Investigation of shape, position, and permeability of shielding material in quadruple butterfly coil for focused transcranial magnetic stimulation

Transcranial magnetic stimulation has been gaining popularity in the therapy for several neurological disorders. A time-varying magnetic field is used to generate electric field in the brain. As the development of TMS methods takes place, emphasis on the coil design increases in order to improve focal stimulation. Ideally reduction of stimulation of neighboring regions of the target area is desired. This study, focused on the improvement of the focality of the Quadruple Butterfly Coil (QBC) with supplemental use of different passive shields. Parameters such as shape, position and permeability of the shields have been explored to improve the focus of stimulation. Results have been obtained with the help of computer modelling of a MRI derived heterogeneous head model over the vertex position and the dorsolateral prefrontal cortex position using a finite element tool. Variables such as maximum electric field induced on the grey matter and scalp, volume and area of stimulation above half of the maximum value of electric field on the grey matter, and ratio of the maximum electric field in the brain versus the scalp have been investigated

Doing housework and having regular daily routine standing out as factors associate with physical function in the older people

Background and objectivesNationwide data were used to explore factors associated with physical function in order to identify interventions that could improve and maintain physical function in the older people.MethodsThe physical function was assessed by gait speed (GS). We selected 2,677 male and 2,668 female older adults (aged ≥60) who could perform the GS test as study subjects. GS was measured by having subjects walk across and back a 10-m course. A gait speed less than 20% that of a reference population (<0.7 m/s) was used as the definition of slow gait speed (SGS). Co-morbidity, polypharmacy, medical expenses, need for care, and hospitalization were used to evaluate health status. A stepwise logistic regression model was used to determine factors associated with SGS.ResultsSGS was associated with poorer health status, higher medical cost, lower ranking on the Geriatric Depression Scale (GDS) and decreased Mini-mental State Examination (MMSE). Co-morbidity (OR = 1.81, 1.58–2.07), polypharmacy (OR = 1.47, 1.25–1.74), MMSE <24 (OR = 1.85, 1.54–2.22), and GDS ≥ 11 (OR = 1.40, 1.18–1.65) were associated with SGS. In contrast, doing housework (DHW, OR = 0.43, 0.38–0.49), having a regular daily routine (RDR, OR = 0.64, 0.45–0.91), and current alcohol consumption (OR = 0.74, 0.62–0.90) were inversely associated with SGS. DHW plus having RDR could greatly reduce the risk of SGS (OR = 0.29, 0.19–0.43).ConclusionPoor physical function is associated with poorer health status in Chinese older people. Maintaining a regular daily routine and doing some housework may be important factors that can help older people preserve their physical function

A Novel Application of Image-to-Image Translation: Chromosome Straightening Framework by Learning from a Single Image

In medical imaging, chromosome straightening plays a significant role in the pathological study of chromosomes and in the development of cytogenetic maps. Whereas different approaches exist for the straightening task, typically geometric algorithms are used whose outputs are characterized by jagged edges or fragments with discontinued banding patterns. To address the flaws in the geometric algorithms, we propose a novel framework based on image-to-image translation to learn a pertinent mapping dependence for synthesizing straightened chromosomes with uninterrupted banding patterns and preserved details. In addition, to avoid the pitfall of deficient input chromosomes, we construct an augmented dataset using only one single curved chromosome image for training models. Based on this framework, we apply two popular image-to-image translation architectures, U-shape networks and conditional generative adversarial networks, to assess its efficacy. Experiments on a dataset comprised of 642 real-world chromosomes demonstrate the superiority of our framework, as compared to the geometric method in straightening performance, by rendering realistic and continued chromosome details. Furthermore, our straightened results improve the chromosome classification by 0.98%-1.39% mean accuracy.Comment: This work has been accepted by CISP-BMEI202

Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation.

TREM2 is a pattern recognition receptor, expressed on microglia and myeloid cells, detecting lipids and Aβ and inducing an innate immune response. Missense mutations (e.g., R47H) of TREM2 increase risk of Alzheimer's disease (AD). The soluble ectodomain of wild-type TREM2 (sTREM2) has been shown to protect against AD in vivo, but the underlying mechanisms are unclear. We show that Aβ oligomers bind to cellular TREM2, inducing shedding of the sTREM2 domain. Wild-type sTREM2 bound to Aβ oligomers (measured by single-molecule imaging, dot blots, and Bio-Layer Interferometry) inhibited Aβ oligomerization and disaggregated preformed Aβ oligomers and protofibrils (measured by transmission electron microscopy, dot blots, and size-exclusion chromatography). Wild-type sTREM2 also inhibited Aβ fibrillization (measured by imaging and thioflavin T fluorescence) and blocked Aβ-induced neurotoxicity (measured by permeabilization of artificial membranes and by loss of neurons in primary neuronal-glial cocultures). In contrast, the R47H AD-risk variant of sTREM2 is less able to bind and disaggregate oligomeric Aβ but rather promotes Aβ protofibril formation and neurotoxicity. Thus, in addition to inducing an immune response, wild-type TREM2 may protect against amyloid pathology by the Aβ-induced release of sTREM2, which blocks Aβ aggregation and neurotoxicity. In contrast, R47H sTREM2 promotes Aβ aggregation into protofibril that may be toxic to neurons. These findings may explain how wild-type sTREM2 apparently protects against AD in vivo and why a single copy of the R47H variant gene is associated with increased AD risk.European Unio

SORL1 mutations in early- and late-onset Alzheimer disease.

OBJECTIVE: To characterize the clinical and molecular effect of mutations in the sortilin-related receptor (SORL1) gene. METHODS: We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants. The phenotypic consequences associated with SORL1 mutations were characterized based on clinical reviews of medical records. Functional studies were completed to evaluate β-amyloid (Aβ) production and amyloid precursor protein (APP) trafficking associated with SORL1 mutations. RESULTS: SORL1 alterations were present in 2 EOAD families. In one, a SORL1 T588I change was identified in 4 individuals with AD, 2 of whom had parkinsonian features. In the second, an SORL1 T2134 alteration was found in 3 of 4 AD cases, one of whom had postmortem Lewy bodies. Among LOAD cases, 4 individuals with either SORL1 A528T or T947M alterations had parkinsonian features. Functionally, the variants weaken the interaction of the SORL1 protein with full-length APP, altering levels of Aβ and interfering with APP trafficking. CONCLUSIONS: The findings from this study support an important role for SORL1 mutations in AD pathogenesis by way of altering Aβ levels and interfering with APP trafficking. In addition, the presence of parkinsonian features among select individuals with AD and SORL1 mutations merits further investigation

Pax6/c-Myb regulates neuronal apoptosis in a mouse model of Alzheimer's disease

Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder which is characterized by impaired mental functions such as memory, language, perception, behavior and personality, as well as cognitive skills. The molecular mechanisms underlying this disease is still largely unknown, but numerous evidence emerge to support a cell cycle hypothesis which implicates the deregulation of cell cycle proteins as key mediators of neuronal dysfunction and loss in AD brains. One of these signals in Aβ-induced neuronal death model is Cdk/Rb/E2F pathway, where Aβ insult evokes activation of Cdk4/6, which subsequently phosphorylates pRb protein, resulting in activation of E2F transcription factors. However, the mechanism(s) by which Cdk/Rb/E2F mediates neuronal death remains elusive. Therefore, the goal of this project is to characterize the downstream events of cell cycle pathway, which include the involvement of transcription factors c-Myb, Pax6 and Patz1 in Aβ-induced neuronal death signaling. In this study, we showed that Pax6 is a direct target gene for Both E2F1 and c-Myb. Both Pax6 and c-Myb are up-regulated by Aβ insults in cultured cortical neurons. And with E2F1 silencing by siRNA, Aβ-induced Pax6 and c-Myb expression is blocked, suggesting E2F1 is responsible for their elevation. Importantly, siRNA-mediated downregulation of either c-Myb or Pax6 protects neurons from death evoked by Aβ peptide, suggesting they are proapoptotic proteins, delivering death signals sent from upstream E2F1. Next, though ChIP assay, we identified two target genes for Pax6. One is Patz1, another transcription factor that is Aβ-induced pro-apoptotic protein. The other one is GSK3β, which is a pathogenic kinase involved in Tau protein hyperphosphorylation and NFT formation. In conclusion, this dissertation shows that cell cycle regulators Cdk/Rb/E2F modulate neuronal death signals by activating downstream transcription factors c-Myb and Pax6, further upregulating GSK3β. We provided evidence suggesting that Aβ induced neurotoxicity leads to Tau hyperphosphorylation through a mechanism involving cell cycle activation and subsequent activation of c-Myb/Pax6/GSK3β. In brief, in the present study, we delineate a transcriptional cascade downstream of cell cycle pathway leads to neuronal apoptosis as well as Tau/NFT pathology. The characterization of this novel pathway lends support for development of new therapeutic agents and for better experimental models for AD. Lastly, the cascade between cell cycle activation and tauopathy in Aβ-induced neuronal death needs to be further researched in the future.HKU 3 Minute Thesis Award, Champion (2011)published_or_final_versionBiochemistryDoctoralDoctor of Philosoph

Measuring Ultrasonic and Electrical Properties of Early-Age Cemented Tailings Backfill

The setting behavior strongly affects the workability and loading capacity of a fresh cemented tailings backfill (CTB). The Vicat test is a conventional way to measure the setting time of a fresh cementitious mixture, using a standard needle to detect penetration resistance. However, this method is limited to laboratory testing, it is difficult to carry out in underground closed stopes. In this study, two nondestructive methods, the ultrasonic pulse and electrical conductivity tests, contrasting two traditional methods, hydration heat measurement and the Vicat test, are used to illustrate the setting process of early-age CTB. The effect of cement content (e.g., 2.5%, 5% and 7.5%) and tailings type (silica tailings and iron mine tailings) on the hydration heat of early-age CTB are recorded as well. The results show that, as the CTBs change from solid–liquid mixtures to solids, the ultrasonic pulse frequency converts from low to high and the electrical conductivity turns from growth to decline. As the degree of hydration increases, the solid connections continuously increase, which increases the ultrasonic amplitude rapidly and decreases electrical conductivity. The TG value can be effectively used to predict the initial set time of cemented silica tailings backfill. For cemented iron tailings backfill, although the solid phase ultrasonic path is formed, more hydration products are needed to reach the specific shear stiffness, meaning the initial set lags behind the change in ultrasonic frequency signal

Measuring Ultrasonic and Electrical Properties of Early-Age Cemented Tailings Backfill

The setting behavior strongly affects the workability and loading capacity of a fresh cemented tailings backfill (CTB). The Vicat test is a conventional way to measure the setting time of a fresh cementitious mixture, using a standard needle to detect penetration resistance. However, this method is limited to laboratory testing, it is difficult to carry out in underground closed stopes. In this study, two nondestructive methods, the ultrasonic pulse and electrical conductivity tests, contrasting two traditional methods, hydration heat measurement and the Vicat test, are used to illustrate the setting process of early-age CTB. The effect of cement content (e.g., 2.5%, 5% and 7.5%) and tailings type (silica tailings and iron mine tailings) on the hydration heat of early-age CTB are recorded as well. The results show that, as the CTBs change from solid–liquid mixtures to solids, the ultrasonic pulse frequency converts from low to high and the electrical conductivity turns from growth to decline. As the degree of hydration increases, the solid connections continuously increase, which increases the ultrasonic amplitude rapidly and decreases electrical conductivity. The TG value can be effectively used to predict the initial set time of cemented silica tailings backfill. For cemented iron tailings backfill, although the solid phase ultrasonic path is formed, more hydration products are needed to reach the specific shear stiffness, meaning the initial set lags behind the change in ultrasonic frequency signal

Stepwise inertial intelligent control for wind power frequency support based on modified stacked denoising autoencoder

Due to the large-scale popularization of renewable energy, the rotational inertia of modern power system is reduced, which increases the risk of power system failure and power outage when disturbance events occur. The wind turbine (WT) must be involved in frequency control to respond to power imbalance in the grid when it is detected. Stepwise inertial control (SIC) is one of the important frequency modulation strategies, but it will bring about secondary frequency drop (SFD). In order to minimize SFD while ensuring excellent frequency modulation effect, it is necessary to solve the optimal parameters of SIC, and the traditional method is very time-consuming to solve the parameters in different scenarios. In order to obtain the parameters quickly and accurately when the disturbance events occur, a stepwise inertial control of frequency modulation for wind power based on modified stacked denoising autoencoder is proposed in this paper. First, the sparrow search algorithm is used to obtain the required data. Then, the network model of the modified stacked denoising autoencoder is constructed. The “pre-training, fine-tuning” method is used to train the network parameters, and the Adamax optimization method is introduced to fine-tune the network parameters, which improves the training effect. Finally, the optimal SIC parameters are predicted by adding the scene data into the model. The proposed method is tested in IEEE 9 bus test system. Compared with the traditional method, the proposed method has faster computing speed, excellent prediction accuracy and generalization ability

Relationships between Serum Albumin and Urea Level and the Clinical Pathological Characteristics and Survival Time in Patients with Lung Cancer

Background and objective Lung cancer is the most common malignancy and is the leading cause of cancer-related death worldwide. Thus, this disease severely threatens human health. This study aims to identify the relationships between serum albumin and urea level and the clinical pathological characteristics and survival time in patients with lung cancer. Methods A total of 1,098 patients with lung cancer were diagnosed by pathology and tested the serum albumin and urea level in West China Hospital of Sichuan University during January 2008 to December 2013. According to the levels of albumin and urea, patients were divided into the normal level group (negative group) and abnormal level group (positive group). The differences of patients' clinical pathological characteristics and survival time in the two groups were analyzed. Results Differences in age, sex, histological classification, liver metastasis and pleural metastasis were statistically significant between the two groups of serum albumin (P<0.05). Differences in age, intrapulmonary metastasis of 312 patients of squamous cell carcinoma and differences in age, sex, stages, pleural metastasis of 612 patients of adenocarcinoma between the two groups of serum albumin (P<0.05). There were no significant differences between the two groups of urea. In different histological classification between the two groups of serum albumin, the median survival period of squamous cell carcinoma was 36 months and 19 monthes, adenocarcinoma was 35 months and 15 monthes, the abnormal group were all significantly lower than those in the normal group. The median survival period was no significant difference between the two groups of urea. Conclusion The level of serum albumin is an important indicator for prognosis