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L-Sort: On-chip Spike Sorting with Efficient Median-of-Median Detection and Localization-based Clustering
Get PDFSpike sorting is a critical process for decoding large-scale neural activity from extracellular recordings. The advancement of neural probes facilitates the recording of a high number of neurons with an increase in channel counts, arising a higher data volume and challenging the current on-chip spike sorters. This paper introduces L-Sort, a novel on-chip spike sorting solution featuring median-of-median spike detection and localization-based clustering. By combining the median-of-median approximation and the proposed incremental median calculation scheme, our detection module achieves a reduction in memory consumption. Moreover, the localization-based clustering utilizes geometric features instead of morphological features, thus eliminating the memory-consuming buffer for containing the spike waveform during feature extraction. Evaluation using Neuropixels datasets demonstrates that L-Sort achieves competitive sorting accuracy with reduced hardware resource consumption. Implementations on FPGA and ASIC (180 nm technology) demonstrate significant improvements in area and power efficiency compared to state-of-the-art designs while maintaining comparable accuracy. If normalized to 22 nm technology, our design can achieve roughly x 10 area and power efficiency with similar accuracy, compared with the state-of-the-art design evaluated with the same dataset. Therefore, L-Sort is a promising solution for real-time, high-channel-count neural processing in implantable devices.</p
The last non-avian theropods of Europe: Palaeoecology and Biogeography inferred from dental records from the uppermost Maastrichtian of Catalonia, Spain
No full textNon-avian theropods were essential components of terrestrial ecosystems during the Mesozoic, were highly diverse in size and lifestyles across different regions of the planet. Here we assess the composition and diversity of the theropod fauna of the Ibero-Armorican island (the ancient region that encompassed present-day areas of Spain, Portugal, and France) during the final few hundred thousand years of the Cretaceous, by reviewing the theropod teeth assemblage from the locality of Molí del Baró-1 (upper Maastrichtian, C29r, Catalonia, Spain). Our study indicates a diverse fauna of small non-avian theropods with different feeding strategies and ecological niches. The tooth assemblage is significantly more diverse than previously thought and includes dental elements referred to dromaeosaurines, velociraptorines, troodontids, and an undetermined Dromaeosauridae tooth with similarities to microraptorines, as well as previously-referred teeth of cf. ?Richardoestesia and aff. Paronychodon. Microwear analysis reveals diverse feeding styles among these theropods, and particularly indicates that the troodontid had an omnivorous diet heavy in plant consumption. The assemblage of small-sized non-avian theropods and medium-to large-sized abelisaurids from the uppermost Maastrichtian of Ibero-Armorica differs from others from the European archipelago and worldwide, illustrating the high regional variability of theropod faunas around the time the asteroid impact ended the Cretaceous
Toward a consensus on dyslexia:Findings from a Delphi study
No full textBackground: Dyslexia is one of the most common neurodevelopmental disorders. There have been many definitions over the past century, and debate continues as to how dyslexia should be defined. This debate contributes to confusion and misinformation. We move beyond the debate by establishing areas of consensus among a wide range of experts. Methods: We conducted a Delphi study with a panel of dyslexia experts, including academics, specialist teachers, educational psychologists, and individuals with dyslexia, asking them for their views on a set of key statements about dyslexia. We carried out two survey rounds, in each case accepting statements with greater than 80% consensus and reviewing and revising other statements using feedback from the expert panel. This was followed by discussion with a subset of the panel around a few statements with marginal consensus. Results: Forty-two statements were ultimately accepted. In the current paper we review those statements that pertain to a definition of dyslexia, demonstrate how they align with the research literature, and build on previous definitions of dyslexia. Conclusions: There was considerable consensus in our expert panel that dyslexia is a difficulty in reading and spelling, associated with multiple factors, and that it frequently co-occurs with other developmental disorders. It was agreed that difficulties in reading fluency and spelling are key markers of dyslexia across different ages and languages. We conclude with a proposed new definition of dyslexia
Mechanosensitive PIEZO2 channels shape coronary artery development
No full textCoronary arteries develop under constant mechanical stress. However, the role of mechanosensitive ion channels in this process remains poorly understood. Here we show that the ion channel PIEZO2, which responds to mechanical stimuli, is expressed in specific coronary endothelial cell populations during a critical phase of coronary vasculature remodeling. These Piezo2+ coronary endothelial cells show distinct transcriptional profiles and have mechanically activated ionic currents. Strikingly, PIEZO2 loss-of-function mouse embryos and mice with human pathogenic variants of PIEZO2 show abnormal coronary vessel development and cardiac left ventricular hyperplasia. We conclude that an optimal balance of PIEZO2 channel function contributes to proper coronary vessel formation, structural integrity and remodeling, and is likely to support normal cardiac function. Our study highlights the importance of mechanical cues in cardiovascular development and suggests that defects in this mechanosensing pathway may contribute to congenital heart conditions
Optimizing international market selection:A dynamic approach integrating export and FDI entry modes
No full textEffectively evaluating and selecting foreign markets is essential for successful internationalization. Traditional International Market Selection (IMS) frameworks typically follow a linear, sequential process: identifying motives, selecting markets, and subsequently determining entry modes. However, such sequential frameworks inadequately account for today's dynamic global market conditions, often resulting in firms entering appropriate markets via an unsuitable entry mode—termed herein as Type III error. Addressing this dangerous error, our study proposes a novel IMS approach that simultaneously integrates market attractiveness and considerations of the suitability of the entry mode selected. Using a dual-criteria ranking method combined with a 45° line analysis, we evaluate 86 prospective international markets across 30 variables. This approach enables firms to align market selection and entry mode decisions from the outset and responds directly to recent research emphasizing their interdependent nature. Our findings reveal that not all markets are analogous, that is, equally attractive for export and FDI, and that some markets are quite distinct, requiring specific entry modes. By adopting this integrated, flexible framework, firms can make more nuanced, strategically coherent internationalization decisions, minimizing risks associated with entry mode misalignment and enhancing their global strategic effectiveness.</p
The UK Biobank mental health enhancement 2022:Methods and results
No full textBACKGROUND: This paper introduces the UK Biobank (UKB) second mental health questionnaire (MHQ2), describes its design, the respondents and some notable findings. UKB is a large cohort study with over 500,000 volunteer participants aged 40-69 years when recruited in 2006-2010. It is an important resource of extensive health, genetic and biomarker data. Enhancements to UKB enrich the data available. MHQ2 is an enhancement designed to enable and facilitate research with psychosocial and mental health aspects.METHODS: UKB sent participants a link to MHQ2 by email in October-November 2022. The MHQ2 was designed by a multi-institutional consortium to build on MHQ1. It characterises lifetime depression further, adds data on panic disorder and eating disorders, repeats 'current' mental health measures and updates information about social circumstances. It includes established measures, such as the PHQ-9 for current depression and CIDI-SF for lifetime panic, as well as bespoke questions. Algorithms and R code were developed to facilitate analysis.RESULTS: At the time of analysis, MHQ2 results were available for 169,253 UKB participants, of whom 111,275 had also completed the earlier MHQ1. Characteristics of respondents and the whole UKB cohort are compared. The major phenotypes are lifetime: depression (18%); panic disorder (4.0%); a specific eating disorder (2.8%); and bipolar affective disorder I (0.4%). All mental disorders are found less with older age and also seem to be related to selected social factors. In those participants who answered both MHQ1 (2016) and MHQ2 (2022), current mental health measure showed that fewer respondents have harmful alcohol use than in 2016 (relative risk 0.84), but current depression (RR 1.07) and anxiety (RR 0.98) have not fallen, as might have been expected given the relationship with age. We also compare lifetime concepts for test-retest reliability.CONCLUSIONS: There are some drawbacks to UKB due to its lack of population representativeness, but where the research question does not depend on this, it offers exceptional resources that any researcher can apply to access. This paper has just scratched the surface of the results from MHQ2 and how this can be combined with other tranches of UKB data, but we predict it will enable many future discoveries about mental health and health in general.</p
The geographical spillover effect of a house purchase deregulation policy:Evidence from a quasi-experiment in China
No full textPurpose In this paper, we quantitatively test the impact of removing home purchase restrictions (HPRs) on the second-hand housing market in neighboring regions to study the potential geographical spillover effect of real estate regulations. Design/methodology/approach We use a policy that removes HPRs in a sub-district of Suzhou City, China, as a quasi-experiment to investigate the effect of a house deregulation policy on sales of second-hand houses in an area not directly impacted by the policy but geographically nearby. The geographical proximity between the regions considered and the unanticipated nature of the policy help to reduce the influence of omitted factors in our difference-in-differences analyses. Findings We find that listing and transaction prices in the area surrounding the deregulated district significantly decrease following the introduction of the policy, while the number of houses sold significantly increases. The impact of the policy on prices diminishes as the distance from the deregulated district’s border increases. With the cancellation of the purchase limit in a sub-region, residents who were not previously eligible to buy houses become eligible to buy properties in the deregulation-targeted district. Such a change reduces future demand for properties in the neighboring area, which motivates sellers to reduce their listing prices and accept lower transaction prices based on their updated demand belief. Originality/value We contribute to the literature by utilizing micro-level transaction data to study the emerging trend of home purchase restrictions being lifted in China and by examining the geographical spillover effects on nearby regions.</p
Macrophage IL-4 polarization is restricted by soluble CD40 agonists and antigen-induced CD154 but not by constitutive CD154 expressed by CD4+ T cells.
No full textStimulation of macrophages via CD40 promotes their classical activation. Therefore, CD154 (CD40 ligand) can be expected to oppose macrophage polarization and proliferation induced by IL-4. However, there is limited experimental data to support this, which is additionally complicated by the possibility of differential effects of CD40 agonists in different formats/contexts. Whereas canonically CD4+ T cells upregulate CD154 strongly following exposure to cognate antigen, naïve CD4+ cells constitutively express significant levels of CD154, which could be a tonic signal. Soluble CD154 and agonistic CD40 antibodies also trigger CD40 signaling. We explored these questions in a reductionist model of IL-4 delivery to mouse peritoneal cavity cells in vitro and in vivo. Soluble CD40 agonists inhibited M(IL-4) polarization, with a stronger effect on RELMa than on Ym1 (Chil3), as well as inhibiting IL-4 induced proliferation. CD154 provided by CD4+ cells in the context of an antigen-specific interaction blunted macrophage RELM-a expression but did not affect Ym1. Macrophages negatively regulated, via CD40, constitutive cell-surface CD154 on naïve CD4+ cells, both in vitro and in vivo. The large peritoneal macrophages of CD40 KO mice showed a moderately enhanced RELMa response to IL-4, but this was not a cell-autonomous effect. No differences between WT and CD40 KO mice were detected in IL-4-induced macrophage proliferation. We conclude that strong CD40 stimulation, included stimulation by CD154 expressed by antigen-specific CD4+ cells, blunts selected macrophage responses to IL-4, and that constitutive CD4+-cell CD154, in spite of interacting with CD40 on macrophages, doesnot directly influence macrophage responses to IL-4
Adaptive PRKAA1 variant in Andeans is associated with improved ventilation and sleep phenotypes
Get PDFHighland groups have adapted to the extreme selective pressures of hypoxia at high altitude via alterations in the oxygen-transport cascade. PRKAA1, which encodes the catalytic subunit of the AMP-activated protein kinase (AMPK), is a notable target of natural selection in Andeans and has been associated with protective fetal phenotypes in this population. AMPK is a universal cellular energy sensor involved in a multitude of physiological processes, including ventilation and the hypoxic ventilatory response (HVR) in animal models. We localized a signal of positive selection and identified a regulatory promoter variant (rs10035235, C>T) of adaptive significance that is associated with ventilatory and sleep phenotypes in male Andean highlanders as well as sleep phenotypes in publicly available lowland cohorts. This work identifies a functional, adaptive, and likely pleiotropic regulatory variant in PRKAA1 in Andeans that may accentuate hypoxia-induced ventilation and provide protection from sleep-disordered breathing in both high- and lowland populations. </p
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