Miracle-dz/UniFAR-FTUs huggingface dataset:
KIBRA Regulates AMPA Receptor Expression, Synaptic Plasticity, and Memory in an Age-Dependent Manner

The biological mechanisms supporting age-dependent changes in learning and memory remain elusive. While a growing body of human literature implicates KIBRA in memory and neurodevelopmental disorders, KIBRA’s molecular function and contribution to maturation of synaptic function and cognition remain poorly understood. Despite being expressed throughout early postnatal development, germline deletion of KIBRA impairs synaptic plasticity selectively in adult rodents. However, it is unclear whether KIBRA facilitates proper brain maturation necessary for adult plasticity or whether it plays a distinct role in plasticity in the adult brain. Here, using an inducible KIBRA knockout mouse, we demonstrate that acutely deleting KIBRA in adult forebrain neurons impairs both spatial memory and long-term potentiation (LTP). The deficits in LTP correlate with an adult-selective decrease in extrasynaptic AMPA receptors under basal conditions. We also identify a novel role for KIBRA in LTP-induced AMPAR upregulation. In contrast, acute deletion of KIBRA in juvenile forebrain neurons did not affect LTP and had minimal effects on basal AMPAR expression. These data suggest that KIBRA serves a unique role in adult hippocampal function through regulation of basal and activity-dependent AMPAR proteostasis that supports synaptic plasticity. Significance Statement Synaptic plasticity supported by trafficking of postsynaptic AMPA receptors is a conserved mechanism underlying learning and memory. The nature and efficacy of learning and memory undergo substantial changes during childhood and adolescent development, but the mechanisms underlying this cognitive maturation remain poorly understood. Here, we demonstrate that the human memory- and neurodevelopmental disorder-associated gene KIBRA facilitates memory and hippocampal synaptic plasticity selectively in the adult hippocampus. Furthermore, we show that selective loss of KIBRA from adult but not juvenile neurons reduces expression of extrasynaptic AMPA receptors and prevents LTP-induced increases in AMPAR expression. Overall, our results suggest that KIBRA participates in cellular and molecular processes that become uniquely necessary for memory and synaptic plasticity in early adulthood.
Characterization of altered molecular mechanisms in Parkinson’s disease through cell type–resolved multiomics analyses

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. However, cell type–dependent transcriptional regulatory programs responsible for PD pathogenesis remain elusive. Here, we establish transcriptomic and epigenomic landscapes of the substantia nigra by profiling 113,207 nuclei obtained from healthy controls and patients with PD. Our multiomics data integration provides cell type annotation of 128,724 cis-regulatory elements (cREs) and uncovers cell type–specific dysregulations in cREs with a strong transcriptional influence on genes implicated in PD. The establishment of high-resolution three-dimensional chromatin contact maps identifies 656 target genes of dysregulated cREs and genetic risk loci, uncovering both potential and known PD risk genes. Notably, these candidate genes exhibit modular gene expression patterns with unique molecular signatures in distinct cell types, highlighting altered molecular mechanisms in dopaminergic neurons and glial cells including oligodendrocytes and microglia. Together, our single-cell transcriptome and epigenome reveal cell type–specific disruption in transcriptional regulations related to PD.
Predicting vertical ground reaction forces from 3D accelerometry using reservoir computers leads to accurate gait event detection

Accelerometers are low-cost measurement devices that can readily be used outside the lab. However, determining isolated gait events from accelerometer signals, especially foot-off events during running, is an open problem. We outline a two-step approach where machine learning serves to predict vertical ground reaction forces from accelerometer signals, followed by force-based event detection. We collected shank accelerometer signals and ground reaction forces from 21 adults during comfortable walking and running on an instrumented treadmill. We trained one common reservoir computer using segmented data using both walking and running data. Despite being trained on just a small number of strides, this reservoir computer predicted vertical ground reaction forces in continuous gait with high quality. The subsequent foot contact and foot off event detection proved highly accurate when compared to the golden standard based on co-registered ground reaction forces. Our proof-of-concept illustrates the capacity of combining accelerometry with machine learning for detecting isolated gait events irrespective of mode of locomotion.
Canonical Wnt Signaling Promotes Formation of Somatic Permeability Barrier for Proper Germ Cell Differentiation

Morphogen-mediated signaling is critical for proper organ development and stem cell function, and well-characterized mechanisms spatiotemporally limit the expression of ligands, receptors, and ligand-binding cell-surface glypicans. Here, we show that in the developing Drosophila ovary, canonical Wnt signaling promotes the formation of somatic escort cells (ECs) and their protrusions, which establish a physical permeability barrier to define morphogen territories for proper germ cell differentiation. The protrusions shield germ cells from Dpp and Wingless morphogens produced by the germline stem cell (GSC) niche and normally only received by GSCs. Genetic disruption of EC protrusions allows GSC progeny to also receive Dpp and Wingless, which subsequently disrupt germ cell differentiation. Our results reveal a role for canonical Wnt signaling in specifying the ovarian somatic cells necessary for germ cell differentiation. Additionally, we demonstrate the morphogen-limiting function of this physical permeability barrier, which may be a common mechanism in other organs across species.
The exchange rates of amide and arginine guanidinium CEST in the mouse brain

Purpose To develop a pipeline for measuring the exchange rates and concentrations of in vivo excgangeable protons, and to demonstrate this for the amide and arginine (Arg) guanidinium (Guan) protons in mobile proteins in the mouse brain. Methods An ultra-short echo (UTE) CEST sequence with a continuous wave presaturation (preRadCEST) was applied to acquire Z-spectra with robustness to motion and physiological fluctuations. AmideCEST and Arginine guanCEST (ArgCEST) were extracted and their proton concentrations and exchange rates obtained using a two-step multi-B1 Bloch fitting approach that included the semisolid macromolecular background. To minimize contamination from the amine protons from creatine and phosphocreatine, ArgCEST measurements were performed on the Guanidinoacetate N-methyltransferase deficiency (GAMT-/-) mouse characterized by low creatine and phosphocreatine concentrations in the brain. Results For the amideCEST proton pool, the exchange rate and concentrations were found to be 59.6 ± 9.0 s-1 and 41.7 ± 7.0 mM, respectively, with the maximum signal observed at B1 = 0.8 μT. For the ArgCEST proton, the guanidinium exchange these were 70.1 ± 5.5 s-1 and 10.1 ± 1.3 mM, respectively, with the maximum effect observed at B1 = 0.9 μT. The current study suggests that the inverse pH dependence in GuanCEST of brain is led by the CrCEST component, not ArgCEST. Conclusion The current pipeline is expected to have general use for in vivo CEST quantitation and optimization of visible CEST resonances.
Design methodologies for built-in testing of integrated RF transceivers with the on-chip loopback technique

Design methodologies for built-in testing of integrated RF transceivers with the on-chip loopback technique (December 2007) Marvin Olufemi Onabajo Chair of Advisory Committee: Jose Silva-Martinez Advances toward increased integration and complexity of radio frequency (RF) andmixed-signal integrated circuits reduce the effectiveness of contemporary testmethodologies and result in a rising cost of testing. The focus in this research is on thecircuit-level implementation of alternative test strategies for integrated wirelesstransceivers with the aim to lower test cost by eliminating the need for expensive RFequipment during production testing.The first circuit proposed in this thesis closes the signal path between the transmitterand receiver sections of integrated transceivers in test mode for bit error rate analysis atlow frequencies. Furthermore, the output power of this on-chip loopback block wasmade variable with the goal to allow gain and 1-dB compression point determination forthe RF front-end circuits with on-chip power detectors. The loopback block is intendedfor transceivers operating in the 1.9-2.4GHz range and it can compensate for transmitterreceiveroffset frequency differences from 40MHz to 200MHz. The measuredattenuation range of the 0.052mm2 loopback circuit in 0. 13μm CMOS technology was 26-41dB with continuous control, but postlayout simulation results indicate that theattenuation range can be reduced to 11-27dB via optimizations.Another circuit presented in this thesis is a current generator for built-in testing ofimpedancematched RF front-end circuits with current injection. Since this circuit hashigh output impedance (>1k up to 2.4GHz), it does not influence the input matchingnetwork of the low-noise amplifier (LNA) under test. A major advantage of the currentinjection method over the typical voltage-mode approach is that the built-in test canexpose fabrication defects in components of the matching network in addition to on-chipdevices. The current generator was employed together with two power detectors in arealization of a built-in test for a LNA with 14% layout area overhead in 0. 13μm CMOStechnology (<1.5% for the 0.002mm2 current generator). The post-layout simulationresults showed that the LNA gain (S21) estimation with the external matching networkwas within 3.5% of the actual gain in the presence of process-voltage-temperaturevariations and power detector imprecision.
Broadband rotational symmetry circularly polarised antenna

A new broadband circularly polarised printed antenna is proposed. This antenna is evolved from a bow-tie dipole antenna, which have wideband impendence bandwidth (IBW). It uses a configuration of rotational symmetry dipole structure to be radiators. This rotational symmetry structure makes the surface currents to produce a circular polarisation wave. The simulation and measurement results are very consistent. The results show good performance of IBW is ∼140.6% (1.91–10.95 GHz) for S 11<−10 dB, 3 dB axial-ratio bandwidth is ∼96.6% (3.70–10.62 GHz).
Forms that Work: Designing Web Forms for Usability

Forms are everywhere on the web - for registration and communicating, for commerce and government. Good forms make for happier customers, better data, and reduced support costs. Bad forms fill your organization's databases with inaccuracies and duplicates and can cause loss of potential consumers. Designing good forms is trickier than people think. Jarrett and Gaffney come to the rescue with Designing Forms that Work, clearly explaining exactly how to design great forms for the web. Liberally illustrated with full-color examples, it guides readers on how to define requirements, how to write questions that users will understand and want to answer, and how to deal with instructions, progress indicators and errors. *Provides proven and practical advice that will help you avoid pitfalls, and produce forms that are aesthetically pleasing, efficient and cost-effective. *Features invaluable design methods, tips, and tricks to help ensure accurate data and satisfied customers. *Includes dozens of examples -- from nitty-gritty details (label alignment, mandatory fields) to visual designs (creating good grids, use of color). *Foreword by Steve Krug, author of the best selling Don't Make Me Think!
Correlation Between Thrombus Signal Intensity and Aneurysm Wall Thickness in Partially Thrombosed Intracranial Aneurysms Using 7T Magnetization-Prepared Rapid Acquisition Gradient Echo Magnetic Resonance Imaging

Objective The objective of this study is to investigate the relationship between the thrombus signal intensity and aneurysm wall thickness in partially thrombosed intracranial aneurysms in vivo with magnetization-prepared rapid acquisition gradient echo (MPRAGE) taken using 7T magnetic resonance imaging (MRI) and correlate the findings to wall instability. Methods Sixteen partially thrombosed intracranial aneurysms were evaluated using a 7T whole-body MR system with nonenhanced MPRAGE. To normalize the thrombus signal intensity, its highest signal intensity was compared to that of the anterior corpus callosum of the same subject, and the signal intensity ratio was calculated. The correlation between the thrombus signal intensity ratio and the thickness of the aneurysm wall was analyzed. Furthermore, aneurysmal histopathological specimens from six tissue samples were compared with radiological findings to detect any correlation. Results The mean thrombus signal intensity ratio was 0.57 (standard error of the mean [SEM] 0.06, range 0.25–1.01). The mean thickness of the aneurysm wall was 1.25 (SEM 0.08, range 0.84–1.55) mm. The thrombus signal intensity ratio significantly correlated with the aneurysm wall thickness (p < 0.01). The aneurysm walls with the high thrombus signal intensity ratio were significantly thicker. In histopathological examinations, three patients with a hypointense thrombus had fewer macrophages infiltrating the thrombus and a thin degenerated aneurysmal wall. In contrast, three patients with a hyperintense thrombus had abundant macrophages infiltrating the thrombus. Conclusion The thrombus signal intensity ratio in partially thrombosed intracranial aneurysms correlated with aneurysm wall thickness and histologic features, indicating wall instability.
Contributions of the International Narcotics Research Conference to Opioid Research Over the Past 50 years

The International Narcotics Research Conference (INRC), founded in 1969, has been a successful forum for research into the actions of opiates, with an annual conference since 1971. Every year, scientists from around the world have congregated to present the latest data on novel opiates, opiate receptors and endogenous ligands, mechanisms of analgesic activity and unwanted side effects, etc. All the important discoveries in the opiate field were discussed, often first, at the annual INRC meeting. With an apology to important events and participants not discussed, this review presents a short history of INRC with a discussion of groundbreaking discoveries in the opiate field and the researchers who presented from the first meeting up to the present.
Effect of Home Enteral Nutritional Support Compared With Normal Oral Diet in Postoperative Subjects With Upper Gastrointestinal Cancer Resection: A Meta-Analysis

Introduction We performed a meta-analysis to evaluate the influence of a home enteral nutritional support compared with a normal oral diet in postoperative subjects with upper gastrointestinal cancer resection. Methods A systematic literature search up to December 2021 was done and 23 studies included 3,010 subjects with upper gastrointestinal cancer resection at the start of the study; 1,556 of them were given home enteral nutritional support and 1,454 were normal oral diet. We calculated the odds ratio (OR) and mean difference (MD) with 95% CIs to evaluate the influence of home enteral nutritional support compared with a normal oral diet in postoperative subjects with upper gastrointestinal cancer resection by the dichotomous or continuous methods with a random or fixed-influence model. Results Home enteral nutritional support had significantly higher quality of life (MD, 2.08; 95% CI, 1.50–2.67, p < 0.001), better body weight change (MD, 1.87; 95% CI, 1.31–2.43, p < 0.001), higher albumin (MD, 1.27; 95% CI, 0.72–1.82, p < 0.001), and higher pre-albumin (MD, 30.79; 95% CI, 7.29–54.29, p = 0.01) compared to the normal oral diet in subjects with upper gastrointestinal cancer resection. However, home enteral nutritional support had no significant impact on the hemoglobin (MD, 4.64; 95% CI, −4.17 to 13.46, p = 0.30), and complications (OR, 1.03; 95% CI, 0.76–1.40, p = 0.83) compared to the normal oral diet in subjects with upper gastrointestinal cancer resection. Conclusions Home enteral nutritional support had a significantly higher quality of life, better body weight change, higher albumin, and higher pre-albumin, and had no significant impact on the hemoglobin and complications compared to the normal oral diet in subjects with upper gastrointestinal cancer resection. Further studies are required.
Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan

Herein we review current practice regarding the management of chronic graft-vs.-host disease (cGvHD) in paediatric patients after allogeneic haematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukaemia (ALL). Topics covered include: (i) the epidemiology of cGvHD; (ii) an overview of advances in our understanding cGvHD pathogenesis; (iii) current knowledge regarding risk factors for cGvHD and prevention strategies complemented by biomarkers; (iii) the paediatric aspects of the 2014 National Institutes for Health-defined diagnosis and grading of cGvHD; and (iv) current options for cGvHD treatment. We cover topical therapy and newly approved tyrosine kinase inhibitors, emphasising the use of immunomodulatory approaches in the context of the delicate counterbalance between immunosuppression and immune reconstitution as well as risks of relapse and infectious complications. We examine real-world approaches of response assessment and tapering schedules of treatment. Furthermore, we report on the optimal timepoints for therapeutic interventions and changes in relation to immune reconstitution and risk of relapse/infection. Additionally, we review the different options for anti-infectious prophylaxis. Finally, we put forth a theory of a holistic view of paediatric cGvHD and its associated manifestations and propose a checklist for individualised risk evaluation with aggregated considerations including site-specific cGvHD evaluation with attention to each individual's GvHD history, previous medical history, comorbidities, and personal tolerance and psychosocial circumstances. To complement this checklist, we present a treatment algorithm using representative patients to inform the personalised management plans for patients with cGvHD after HSCT for ALL who are at high risk of relapse.
Future Changes of Summer Heat Waves Over Urban Agglomerations in Eastern China Under 1.5°C and 2.0°C Global Warming

Extreme hot events have increased evidently under global warming, particularly in the urban areas. This study aims to explore the detailed features of future changes in summer heat waves (HWs) over three major urban agglomerations (Beijing Tianjin Hebei, BTH; Yangtze River Delta, YRD; Pearl River Delta, PRD) in eastern China under 1.5 and 2.0°C warming scenario by using the Weather Research and Forecasting model (WRF) with the updated land cover data for China (ChinaLC), which is also coupled with urban canopy model. Based on the future projection results from Community Earth System Model (CESM) under the Representative Concentration Pathway (RCP) 4.5, dynamic downscaling with high-resolution WRF has been performed to project the future changes in frequency, duration and intensity of summer HWs in urban agglomerations under 1.5 and 2.0°C warming scenarios respectively. Compared with the historical period, it is found that both the summer HWs indices and the HWs affected areas all increase significantly under 1.5 and 2.0°C warming scenarios. The increasing rates of the three HWs indices are above 50% under 1.5°C warming situation, and 70% for 2.0°C warming scenario, with the increasing rate of HWs intensity even exceeding 200%. It is noted that an additional 0.5°C warming from 1.5 to 2.0°C can produce much larger impact on the future HWs changes in YRD, with the HWs intensity increased by 75.5% from 1.5 to 2.0°C warming scenarios. It is further found that the changes of HWs indices in urban area is much higher than that of non-urban areas under 1.5 and 2.0°C warming, indicating that the urban areas will face higher risk of heat-related illness or environments than suburban or rural areas in the future. Our results can provide further scientific support for the mitigation and adaption strategy for the future HWs risk in mega-cities.
Non-Pharmaceutical Interventions Implemented to Control the COVID-19 Were Associated With Reduction of Influenza Incidence

Background Non-pharmaceutical interventions were implemented in most countries to reduce the transmission of COVID-19. We aimed to describe the incidence of influenza in four countries in the 2019–2020 season and examined the effect of these non-pharmaceutical interventions on the incidence of influenza. Methods We used the network surveillance data from 2015 to 2020 to estimate the percentage increase in influenza cases to explore the effect of non-pharmaceutical interventions implemented to control the COVID-19 on the incidence of influenza in China, the United States, Japan, and Singapore. Results We found that the incidence of influenza has been almost zero and reached a persistent near-zero level for a continuous period of six months since epidemiologic week 14 of 2020 in the four countries. Influenza incidence decreased by 77.71% and 60.50% in the early days of COVID-19 in the 2019–2020 season compared to the same period in preceding years in Japan and Singapore, respectively. Furthermore, influenza incidence decreased by 60.50–99.48% during the period of compulsory interventions in the 2019–2020 season compared to the same period in preceding years in the four countries. Conclusion These findings suggest that the application of non-pharmaceutical interventions, even everyday preventive action, was associated with a reduction of influenza incidence, which highlights that more traditional public health interventions need to be reasserted and universalized to reduce influenza incidence.
Design and Implementation of Digital AGC

The characteristic of troposcatter communications is analyzed,and the disadvantages of two AGC circuits that often used in troposcatter communications are introduced.Then a new circuit of full-digital AGC is realized by the way of VHDL language.This design is implemented on the chip EP1S40F1020I6,with advantages of high precision,fast adjustment,light environment influence,good stability and excellent reliability,and 40 dB dynamic range is achieved.In the end the circuits which are composed of digital AGC and analog AGC using AD8367 are tested.The result of the test indicates that 65 dB dynamic range can be reached.