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13C-bicarbonate is a crucial measure of pyruvate oxidation and TCA cycle flux, but is challenging to measure due to its relatively low concentration and thus will greatly benefit from improved signal-to-noise ratio (SNR). To address this, we developed and investigated the feasibility of a 3D stack-of-spirals metabolite-specific balanced steady-state free precession (MS-bSSFP) sequence for improving the SNR and spatial resolution of dynamic 13C-bicarbonate imaging in hyperpolarized [1-13C]pyruvate studies. The bicarbonate MS-bSSFP sequence was evaluated by simulations, phantoms studies, preclinical studies on five rats, brain studies on two healthy volunteers and renal study on one renal cell carcinoma patient. The simulations and phantom results showed that the bicarbonate-specific pulse had minimal perturbation of other metabolites (<1%). In the animal studies, the MS-bSSFP sequence provided an approximately 2.6-3 × improvement in 13C-bicarbonate SNR compared to a metabolite-specific gradient echo (MS-GRE) sequence without altering the bicarbonate or pyruvate kinetics, and the shorter spiral readout in the MS-bSSFP approach reduced blurring. Using the SNR ratio between MS-bSSFP and MS-GRE, the T2 values of bicarbonate and lactate in the rat kidneys were estimated as 0.5 s and 1.1 s, respectively. The in-vivo feasibility of bicarbonate MS-bSSFP sequence was demonstrated in two human brain studies and one renal study. These studies demonstrate the potential of the sequence for in-vivo applications, laying the foundation for future studies to observe this relatively low concentration metabolite with high-quality images and improve measurements of pyruvate oxidation.

Healthcare organizations have been adapting ways to be more efficient and data-driven. The public health relevance of healthcare information technology is that it can help providers access patient information promptly and communicate healthcare information to the patient populations. Many organizations have used healthcare information technology to cope with the rising healthcare cost for over a decade. They use healthcare information technology to improve patient-centered care and reduce medication errors and patient safety events. Overall, there are many known industry benefits of implementing healthcare information technology. However, the use of healthcare information technology is not without its drawbacks and challenges. First, the essay will examine specific ways and mechanisms of how healthcare information technology can improve healthcare quality outcomes and reduce healthcare costs. At the same time, this essay will also discuss the shortfalls of implementing healthcare information technology. Based on the literature analysis, the essay will identify action steps that would help healthcare organizations to better adopt healthcare information technologies in the future. The future of HITs is promising if healthcare stakeholders can work together to address HITs-related challenges.

Healthcare organizations have been adapting ways to be more efficient and data-driven. The public health relevance of healthcare information technology is that it can help providers access patient information promptly and communicate healthcare information to the patient populations. Many organizations have used healthcare information technology to cope with the rising healthcare cost for over a decade. They use healthcare information technology to improve patient-centered care and reduce medication errors and patient safety events. Overall, there are many known industry benefits of implementing healthcare information technology. However, the use of healthcare information technology is not without its drawbacks and challenges. First, the essay will examine specific ways and mechanisms of how healthcare information technology can improve healthcare quality outcomes and reduce healthcare costs. At the same time, this essay will also discuss the shortfalls of implementing healthcare information technology. Based on the literature analysis, the essay will identify action steps that would help healthcare organizations to better adopt healthcare information technologies in the future. The future of HITs is promising if healthcare stakeholders can work together to address HITs-related challenges.

Centralized training is widely utilized in the field of multi-agent reinforcement learning (MARL) to assure the stability of training process. Once a joint policy is obtained, it is critical to design a value function factorization method to extract optimal decentralized policies for the agents, which needs to satisfy the individual-global-max (IGM) principle. While imposing additional limitations on the IGM function class can help to meet the requirement, it comes at the cost of restricting its application to more complex multi-agent environments. In this paper, we propose QFree, a universal value function factorization method for MARL. We start by developing mathematical equivalent conditions of the IGM principle based on the advantage function, which ensures that the principle holds without any compromise, removing the conservatism of conventional methods. We then establish a more expressive mixing network architecture that can fulfill the equivalent factorization. In particular, the novel loss function is developed by considering the equivalent conditions as regularization term during policy evaluation in the MARL algorithm. Finally, the effectiveness of the proposed method is verified in a nonmonotonic matrix game scenario. Moreover, we show that QFree achieves the state-of-the-art performance in a general-purpose complex MARL benchmark environment, Starcraft Multi-Agent Challenge (SMAC).

PURPOSE: This study aimed to develop and demonstrate the in vivo feasibility of a 3D stack-of-spiral balanced steady-state free precession(3D-bSSFP) urea sequence, interleaved with a metabolite-specific gradient echo (GRE) sequence for pyruvate and metabolic products, for improving the SNR and spatial resolution of the first hyperpolarized 13 C-MRI human study with injection of co-hyperpolarized [1-13 C]pyruvate and [13 C,15 N2 ]urea. METHODS: A metabolite-specific bSSFP urea imaging sequence was designed using a urea-specific excitation pulse, optimized TR, and 3D stack-of-spiral readouts. Simulations and phantom studies were performed to validate the spectral response of the sequence. The image quality of urea data acquired by the 3D-bSSFP sequence and the 2D-GRE sequence was evaluated with 2 identical injections of co-hyperpolarized [1-13 C]pyruvate and [13 C,15 N2 ]urea formula in a rat. Subsequently, the feasibility of the acquisition strategy was validated in a prostate cancer patient. RESULTS: Simulations and phantom studies demonstrated that 3D-bSSFP sequence achieved urea-only excitation, while minimally perturbing other metabolites (<1%). An animal study demonstrated that compared to GRE, bSSFP sequence provided an ∼2.5-fold improvement in SNR without perturbing urea or pyruvate kinetics, and bSSFP approach with a shorter spiral readout reduced blurring artifacts caused by J-coupling of [13 C,15 N2 ]urea. The human study demonstrated the in vivo feasibility and data quality of the acquisition strategy. CONCLUSION: The 3D-bSSFP urea sequence with a stack-of-spiral acquisition demonstrated significantly increased SNR and image quality for [13 C,15 N2 ]urea in co-hyperpolarized [1-13 C]pyruvate and [13 C,15 N2 ]urea imaging studies. This work lays the foundation for future human studies to achieve high-quality and high-SNR metabolism and perfusion images.

Incorrect placement of methods within classes is a typical code smell called Feature Envy, which causes additional maintenance and cost during evolution. To remove this design flaw, several Move Method refactoring tools have been proposed. To the best of our knowledge, state-of-the-art related techniques can be broadly divided into two categories: the first line is non-machine-learning-based approaches built on software measurement, while the selection and thresholds of software metrics heavily rely on expert knowledge. The second line is machine learning-based approaches, which suggest Move Method refactoring by learning to extract features from code information. However, most approaches in this line treat different forms of code information identically, disregarding their significant variation on data analysis. In this paper, we propose an approach to recommend Move Method refactoring named RMove by automatically learning structural and semantic representation from code fragment respectively. We concatenate these representations together and further train the machine learning classifiers to guide the movement of method to suitable classes. We evaluate our approach on two publicly available datasets. The results show that our approach outperforms three state-of-the-art refactoring tools including PathMove, JDeodorant, and JMove in effectiveness and usefulness. The results also unveil useful findings and provide new insights that benefit other types of feature envy refactoring techniques., Comment: 13 pages, 6 figures. This paper is the corrected version of the "RMove: Recommending Move Method Refactoring Opportunities using Structural and Semantic Representations of Code", which has published on ICSME22,and the missing part, "Method Structural Information Collection", is added in Chapter 3

The great influence of Bitcoin has promoted the rapid development of blockchain-based digital currencies, especially the altcoins, since 2013. However, most altcoins share similar source codes, resulting in concerns about code innovations. In this paper, an empirical study on existing altcoins is carried out to offer a thorough understanding of various aspects associated with altcoin innovations. Firstly, we construct the dataset of altcoins, including source code repositories, GitHub fork relations, and market capitalizations (cap). Then, we analyze the altcoin innovations from the perspective of source code similarities. The results demonstrate that more than 85% of altcoin repositories present high code similarities. Next, a temporal clustering algorithm is proposed to mine the inheritance relationship among various altcoins. The family pedigrees of altcoin are constructed, in which the altcoin presents similar evolution features as biology, such as power-law in family size, variety in family evolution, etc. Finally, we investigate the correlation between code innovations and market capitalization. Although we fail to predict the price of altcoins based on their code similarities, the results show that altcoins with higher innovations reflect better market prospects., Comment: 10 pages

Dnmt3a2, ade novoDNA methyltransferase, is induced by neuronal activity and participates in long-term memory formation with the increased expression of synaptic plasticity genes. We wanted to determine if Dnmt3a2 with its partner Dnmt3L may influence motor behavior via the dopaminergic system. To this end, we generated a mouse line, Dnmt3a2/3L(Dat/wt), with dopamine transporter (DAT) promotor driven Dnmt3a2/3L overexpression. The mice were studied with behavioral paradigms (e.g., cylinder test, open field, and treadmill), brain slice patch clamp recordings, ex vivo metabolite analysis, and in vivo positron emission tomography (PET) using the dopaminergic tracer 6-[F-18]FMT. The results showed that spontaneous activity and exercise performance were enhanced in Dnmt3a2/3L(Dat/wt)mice compared to Dnmt3a2/3L(wt/wt)controls. Dopaminergic substantia nigra pars compacta neurons of Dnmt3a2/3L(Dat/wt)animals displayed a higher fire frequency and excitability. However, dopamine concentration was not increased in the striatum, and dopamine metabolite concentration was even significantly decreased. Striatal 6-[F-18]FMT uptake, reflecting aromatic L-amino acid decarboxylase activity, was the same in Dnmt3a2/3L(Dat/wt)mice and controls. [F-18]FDG PET showed that hypothalamic metabolic activity was tightly linked to motor behavior in Dnmt3a2/3L(Dat/wt)mice. Furthermore, dopamine biosynthesis and motor-related metabolic activity were correlated in the hypothalamus. Our findings suggest that Dnmt3a2/3L, when overexpressed in dopaminergic neurons, modulates motor performance via activation of the nigrostriatal pathway. This does not involve increased dopamine synthesis.

Purpose: Crush and Culotte techniques have been used increasingly to treat patients with complex unprotected left main coronary artery bifurcation lesions. This article compares published data on these two techniques. Methods: Databases, including PubMed, Embase, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure, were searched for articles published before Aug 21, 2019 to identify all relevant studies on left main coronary artery bifurcation lesions treated by Crush versus Culotte techniques. The pooled data were analyzed using either fixed- or random-effects model depending on heterogeneity (assessed via the I2 index). The endpoints were major adverse cardiac events, target lesion revascularization, cardiac death, stent thrombosis, myocardial infarction and target vessel revascularization. Results: Eight articles with a total of 1,283 patients were included, and 710 patients were treated with Crush, and 573 ones with Culotte. Crush group was trend to decreased major adverse cardiac event compared with Culotte group [Relative ratio (RR) 0.63,95% confidence interval(CI) 0.39-1.04, I2 =72.7%], mainly driven by decreased cardiac death [RR 0.49, 95% CI(0.25-0.99), I2 =0%], decreased myocardial infarction [RR 0.40, 95% CI(0.21-0.76), I2 =21.6%],and lower stent thrombosis [RR 0.39, 95% CI(0.16-0.98), I2 =39.4%]. There was no significant difference in target lesion revascularization and target vessel revascularization between Crush and Culotte [RR 0.77, 95% CI 0.46-1.28, I2=61.1%; RR 0.78, 95% CI (0.30-2.02), I2 =73.1%, respectively]. Conclusion: Crush was superior to Culotte for treatment of left main coronary artery bifurcation lesions with a trend of lower incidence of long-term major adverse cardiac events, mainly derived from decreased myocardial infarction, stent thrombosis and cardiac death.

Dnmt3a2, ade novoDNA methyltransferase, is induced by neuronal activity and participates in long-term memory formation with the increased expression of synaptic plasticity genes. We wanted to determine if Dnmt3a2 with its partner Dnmt3L may influence motor behavior via the dopaminergic system. To this end, we generated a mouse line, Dnmt3a2/3L(Dat/wt), with dopamine transporter (DAT) promotor driven Dnmt3a2/3L overexpression. The mice were studied with behavioral paradigms (e.g., cylinder test, open field, and treadmill), brain slice patch clamp recordings, ex vivo metabolite analysis, and in vivo positron emission tomography (PET) using the dopaminergic tracer 6-[F-18]FMT. The results showed that spontaneous activity and exercise performance were enhanced in Dnmt3a2/3L(Dat/wt)mice compared to Dnmt3a2/3L(wt/wt)controls. Dopaminergic substantia nigra pars compacta neurons of Dnmt3a2/3L(Dat/wt)animals displayed a higher fire frequency and excitability. However, dopamine concentration was not increased in the striatum, and dopamine metabolite concentration was even significantly decreased. Striatal 6-[F-18]FMT uptake, reflecting aromatic L-amino acid decarboxylase activity, was the same in Dnmt3a2/3L(Dat/wt)mice and controls. [F-18]FDG PET showed that hypothalamic metabolic activity was tightly linked to motor behavior in Dnmt3a2/3L(Dat/wt)mice. Furthermore, dopamine biosynthesis and motor-related metabolic activity were correlated in the hypothalamus. Our findings suggest that Dnmt3a2/3L, when overexpressed in dopaminergic neurons, modulates motor performance via activation of the nigrostriatal pathway. This does not involve increased dopamine synthesis.

Zhe Zhang,1,2 Di Cui,1,2 Tan Zhang,1,2 Yi Sun,1,2 Shuzhe Ding1,2 1Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of China; 2College of Physical Education and Health, East China Normal University, Shanghai 200241, People’s Republic of ChinaCorrespondence: Shuzhe DingKey Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of ChinaTel +86 13601798505Email szding@tyxx.ecnu.edu.cnPurpose: Mitochondrial dysfunction and endoplasmic reticulum stress (ERS) are associated with metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). Mitochondria and ER are connected via mitochondria-associated membranes (MAM) that are involved in glucose homeostasis and insulin resistance. We postulated that exercise might positively benefit T2DM-induced ER and mitochondrial dysfunction that might be associated with MAM.Materials and Methods: Mice were fed a high-fat diet and injected with streptozotocin (STZ) to create T2DM models. Glucose tolerance, mitochondrial quality, MAM quality, and ERS were investigated in diabetic mice after six weeks of swimming.Results: Type 2 DM induced decreased MAM quantity, impaired mitochondrial quality, and deteriorated ERS in skeletal muscle that led to endoplasmic reticulum-associated degradation (ERAD). Swimming alleviated strong ERS caused by T2DM. Importantly, MAM quantity was positively associated with mitochondrial function and tended to negatively correlate with the ERS branch, ATF6. Moreover, both ATF6 branches of ERS and ERAD were positively associated with the pIRE1α branch of ERS.Conclusion: Type 2 DM induced glucose intolerance, powerful ERS, and mitochondrial dysfunction associated with decreased amounts of MAM. Swimming improved glucose intolerance an

Dramatic tool temperature variation in end milling can cause excessive tool wear and shorten its life, especially in machining of difficult-to-machine materials. In this study, a new analytical model-based method for the prediction of cutting tool temperature in end milling is presented. The cutting cycle is divided into temperature increase and decrease phases. For the temperature increase phase, a temperature prediction model considering real friction state between the chip and tool is proposed, and the heat flux and tool-chip contact length are then obtained through finite element simulation. In the temperature decrease phase, a temperature decrease model based on the one-dimension plate heat convection is proposed. A single wire thermocouple is employed to measure the tool temperature in the conducted milling experiments. Both of the theoretical and experimental results are obtained with cutting conditions of the cutting speed ranging from 60 m/min to 100 m/min, feed per tooth from 0.12 mm/z to 0.20 mm/z, and the radial and axial depth of cut respectively being 4 mm and 0.5 mm. The comparison results show high agreement between the physical cutting experiments and the proposed cutting tool temperature prediction method. © 2016 Chinese Society of Aeronautics and Astronautics

The expression of acetylcholinesterase (AChE), an enzyme hydrolyzes neurotransmitter acetylcholine at vertebrate neuromuscular junction, is regulated during myogenesis, indicating the significance of muscle intrinsic factors in controlling the enzyme expression. DNA methylation is essential for temporal control of myogenic gene expression during myogenesis; however, its role in AChE regulation is not known. The promoter of vertebrate ACHE gene carries highly conserved CG-rich regions, implying its likeliness to be methylated for epigenetic regulation. A DNA methyltransferase inhibitor, 5-azacytidine (5-Aza), was applied onto C2C12 cells throughout the myotube formation. When DNA methylation was inhibited, the promoter activity, transcript expression and enzymatic activity of AChE were markedly increased after day 3 of differentiation, which indicated the putative role of DNA methylation. By bisulfite pyrosequencing, the overall methylation rate was found to peak at day 3 during C2C12 cell differentiation; a SP1 site located at -1826 bp upstream of mouse ACHE gene was revealed to be heavily methylated. The involvement of transcriptional factor SP1 in epigenetic regulation of AChE was illustrated here: (i) the SP1-driven transcriptional activity was increased in 5-Aza-treated C2C12 culture; (ii) the binding of SP1 onto the SP1 site of ACHE gene was fully blocked by the DNA methylation; and (iii) the sequence flanking SP1 sites of ACHE gene was precipitated by chromatin immuno-precipitation assay. The findings suggested the role of DNA methylation on AChE transcriptional regulation and provided insight in elucidating the DNA methylation-mediated regulatory mechanism on AChE expression during muscle differentiation. © 2016 Elsevier B.V. All rights reserved.

Purinergic signaling, mediated by purine and pyrimidine nucleosides, regulates various cellular functions in central nervous system (CNS). Adenosine 5’-triphosphate (ATP), as the dominant purinergic signal molecule, acts a neurotransmitter and a neuromodulator and activate downstream purinergic receptors. The signal of extracellular ATP is predominantly mediated by P2Y1 receptor (P2Y1R), the most abundant purinergic receptor expressed in CNS. Previous studies demonstrated that stimulation of ATP/P2Y1R regulated down-stream gene expression and multiple neuronal process, including cholinergic and glutamatergic neurotransmission, as well as neurite outgrowth. However, the effects of P2Y1R deficiency in the brain have not been revealed. In this study, by using P2Y1R gene knockout (P2Y1R-/-) mouse as a model, we aimed to investigate the regulation of neuronal functions that could be mediated by ATP/P2Y1R signaling. To evaluate the function of cholinergic system in P2Y1R-deficient mouse brain, the expression of globular form acetylcholinesterase (AChE) was tested in P2Y1R-/- mouse. In P2Y1R-/- mouse brain, the amounts of AChE activity, AChE catalytic subunit and structure subunit PRiMA, as well as the amount of acetylcholine (Ach), were not significantly altered, suggesting an unchanged function of cholinergic system in P2Y1R-deficient brain. In addition, the expressions of a series of neuronal development markers, i.e. neurofilaments, were reduced in P2Y1R-/- mouse brain, indicating P2Y1R might be involved in neuronal development process and regulate axon elongation. On the other hand, we found that the amount of a series of neurotransmitters, including glutamate, GABA, dopamine and serotonin, were decreased in P2Y1R-/- mouse brain by HPLC-MS/MS technique, probably due to the down-regulated expression of metabolic enzymes in trans

Adenosine 5′-triphosphate (ATP), a neurotransmitter and a neuromodulator, has been shown to be co-stored and co-released with acetylcholine (ACh) at the pre-synaptic vesicles in vertebrate neuromuscular junction (nmj). Several lines of studies demonstrated that binding of ATP to its corresponding P2Y1 receptors (P2Y1R) in muscle and neuron regulated the post-synaptic gene expressions. Indeed, the expression of acetylcholinesterase (AChE) in muscle was markedly decreased in P2Y1R−/− (P2Y1R knock-out) mice. In order to search for possible role of P2Y1R in cholinergic function of the brain, the expression of globular form AChE was determined in the brain of P2Y1R−/− mice. In contrast to that in muscle, the amounts of AChE activity, AChE catalytic subunit, structure subunit PRiMA and the amount of ACh, in the brain were not, significantly, altered, suggesting the role of P2Y1R in neuron could have different function as that in muscle. However, the expressions of a series of neuronal development markers, i.e. neurofilaments, were reduced in P2Y1R−/− mouse brain, indicating P2Y1R may be involved in neuronal development process. © 2016 Elsevier Ireland Ltd

Purinergic signaling, mediated by purine and pyrimidine nucleosides, regulates various cellular functions in central nervous system (CNS). Adenosine 5’-triphosphate (ATP), as the dominant purinergic signal molecule, acts a neurotransmitter and a neuromodulator and activate downstream purinergic receptors. The signal of extracellular ATP is predominantly mediated by P2Y1 receptor (P2Y1R), the most abundant purinergic receptor expressed in CNS. Previous studies demonstrated that stimulation of ATP/P2Y1R regulated down-stream gene expression and multiple neuronal process, including cholinergic and glutamatergic neurotransmission, as well as neurite outgrowth. However, the effects of P2Y1R deficiency in the brain have not been revealed. In this study, by using P2Y1R gene knockout (P2Y1R-/-) mouse as a model, we aimed to investigate the regulation of neuronal functions that could be mediated by ATP/P2Y1R signaling. To evaluate the function of cholinergic system in P2Y1R-deficient mouse brain, the expression of globular form acetylcholinesterase (AChE) was tested in P2Y1R-/- mouse. In P2Y1R-/- mouse brain, the amounts of AChE activity, AChE catalytic subunit and structure subunit PRiMA, as well as the amount of acetylcholine (Ach), were not significantly altered, suggesting an unchanged function of cholinergic system in P2Y1R-deficient brain. In addition, the expressions of a series of neuronal development markers, i.e. neurofilaments, were reduced in P2Y1R-/- mouse brain, indicating P2Y1R might be involved in neuronal development process and regulate axon elongation. On the other hand, we found that the amount of a series of neurotransmitters, including glutamate, GABA, dopamine and serotonin, were decreased in P2Y1R-/- mouse brain by HPLC-MS/MS technique, probably due to the down-regulated expression of metabolic enzymes in trans

Dramatic tool temperature variation in end milling can cause excessive tool wear and shorten its life, especially in machining of difficult-to-machine materials. In this study, a new analytical model-based method for the prediction of cutting tool temperature in end milling is presented. The cutting cycle is divided into temperature increase and decrease phases. For the temperature increase phase, a temperature prediction model considering real friction state between the chip and tool is proposed, and the heat flux and tool-chip contact length are then obtained through finite element simulation. In the temperature decrease phase, a temperature decrease model based on the one-dimension plate heat convection is proposed. A single wire thermocouple is employed to measure the tool temperature in the conducted milling experiments. Both of the theoretical and experimental results are obtained with cutting conditions of the cutting speed ranging from 60 m/min to 100 m/min, feed per tooth from 0.12 mm/z to 0.20 mm/z, and the radial and axial depth of cut respectively being 4 mm and 0.5 mm. The comparison results show high agreement between the physical cutting experiments and the proposed cutting tool temperature prediction method. © 2016 Chinese Society of Aeronautics and Astronautics

The expression of acetylcholinesterase (AChE), an enzyme hydrolyzes neurotransmitter acetylcholine at vertebrate neuromuscular junction, is regulated during myogenesis, indicating the significance of muscle intrinsic factors in controlling the enzyme expression. DNA methylation is essential for temporal control of myogenic gene expression during myogenesis; however, its role in AChE regulation is not known. The promoter of vertebrate ACHE gene carries highly conserved CG-rich regions, implying its likeliness to be methylated for epigenetic regulation. A DNA methyltransferase inhibitor, 5-azacytidine (5-Aza), was applied onto C2C12 cells throughout the myotube formation. When DNA methylation was inhibited, the promoter activity, transcript expression and enzymatic activity of AChE were markedly increased after day 3 of differentiation, which indicated the putative role of DNA methylation. By bisulfite pyrosequencing, the overall methylation rate was found to peak at day 3 during C2C12 cell differentiation; a SP1 site located at -1826 bp upstream of mouse ACHE gene was revealed to be heavily methylated. The involvement of transcriptional factor SP1 in epigenetic regulation of AChE was illustrated here: (i) the SP1-driven transcriptional activity was increased in 5-Aza-treated C2C12 culture; (ii) the binding of SP1 onto the SP1 site of ACHE gene was fully blocked by the DNA methylation; and (iii) the sequence flanking SP1 sites of ACHE gene was precipitated by chromatin immuno-precipitation assay. The findings suggested the role of DNA methylation on AChE transcriptional regulation and provided insight in elucidating the DNA methylation-mediated regulatory mechanism on AChE expression during muscle differentiation. © 2016 Elsevier B.V. All rights reserved.

Adenosine 5′-triphosphate (ATP), a neurotransmitter and a neuromodulator, has been shown to be co-stored and co-released with acetylcholine (ACh) at the pre-synaptic vesicles in vertebrate neuromuscular junction (nmj). Several lines of studies demonstrated that binding of ATP to its corresponding P2Y1 receptors (P2Y1R) in muscle and neuron regulated the post-synaptic gene expressions. Indeed, the expression of acetylcholinesterase (AChE) in muscle was markedly decreased in P2Y1R−/− (P2Y1R knock-out) mice. In order to search for possible role of P2Y1R in cholinergic function of the brain, the expression of globular form AChE was determined in the brain of P2Y1R−/− mice. In contrast to that in muscle, the amounts of AChE activity, AChE catalytic subunit, structure subunit PRiMA and the amount of ACh, in the brain were not, significantly, altered, suggesting the role of P2Y1R in neuron could have different function as that in muscle. However, the expressions of a series of neuronal development markers, i.e. neurofilaments, were reduced in P2Y1R−/− mouse brain, indicating P2Y1R may be involved in neuronal development process.

Purinergic signaling, mediated by purine and pyrimidine nucleosides, regulates various cellular functions in central nervous system (CNS). Adenosine 5’-triphosphate (ATP), as the dominant purinergic signal molecule, acts a neurotransmitter and a neuromodulator and activate downstream purinergic receptors. The signal of extracellular ATP is predominantly mediated by P2Y1 receptor (P2Y1R), the most abundant purinergic receptor expressed in CNS. Previous studies demonstrated that stimulation of ATP/P2Y1R regulated down-stream gene expression and multiple neuronal process, including cholinergic and glutamatergic neurotransmission, as well as neurite outgrowth. However, the effects of P2Y1R deficiency in the brain have not been revealed. In this study, by using P2Y1R gene knockout (P2Y1R-/-) mouse as a model, we aimed to investigate the regulation of neuronal functions that could be mediated by ATP/P2Y1R signaling. To evaluate the function of cholinergic system in P2Y1R-deficient mouse brain, the expression of globular form acetylcholinesterase (AChE) was tested in P2Y1R-/- mouse. In P2Y1R-/- mouse brain, the amounts of AChE activity, AChE catalytic subunit and structure subunit PRiMA, as well as the amount of acetylcholine (Ach), were not significantly altered, suggesting an unchanged function of cholinergic system in P2Y1R-deficient brain. In addition, the expressions of a series of neuronal development markers, i.e. neurofilaments, were reduced in P2Y1R-/- mouse brain, indicating P2Y1R might be involved in neuronal development process and regulate axon elongation. On the other hand, we found that the amount of a series of neurotransmitters, including glutamate, GABA, dopamine and serotonin, were decreased in P2Y1R-/- mouse brain by HPLC-MS/MS technique, probably due to the down-regulated expression of metabolic enzymes in trans

Dramatic tool temperature variation in end milling can cause excessive tool wear and shorten its life, especially in machining of difficult-to-machine materials. In this study, a new analytical model-based method for the prediction of cutting tool temperature in end milling is presented. The cutting cycle is divided into temperature increase and decrease phases. For the temperature increase phase, a temperature prediction model considering real friction state between the chip and tool is proposed, and the heat flux and tool-chip contact length are then obtained through finite element simulation. In the temperature decrease phase, a temperature decrease model based on the one-dimension plate heat convection is proposed. A single wire thermocouple is employed to measure the tool temperature in the conducted milling experiments. Both of the theoretical and experimental results are obtained with cutting conditions of the cutting speed ranging from 60 m/min to 100 m/min, feed per tooth from 0.12 mm/z to 0.20 mm/z, and the radial and axial depth of cut respectively being 4 mm and 0.5 mm. The comparison results show high agreement between the physical cutting experiments and the proposed cutting tool temperature prediction method.

CorrigendumBurke DT, Tran D, Cui D, et al. Open Access J Sports Med. 2013;4:211–219.On page 212, second paragraph of the Methods section, line 3 from the bottom, "45 kg" should be "30%".On page 213, first column, lines 9, 22 and 34, "45 kg" should be "30%".Table 1 on page 214, data entered into the Chest column under Maximum loads lifted, kg was incorrect. The corrected table is shown below.View original paper by Burke and colleagues.

David T Burke,1 David Tran,1 Di Cui,1 Daniel P Burke,2 Samir Al-Adawi,3 Atsu SS Dorvlo41Emory University Medical School, Atlanta, GA, USA; 2Georgia College and State University, GA, USA; 3Department of Behavioral Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman; 4Department of Mathematics and Statistics, College of Science, Sultan Qaboos University, Muscat, OmanAbstract: In an age of increasing numbers of lifestyle diseases and plasticity of longevity, exercise and weight training have been increasingly recognized as both preventing and mitigating the severity of many illnesses. This study was designed to determine whether significant weight-lifting gains could be realized through the Anatoly Gravitational System. Specifically, this study sought to determine whether this once-weekly weight-training system could result in significant weekly strength gains during a 10-week training period. A total of 50 participants, ranging in age from 17 to 67 years, completed at least 10 weekly 30-minute training sessions. The results suggest participants could, on average, double their weight-lifting capacity within 10 sessions. This preliminary study, which would require further scrutiny, suggests the Anatoly Gravitational System provides a rather unique opportunity to load the musculoskeletal system with extremely high loads, with rapid weekly weight gains, using only short weekly training sessions. More studies are warranted to scrutinize these findings.Keywords: Anatoly Gravitational System, weight training, musculoskeletal systemCorrigendum for this paper has been published.

A series of biodegradable alkylamino hydrazide hyaluronic acid (HA) derivatives were prepared and used to design new biocompatible films able to release hydrophobic drugs in a controlled manner. The first step of this work thus consisted in optimizing the synthetic conditions of hydrazide HA derivatives bearing pendant hexyl, octyl, decyl, and citronellyl chains with a degree of substitution of 0.05 or 0.10. The behavior in aqueous solution of these water-soluble modified HA samples was then examined in the semidilute regime. The decylamino hydrazide derivatives of HA exhibited remarkable associating properties, giving rise to transparent gels. These gels were found to be more resistant to degradation by hyaluronidase compared to solutions of nonmodified HA at the same concentration. The other derivatives of which the lengths of grafted alkyl chains range from 6 to 8 carbon atoms lead to more or less viscous solutions. Different viscometric features for these derivatives could be observed as a function of the molecular weight of HA. As derivatives prepared from a HA sample of 600 000 g/mol (HA-600) exhibited a much higher tendency to self-aggregate than their counterparts prepared from a HA sample of 200 000 g/mol (HA-200), the latter derivatives were selected for the build up of multilayer films. The topography and z-section of (PLL/HA derivatives) films assembled layer-by-layer were observed by atomic force microscopy (AFM) in liquid and confocal laser scanning microscopy (CLSM) using PLL(FITC) as ending layer. Moreover, the ability of the films made of the different HA derivatives to incorporate the hydrophobic dye nile red (NR) was investigated. Films containing decylamino hydrazide HA derivatives were the most efficient for incorporating and retaining nile red, which confirms the formation of stable hydrophobic nanodomains in the films.