Konstruktion, Dekonstruktion und Rekonstruktion: Minimalistische und (trotzdem) konstruktivistische Überlegungen zum Spracherwerb

Der kindliche Spracherwerb zeichnet sich sowohl durch seine Robustheit als auch durch eine spezifische Dynamik aus. Im Mittelpunkt des Beitrags stehen frühe Phasen des Erwerbs des Deutschen, in denen Konstruktionen unterschiedlicher Analysetiefe koexistieren, die im Laufe der Zeit immer wieder reanalysiert werden und schließlich auf einen einzigen abstrakten Bauplan hin konvergieren. Anhand von Daten aus diversen Fallstudien wird gezeigt, dass die Entwicklung der so genannten „Satzklammer“ des Deutschen als Konvergenzprozess verstanden werden kann, bei dem Lerner bewährte Teilsysteme, darunter anfängliche teilproduktive Formeln, dekonstruieren und auf abstrakterer Ebene rekonstruieren. Untersucht werden typische Übergangsphänomene, u.a. die Verwendung von Platzhaltern und Doppelbesetzungen, die diese Konstruktionsleistung erkennen lassen. Argumentiert wird, dass sich generative und dynamische, konstruktivistische Ansätze bei dem Bemühen um eine Erklärung dieses Erwerbsprozesses sinnvoll ergänzen

Wireless Sensors and their Applications in Controlling Vibrations

As wireless devices are becoming more powerful, more flexible and less costly to produce, they are often being applied in new ways. Combining wireless technology with new types of sensors results in the ability to monitor and control the environment in ways not previously possible. For example, an intelligent wireless sensor system that consists of a sensor, digital processor and a transceiver can be mounted on a board the size of a coin. The data collected by these devices are then transmitted to a central unit which is able to thoroughly process and store this data. Not only can the central processing station provide reports about certain physical parameters in the environment, it can also control the environment and other parameters of interest. The design process of these wireless sensor platforms is a well-developed area of research that covers concepts like networking, circuit design, Radio-Frequency (RF) circuits and antenna design. The design of a wireless sensor can be as simple as putting together a microcontroller, a transceiver and a sensor chip or as complicated as implementing all the necessary circuitry into a single integrated circuit. One of the main applications of the sensors is in a control loop which controls physical characteristics in an environment. Specifically, if the objective of a control system is to limit the amount of vibrations in a structure, vibration sensors such as accelerometers are usually used. In environments where the use of wires is costly or impossible, it makes sense to use wireless accelerometers instead. Among the numerous applications that can use such devices are the automotive and medical vibration control systems. In the automotive industry it is desirable to reduce the amount of vibrations in the vehicle felt by the passengers. These vibrations can originate from the engine or the uneven road, but they are damped using passive mechanical elements like rubber, springs and shocks. It is possible however, to have a more effective vibration suppression using active sensor-actuator systems. Since adding and maintaining wires in a vehicle is costly, a wireless accelerometer can be put to good use there. A medical application for wireless accelerometers can be used with a procedure called Deep Brain Stimulation (DBS). DBS is a relatively new and very effective treatment for advanced Parkinson’s disease. The purpose of DBS is to reduce tremors in the patients. In DBS a set of voltages is applied to the brain of the patient as some optimum combinations of voltages will have a very positive effect on the tremors. Those optimum voltages are currently found by trial and error while a doctor is observing the patient for tremors. Wireless accelerometers with the use of a computer algorithm can assist in this process by finding the optimum voltages using the feedback provided by the accelerometers. The algorithm will assist the doctor in making decisions and has the potential of finding the optimums completely on its own

Heritage Speakers as Part of the Native Language Continuum

We argue for a perspective on bilingual heritage speakers as native speakers of both their languages and present results from a large-scale, cross-linguistic study that took such a perspective and approached bilinguals and monolinguals on equal grounds. We targeted comparable language use in bilingual and monolingual speakers, crucially covering broader repertoires than just formal language. A main database was the open-access RUEG corpus, which covers comparable informal vs. formal and spoken vs. written productions by adolescent and adult bilinguals with heritage-Greek, -Russian, and -Turkish in Germany and the United States and with heritage-German in the United States, and matching data from monolinguals in Germany, the United States, Greece, Russia, and Turkey. Our main results lie in three areas. (1) We found non-canonical patterns not only in bilingual, but also in monolingual speakers, including patterns that have so far been considered absent from native grammars, in domains of morphology, syntax, intonation, and pragmatics. (2) We found a degree of lexical and morphosyntactic inter-speaker variability in monolinguals that was sometimes higher than that of bilinguals, further challenging the model of the streamlined native speaker. (3) In majority language use, non-canonical patterns were dominant in spoken and/or informal registers, and this was true for monolinguals and bilinguals. In some cases, bilingual speakers were leading quantitatively. In heritage settings where the language was not part of formal schooling, we found tendencies of register leveling, presumably due to the fact that speakers had limited access to formal registers of the heritage language. Our findings thus indicate possible quantitative differences and different register distributions rather than distinct grammatical patterns in bilingual and monolingual speakers. This supports the integration of heritage speakers into the native-speaker continuum. Approaching heritage speakers from this perspective helps us to better understand the empirical data and can shed light on language variation and change in native grammars. Furthermore, our findings for monolinguals lead us to reconsider the state-of-the art on majority languages, given recurring evidence for non-canonical patterns that deviate from what has been assumed in the literature so far, and might have been attributed to bilingualism had we not included informal and spoken registers in monolinguals and bilinguals alike

The Debate on Maturational Constraints in Bilingual Development: A Perspective from First-Language Attrition

A controversial topic in research on second-language acquisition is whether residual variability and optionality in high-proficiency late second-language (L2) learners is merely the outcome of cross-linguistic transfer, competition, and processing limitations, or whether late learners have an underlying representational deficit due to maturational constraints on ultimate attainment in L2. This study argues that insights into this question can be gained by comparing advanced late L2 learners with late bilinguals who grew up with the language under investigation as their first language (L1), prior to emigrating to another country. The latter group, who use the language of the host country predominantly in their daily lives, typically exhibit increased optionality in their native language as a result of cross-linguistic transfer and L1 attrition. They do not, however, have a representational deficit in their L1, having acquired it monolingually during childhood. Such a comparison has the potential to distinguish grammatical features that are prone to bilingualism effects from those that natives can maintain but with which L2ers struggle persistently, possibly due to maturational limitations. This study compares 20 long-term attriters (English L2) with 20 highly advanced immersed learners of German (English L1) and 20 predominantly monolingual controls. The bilingual populations are matched for proficiency and for their use of German in daily life. The analysis comprises a group comparison and an investigation of individual performance, to assess whether there are L2 speakers who perform within the accuracy ranges of a larger population of attriters (n = 53) on all features, and similarly, whether any of the attriters perform within the accuracy range of a population of native controls (n = 53). The findings indicate that there are some areas of grammar (e.g., obligatory word order) where the L2 speakers are similar to the L1 attriters, and others (in particular noun phrase morphology) where attriters and monolinguals behave differently from the L2ers. This finding is interpreted as being consistent with an account that assumes some form of maturational constraint on language learning

Investigation of NRXN1 deletions: Clinical and molecular characterization

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P  = 6.08 × 10 −7 ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97220/1/35780_ftp.pd

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers

ADDITIONAL FILE 1: FIGURE S1. Concordant SV call generation from Manta and GRIDSS. FIGURE S2. Summary of SVs in each type, compared to other studies. FIGURE S3. CIRCOS plot of hyper-SV mutated tumours. FIGURE S4. The spread of SV breakpoints and samples in each 1 Mbp genomic bin. FIGURE S5. TMPRSS2-ERG fusion with interstitial region retention. TABLE S1. Clinical and pathological characteristics of 180 prostate cancer patients included in this study. TABLE S2. Biallelic assessment of CDK12 in hyper-duplicated samples. TABLE S3. Biallelic assessment of BRCA2 in hyper-deleted samples.ADDITIONAL FILE 2: TABLE S4. Summary of gene fusions identified from SVs. ADDITIONAL FILE 3: TABLE S5. SV calls resulting in gene fusions.DATA AND MATERIALS AVAILABILITY : The datasets analysed in this study were obtained and accessible through Jaratlerdsiri et al [6], with sequence data deposited in the European GenomePhenome Archive (EGA; https://ega-archive.org) under overarching accession EGAS00001006425 and including the Southern African Prostate Cancer Study (SAPCS) Dataset (EGAD00001009067) and Garvan/St Vincent’s Prostate Cancer Database (EGAD00001009066). The computational code used to analyse SV subtypes, SV hotspots and gene fusions is available on GitHub [68].BACKGROUND : African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub- Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation. METHODS : Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (African versus European), with a focus on African men from southern Africa. RESULTS : Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion partners were identified, including LINC01525, FBXO7, GTF3C2, NTNG1 and YPEL5. Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, with CADM2, LSAMP, PTPRD, PDE4D and PACRG having therapeutic implications for African patients. CONCLUSIONS : In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry.The Medical Health and Medical Research Council (NHMRC) of Australia, University of Sydney Bridging Grant, the USA. Department of Defense (DoD) Prostate Cancer Research Program (PCRP) Idea Development.https://genomemedicine.biomedcentral.comam2023School of Health Systems and Public Health (SHSPH

African-specific molecular taxonomy of prostate cancer

Data availability DNA-sequencing data have been deposited at the European Genome- Phenome Archive (EGA) under overarching accession EGAS00001006425 and including the Southern African Prostate Cancer Study (SAPCS) Dataset (EGAD00001009067 and Garvan/St Vincent’s Prostate Cancer Database EGAD00001009066). Academic researchers meeting the data-access policy criteria may apply for data access through the respective data access committees. CPGEA data are available through http://www.cpgea.com. PCAWG data are available at ICGC Data Portal (https://dcc.icgc.org/releases/PCAWG).Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages. The contributing genetic and non-genetic factors, and associated mutational processes, are unknown. Here, through whole-genome sequencing of treatment-naive prostate cancer samples from 183 ancestrally (African versus European) and globally distinct patients, we generate a large cancer genomics resource for sub-Saharan Africa, identifying around 2 million somatic variants. Significant African-ancestry-specific findings include an elevated tumour mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations and a higher total of mutational signatures, and the driver genes NCOA2, STK19, DDX11L1, PCAT1 and SETBP1. Examining all somatic mutational types, we describe a molecular taxonomy for prostate cancer differentiated by ancestry and defined as global mutational subtypes (GMS). By further including Chinese Asian data, we confirm that GMS-B (copy-number gain) and GMS-D (mutationally noisy) are specific to African populations, GMS-A (mutationally quiet) is universal (all ethnicities) and the African–European-restricted subtype GMS-C (copy-number losses) predicts poor clinical outcomes. In addition to the clinical benefit of including individuals of African ancestry, our GMS subtypes reveal different evolutionary trajectories and mutational processes suggesting that both common genetic and environmental factors contribute to the disparity between ethnicities. Analogous to gene–environment interaction—defined here as a different effect of an environmental surrounding in people with different ancestries or vice versa—we anticipate that GMS subtypes act as a proxy for intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.The National Health and Medical Research Council (NHMRC) of Australia, NHMRC Ideas Grants, University of Sydney Bridging Grant, the US Department of Defense (DoD) Prostate Cancer Research Program (PCRP) Idea Development Award TARGET Africa.http://www.nature.com/natuream2023School of Health Systems and Public Health (SHSPH

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder