Search

Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross‐sectional studies indicated certain motor and non‐motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed‐effect models were respectively conducted to investigate the cross‐sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross‐sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society‐Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS‐UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]‐adjusted p = 0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR‐adjusted p = 0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR‐adjusted p = 0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid‐eye‐movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR‐adjusted p = 0.0120). Furthermore, changes in MDS‐UPDRS scores and the State–Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p = 0.005 and p = 0.032, respectively). Our findings clarified quantitative associations between certain motor and non‐motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most frequently diagnosed cancer in women and is the major cause of most cancer-related deaths. We previously reported that Brachyury, as a sensitive and specific marker, has been verified to involve in the process of carcinogenesis and progression of breast cancer, but the mechanism by which Brachyury promotes breast cancer cells proliferation and migration still remains less clear. In this study, we identified that Brachyury was markedly increased in breast cancer compared with the adjacent tissues. We have also shown that Brachyury knockdown could decrease the proliferation and migration capability in breast cancer cells both in vitro and in vivo. Finally, we found an important transcriptional factor, E2F3, which is a direct downstream target gene of Brachyury by chromatin immunoprecipitation (ChIP) analysis. Knockdown of E2F3 also decreased breast cancer cell proliferation and migration. Taken together, we reported that Brachyury may act as an oncogenic role in the progression of breast cancer by positively-regulating E2F3 expression. [ABSTRACT FROM AUTHOR]

Non-planar morphology is a common feature of devices applied in various physical fields, such as light or fluid, which pose a great challenge for surface nano-patterning to improve their performance. The present study proposes a discretely-supported nanoimprint lithography (NIL) technique to fabricate nanostructures on the extremely non-planar surface, namely high-spatial-frequency stepped surface. The designed discretely imprinting template implanted a discretely-supported intermediate buffer layer made of sparse pillars arrays. This allowed the simultaneous generation of air-cushion-like buffer and reliable support to the thin structured layer in the template. The resulting low bending stiffness and distributed concentrated load of the template jointly overcome the contact difficulty with a stepped surface, and enable the template to encase the stepped protrusion as tight as possible. Based on the proposed discretely-supported NIL, nanostructures were fabricated on the luminous interface of light emitting diodes chips that covered with micrometer step electrodes pad. About 96% of the utilized indium tin oxide transparent current spreading layer surface on top of the light emitting diode (LED) chips was coated with nanoholes array, with an increase by more than 40% in the optical output power. The excellent ability of nanopatterning a non-planar substrate could potentially lead innovate design and development of high performance device based on discretely-supported NIL. [ABSTRACT FROM AUTHOR]

Sleep–wake disruptions are among the most prevalent and burdensome non-motor symptoms of Parkinson's disease (PD). Clinical studies have demonstrated that these disturbances can precede the onset of typical motor symptoms by years, indicating that they may play a primary function in the pathogenesis of PD. Animal studies suggest that sleep facilitates the removal of metabolic wastes through the glymphatic system via convective flow from the periarterial space to the perivenous space, upregulates antioxidative defenses, and promotes the maintenance of neuronal protein homeostasis. Therefore, disruptions to the sleep–wake cycle have been associated with inefficient metabolic clearance and increased oxidative stress in the central nervous system (CNS). This leads to excessive accumulation of alpha-synuclein and the induction of neuronal loss, both of which have been proposed to be contributing factors to the pathogenesis and progression of PD. Additionally, recent studies have suggested that PD-related pathophysiological alterations during the prodromal phase disrupt sleep and circadian rhythms. Taken together, these findings indicate potential mechanistic interactions between sleep–wake disorders and PD progression as proposed in this review. Further research into the hypothetical mechanisms underlying these interactions would be valuable, as positive findings may provide promising insights into novel therapeutic interventions for PD. [ABSTRACT FROM AUTHOR]

Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects of zonisamide in this condition. Most clinical trials of zonisamide in Parkinson disease were from Japan. The vast majority of studies used changes in the Unified Parkinson's Disease Rating Scale (UPDRS) scores and daily "OFF" time as primary endpoints. Based on adequate randomized controlled trials, zonisamide is considered a safe and efficacious add-on treatment in Parkinson disease. The most convincing proof is available for a dosage of 25–50 mg, which was shown to lead to a significant reduction in the UPDRS III score and daily "OFF" time, without increasing disabling dyskinesia. Furthermore, zonisamide may play a beneficial role in improving non-motor symptoms in PD, including impulsive–compulsive disorder, rapid eye movement sleep behavior disorder, and dementia. Among the various mechanisms reported, inhibition of monoamine oxidase-B, blocking of T-type calcium channels, modulation of the levodopa–dopamine metabolism, modulation of receptor expression, and neuroprotection are the most often cited. The mechanisms underlying neuroprotection, including modulation of dopamine turnover, induction of neurotrophic factor expression, inhibition of oxidative stress and apoptosis, inhibition of neuroinflammation, modulation of synaptic transmission, and modulation of gene expression, have been most extensively studied. This review focuses on structure, pharmacokinetics, mechanisms, therapeutic effectiveness, and safety and tolerability of zonisamide in patients with Parkinson disease. [ABSTRACT FROM AUTHOR]

Underground coal fires (UCFs) exist in almost all coal mining countries. In this paper, an optimised Thermal-Hydraulic-Chemical model, which includes variable reaction kinetics of coal and permeability variation in UCF zones, was developed for the simulation of dynamic temperature evolution of an actual UCF in Xinjiang, China. The model was also adopted in the analysis of the effect of surface coverage permeability on the temperature field, providing a theoretical reference for UCFs control. The results demonstrate that the temperature evolution included three distinct stages which were slow-heating stage, rapid-heating stage and stable-development stage. The slow-heating stage was occupied by the low-temperature oxidation of residual coal. During the rapid-heating stage, a hotspot (combustion centre) formed in residual coal zone and moved toward the air inlet side when the temperature reached a certain threshold. And before moving back into the deeper coal seam, the hotspot developed the temperature to the maximum when it got to the air inlet side. In the stable-development stage, the hotspot spread along the coal seam with the maximum temperature staying between about 800°C and 1000°C, creating elliptical temperature anomalies around the combustion centre. The simulation proved to be in good agreement with the in situ measurements. Surface covering will extinguish the UCF when the permeability of the coverage layer is lower than 10-10 m2, otherwise the fire will persist and continue to spread. [ABSTRACT FROM AUTHOR]

Equipped with easy-to-access micro computation access points, the fog computing architecture provides low-latency and ubiquitously available computation offloading services to many simple and cheap Internet of Things devices with limited computing and energy resources. One obstacle, however, is how to seamlessly hand over mobile IoT devices among different computation access points when computation offloading is in action so that the offloading service is not interrupted -- especially for time-sensitive applications. In this article, we propose Follow Me Fog (FMF), a framework supporting a new seamless handover timing scheme among different computation access points. Intrinsically, FMF supports a job pre-migration mechanism, which pre-migrates computation jobs when the handover is expected to happen. Such expectations can be indicated by constantly monitoring received signal strengths. Then we present the design and a prototype implementation of FMF. Our evaluation results demonstrate that FMF can achieve a substantial latency reduction (36.5 percent in our experiment). In conclusion, the FMF design clears a core obstacle, allowing fog computing to provide interruption-resistant services to mobile IoT devices. [ABSTRACT FROM PUBLISHER]