Continuous ASL perfusion fMRI investigation of higher cognition: Quantification of tonic CBF changes during sustained attention and working memory tasks

Arterial spin labeling (ASL) perfusion fMRI is an emerging method in clinical neuroimaging. Its non-invasiveness, absence of low frequency noise, and ability to quantify the absolute level of cerebral blood flow (CBF) make the method ideal for longitudinal designs or low frequency paradigms. Despite the usefulness in the study of cognitive dysfunctions in clinical populations, perfusion activation studies to date have been conducted for simple sensorimotor paradigms or with single-slice acquisition, mainly due to technical challenges. Using our recently developed amplitude-modulated continuous ASL (CASL) perfusion fMRI protocol, we assessed the feasibility of a higher level cognitive activation study in twelve healthy subjects. Taking advantage of the ASL noise properties, we were able to study tonic CBF changes during uninterrupted 6-min continuous performance of working memory and sustained attention tasks. For the visual sustained attention task, regional CBF increases (6–12 ml/100 g/min) were detected in the right middle frontal gyrus, the bilateral occipital gyri, and the anterior cingulate/medial frontal gyri. During the 2-back working memory task, significantly increased activations (7–11 ml/100 g/min) were found in the left inferior frontal/precentral gyri, the left inferior parietal lobule, the anterior cingulate/medial frontal gyri, and the left occipital gyrus. Locations of activated and deactivated areas largely concur with previous PET and BOLD fMRI studies utilizing similar paradigms. These results demonstrate that CASL perfusion fMRI can be successfully utilized for the investigation of the tonic CBF changes associated with high level cognitive operations. Increased applications of the method to the investigation of cognitively impaired populations are expected to follow

Original contribution Reduced susceptibility effects in perfusion fMRI with single-shot spin- echo EPI acquisitions at 1.5 Tesla

Abstract Arterial spin labeling (ASL) perfusion contrast is not based on susceptibility effects and can therefore be used to study brain function in regions of high static inhomogeneity. As a proof of concept, single-shot spin-echo echo-planar imaging (EPI) acquisition was carried out with a multislice continuous ASL (CASL) method at 1.5T. A bilateral finger tapping paradigm was used in the presence of an exogenously induced susceptibility artifact over left motor cortex. The spin-echo CASL technique was compared with a regular gradient-echo EPI sequence with the same slice thickness, as well as other imaging methods using thin slices and spin-echo acquisitions. The results demonstrate improved functional sensitivity and efficiency of the spin-echo CASL approach as compared with gradient-echo EPI techniques, and a trend of improved sensitivity as compared with spin-echo EPI approach in the brain regions affected by the susceptibility artifact. ASL images, either with or without subtraction of the control, provide a robust alternative to blood oxygenation level dependant (BOLD) methods for activation imaging in regions of high static field inhomogeneity

From Tuberculosis Bedside to Bench: UBE2B Splicing as a Potential Biomarker and Its Regulatory Mechanism

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB

Research on the Design of Auxiliary Generator for Enthalpy Reduction and Steady Speed Scroll Expander

To help the reverse Brayton cycle cool the refrigerant from 100 K to 50 K, an auxiliary generator, with a housed stator, is studied and optimized, and the influences of weights in the cost- function on the results are discussed. The power demand and adiabatic characteristics of reverse Brayton cycle expansion are analyzed, after which the optimization indexes, including output rated power, efficiency, the air gap between rotor and stator, loss, and volume, are decided. The initial model of the auxiliary generator is then constructed and the parameters to be optimized are also determined. Taking the low loss and sinusoidal back-EMF as the evaluation indexes, the single parameter optimizations of the auxiliary generator are carried out. The co-simulation of the generator and its corresponding driving circuit is investigated, with which the power generation efficiency is calculated. The global optimizations of the generator parameters are carried out using a genetic algorithm. A suitable analytic hierarchy process (AHP) model is proposed, with which a three-order judgment matrix is constructed, and the effects of different weight combinations, in the cost-function, on generator performance are compared. The experimental results show that the output back-EMF amplitude is 28.2 V, which is about 10% smaller than the simulation results; the output power of the auxiliary generator under load is about 3.7 W, meeting the rated demand

High Frequency InGaAs MOSFET with Nitride Sidewall Design for Low Power Application

InxGa1-xAs devices have been widely researched for low power high frequency applications due to the outstanding electron mobility and small bandgap of the materials. Regrown source/drain technology is highly appreciated in InGaAs MOSFET, since it is able to reduce the thermal budget induced by ion implantation, as well as reduce the source/drain resistance. However, regrown source/drain technology has problems such as high parasitic capacitance and high electric field at gate edge towards the drain side, which will lead to large drain leakage current and compromise the frequency performance. To alleviate the drain leakage current problem for low power applications and to improve the high frequency performance, a novel Si3N4 sidewall structure was introduced to the InGaAs MOSFET. Device simulation was carried out with different newly proposed sidewall designs. The results showed that both the drain leakage current and the source/drain parasitic capacitance were reduced by applying Si3N4 sidewall together with InP extended layer in InGaAs MOSFET. The simulation results also suggested that the newly created “recessed” sidewall was able to bring about the most frequency favorable characteristic with no current sacrifice

Effects of prior knowledge on brain activation and functional connectivity during memory retrieval

Abstract Previous studies have shown that the ventral medial prefrontal cortex (vmPFC) plays an important role in schema-related memory. However, there is an intensive debate to what extent the activation of subregions of the hippocampus is involved in retrieving schema-related memory. In addition, it is unclear how the functional connectivity (FC) between the vmPFC and the hippocampus, as well as the connectivity of the vmPFC with other regions, are modulated by prior knowledge (PK) during memory retrieval over time. To address these issues, participants learned paragraphs that described features of each unfamiliar word from familiar and unfamiliar categories (i.e., high and low PK conditions) 20 min, 1 day, and 1 week before the test. They then performed a recognition task to judge whether the sentences were old in the scanner. The results showed that the activation of the anterior-medial hippocampus (amHPC) cluster was stronger when the old sentences with high (vs. low) PK were correctly retrieved. The activation of the posterior hippocampus (pHPC) cluster, as well as the vmPFC, was stronger when the new sentences with high (vs. low) PK were correctly rejected (i.e., CR trials), whereas the cluster of anterior-lateral hippocampus (alHPC) showed the opposite. The FC of the vmPFC with the amHPC and perirhinal cortex/inferior temporal gyrus was stronger in the high (vs. low) PK condition, whereas the FC of the vmPFC with the alHPC, thalamus and frontal regions showed the opposite for the CR trials. This study highlighted that different brain networks, which were associated with the vmPFC, subregions of the hippocampus and cognitive control regions, were responsible for retrieving the information with high and low PK

Acquiring New Factual Information: Effect of Prior Knowledge

One influential theory on object knowledge is feature-based model, which proposes that the object knowledge is organized by different feature types, such as sensory/perceptual and motor/functional ones. Previous studies have shown that prior knowledge enhances the processes of acquiring and remembering relevant information. However, whether the effect of prior knowledge is applied to different types of conceptual information over time remains unclear. In this study, we addressed this question by testing memory of different types of object features at various retention intervals. The level of prior knowledge was manipulated as object features from familiar and unfamiliar categories. In Experiments 1 and 2, sentences that described the perceptual and functional features of new words were presented. Sentences with episodic features were additionally presented in Experiment 2. The participants were then tested with recognition (Experiment 1) and recall (Experiment 2) tasks at different retention intervals. The results showed that prior knowledge enhanced memory for perceptual features but not for functional and episodic features. Such enhancement depended on the recollection process. In addition, the effect of prior knowledge on perceptual features remained stable over time. This study clarified how different types of new factual information were acquired and maintained and highlighted the importance of prior knowledge in acquiring new conceptual knowledge with the passage of time

Design and Implementation of RF Front-End Module Based on 3D Heterogenous-Integrated Wafer-Level Packaging

In this paper, a three-dimensional heterogenous-integrated (3DHI) wafer-level packaging (WLP) process is proposed, and a radio frequency (RF) front-end module with two independent ultra-high frequency (UHF) receiving channels are designed and implemented, which covers 400 MHz–600 MHz and 2050 MHz–2200 MHz respectively for unmanned aerial vehicle (UAV) applications. The module is formed by wafer-to-wafer (W2W) bonding of two high-resistivity silicon (HR-Si) interposers with embedded bare dies and through silicon via (TSV) interconnections. Double-sided deep reactive ion etching (DRIE) and conformal electroplating process are introduced to realize the high-aspect-ratio TSV connection within 290 µm-thick cap interposer. Co-plane waveguide (CPW) transmission lines are fabricated as the process control monitor (PCM), the measured insertion loss of which is less than 0.18 dB/mm at 35 GHz. The designed RF front-end module is fabricated and measured. The measured return loss and gain of each RF channel is better than 13 dB and 21 dB, and the noise figure is less than 1.5 dB. In order to evaluate the capability of the 3DHI process for multi-layer interposers, the module is re-designed and fabricated with four stacked high-resistivity silicon interposers. After W2W bonding of two pairs of interposers and wafer slicing, chip-to chip (C2C) bonding is applied to form a four-layer module with operable temperature gradient