Augmenting the Heat Sink for Better Heat Dissipation

Heat sinks were invented to absorb heat from an electronic circuit conduct, and then to dissipate or radiate this heat to the surrounding supposedly, ventilated space, at a rate equal to or faster than that of its buildup. Ventilation was not initially recognized as an essential factor to thermal dispersion. However, as electronic circuit-boards continued to heat up, circuit failure became a problem, forcing the inclusion of miniaturized high speed fans. Later, heat sinks with fins and quiet fans were incorporated in most manufactured circuits. Now heat sinks come in the form of a fan with fans made to function as fins to disperse heat. Heat sinks absorb and radiate excess heat from circuit-boards in order to prolong the circuit’s life span. The higher the thermal conductivity of the material used the more efficient and effective the heat sink is. This paper is an attempt to theoretically design a heat sink with a temperature gradient lower than that of the circuit board’s excess heat.

The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines

Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein kinase-1 (PDK1), the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated proteins form a network participating in protein synthesis, bio-energy generation, signaling for apoptosis with the help of HSPs. A cancer cell synthesizes proteins at fast rate and needs more HSPs to work on quality control. Shutting down this network would lead to cell death. Thus inhibitors of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to apoptosis—a “passive approach”. On the other hand, HSPs form complexes with polypeptides characteristic of the cancer cells;on excretion from the cell, they becomes antigens for the immunity cells, eventually leading to maturation of the cytotoxic T cells, forming the basic principle of preparing cancer-specific, person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer cell and expel its analog to extracellular region, giving the hope to prepare a non-person-specific vaccine covering a variety of cancers. Activation of anti-cancer immunity is the “active approach”. On the other hand, mild hyperthermia, with increase of intracellular HSPs, has been found to activate the immunity response, and demonstrate anti-cancer effects. There are certain “mysteries” behind the mechanisms of the active and passive approaches. We analyze the mechanisms involved and provide explanations to some mysteries. We also suggest future research to improve our understanding of these two approaches, in which HSPs play many roles.

A Tree Formulation for Signaling Games with Noise

The paper provides an analysis of a sender-receiver sequential signaling game. The private information of the sender is transmitted with noise by a Machine, i.e. does not always correctly reflect the state of nature. Hence, a truthful revelation by the sender of his information does not necessarily imply that the signal he sends is correct. Also, the receiver can take a correct action even if the sender transmits an incorrect signal. The payoffs of the two players depend on their combined actions. Perfect Bayesian Equilibria which can result from different degrees of noise is analysed. The Bayesian updating of probabilities is explained. The fixed point theorem which makes the connection with the idea of rational expectations in economics is calculated. Given a number of equilibria, we comment on the most credible one on the basis of the implied payoffs for both players. The equilibrium signals are an example of the formation of a language convention discussed by D. Lewis.

A Workable Solution for Reducing the Large Number of Vehicle and Pedestrian Accidents Occurring on a Yellow Light

Traffic intersections are incredibly dangerous for drivers and pedestrians. Statistics from both Canada and the U.S. show a high number of fatalities and serious injuries related to crashes at intersections. In Canada, during 2019, the National Collision Database shows that 28% of traffic fatalities and 42% of serious injuries occurred at intersections. Likewise, the U.S. National Highway Traffic Administration (NHTSA) found that about 40% of the estimated 5,811,000 accidents in the U.S. during the year studied were intersection-related crashes. In fact, a major survey by the car insurance industry found that nearly 85% of drivers could not identify the correct action to take when approaching a yellow traffic light at an intersection. One major reason for these accidents is the “yellow light dilemma,” the ambiguous situation where a driver should stop or proceed forward when unexpectedly faced with a yellow light. This situation is even further exacerbated by the tendency of aggressive drivers to inappropriately speed up on the yellow just to get through the traffic light. A survey of Canadian drivers conducted by the Traffic Injury Research Foundation found that 9% of drivers admitted to speeding up to get through a traffic light. Another reason for these accidents is the increased danger of making a left-hand turn on yellow. According to the National Highway Traffic Safety Association (NHTSA), left turns occur in approximately 22.2% of collisions—as opposed to just 1.2% for right turns. Moreover, a study by CNN found left turns are three times as likely to kill pedestrians than right turns. The reason left turns are so much more likely to cause an accident is because they take a driver against traffic and in the path of oncoming cars. Additionally, most of these left turns occur at the driver’s discretion—as opposed to the distressingly brief left-hand arrow at busy intersections. Drive Safe Now proposes a workable solution for reducing the number of accidents occurring during a yellow light at intersections. We believe this fairly simple solution will save lives, prevent injuries, reduce damage to public and private property, and decrease insurance costs.

骨质疏松分子生物学研究专家共识

骨质疏松分子生物学研究在骨代谢分子信号通路、骨质疏松易感基因、骨质疏松相关蛋白、骨质疏松靶向治疗等方向取得了很大进展。核因子κB受体活化因子/核因子κB受体活化因子配体/骨保护素(RANK/RANKL/OPG)信号通路、核因子κB受体活化因子(NF-κB)信号通路、丝裂原活化蛋白激酶/细胞外调节蛋白激酶(MAPK/ERK)信号通路、巨噬细胞集落刺激因子(M-CSF)信号通路、钙离子(Ca^(2+))信号通路、酪氨酸激酶、蛋白激酶B(Src、Akt)信号通路、蛋白激酶C(PKC)信号通路等骨代谢重要通路,维生素D受体(VDR)基因、低密度脂蛋白相关蛋白5(LRP5)基因、亚甲基四氢叶酸还原酶(MTHFR)基因、雌激素受体(ER)基因等易感基因,载脂蛋白E(Apo E)、Klotho蛋白(Klotho)、骨形态发生蛋白(BMP)、骨涎蛋白(BSP)等相关蛋白,以直接或间接的方式参与调控骨代谢,作用重叠相互联系,互为结果,已在本专业领域达成共识。

Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

Atsttrin reduces lipopolysaccharide-induced neuroinflammation by inhibiting the nuclear factor kappa B signaling pathway

Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). Atsttrin(2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1β, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the concentration of tumor necrosis factor α and interleukin-1β in the supernatant. Furthermore, Atsttrin significantly reduced the levels of phospho-nuclear factor kappa B inhibitor α in the brain of lipopolysaccharide-treated progranulin knockout mice and astrocytes, and it decreased the expression of nuclear factor kappa B2 in astrocytes. Collectively, our findings show that the anti-neuroinflammatory effect of Atsttrin involves inhibiton of the nuclear factor kappa B signaling pathway, and they suggest that Atsttrin may have clinical potential in neuroinflammatory therapy.

Effect of Jianpi Xiaowei Decoction on Gastric Function and Quality of Life in Elderly Patients with Chronic Atrophic Gastritis of Liver-Stomach Stagnation Heat Type

[Objectives]To observe the effect of Jianpi Xiaowei Decoction on gastric function and quality of life in elderly patients with chronic atrophic gastritis(CAG)of liver-stomach heat stagnation type.[Methods]Seventy-two elderly patients with CAG of liver-stomach stagnation-heat type were randomly divided into study group and control group.The two groups were treated with Jianpi Xiaowei Decoction and Rabeprazole Enteric-coated Tablets respectively.The curative effect of TCM syndromes,serum pepsinogen I and II(PG-I and PG-II),gastrin-17(G-17)and quality of life(SF-36 table)scores of gastric function indicators before and after treatment were observed.[Results]After treatment,the total effective rate of the study group was 97.22%(35/36),which was significantly higher than that of the control group 77.78%(28/36)(P<0.05).Before treatment,there was no significant difference in the levels of gastric function indicators between the two groups(P>0.05).After treatment,the indicators of the study group were significantly lower than those of the control group(t=12.239,6.010,5.928,10.420,P<0.05).Before treatment,there was no significant difference in SF-36 scores between the two groups(P>0.05).After treatment,the SF-36 scores in the study group were significantly lower than those in the control group(t=3.520,10.335,11.300,9.693,P<0.05).[Conclusions]Jianpi Xiaowei Decoction can achieve significant curative effect in the treatment of CAG with liver and stomach stagnation heat type in the elderly,and can significantly improve the key gastrointestinal hormone levels and quality of life of elderly patients.It is worthy of promotion in the same clinical cases.

Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

An Analytical Theory of the Signal-to-Noise Ratio of Hall Plates with Four Contacts and a Single Mirror Symmetry

This work gives an analytical theory of the signal-to-thermal-noise ratio (SNR) of classical Hall plates with four contacts at small magnetic field. In contrast to previous works, the symmetry of the Hall plates is reduced to only a single mirror axis, whereby the average of potentials of the two output contacts off this mirror axis differs from the average of potentials at the two supply contacts on the mirror axis, i.e. the output common mode differs from 50%. Surprisingly, at fixed power dissipated in the Hall plate, the maximum achievable SNR is only 9% smaller for output common modes of 30% and 70% when compared to the overall optimum at output common modes of 50%. The theory is applied to Vertical Hall effect devices with three contacts on the top surface and one contact being the buried layer in a silicon BiCMOS process. Geometries are found with large contacts and only a moderate loss in SNR.

Thermodynamic Simulation of CCP in Air-Cooled Heat Pump Unit with HFCs and CO₂Trans-Critical

The exergy analysis and finite time thermodynamic methods had been employed to analyze the compound condensation process (CCP). It was based on the air-cooling heat pump unit. The cooling capacity of the chiller unit is about 1 kW, and the work refrigerant is R22/R407C/R410A/CO2. The MATLAB/SIMULINK software was employed to build the simulation model. The thermodynamic simulation model is significant for the optimization of parameters of the unit, such as condensation and evaporation temperature and mass flow of the sanitary hot water and size of hot water storage tank. The COP of the CCP of R410A system is about 3% - 5% higher than the CCP of the R22 system, while CCP of the R407C system is a little lower than the CCP of R22 system. And the CCP of CO2 trans-critical system has advantage in the hot supply mode. The simulation method provided a theoretical reference for developing the production of CCP with substitute refrigerant R407C/R410A/CO2.

Technical and Economic Aspects and Experience from 6 Years of Operating the Technology Using the Waste Heat from the Exhaust Gases of Heat Sources and 3 Years of Operating a Heating Plant in an Autonomous, Island Regime

This article is focused on technical and economic evaluation of more than 6-years experiences of operating the Waste Heat Recovery technology—the manner and system of flue gas processing generated in the combustion process in heat & power plants, cogeneration units, etc., which burn the gaseous fuel, primarily natural gas, or methane, biogas, geothermal gas, or other gaseous mixtures containing hydrogen. The solution proposes a more effective and non-traditional use of gaseous fuel for heating, the flue gases of which are processed in order to extract additional utilisable heat, with potential elimination of CO2 from them. Deploying of the heating plant in an island regime (OFF-GRID) enables definition of the benefits brought by the 3 years of operational experience and presents visions for the future offering the possibility to utilise the support energy services at the municipal as well as regional level.

Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage.Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham(injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1(rhwnt1), small interfering Wnt1(siwnt1) RNA, and monoclonal antibody of Frizzled1(anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury(within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of β-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines(interleukin-1β, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC,Division of Life Sciences and Medicine, University of Science and Technology of China(approval No. LLSC-20180202) in May 2017.

The assessment of time dependent flow of Williamson fluid with radiative blood flow against a wedge

The present pagination reports both Brownian diffusion and thermophoresis aspects subject to magneto hydrodynamic Williamson fluid model.Assuming the flow is unsteady and blood is treated as Williamson fluid over a wedge with radiation.The governing equations are transformed into ordinary differential equations by using similarity variables.The analytical solutions of the transformed governing equations are obtained by using the RK 4th order method along with shooting technique solver.The effects of various physical parameters such as Hartmann number,local Weissenberg number,radiation parameter,unsteadiness parameter,Prandtl number,Lewis number,Brownian diffusion,thermophoresis,wedge angle parameter,moving wedge parameter,on velocity,temperature,concentration,skin friction,heat transfer rate and mass transfer rate have been discussed in detail.The velocity and temperature profile deprives for larger We and an opposite trend is observed for concentration.The radiation parameter is propositional to temperature and a counter behaviour is observed for Pr.

Geologic-Geophysical Indicators of the Deep Structure of Zones of Geothermal Anomalies for Allocation of Channels of the Deep Heat and Mass Transfer

On the basis of the analysis of field thermogeochemical data along abnormal zones of a thermal stream in the Bukhara-Khiva, oil-and-gas region of the Turan (Tegermen, Chagakul, Shimoly Alat, Beshtepa) was succeeded to obtain important data on a deep structure of sites. Data of gas-chemical and geothermal observations show about confinedness of abnormal concentration of methane to zones of the increased values of the temperature field the measured values of temperatures (Tegermen Square and others). On geoelectric section mines 2-D of inversion of the MT-field depth of 4000 m are lower, among very high-resistance the chemogenic and carbonate deposits of the Paleozoic is traced the subvertical carrying-out abnormal zone. This zone is identified as the channel of a deep heat and mass transfer with which hydrocarbon (HC) deposits are connected. It is shown that electro-investigation when using a geophysical complex can and has to become “advancing” at exploration by oil and gas.

Mathematical Modeling of Heat Flux Distribution in Raw Cotton Stored in Bunt

The scientific article examines the physical and mechanical properties of raw cotton stored in buntings in cotton palaces. Because during the storage of raw cotton in bunts, some of its properties deteriorate, some improvements. Therefore, the mathematical modeling of storage conditions of raw cotton in bunts and the physical and mechanical conditions that occur in it is of great importance. In the developed mathematical model, the main factor influencing the physical and mechanical properties of raw cotton is the change in temperature. Due to the temperature, kinetic and biological processes accumulated in the raw cotton in Bunt, it can spread over a large surface, first in a small-local state, over time with a nonlinear law. As a result, small changes in temperature lead to a qualitative change in physical properties. In determining the law of temperature distribution in the raw cotton in Bunt, Laplace’s differential equation of heat transfer was used. The differential equation of heat transfer in Laplace’s law was replaced by a system of ordinary differential equations by approximation. Conditions are solved in MAPLE-17 program by numerical method. As a result, graphs of temperature changes over time in raw cotton were obtained. In addition, the table shows the changes in density, pressure and mass of cotton, the height of the bun. As the density of the cotton raw material increases from the top layer of the bunt to the bottom layer, an increase in the temperature in it has been observed. This leads to overheating of the bottom layer of cotton and is the main reason for the deterioration of the quality of raw materials.

Research on Estimation of Time Delay Difference in Passive Locating for Impulse Signal

Analyzed the relation between time delay difference and time delay estimation errors, based on the principles of three-point locating, a reformed threshold method for time delay difference estimation of impulse signals, called as amendment estimation for short, is developed by introducing channel equalization technique to its conventional version, named as direct estimation in this paper, to improve the estimation stability. After inherent relationship between time delay and phase shift of signals is analyzed, an integer period error compensation method utilized the diversities of both contribution share and contribution mode of concerned estimates is proposed under the condition of high precision phase lag estimation. Finally, a cooperative multi-threshold estimation method composed of amendment and direct estimations to process impulse signals with three thresholds is established. In sea trials data tests of passive locating, this method improves the estimation precision of time delay difference efficiently. The experiments verify the theoretical predictions.

Applications of advanced signal processing and machine learning in the neonatal hypoxic-ischemic electroencephalography

Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research community with an opportunity to develop automated real-time identification techniques to detect the signs of hypoxic-ischemic-encephalopathy in larger electroencephalography/amplitude-integrated electroencephalography data sets more easily. This review details the recent achievements, performed by a number of prominent research groups across the world, in the automatic identification and classification of hypoxic-ischemic epileptiform neonatal seizures using advanced signal processing and machine learning techniques. This review also addresses the clinical challenges that current automated techniques face in order to be fully utilized by clinicians, and highlights the importance of upgrading the current clinical bedside sampling frequencies to higher sampling rates in order to provide better hypoxic-ischemic biomarker detection frameworks. Additionally, the article highlights that current clinical automated epileptiform detection strategies for human neonates have been only concerned with seizure detection after the therapeutic latent phase of injury. Whereas recent animal studies have demonstrated that the latent phase of opportunity is critically important for early diagnosis of hypoxic-ischemic-encephalopathy electroencephalography biomarkers and although difficult, detection strategies could utilize biomarkers in the latent phase to also predict the onset of future seizures.

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.