Discrimination of small forms in a deviant-detection paradigm by 10-month-old infants

Using eye tracking, we investigated if 10-month-old infants could discriminate between members of a set of small forms based on geometric properties in a deviant-detection paradigm, as suggested by the idea of a core cognitive system for Euclidian geometry. We also investigated the precision of infants' ability to discriminate as well as how the discrimination process unfolds over time. Our results show that infants can discriminate between small forms based on geometrical properties, but only when the difference is sufficiently large. Furthermore, our results also show that it takes infants, on average, <3.5 s to detect a deviant form. Our findings extend previous research in three ways: by showing that infants can make similar discriminative judgments as children and adults with respect to geometric properties; by providing a first crude estimate on the limit of the discriminative abilities in infants, and finally; by providing a first demonstration of how the discrimination process unfolds over time

Data Safety, Sources, and Data Flow in the Offshore Industry

Digitization may provide increased access to and more efficient use of real-time and historical data, internally as well as externally in an organization. However, when information from industrial control systems (ICS) becomes more available in office IT systems and in the "cloud", ICS systems may become more vulnerable and attractive targets for cyberattacks. We have investigated data safety in ICS in the Norwegian offshore sector when data is processed from ICS to the office network. The work is mainly based on document review and nine interviews with selected oil companies, rig companies and service providers of operational data. The paper addresses strengths and threats related to data safety with emphasis on (1) Data sources and data flow, (2) Safety and security of data, (3) Data cleaning and processing, (4) Contextualization, (5) Validation, and (6) Quality assurance. We also discuss shortcomings for functional safety in current standards such as IEC 61508 and IEC 61511 and standard series for security, IEC 62443. It is a major challenge for the industry that there are no good international standards and guidelines that define the relevant terminology across IT systems and ICS. Future work should address data safety challenges when applying artificial intelligence and machine learning in ICS systems.publishedVersio

Refined Ordovician timescale reveals no link between asteroid breakup and biodiversification

The catastrophic disruption of the L chondrite parent body in the asteroid belt c. 470 Ma initiated a prolonged meteorite bombardment of Earth that started in the Ordovician and continues today. Abundant L chondrite meteorites in Middle Ordovician strata have been interpreted to be the consequence of the asteroid breakup event. Here we report a zircon U-Pb date of 467.50±0.28 Ma from a distinct bed within the meteorite-bearing interval of southern Sweden that, combined with published cosmic-ray exposure ages of co-occurring meteoritic material, provides a precise age for the L chondrite breakup at 468.0±0.3 Ma. The new zircon date requires significant revision of the Ordovician timescale that has implications for the understanding of the astrogeobiologic development during this period. It has been suggested that the Middle Ordovician meteorite bombardment played a crucial role in the Great Ordovician Biodiversification Event, but this study shows that the two phenomena were unrelated

Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation

Reinforcement learning theorizes that strengthening of synaptic connections in medium spiny neurons of the striatum occurs when glutamatergic input (from cortex) and dopaminergic input (from substantia nigra) are received simultaneously. Subsequent to learning, medium spiny neurons with strengthened synapses are more likely to fire in response to cortical input alone. This synaptic plasticity is produced by phosphorylation of AMPA receptors, caused by phosphorylation of various signalling molecules. A key signalling molecule is the phosphoprotein DARPP-32, highly expressed in striatal medium spiny neurons. DARPP-32 is regulated by several neurotransmitters through a complex network of intracellular signalling pathways involving cAMP (increased through dopamine stimulation) and calcium (increased through glutamate stimulation). Since DARPP-32 controls several kinases and phosphatases involved in striatal synaptic plasticity, understanding the interactions between cAMP and calcium, in particular the effect of transient stimuli on DARPP-32 phosphorylation, has major implications for understanding reinforcement learning. We developed a computer model of the biochemical reaction pathways involved in the phosphorylation of DARPP-32 on Thr34 and Thr75. Ordinary differential equations describing the biochemical reactions were implemented in a single compartment model using the software XPPAUT. Reaction rate constants were obtained from the biochemical literature. The first set of simulations using sustained elevations of dopamine and calcium produced phosphorylation levels of DARPP-32 similar to that measured experimentally, thereby validating the model. The second set of simulations, using the validated model, showed that transient dopamine elevations increased the phosphorylation of Thr34 as expected, but transient calcium elevations also increased the phosphorylation of Thr34, contrary to what is believed. When transient calcium and dopamine stimuli were paired, PKA activation and Thr34 phosphorylation increased compared with dopamine alone. This result, which is robust to variation in model parameters, supports reinforcement learning theories in which activity-dependent long-term synaptic plasticity requires paired glutamate and dopamine inputs

Infiltration sintering of WCu alloys from copper-coated tungsten composite powders for superior mechanical properties and arc-ablation resistance

W70Cu30(W-30 wt.% Cu) alloys were fabricated using cold pressing and infiltration sintering methods from two types of powders, i.e., mixed copper-tungsten (M-Cu-W) powders and our newly developed copper-coated tungsten composite (Cu@W) powders. Microstructure, mechanical and arc-ablation properties of the W70Cu30 alloys were investigated, and the mechanism of enhanced physical/mechanical properties and arc-erosion resistance of the W70Cu30 alloys was discussed. For the W70Cu30 alloys prepared using the Cu@W powders, their physical properties, including hardness, electrical conductivity and relative density were much better than those prepared from the M-Cu-W powders. The W70Cu30 alloys fabricated from the Cu@W powders were free of cracks, and showed homogenous distributions of W and Cu network structures. Whereas for the alloys prepared from the M-Cu-W powders, segregation of Cu was observed and the segregation size was about 40–100 μm. Characterization of arc-erosion morphologies of the W70Cu30 alloys prepared with the Cu@W powders revealed the occurrence of evaporation of Cu phase; whereas that of W70Cu30 alloys prepared with the M-Cu-W powders revealed the occurrence of the sputtering of Cu. After arc breakdown for 200 times, mass loss of alloys made using the mixed powders was twice as much as those made using the coated composite powders. Based on the experimental results and theoretical analysis, an arc breakdown mechanism of the WCu-C alloys using the composite powders was proposed which is attributed to the formation of a homogeneous Cu-Cu network structure to uniformly disperse arc energy and dissipate the generated heat, thus prolonging the service life of the WCu alloy contacts

The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty

The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of spermatogenesis. To characterize this understudied process, we profiled and analyzed single-cell transcriptomes of similar to 10,000 testicular cells from four boys spanning puberty and compared them to those of infants and adults. During puberty, undifferentiated spermatogonia sequentially expand and differentiate prior to the initiation of gametogenesis. Notably, we identify a common pre-pubertal progenitor for Leydig and myoid cells and delineate candidate factors controlling pubertal differentiation. Furthermore, pre-pubertal Sertoli cells exhibit two distinct transcriptional states differing in metabolic profiles before converging to an alternative single mature population during puberty. Roles for testosterone in Sertoli cell maturation, antimicrobial peptide secretion, and spermatogonial differentiation are further highlighted through single-cell analysis of testosterone-suppressed transfemale testes. Taken together, our transcriptional atlas of the developing human testis provides multiple insights into developmental changes and key factors accompanying male puberty

High-level integration of murine intestinal transcriptomics data highlights the importance of the complement system in mucosal homeostasis.

BACKGROUND: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. RESULTS: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. CONCLUSIONS: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis

DARPP-32 in the striatum : Multiple regulation and physiological role

Protein phosphorylation is an important mechanism involved in intracellular signal transduction. The activity of many proteins is affected by their state of phosphorylation, which in turn is determined by the combined activities of protein kinases and protein phosphatases. DARPP-32 (dopamine and cAMP regulated phosphoprotein of 32 kDa) is a neuronal phosphoprotein expressed at particular high levels in the projection neurons of the striatum. This brain region is the major receiving component of the basal ganglia, and integrates inputs from several neurotransmitters, e.g. glutamate from the cortex and dopamine from the substantia nigra. When DARPP-32 is phosphorylated on the threonyl residue, Thr34 it is a potent inhibitor of protein phosphatase- 1 (PP- 1). Conversely, when DARPP-32 is phosphorylated on the threonyl residue, Thr75, it is an inhibitor of PKA. The DARPP-32/PP- 1 /PKA cascade is important in regulating the state of phosphorylation, and thereby the activity, of several effector proteins, e.g. Ca2+ and Na+ channels. This study shows that, in rat striatal slices, activation of dopamine D, receptors and adenosine A 2A receptors stimulates the phosphorylation of DARPP-32 on Thr34 through activation of the cAMP/PKA pathway. Conversely, activation of dopamine D2 receptors inhibits both A 2A and D, receptor-mediated phosphorylation of DARPP-32 on Thr 34. Dopamine D 2 receptors interact with adenosine A 2A receptors at the level of the same striatal projection neurons whereas the effect of a D 2 receptor agonist on D, stimulated DARPP-32 phosphorylation appears to require cell-cell interaction. Opioid receptors are also involved in the regulationof the state of phosphorylation of DARPP32. Activation of mu-opioid receptors selectively counteracts D, receptor stimu ate DARPP-32 phosphorylation on Thr34, whereas activation of delta-opioid receptors reduces A 2A receptor stimulated phosphorylation. In vivo, blockade of D 2 receptors increases the amount of phospho[Thr34]DARPP- 32, and this effect is prevented by concomitant blockade of D, and A 2A receptors. Thus, under normal conditions, the state of phosphorylation of DARPP-32 at Thr34 is determined by tonic activation of adenosine and dopamine receptors. In contrast, phosphorylation of DARPP-32 on Thr75 is induced by blocking the adenosine A 2A receptor using a specific A 2A receptor antagonist or the psychostimulant drug caffeine. This effect appears to require a constitutive level of CDK5 activity. DARPP-32 is important for the behavioural effects of adenosine, since the motor stimulant effects of caffeine or a specific adenosine A 2A antagonist are significantly reduced in mice lacking the gene coding for DARPP-32. The motor depressant effect of an adenosine A 2A receptor agonist is also markedly reduced in DARPP-32 knock-out mice. Taken together these results show that under normal conditions, the phosphorylation, and activity, of DARPP-32 is regulated through the interaction of dopamine and adenosine and that DARPP-32 is implicated in the modulation of voluntary movements exerted by adenosine agonists and antagonists