Miracle-dz/UniFAR-FTUs huggingface dataset:
CNNM2 Mutations Cause Impaired Brain Development and Seizures in Patients with Hypomagnesemia

Intellectual disability and seizures are frequently associated with hypomagnesemia and have an important genetic component. However, to find the genetic origin of intellectual disability and seizures often remains challenging because of considerable genetic heterogeneity and clinical variability. In this study, we have identified new mutations in CNNM2 in five families suffering from mental retardation, seizures, and hypomagnesemia. For the first time, a recessive mode of inheritance of CNNM2 mutations was observed. Importantly, patients with recessive CNNM2 mutations suffer from brain malformations and severe intellectual disability. Additionally, three patients with moderate mental disability were shown to carry de novo heterozygous missense mutations in the CNNM2 gene. To elucidate the physiological role of CNNM2 and explain the pathomechanisms of disease, we studied CNNM2 function combining in vitro activity assays and the zebrafish knockdown model system. Using stable Mg2+ isotopes, we demonstrated that CNNM2 increases cellular Mg2+ uptake in HEK293 cells and that this process occurs through regulation of the Mg2+-permeable cation channel TRPM7. In contrast, cells expressing mutated CNNM2 proteins did not show increased Mg2+ uptake. Knockdown of cnnm2 isoforms in zebrafish resulted in disturbed brain development including neurodevelopmental impairments such as increased embryonic spontaneous contractions and weak touch-evoked escape behaviour, and reduced body Mg content, indicative of impaired renal Mg2+ absorption. These phenotypes were rescued by injection of mammalian wild-type Cnnm2 cRNA, whereas mammalian mutant Cnnm2 cRNA did not improve the zebrafish knockdown phenotypes. We therefore concluded that CNNM2 is fundamental for brain development, neurological functioning and Mg2+ homeostasis. By establishing the loss-of-function zebrafish model for CNNM2 genetic disease, we provide a unique system for testing therapeutic drugs targeting CNNM2 and for monitoring their effects on the brain and kidney phenotype.
www.econstor.eu Spatial Externalities and Local Economic Growth

A vast body of literature has addressed in the last decade the influence of local externalities on industry location and growth. This literature has, however, paid not too much attention to the wider scenario where such phenomena are rooted, that of an ongoing process of structural change which is transforming our economies from manufacturing to service ones. The main objective of this paper is to assess the role of a large set of potential determinants on the process of local agglomeration of economic activity distinguishing between manufacturing and service sectors. We focus on the case of Italy making use of a very ample database on socio-economic indicators for 784 Local Labour Systems and 34 sectors over the period 1991-96. Our database covers both the manufacturing and the service sectors so that the whole economic system is considered. Our econometric results show that local growth in Italy is not a homogeneous process. On the contrary, it is characterized by significant differences across macro regions and especially across sectors. Among the most important determinants of local industry growth, it is worth mentioning the positive role of the diversity externalities. We also find robust evidence of the negative influence of specialisation externalities on labour dynamics at the local industry level. Moreover, we have assessed the effects of other determinants of local growth like human capital, social environment and network externalities. Finally, the spatial analysis shows that in the aggregate economy and also in some sectors there is spatial autocorrelation and, therefore, dynamic spatial models have to be estimated. JEL: R11, R12, L60, O52
3D CNN and dMRI Rotation Invariant Features allow MS patients stratiﬁcation

Diﬀusion Magnetic Resonance Imaging (dMRI) is one of the few non-invasive in-vivo imaging techniques able to provide information on the human brain structure. Recently, a novel computational framework has been developed for the analytical generation of a complete set of algebraically independent Rotation Invariant Features (RIFs) for spherical functions. In this work, we extract such new RIFs from dMRI data and use them to feed a 3D-CNN architecture aiming at patients stratiﬁcation in Multiple sclerosis (MS). This allows to characterize the potential of RIFs as numerical biomarkers in diﬀerentiating cortical and subcortical microstructural modulations in two progression states of MS that is Progressive [PMS] and Relapsing Remitting [RRMS]. Experiments are performed on a two-shell dMRI acquisition dataset of 60 subjects including 30 PMS and 30 RRMS. The ﬁrst two RIFs per shell are calculated directly on the diﬀusion signal and only grey matter is considered. Two 3D-CNN models having as input the two RIFs are proposed (RIF1-CNN and RIF2-CNN respectively). The classiﬁcation accuracy is 0 . 83 ± 0 . 06 for RIF1-CNN and 0 . 71 ± 0 . 05 for RIF2-CNN. This provides evidence of the capability of the considered RIF-CNN models of capturing subtle microstructural variations between the two patients evolution stages of the disease, opening new perspectives for diagnosis, prognosis and treatment.
Two critical periods in early visual cortex during figure–ground segregation

The ability to distinguish a figure from its background is crucial for visual perception. To date, it remains unresolved where and how in the visual system different stages of figure–ground segregation emerge. Neural correlates of figure border detection have consistently been found in early visual cortex (V1/V2). However, areas V1/V2 have also been frequently associated with later stages of figure–ground segregation (such as border ownership or surface segregation). To causally link activity in early visual cortex to different stages of figure–ground segregation, we briefly disrupted activity in areas V1/V2 at various moments in time using transcranial magnetic stimulation (TMS). Prior to stimulation we presented stimuli that made it possible to differentiate between figure border detection and surface segregation. We concurrently recorded electroencephalographic (EEG) signals to examine how neural correlates of figure–ground segregation were affected by TMS. Results show that disruption of V1/V2 in an early time window (96–119 msec) affected detection of figure stimuli and affected neural correlates of figure border detection, border ownership, and surface segregation. TMS applied in a relatively late time window (236–259 msec) selectively deteriorated performance associated with surface segregation. We conclude that areas V1/V2 are not only essential in an early stage of figure–ground segregation when figure borders are detected, but subsequently causally contribute to more sophisticated stages of figure–ground segregation such as surface segregation.
Default Mode Network Connectivity in Stroke Patients

The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which includes the medial temporal lobe, is a functional network that is associated with episodic memory processing. We investigated whether the default mode network activity is reduced in stroke patients compared to healthy control subjects in the resting state condition. We assessed the whole brain network properties during resting state functional MRI in 21 control subjects and 20 ‘first-ever’ stroke patients. Patients were scanned 9–12 weeks after stroke onset. Stroke lesions were located in various parts of the brain. Independent component analyses were conducted to identify the default mode network and to compare the group differences of the default mode network. Furthermore, region-of-interest based analysis was performed to explore the functional connectivity between the regions of the default mode network. Stroke patients performed significantly worse than control subjects on the delayed recall score on California verbal learning test. We found decreased functional connectivity in the left medial temporal lobe, posterior cingulate and medial prefrontal cortical areas within the default mode network and reduced functional connectivity between these regions in stroke patients compared with controls. There were no significant volumetric differences between the groups. These results demonstrate that connectivity within the default mode network is reduced in ‘first-ever’ stroke patients compared to control subjects. This phenomenon might explain the occurrence of post-stroke cognitive dysfunction in stroke patients.
Selection Performance Using a Scaled Virtual Stylus Cursor in VR

We propose a surface warping technique we call warped virtual surfaces (WVS). WVS is similar to applying CD gain to mouse cursor on a screen and is used with traditionally 1:1 input devices, in our case, a tablet and stylus, for use with VR head-mounted displays (HMDs). WVS allows users to interact with arbitrarily large virtual panels in VR while getting the benefits of passive haptic feedback from a fixed-sized physical panel. To determine the extent to which WVS affects user performance, we conducted an experiment with 24 participants using a Fitts' law reciprocal tapping task to compare different scale factors. Results indicate there was a significant difference in movement time for large scale factors. However, for throughput (ranging from 3.35 - 3.47 bps) and error rate (ranging from 3.6 - 5.4%), our analysis did not find a significant difference between scale factors. Using non-inferiority statistical testing (a form of equivalence testing), we show that performance in terms of throughput and error rate for large scale factors is no worse than a 1-to-1 mapping. Our results suggest WVS is a promising way of providing large tactile surfaces in VR, using small physical surfaces, and with little impact on user performance.
Bromocriptine Does Not Alter Speed–Accuracy Tradeoff

Being quick often comes at the expense of being accurate. This speed–accuracy tradeoff is a central feature of many types of decision making. It has been proposed that dopamine plays an important role in adjusting responses between fast and accurate behavior. In the current study we investigated the role of dopamine in perceptual decision making in humans, focusing on speed–accuracy tradeoff. Using a cued version of the random dot motion task, we instructed subjects to either make a fast or an accurate decision. We investigated decision making behavior in subjects who were given bromocriptine (a dopamine receptor agonist) or placebo. We analyzed the behavioral data using two accumulator models, the drift diffusion model, and the linear ballistic accumulator model. On a behavioral level, there were clear differences in decision threshold between speed and accuracy focus, but decision threshold did not differ between the drug and placebo sessions. Bayesian analyses support the null hypothesis that there is no effect of bromocriptine on decision threshold. On the neural level, we replicate previous findings that the striatum and pre-supplementary motor area are active when preparing for speed, compared with accurate decisions. We do not find an effect of bromocriptine on this activation. Therefore, we conclude that bromocriptine does not alter speed–accuracy tradeoff.
Can E-Commerce Adoption Improve SME’s Performance? (Case Studies on Micro, Small and Medium Enterprises with Gojek Services in Indonesia)

This study aims to see whether organizational readiness, technology readiness, external environment influences e-commerce adoption, and also aims to see whether e-commerce adoption plays a role in improving performance in small, micro and medium enterprises in Medan City. This research is a quantitative research using primary data collected through questionnaire surveys. The sample technique uses random sampling, with 222 samples. The analytical method uses descriptive method with multiple linear regression statistical analysis. Hypothesis testing using t-test, as well as F test with a significant level of 5%. The results of the study found that organizational readiness, technology readiness, external environment, e-commerce adoption simultaneously had a significant positive effect on financial performance. While partially the organizational readiness and technology readiness have a significant positive effect while the external environment has a positive and insignificant influence on e-commerce adoption, and e-commerce adoption has a significant positive effect on financial performance.
UvA-DARE (Digital Academic Repository) Are there multiple visual short-term memory stores

Background: Classic work on visual short-term memory (VSTM) suggests that people store a limited amount of items for subsequent report. However, when human observers are cued to shift attention to one item in VSTM during retention, it seems as if there is a much larger representation, which keeps additional items in a more fragile VSTM store. Thus far, it is not clear whether the capacity of this fragile VSTM store indeed exceeds the traditional capacity limits of VSTM. The current experiments address this issue and explore the capacity, stability, and duration of fragile VSTM representations. Methodology/PrincipalFindings: We presented cues in a change-detection task either just after off-set of the memory array ( iconic-cue ), 1,000 ms after off-set of the memory array ( retro-cue ) or after on-set of the probe array ( post-cue ). We observed three stages in visual information processing 1) iconic memory with unlimited capacity, 2) a four seconds lasting fragile VSTM store with a capacity that is at least a factor of two higher than 3) the robust and capacity-limited form of VSTM. Iconic memory seemed to depend on the strength of the positive after-image resulting from the memory display and was virtually absent under conditions of isoluminance or when intervening light masks were presented. This suggests that iconic memory is driven by prolonged retinal activation beyond stimulus duration. Fragile VSTM representations were not affected by light masks, but were completely overwritten by irrelevant pattern masks that spatially overlapped the memory array. Conclusions/Significance: We find that immediately after a stimulus has disappeared from view, subjects can still access information from iconic memory because they can see an after-image of the display. After that period, human observers can still access a substantial, but somewhat more limited amount of information from a high-capacity, but fragile VSTM that is overwritten when new items are presented to the eyes. What is left after that is the traditional VSTM store, with a limit of about four objects. We conclude that human observers store more sustained representations than is evident from standard change detection tasks and that these representations can be accessed at will.
Family and Population-Based Studies of Variation within the Ghrelin Receptor Locus in Relation to Measures of Obesity

Background The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites. Methodology/Principal Findings In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p<0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27±4 kg/m2) versus non-carriers (mean BMI: 28±5 kg/m2) (p>0.05) could be shown. Conclusions/Significance In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.
A Putative Plant Aminophospholipid Flippase, the Arabidopsis P4 ATPase ALA1, Localizes to the Plasma Membrane following Association with a β-Subunit

Plasma membranes in eukaryotic cells display asymmetric lipid distributions with aminophospholipids concentrated in the inner leaflet and sphingolipids in the outer leaflet. This unequal distribution of lipids between leaflets is, amongst several proposed functions, hypothesized to be a prerequisite for endocytosis. P4 ATPases, belonging to the P-type ATPase superfamily of pumps, are involved in establishing lipid asymmetry across plasma membranes, but P4 ATPases have not been identified in plant plasma membranes. Here we report that the plant P4 ATPase ALA1, which previously has been connected with cold tolerance of Arabidopsis thaliana, is targeted to the plasma membrane and does so following association in the endoplasmic reticulum with an ALIS protein β-subunit.
The Effect of Leptin on Luteal Angiogenic Factors in the Developing Porcine Corpus Luteum

Defects or abnormalities in a CL are believed to account for approximately 65% of recurrent miscarriages. Abnormalities can be associated with incomplete angiogenesis, which leads to a decrease in progesterone production and potential loss of a conceptus. Luteal angiogenesis is regulated by factors, such as fibroblast growth factor-2 (FGF2), vascular endothelial growth factor (VEGF), and angiopoietin-1 (Ang1). Leptin can influence the expression of VEGF, Ang1, and FGF2 in a caprine CL. Therefore, it is hypothesized that leptin is involved in luteal angiogenesis during CL development in the porcine species. Twenty-four mature crossbred gilts were allocated to one of four groups relative to day of the estrous cycle in preparation for CL collection: day (D) 4, 5, 6, or 7 of the estrous cycle (n = 6 gilts/D). Luteal tissue was divided and either frozen in liquid nitrogen for RNA analysis or enzymatically dispersed for cell culture. Gene expression for VEGF, Ang1, FGF2, leptin (tissue only), and leptin receptor (ObRb, tissue only) in CL tissue and cell cultures was determined by qPCR. Dispersed cells were cultured with or without leptin (0, 10-12, 10-11, 10-10, 10-9, 10-8 M; n = 3 wells/dose/gilt) for 24 hours. The expression of FGF2 in luteal tissue significantly (P<0.0003) varied relative to D and Ang1 tended (P=0.1) to be highest in D 6 CL. Leptin increased (P<0.05) Ang1 in D4 cultured dispersed lutea and decreased (P<0.03) FGF2 in D7 cultured dispersed lutea. Collectively, leptin appears to be involved in the angiogenic process in the developing CL. ABBREVIATIONS VEGF: Vascular Endothelial Growth Factor; FGF2: Fibroblast Growth Factor; Ang1: Angiopoietin 1; D: Day; CL: Corpus Luteum; IGF-1: Insulin-Like Growth Factor
Hippocampal Theta Modulation of Neocortical Spike Times and Gamma Rhythm: A Biophysical Model Study

The hippocampal theta and neocortical gamma rhythms are two prominent examples of oscillatory neuronal activity. The hippocampus has often been hypothesized to influence neocortical networks by its theta rhythm, and, recently, evidence for such a direct influence has been found. We examined a possible mechanism for this influence by means of a biophysical model study using conductance-based model neurons. We found, in agreement with previous studies, that networks of fast-spiking GABA -ergic interneurons, coupled with shunting inhibition, synchronize their spike activity at a gamma frequency and are able to impose this rhythm on a network of pyramidal cells to which they are coupled. When our model was supplied with hippocampal theta-modulated input fibres, the theta rhythm biased the spike timings of both the fast-spiking and pyramidal cells. Furthermore, both the amplitude and frequency of local field potential gamma oscillations were influenced by the phase of the theta rhythm. We show that the fast-spiking cells, not pyramidal cells, are essential for this latter phenomenon, thus highlighting their crucial role in the interplay between hippocampus and neocortex.
The Role Culture and Personality Play in an Authentic Online Group Learning Experience

Both educators and students face challenges in successful collaborative work, particularly when students come from a diverse set of backgrounds and cultures. This is especially the case at business schools, which have some of the most diverse student populations in the UK. One explanation for this could be that culture and personality influence behaviour in group work, creating mismatched expectations. This assumption has led to current research focusing upon student reflections and perceptions of these challenges, while few studies objectively explore what influences actual student behaviours in group work. Therefore, this paper describes a learning analytics study of an activity designed to replicate a group learning experience. In a lab environment, 58 students at a UK business school were placed in small groups to work with a Harvard Business School case study using an online chat to communicate with all members of their group. Student contributions were analysed and compared using Hofstede’s Cultural Dimensions (Hofstede, Hofstede, & Minkov, 2010) and the Big Five Ten Item Personality Measure (Gosling, Rentfrom, & Swann, 2003). Our analysis suggests that cultural traits in particular influences and can predict student group work behaviours.
Dynamic time warping applied to Tamil character recognition

This paper describes the use of dynamic time warping (DTW) for classifying handwritten Tamil characters. Since DTW can match characters of arbitrary length, it is particularly suited for this domain. We built a prototype based classifier that uses DTW both for generating prototypes and for calculating a list of nearest prototypes. Prototypes were automatically generated and selected. Two tests were performed to measure the performance of our classifier in a writer dependent, and in a writer independent setting. Furthermore, several strategies were developed for rejecting uncertain cases. Two different rejection variables were implemented and using a Monte Carlo simulation, the performance of the system was tested in various configurations. The results are promising and show that the classifier can be of use in both writer dependent and writer independent automatic recognition of handwritten Tamil characters.