Negative Version Research Articles

Deciphering multi-phase inversion tectonics in the southern Dezful Embayment: insights from the Rag-e-Sefid Oilfield, SW Iran

ABSTRACT Identification of inversion tectonics and inverted structures is very important in petroleum exploration and production due to the positive or negative impacts they can exert on the hydrocarbon traps. In order to characterize the occurrence of multi-phase inversion tectonics and its effect in the Rag-e-Sefid Oilfield, located in the southern Dezful Embayment (SW Iran), this research describes the structural style and deformation history through structural and tectono-sedimentary analyses. The results obtained from the interpretation of seismic profiles and the investigation of the geometry of the sedimentary layers across the growth structures indicate that the Rag-e-Sefid anticline is created from multiple fault-propagation folds. The final shape and geometry of the Rag-e-Sefid anticline are affected by the Rag-e-Sefid and Nourooz-Hendijan-Izeh Faults activity. The deformation history in the north-western part of the Rag-e-Sefid anticline is older than the south-eastern part of it. The Rag-e-Sefid Fault set in the north-western and south-eastern parts of the Rag-e-Sefid Oilfield experienced activity at least during seven and four tectonic phases, respectively. Multiple fault-propagation folding and the fold axis rotation in the north-western part of the Rag-e-Sefid anticline controlled by the presence of several décollement surfaces and the occurrence of inversion tectonics along the pre-existing basement structures. Three-phase inversion tectonics along the Nourooz-Hendijan-Izeh Fault and the Rag-e-Sefid Fault set in the north-western part of the Rag-e-Sefid Oilfield occurred at the Late Devonian-Carboniferous (positive inversion), Permian-Early Triassic (negative inversion), and Late Cenomanian-Early Turonian (positive inversion) boundaries and modified the evolutionary history of the sedimentary basin. The inversion affected hydrocarbon trap development at the Late Cretaceous and controlled their current conditions in the southern Dezful Embayment. Based on the hydrocarbon migration in these regions from the Late Miocene to the present day, the N-S trending (Pan Africa trend) north-western part of the Rag-e-Sefid anticline has a larger share of oil and gas compared to the NW-SE trending (Zagros trend) south-eastern part. The results of this study could add data to worldwide examples of the positive impact of tectonic inversion on the hydrocarbon traps development in the foreland of a collisional orogen.

An explainable artificial intelligence-enabled electrocardiogram analysis model for the classification of reduced left ventricular function.

The black box nature of artificial intelligence (AI) hinders the development of interpretable AI models that are applicable in clinical practice. We aimed to develop an AI model for classifying patients of reduced left ventricular ejection fraction (LVEF) from 12-lead electrocardiograms (ECG) with the decision-interpretability. We acquired paired ECG and echocardiography datasets from the central and co-operative institutions. For the central institution dataset, a random forest model was trained to identify patients with reduced LVEF among 29 907 ECGs. Shapley additive explanations were applied to 7196 ECGs. To extract the model's decision criteria, the calculated Shapley additive explanations values were clustered for 192 non-paced rhythm patients in which reduced LVEF was predicted. Although the extracted criteria were different for each cluster, these criteria generally comprised a combination of six ECG findings: negative T-wave inversion in I/V5-6 leads, low voltage in I/II/V4-6 leads, Q wave in V3-6 leads, ventricular activation time prolongation in I/V5-6 leads, S-wave prolongation in V2-3 leads, and corrected QT interval prolongation. Similarly, for the co-operative institution dataset, the extracted criteria comprised a combination of the same six ECG findings. Furthermore, the accuracy of seven cardiologists' ECG readings improved significantly after watching a video explaining the interpretation of these criteria (before, 62.9% ± 3.9% vs. after, 73.9% ± 2.4%; P = 0.02). We visually interpreted the model's decision criteria to evaluate its validity, thereby developing a model that provided the decision-interpretability required for clinical application.

Learning Lessons from the Populist Defeats: From Negative to Positive Constitutionalism

The article explains how populists have exploited the weaknesses of liberal constitutionalism and the public-private divide. It argues that populists have not rejected constitutionalism as a project but a negative version of it. In its place, they incorporated their vision of a government unrestricted by individual rights and entered the private sphere with their doctrines. The lesson from the victories of populism is therefore to move toward positive constitutionalism that ensures the well-being of all. Drawing on the concept of relational autonomy, the article explains what this shift consists of in the areas of reproductive rights and gender-based violence. The conclusions outline a shift in the operation of the basic principles of constitutionalism, focusing on the relational nature of rights understood not only as shields, but also as claims to positive state action.

More than words: Speech production in first-episode psychosis predicts later social and vocational functioning.

Several disturbances in speech are present in psychosis; however, the relationship between these disturbances during the first-episode of psychosis (FEP) and later vocational functioning is unclear. Demonstrating this relationship is critical if we expect speech and communication deficits to emerge as targets for early intervention. We analyzed three 1-min speech samples using automated speech analysis and Bayes networks in an antipsychotic-naive sample of 39 FEP patients and followed them longitudinally to determine their vocational status (engaged or not engaged in employment education or training-EET vs. NEET) after 6-12 months of treatment. Five baseline linguistic variables with prior evidence of clinical relevance (total and acausal connectives use, pronoun use, analytic thinking, and total words uttered in a limited period) were included in a Bayes network along with follow-up NEET status and Social and Occupational Functioning Assessment Scale (SOFAS) scores to determine dependencies among these variables. We also included clinical (Positive and Negative Syndrome Scale 8-item version (PANSS-8)), social (parental socioeconomic status), and cognitive features (processing speed) at the time of presentation as covariates. The Bayes network revealed that only total words spoken at the baseline assessment were directly associated with later NEET status and had an indirect association with SOFAS, with a second set of dependencies emerging among the remaining linguistic variables. The primary (speech-only) model outperformed models including parental socioeconomic status, processing speed or both as latent variables. Impoverished speech, even at subclinical levels, may hold prognostic value for functional outcomes and warrant consideration when providing measurement based care for first-episode psychosis.

The Fallacy of Misplaced Presumption.

One takes one's word that p when a source vouches for p and one accepts the word of that source. If the source is reliable in this case, p is acceptable. The reliability of the source is a measure of its plausibility. If a source has the relevant competence, credibility, authority, that word is acceptable. Likewise, the word may be acceptable if accompanied by a cogent argument, but presumption may be misplaced. One may recognize a presumption for a statement when such recognition is not justified, the positive version of the fallacy. One may refuse to recognize a presumption for a statement when there really is a presumption for the statement, the negative version of the fallacy. The essay proceeds to explore various dimensions of when it is justified to take a source's word for a claim, and when it is justified to reject a claim from a source. The discussion ranges over considerations of sexism and race, cultural differences, and the relationship of presumptions to fallacies. Also considered is the role of trust in taking someone's word and the factors involved in trusting someone.

Neogene subsidence rates of the southern Peri Pannonian realm (1D basin modeling): Constraints on the extensional geodynamic drivers of the asymmetric Toplica basin (central-southern Serbia)

With the objective to quantify the Neogene extensional geodynamic drivers of the Peri Pannonian Realm s.l., a series of 1D basin models were carried out by integrating the available geological and geochemical data extracted from the landlocked Toplica Basin (central-southern Serbia; Serbo-Macedonian Unit). The modeling was conducted on four wells located immediately south of Jastrebac Mt., in the area of the Toplica Basin. The investigated southernmost point of the Peri Pannonian Ream s.l. (areas surrounding the basin, to the south of rivers Danube and Sava) underwent intense tectonically-driven subsidence episodes, which lasted from the Lower Miocene up to the Pliocene. The restored Neogene burial history (subsidence rates), paleotemperature, and calibrated paleo-heat fluxes (or changes in the ancient crustal or basal heat flow) indicated a two-staged crustal stretching of the wider Toplica area. The combined tectonic, i.e., thermal subsidence, resulted in a very high sedimentation rate, having an average ca. 300–400 m/Ma (Čučale unit). The intense tectonically-driven subsidence is consistent with the involvement of extensional processes, affecting the crustal and lithospheric layers of the retreating Adria/Dinarides, amplified by a distant Carpathian rollback stage. The regional extension led to the asymmetric opening and the formation of the Toplica Lower Miocene mesosaline to the freshwater lacustrine system. Higher participation of mixed microbiologically reworked/terrestrial organic matter incorporated in oil-prone Type II kerogen mainly characterized the investigated lacustrine sedimentary sequence. The latest Oligocene–earliest Neogene subsidence onset was characterized by elevated temperatures, affecting the early development of the oil window (ca. at 16 Ma). The 1D models also showed that the Lower Čučale unit achieved ca. 50% transformation ratio for the Type II organic matter. The two intra-Neogene extensional episodes suggested the existence of the Early Neogene “syn-rift” stage, followed by a thermal sagging. The Neogene continuous thinning of the overriding Serbo-Macedonian continental crust contributed to the “negative inversion” of the former pre-Neogene nappes. Therefore, Neogene tectonic reactivation induced contemporaneous subsidence, further allowing the extensional rise of the Jastrebac core complex.

Negative structural inversion: an overview

The same sense movement on any given fault plane occurs much more frequently compared to the cases when the sense reverses. Therefore, positive or negative structural inversions are regarded as special cases within the much more general and typical process of fault reactivation.Extensional reactivation of former reverse faults or, specifically thrust planes in thrust fold belts, designated as “negative inversion”, received much less attention by both the petroleum industry and the academia than the opposite process.Based on the structural review of many case studies of positive and negative inversion they display contrasting kinematic patterns. One of the obvious structural differences is related to the geometry of short-cut structures developed during the more advanced stage of inversion. In the case of positive inversion, a short-cut thrust develops within the footwall of the major inverted fault to better accommodate the ongoing shortening. In contrast, a short-cut normal fault develops within the hanging wall of the partially inverted master fault during negative inversion.Based on a worldwide compilation there are examples of hydrocarbon fields with valid traps associated with negative inversion. Therefore, we suggest that even though negative inversion may not be as important for petroleum exploration as its positive counterpart, yet, it may produce more traps in the internal parts of thrust fold belt than currently perceived.At present, case studies of negative inversion defined by the extensional reactivation of pre-existing thrust planes are relatively rare, compared to the more frequent documentation of positive structural inversion in published literature. Whether this disparity between negative and positive inversion is a result of non-observation in the subsurface, at the expense of the former, or it is caused by a more fundamental structural difference between the two processes, it remains to be seen.

AutoCRW: Learning based robust watermarking for smart city applications

AbstractDeep learning has become a promising model in the industry due to its superior learning accuracy and efficiency. In addition to conventional applications, such as fraud detection, natural language processing, image classification and reconstruction, object detection and segmentation this model can be widely used for data hiding, that is, watermarking. Existing transformed‐domain‐based watermarking provided better robustness toward attacks. In this article, an interesting autoencoder convolutional neural network (CNN)‐based watermarking technique, AutoCRW, is proposed, which can prevent intellectual property theft of digital images. First, the autoencoder functionality of CNN generates two versions of the same image, namely positive and negative version of the images, which decompose by a transformed domain scheme. Then, watermark information is embedded into the output images, which can be extracted to realize copyright protection and ownership verification. Finally, a denoising convolutional neural network (DnCNN) is employed over the extracted mark to ensure the robustness of the watermarking system. Extensive experiments demonstrate that the proposed algorithm has high invisibility and good robustness against several attacks.

Showing and telling—How directors combine embodied demonstrations and verbal descriptions to instruct in theater rehearsals

In theater as a bodily-spatial art form, much emphasis is placed on the way actors perform movements in space as an important multimodal resource for creating meaning. In theater rehearsals, movements are created in series of directors' instructions and actors' implementations. Directors' instructions on how to conduct a movement often draw on embodied demonstrations in contrast to verbal descriptions. For instance, to instruct an actress to act like a school girl a director can use depictive (he demonstrates the expected behavior) instead of descriptive (“can you act like a school girl”) means. Drawing on a corpus of 400 h video recordings of rehearsal interactions in three German professional theater productions, from which we selected 265 cases, we examine ways to instruct movement-based actions in theater rehearsals. Using a multimodally extended ethnomethodological-conversation analytical approach, we focus on the multimodal details that constitute demonstrations as complex action types. For the present article, we have chosen nine instances, through which we aim to illuminate (1) The difference in using embodied demonstrations versus verbal descriptions to instruct; (2) typical ways directors combine verbal descriptions with embodied demonstrations in their instructions. First, we ask what constitutes a demonstration and what it achieves in comparison to verbal descriptions. Using a typical case, we illustrate four characteristics of demonstrations that all of the cases we studied share. Demonstrations (1) are embedded in instructional activities; (2) show and do not tell; (3) are responded to by emulating what was shown; (4) are rhetorically shaped to convey the instruction's focus. However, none of the 265 demonstrations we investigated were produced without verbal descriptions. In a second step we therefore ask in which typical ways verbal descriptions accompany embodied demonstrations when directors instruct actors how to play a scene. We distinguish four basic types. Verbal descriptions can be used (1) to build the demonstration itself; (2) to delineate a demonstration verbally within an instruction; (3) to indicate positive (what should be done) and negative (what should be avoided) versions of demonstrations; (4) as an independent means to describe the instruction's focus in addition to the demonstration. Our study contributes to research on how embodied resources are used to create meaning and how they combine with and depend on verbal resources.

The Mesozoic tectonic evolution of the East China Sea Basin: New insights from 3D seismic reflection data

The Mesozoic is a significant period in the East China Sea Basin (ECSB), since it recorded the tectonic transition from the Triassic Tethys tectonic domain to the subsequent Jurassic-Cretaceous Paleo-Pacific domain. However, the Mesozoic tectonic evolution of the East China Sea Basin is not well defined, and it has been highly debated in recent years. Here high-quality 3D seismic reflection data, information about fault timing, and fault maps were employed to analyze Mesozoic faulting and evolution of the ECSB. This study significantly improves our understanding of the Mesozoic tectonic evolution of the ECSB. Our results demonstrate that two sets of Mesozoic faults developed in the ECSB: (1) NW-striking faults are typical negative inversion structures and initially formed as low-angle thrusts as the result of multiphase plate convergence during Triassic. Then, the thrusts reactivated as extensional or transtensional faults during Cretaceous, which are interpreted to be related to NNW-SSE oblique extension associated with roll-back of the subduction zone of Paleo-Pacific plate. (2) The NE-striking faults are inferred to be thrust structures formed during the Early to Middle Jurassic. Flat-slab subduction of the Paleo-Pacific plate is introduced to explain the compression event during this stage. The NE-striking reactivated and newly-formed extensional faults were then developed extensively in the ECSB during the Cretaceous. The NNW-SSE oblique extension played a dominant role in this faulting event, which is related to roll-back of the subduction zone of Paleo-Pacific plate. Furthermore, the NE-striking faults continued to propagate cut through the Cenozoic sequence, since the strike of these faults is perpendicular to the Cenozoic extension stress field.

Negative solvatochromism and sign inversion of circularly polarized luminescence in chiral exciplexes as a function of solvent polarity

The properties of chiral donor–acceptor systems displaying CPL sign inversion are investigated in solvents of different polarity. The solvent enables control of their deexcitation pathways favoring either locally excited or charge-transfer states.

ЭКГ-признаки транзиторного синдрома Бругада у пациента после COVID-19

The article presents a description of a clinical case of the appearance of characteristic ECG signs of Brugada syndrome type 1 in the form of incomplete blockade of the right bundle branch block, «convex» ST elevation of 2 mm and negative symmetrical T-wave inversion in V1-V2 in a practically healthy patient after a new coronavirus infection (COVID-19). On the control ECG performed a week later, these signs reduced to a latent form. However, there is an assumption that the Brugada syndrome in a woman had existed in a latent form, and against the background of COVID-19, it transformed into its active variant. Unfortunately, we do not have data on how long these signs were present on the ECG, as the ECG was recorded a week after COVID-19. The clinical case we demonstrate shows a possible relationship between the transient nature of type 1 Brugada syndrome and COVID-19, which requires further study. The article also provides examples of other clinical cases of the appearance of signs of Brugada syndrome on the ECG in patients with COVID-19 according to various literature data.

Negative moments of orthogonal polynomials

Abstract If a sequence indexed by nonnegative integers satisfies a linear recurrence without constant terms, one can extend the indices of the sequence to negative integers using the recurrence. Recently, Cigler and Krattenthaler showed that the negative version of the number of bounded Dyck paths is the number of bounded alternating sequences. In this paper, we provide two methods to compute the negative versions of sequences related to moments of orthogonal polynomials. We give a combinatorial model for the negative version of the number of bounded Motzkin paths. We also prove two conjectures of Cigler and Krattenthaler on reciprocity between determinants.

Transrenal DNA detection of Mycobacterium tuberculosis in patients with pulmonary tuberculosis.

Multiple attempts have been made to use biological samples other than sputum to diagnose tuberculosis (TB). Sputum acid-fast bacillus (AFB) microscopy is the fastest, most straightforward, and most inexpensive method for diagnosing pulmonary TB. However, urine can be used in place of sputum owing to its various advantages, such as a noninvasive method of collection, convenient handling and storage, and minimal risk of infection in health-care workers involved in sample collection. In this study, we aimed to assess the suitability of urine as a sample to obtain transrenal DNA (trDNA) to diagnose TB. This study involved several patients with TB undergoing inpatient treatment, whose AFB microscopy showed negative inversion. Here, 51 urine samples were collected from 40 patients with TB and examined to confirm the presence of trDNA. First, we compared the efficiency of two trDNA extraction methods. Although molecular diagnosis using GeneXpert yielded negative results, a peculiarity was observed. There was no significant difference between GeneXpert findings and our results nor was there any difference in the sequential trDNA samples obtained. However, even when GeneXpert results were negative, trDNA was detected in seven out of ten samples using the anchor extraction method. Further studies are needed to establish biomarkers for the progression of TB treatment.

Effect of transcranialdirect current stimulation on the right brain temporal area on processing approach and avoidance attitudes with negation

Language describes approach/avoidance intentionality by means of attitudinal verbs (e.g., accept vs. reject). The right superior temporal sulcus (rSTS) has been shown to be recruited in processing action goals and approach intentionality in social contexts. In this study, we examine whether transcranial direct current stimulation (tDCS) of this area improves the processing of attitudinal verbs (either of approach or avoidance) in the context of affirmative and negative sentences [e.g., Julio (did not)/included meat on the grocery list]. After being subjected to tDCS, 46 participants were given sentences for passive reading. Sentences were displayed in segments with a fixed time of exposition, and a verb, either the one mentioned in the sentence or an alternative one was displayed 1,500 ms after the sentence (e.g., included vs. excluded, in the example). Participants were told to read them and then press the space bar to continue the experiment. Results showed shorter latencies for approach verbs that were either mentioned in approach sentences or the alternatives in avoidance sentences, both in affirmative and negative versions under anodal conditions compared to sham conditions. Thus, the anodal stimulation of rSTS affected the accessibility of approach verbs that were not modulated either by being mentioned or by sentence polarity. In addition, mentioned verbs had shorter reading times than the alternative ones in negative sentences in the anodal vs. sham condition. This suggests that stimulation caused an effect of negation in the activation of the mentioned verb. Implications are discussed in the context of the role of the rSTS in processing attitudinal verbs and negation to understand better approach and avoidance mediated by language in the framework of the two-step model of negation processing.

Golden Wildebeest Days: Fragmentation and Value in South Africa’s Wildlife Economy After Apartheid

There are renewed global efforts to make wildlife conservation the foundation for broad-based economic development. This article looks at these tendencies in the ‘Kruger to Canyons’ (K2C) biosphere region in South Africa, encompassing the Kruger National Park and adjacent settlement areas and reserves. Various forms of the wildlife economy have a long history in this region. However, it is increasingly posited as a preternatural means for creating jobs. We chronicle the growth of the wildlife economy from its apartheid heyday to the present, showing its fundamental dependence on the ecological and political fragmentation of space. More generally, these biopolitical divisions are part of a broad contestation of wildlife value, organised around changing regimes of protected area enclosure and the spacing of human and non-human life. Despite recent claims by the South African conservation industry that it is demolishing fences and increasing habitat connectivity, political territorialisation and ecological fragmentation continue to be important means of securing profit and reducing perceived risk. While the contradictions of this dynamic have now become acute through the emergence of the rhino-poaching crisis, the growth of that violent industry, we conclude, should not be seen as the negative inversion of a legal wildlife economy. Instead, both the legal and the illegal wildlife economies are manifestations of the same underlying problems: ill-conceived attempts at agrarian reform; the persistent influence of an older veterinary wildlife assemblage; the continued role of the rural poor as an enabling but unacknowledged buffer between development and wildlife.

Episodic volcanic eruption and arid climate during the Triassic-Jurassic transition in the Qiangtang Basin, eastern Tethys: A possible linkage with the end-Triassic biotic crises

During the Triassic-Jurassic (Tr-J) transition, a negative basin inversion, massive volcanic eruption and biological crises occurred in the Qiangtang Basin (eastern Tethys), while the volcanic eruption phases and the paleoenvironment characteristics during this transition were paid little attention. Here we present petrology, whole-rock geochemistry and zircon U-Pb isotopes data from the continuous Triassic-Jurassic sedimentary strata in the northern Qiangtang Basin, in order to reveal the volcanic eruption episodes, paleoenvironment characteristics during this transition, and to discuss the possible linkage with the biological extinction event. Our results show that the Late Triassic volcanic event displays episodic eruption process and contains about four phases. Zircon U-Pb ages of four tuff samples from the Quemo Co south section are, from bottom to top, 220.4 ± 1.1 Ma, 210.9 ± 0.9 Ma, 208.3 ± 0.8 Ma, and 202.9 ± 1.1 Ma, respectively. Statistical analysis of the zircon ages of the Late Triassic suggests that the age of the Late Triassic magmatic event ranges from 227 Ma to 201 Ma and shows about five age peaks. The Tr-J boundary is suggested to be located between the E’erlongba and Quemo Co formations in the eastern Qiangtang Basin. Geochemical indicators such as CIAcorr, C-value, Sr/Cu, and Rb/K ratios indicate that a moderate to high chemical weathering condition, semi-arid to semi-humid climate and normal marine water condition before the Tr-J transition, and suddenly changed to be low chemical weathering, arid to extreme arid climate, and freshwater water environment during the Tr-J transition, and then rebounded to be moderate to high chemical weathering and semi-humid to humid climate after the Tr-J transition. These evidences suggest that the basin inversion, significant paleoenvironment shift and regional regression occurred nearly coincidentally during the Tr-J transition. The extreme arid climate (probably cool) and ocean acidification may play an important role in the end-Triassic mass extinction in the eastern Tethys.

Consumer conceptualisations of food-related wellbeing: An exploration of wellbeing-related terms in four industrialised countries

Perceived (or subjective) wellbeing is regarded as key to understanding consumer food choices and the development of strategies to promote desirable eating habits. Yet, in-depth understanding of the specific factors that contribute to people's perceived wellbeing across cultures is lacking. These factors motivated the present research that used word associations to conduct an exploratory analysis of consumer conceptualisations of food-related wellbeing (WB). Adults (n = 4945) living in the United Kingdom, Australia, Singapore or Germany, and speaking respectively, English or German, took part in the study. Health, pleasure, food quality, positive emotions and social aspects of food consumption were the main associations with food-related wellbeing. Absence hereof was associated with unhealthiness, disgust, negative emotions and poor mental health. The differences in these main associations emphasised the importance of exploring wellbeing, as well as lack hereof. Not doing so leads to an incomplete understanding of this multidimensional construct. The research was conducted with four terms related to wellbeing (each in their positive and negative versions): ‘sense of wellbeing’ and ‘lack of wellbeing’, ‘feeling good’ and ‘feeling bad/unhappy’, ‘satisfied with life’ and ‘dissatisfied with life’ and ‘fulfilled in life’ and ‘unfulfilled in life’. Because these different terms gave rise to different wellbeing associations, researchers in this area must choose their empirical approach with care. The terms ‘sense of wellbeing’ and ‘feeling good’ tended to more frequently give rise to health-related associations. Conversely, ‘satisfied with life’ and ‘fulfilled in life’ tended to more frequently give rise to positive spiritual and emotional associations of food-related wellbeing. The main conceptualisations of food-related wellbeing were cross-culturally similar, but extension of the present research to other Asian countries was recommended based on several differences between Singaporean participants and those from other countries. In ethnically diverse countries like Singapore, further within-country investigations of different cultures will also have merit.

FOFC as a PF phenomenon: Evidence from Basque clausal embedding

The Final-Over-Final Condition (FOFC) accounts for a strong cross-linguistic generalization whereby head-final phrases do not dominate head-initial phrases. This paper evaluates the validity of narrow syntactic vs. PF-interface approaches to this condition by studying the FOFC- violating configurations created by clausal complementation in Basque. It uncovers the decisive role played by the phonological realization of the relevant heads. It shows that whether or not these heads have overt exponence is crucial, but that it also matters whether or not they host raised heads. Among the strategies that ensure FOFC-compliance in Basque clausal embedding are (i) displacing the embedded clause (via extraposition or pied-piping) and (ii) deletion of the higher copy (and lower copy spell out) of the offending heads within the embedded clause. The analysis also accounts for the (apparent) optionalities in embedded clause placement and in negative inversion in Basque.

Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes.

Variants in RAC3, encoding a small GTPase RAC3 which is critical for the regulation of actin cytoskeleton and intracellular signal transduction, are associated with a rare neurodevelopmental disorder with structural brain anomalies and facial dysmorphism.We investigated a cohort of 10 unrelated participants presenting with global psychomotor delay, hypotonia, behavioural disturbances, stereotyped movements, dysmorphic features, seizures and musculoskeletal abnormalities. MRI of brain revealed a complex pattern of variable brain malformations, including callosal abnormalities, white matter thinning, grey matter heterotopia, polymicrogyria/dysgyria, brainstem anomalies and cerebellar dysplasia. These patients harboured eight distinct de novo RAC3 variants, including six novel variants (NM_005052.3): c.34G > C p.G12R, c.179G > A p.G60D, c.186_188delGGA p.E62del, c.187G > A p.D63N, c.191A > G p.Y64C and c.348G > C p.K116N. We then examined the pathophysiological significance of these novel and previously reported pathogenic variants p.P29L, p.P34R, p.A59G, p.Q61L and p.E62K. In vitro analyses revealed that all tested RAC3 variants were biochemically and biologically active to variable extent, and exhibited a spectrum of different affinities to downstream effectors including p21-activated kinase 1. We then focused on the four variants p.Q61L, p.E62del, p.D63N and p.Y64C in the Switch II region, which is essential for the biochemical activity of small GTPases and also a variation hot spot common to other Rho family genes, RAC1 and CDC42. Acute expression of the four variants in embryonic mouse brain using in utero electroporation caused defects in cortical neuron morphology and migration ending up with cluster formation during corticogenesis. Notably, defective migration by p.E62del, p.D63N and p.Y64C were rescued by a dominant negative version of p21-activated kinase 1.Our results indicate that RAC3 variants result in morphological and functional defects in cortical neurons during brain development through variant-specific mechanisms, eventually leading to heterogeneous neurodevelopmental phenotypes.