifying this strategy. Specifically, using a simple one-factor model as an example, we show that the maximum likelihood (ML) estimate of the variance of the latent factor is zero when the initial solution to the optimization problem (i.e., the solution provided by the default procedure) is a negative value. The basis of our argument is the very definition of ML estimation, which requires that the log-likelihood be maximized over the parameter space. We present the results of a small simulation study, which was conducted to evaluate the proposed ML procedure and compare it with Mplus’ default procedure. We found that the proposed ML procedure increased estimation accuracy compared to Mplus’ procedure, rendering the ML procedure an attractive option to deal with inadmissible solutions.
Paradigm gaps are associated with weird "distributional semantics" properties: Russian defective nouns and their case and number paradgim
2022-06-30

This study investigates the phenomenon of defectiveness in Russian case and number noun paradigms from the perspective of distributional semantics. We made use of word embeddings, high-dimensional vectors trained from large text corpora, and compared the observed paradigms of nouns that are defective in the genitive plural, as suggested by Zaliznjak (1977), with the observed paradigms for non-defective paradigms. When the embeddings of about 20,000 inflected forms were projected onto a two-dimensional space, clusters of case and number within case were found, suggesting global semantic similarity for words with the same inflectional features. Moreover, defective lexemes were characterized by lower semantic transparency, in that inflected forms of the same lexeme are semantically less similar to each other, and their meanings are also more idiosyncratic. Furthermore, compared to non-defective lexemes, inflected forms from defective lexemes are further away from the idealized average case-number meanings, obtained by averaging over the vectors of all inflected forms of the same case-number combination. As a consequence, the semantics of defective forms are predicted less precisely by a simple model of conceptualization that assumes that the meaning of a given Russian inflected form is approximated well by the sum of pertinent embeddings of the lexeme, case, and number within case. We conclude that semantics, at least the kind captured by word embeddings, also contributes to the defectiveness of Russian noun paradigms.
A Complete Reconstruction, New Edition and Interpretation of the Sumerian Morality Tale ‘The Old Man and the Young Girl’
2022-06-30

Abstract This paper presents the complete reconstruction of the Sumerian tale ‘The Old Man and the Young Girl.’ The identification of a new manuscript permits not only the recovery of the hitherto missing beginning and end, but also a reassessment of the text’s plot, function, and socio-cultural context. Rather than as a folktale, I propose to interpret it as a satirical morality tale, which was composed in scribal milieux.
Negami: An Augmented Reality App for the Treatment of Spatial Neglect After Stroke (Preprint)
2022-06-30

<sec> <title>BACKGROUND</title> A widely applied and effective rehabilitation method for patients experiencing spatial neglect after a stroke is “visual exploration training.” Patients improve their ipsilesional bias of attention and orientation by training exploration movements and search strategies toward the contralesional side of space. In this context, gamification can have a positive influence on motivation for treatment and thus on the success of treatment. In contrast to virtual reality applications, treatment enhancements through augmented reality (AR) have not yet been investigated, although they offer some advantages over virtual reality. </sec> <sec> <title>OBJECTIVE</title> This study aimed to develop an AR-based app (Negami) for the treatment of spatial neglect that combines visual exploration training with active, contralesionally oriented rotation of the eyes, head, and trunk. </sec> <sec> <title>METHODS</title> The app inserts a virtual element (origami bird) into the real space surrounding the patient, which the patient explores with the camera of a tablet. Subjective reports from healthy elderly participants (n=10) and patients with spatial neglect after stroke (n=10) who trained with the new Negami app were analyzed. Usability, side effects, and game experience were assessed by various questionnaires. </sec> <sec> <title>RESULTS</title> Training at the highest defined difficulty level was perceived as differently challenging but not as frustrating by the group of healthy elderly participants. The app was rated with high usability, hardly any side effects, high motivation, and entertainment. The group of patients with spatial neglect after stroke consistently evaluated the app positively on the dimensions of motivation, satisfaction, and fun. </sec> <sec> <title>CONCLUSIONS</title> The Negami app represents a promising extension by adding AR to traditional exploration training for spatial neglect. Through participants’ natural interaction with the physical surrounding environment during playful tasks, side effects as symptoms of cybersickness are minimized and patients’ motivation appeared to markedly increase. The use of AR in cognitive rehabilitation programs and the treatment of spatial neglect seems promising and should receive further investigation. </sec>
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis
2022-07-01

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by aberrant alternative splicing (AS). Nuclear loss and cytoplasmic accumulation of the splicing factor TDP-43 in motor neurons (MN) are hallmarks of ALS at late stages of the disease. However, it is unknown if altered AS is present before TDP-43 pathology occurs. Here, we investigate altered AS and its origins in early stages of ALS using human induced pluripotent stem cell-derived motor neurons (MNs) from sporadic and familial ALS patients. We find high levels of the RNA-binding proteins NOVA1, NOVA2, and RBFOX2 in the insoluble protein fractions and observe that AS events in ALS-associated MNs are enriched for binding sites of these proteins. Our study points to an early disrupted function of NOVA1 that drives AS changes in a complex fashion, including events caused by a consistent loss of NOVA1 function. NOVA1 exhibits increased cytoplasmic protein levels in early stage MNs without TDP-43 pathology in ALS postmortem tissue. As nuclear TDP-43 protein level depletes, NOVA1 is reduced. Potential indications for a reduction of NOVA1 also came from mice over-expressing TDP-43 lacking its nuclear localization signal and iPSC-MN stressed with puromycin. This study highlights that additional RBP-RNA perturbations in ALS occur in parallel to TDP-43.
Non-Invasive Three-Dimensional Cell Analysis in Bioinks by Raman Imaging
2022-07-01

3D bioprinting is an emerging biofabrication strategy using bioinks, comprising cells and biocompatible materials, to produce functional tissue models. Despite progress in building increasingly complex objects, biological analyses in printed constructs remain challenging. Especially, methods that allow non-invasive and non-destructive evaluation of embedded cells are largely missing. Here, we implemented Raman imaging for molecular-sensitive investigations on bioprinted objects. Different aspects such as culture formats (2D, 3D-cast, and 3D-printed), cell types (endothelial cells and fibroblasts), and the selection of the biopolymer (alginate, alginate/nanofibrillated cellulose, alginate/gelatin) were considered and evaluated. Raman imaging allowed for marker-independent identification and localization of subcellular components against the surrounding biomaterial background. Furthermore, single-cell analysis of spectral signatures, performed by multivariate analysis, demonstrated discrimination between endothelial cells and fibroblasts and identified cellular features influenced by the bioprinting process. In summary, Raman imaging was successfully established to analyze cells in 3D culture in situ and evaluate them with regard to the localization of different cell types and their molecular phenotype as a valuable tool for quality control of bioprinted objects.
Modular-based psychotherapy (MoBa) versus cognitive–behavioural therapy (CBT) for patients with depression, comorbidities and a history of childhood maltreatment: study protocol for a randomised controlled feasibility trial
2022-07-01

Introduction In depression treatment, most patients do not reach response or remission with current psychotherapeutic approaches. Major reasons for individual non-response are interindividual heterogeneity of etiological mechanisms and pathological forms, and a high rate of comorbid disorders. Personalised treatments targeting comorbidities as well as underlying transdiagnostic mechanisms and factors like early childhood maltreatment may lead to better outcomes. A modular-based psychotherapy (MoBa) approach provides a treatment model of independent and flexible therapy elements within a systematic treatment algorithm to combine and integrate existing evidence-based approaches. By optimally tailoring module selection and application to the specific needs of each patient, MoBa has great potential to improve the currently unsatisfying results of psychotherapy as a bridge between disorder-specific and personalised approaches. Methods and analysis In a randomised controlled feasibility trial, N=70 outpatients with episodic or persistent major depression, comorbidity and childhood maltreatment are treated in 20 individual sessions with MoBa or standard cognitive–behavioural therapy for depression. The three modules of MoBa focus on deficits associated with early childhood maltreatment: the systems of negative valence, social processes and arousal. According to a specific questionnaire-based treatment algorithm, elements from cognitive behavioural analysis system of psychotherapy, mentalisation-based psychotherapy and/or mindfulness-based cognitive therapy are integrated for a personalised modular procedure. As a proof of concept, this trial will provide evidence for the feasibility and efficacy (post-treatment and 6-month follow-up) of a modular add-on approach for patients with depression, comorbidities and a history of childhood maltreatment. Crucial feasibility aspects include targeted psychopathological mechanisms, selection (treatment algorithm), sequence and application of modules, as well as training and supervision of the study therapists. Ethics and dissemination This study obtained approval from the independent Ethics Committees of the University of Freiburg and the University of Heidelberg. All findings will be disseminated broadly via peer-reviewed articles in scientific journals and contributions to national and international conferences. Trial registration number DRKS00022093.
Labour realities at Amazon and COVID-19: obstacles and collective possibilities for its warehouse workers and MTurk workers
2022-07-01

The COVID-19 pandemic has only further magnified the already growing political-economic and societal power of platforms. This article delves into the different realities of platform workers by juxtaposing two cases: location-based Amazon warehouse workers and web-based Amazon Mechanical Turk (MTurk) workers. Informed by a historical materialist approach that accounts both for the contextual conditions and the agency of workers, this article asks: how does the organisation of workers (location-based vs. web-based) relate differently to their labour organisation and mobilisation in light of the COVID-19 pandemic? By investigating agency through analysing the structural power of workers (that is, marketplace and workplace), this article argues that both Amazon warehouse workers and MTurk workers experienced a further dwindling of their already weak marketplace power as a result of larger co-evolving political-economic conditions. The former workforce did experience, however, an increase in their workplace power given the growth of Amazon during the pandemic. The fact that they are location-based plays a crucial role in framing their struggle vis-à-vis the direct health risks and their ability to mobilise to disrupt the circulation line. MTurk workers, on the other hand, experienced a further weakening of their workplace power. Given the challenges in disrupting web-based gig labour, workers continue to express their agency through more alternative forms by instrumentalising digital spaces to foster solidarity and support each other for better working conditions. These contrasting case studies shed light therefore on the wider repercussions of the nature of the platform and its relation to the political-economic conditions for labour’s agency.
Are control processes domain-general? A replication of ‘To adapt or not to adapt? The question of domain-general cognitive control’ (Kan et al. 2013)
2022-07-01

Conflict and conflict adaptation are well-studied phenomena in experimental psychology. Standard tasks investigating causes and outcomes of conflict during information processing include the Stroop, the Flanker and the Simon task. Interestingly, recent research efforts have moved toward investigating whether conflict in one task domain influences information processing in another task domain, typically referred to as cross-task conflict adaptation. These transfer effects are of central importance for theories about our cognitive architecture, as they are interpreted as pointing towards domain-general cognitive mechanisms. Given the importance of these cross-task transfer effects, the current paper targets at replicating one of the key findings. Specifically, Kan et al. (Kan et al . 2013 Cognition 129 , 637–651) showed that reading syntactically ambiguous sentences result in processing adjustments in subsequent Stroop trials. This result is in line with the idea that conflict monitoring works in a domain overarching manner. The present paper presents two replication studies: (i) exact replication: identical sentence-reading task intermixed with stimulus-based Stroop task and (ii) conceptual replication: identical sentence-reading task intermixed with response-based Stroop task. Power calculations were based on the original paper. Both experiments were pre-registered. Despite the experiments being closely designed according to the original study, there was no evidence supporting the hypothesis regarding cross-domain conflict adaptation.
A RAS-Independent Biomarker Panel to Reliably Predict Response to MEK Inhibition in Colorectal Cancer
2022-07-01

Background: In colorectal cancer (CRC), mutations of genes associated with the TGF-β/BMP signaling pathway, particularly affecting SMAD4, are known to correlate with decreased overall survival and it is assumed that this signaling axis plays a key role in chemoresistance. Methods: Using CRISPR technology on syngeneic patient-derived organoids (PDOs), we investigated the role of a loss-of-function of SMAD4 in sensitivity to MEK-inhibitors. CRISPR-engineered SMAD4R361H PDOs were subjected to drug screening, RNA-Sequencing, and multiplex protein profiling (DigiWest®). Initial observations were validated on an additional set of 62 PDOs with known mutational status. Results: We show that loss-of-function of SMAD4 renders PDOs sensitive to MEK-inhibitors. Multiomics analyses indicate that disruption of the BMP branch within the TGF-β/BMP pathway is the pivotal mechanism of increased drug sensitivity. Further investigation led to the identification of the SFAB-signature (SMAD4, FBXW7, ARID1A, or BMPR2), coherently predicting sensitivity towards MEK-inhibitors, independent of both RAS and BRAF status. Conclusion: We identified a novel mutational signature that reliably predicts sensitivity towards MEK-inhibitors, regardless of the RAS and BRAF status. This finding poses a significant step towards better-tailored cancer therapies guided by the use of molecular biomarkers.
The advice less taken: The consequences of receiving unexpected advice
2022-07-01

Abstract Although new information technologies and social networks make a wide variety of opinions and advice easily accessible, one can never be sure to get support on a focal judgment task. Nevertheless, participants in traditional advice taking studies are by default informed in advance about the opportunity to revise their judgment in the light of advice. The expectation of advice, however, may affect the weight assigned to it. The present research therefore investigates whether the advice taking process depends on the expectation of advice in the judge-advisor system (JAS). Five preregistered experiments (total N = 2019) compared low and high levels of advice expectation. While there was no evidence for expectation effects in three experiments with block-wise structure, we obtained support for a positive influence of advice expectation on advice weighting in two experiments implementing sequential advice taking. The paradigmatic disclosure of the full procedure to participants thus constitutes an important boundary condition for the ecological study of advice taking behavior. The results suggest that the conventional JAS procedure fails to capture a class of judgment processes where advice is unexpected and therefore weighted less.
Investigating Peptide‐Coenzyme A Conjugates as Chemical Probes for Proteomic Profiling of N‐Terminal and Lysine Acetyltransferases
2022-07-01

Abstract Acetyl groups are transferred from acetyl‐coenzyme A (Ac‐CoA) to protein N‐termini and lysine side chains by N‐terminal acetyltransferases (NATs) and lysine acetyltransferases (KATs), respectively. Building on lysine‐CoA conjugates as KAT probes, we have synthesized peptide probes with CoA conjugated to N‐terminal alanine (α‐Ala‐CoA), proline (α‐Pro‐CoA) or tri‐glutamic acid (α‐3Glu‐CoA) units for interactome profiling of NAT complexes. The α‐Ala‐CoA probe enriched the majority of NAT catalytic and auxiliary subunits, while a lysine CoA‐conjugate bound only a subset of endogenous KATs. Interactome profiling with the α‐Pro‐CoA probe showed reduced NAT recruitment in favor of metabolic CoA binding proteins and α‐3Glu‐CoA steered the interactome towards NAA80 and NatB. These findings agreed with the inherent substrate specificities of the target proteins and showed that N‐terminal CoA‐conjugated peptides are versatile probes for NAT complex profiling in lysates of physiological and pathological backgrounds.
TTC30A and TTC30B Redundancy Protects IFT Complex B Integrity and Its Pivotal Role in Ciliogenesis
2022-07-01

Intraflagellar transport (IFT) is a microtubule-based system that supports the assembly and maintenance of cilia. The dysfunction of IFT leads to ciliopathies of variable severity. Two of the IFT-B components are the paralogue proteins TTC30A and TTC30B. To investigate whether these proteins constitute redundant functions, CRISPR/Cas9 was used to generate single TTC30A or B and double-knockout hTERT-RPE1 cells. Ciliogenesis assays showed the redundancy of both proteins while the polyglutamylation of cilia was affected in single knockouts. The localization of other IFT components was not affected by the depletion of a single paralogue. A loss of both proteins led to a severe ciliogenesis defect, resulting in no cilia formation, which was rescued by TTC30A or B. The redundancy can be explained by the highly similar interaction patterns of the paralogues; both equally interact with the IFT-B machinery. Our study demonstrates that a loss of one TTC30 paralogue can mostly be compensated by the other, thus preventing severe ciliary defects. However, cells assemble shorter cilia, which are potentially limited in their function, especially because of impaired polyglutamylation. A complete loss of both proteins leads to a deficit in IFT complex B integrity followed by disrupted IFT and subsequently no cilia formation.
Inferring Markovian quantum master equations of few-body observables in interacting spin chains
2022-07-01

Abstract Full information about a many-body quantum system is usually out-of-reach due to the exponential growth—with the size of the system—of the number of parameters needed to encode its state. Nonetheless, in order to understand the complex phenomenology that can be observed in these systems, it is often sufficient to consider dynamical or stationary properties of local observables or, at most, of few-body correlation functions. These quantities are typically studied by singling out a specific subsystem of interest and regarding the remainder of the many-body system as an effective bath. In the simplest scenario, the subsystem dynamics, which is in fact an open quantum dynamics, can be approximated through Markovian quantum master equations. Here, we formulate the problem of finding the generator of the subsystem dynamics as a variational problem, which we solve using the standard toolbox of machine learning for optimization. This dynamical or ‘Lindblad’ generator provides the relevant dynamical parameters for the subsystem of interest. Importantly, the algorithm we develop is constructed such that the learned generator implements a physically consistent open quantum time-evolution. We exploit this to learn the generator of the dynamics of a subsystem of a many-body system subject to a unitary quantum dynamics. We explore the capability of our method to recover the time-evolution of a two-body subsystem and exploit the physical consistency of the generator to make predictions on the stationary state of the subsystem dynamics.
Revealing local structural properties of an atomically thin MoSe2 surface using optical microscopy
2022-07-01

Using a triangular molybdenum diselenide (MoSe 2 ) flake as surface-enhanced Raman spectroscopy (SERS) platform, we demonstrate the dependency of the Raman enhancement on laser beam polarization and local structure using copper phthalocyanine (CuPc) as probe. Second harmonic generation (SHG) and photoluminescence spectroscopy and microscopy are used to reveal the structural irregularities of the MoSe 2 flake. The Raman enhancement in the focus of an azimuthally polarized beam, which possesses exclusively an in-plane electric field component is stronger than the enhancement by a focused radially polarized beam, where the out-of-plane electric field component dominates. This phenomenon indicates that the face-on oriented CuPc molecules strongly interact with the MoSe 2 flake via charge transfer and dipole–dipole interaction. Furthermore, the Raman scattering maps on the irregular MoSe 2 surface show a distinct correlation with the SHG and photoluminescence optical images, indicating the relationship between local structure and optical properties of the MoSe 2 flake. These results contribute to understand the impacts of local structural properties on the Raman enhancement at the surface of the 2D transition-metal dichalcogenide.