Peak Power Demand and Energy Consumption Reduction Strategies for Trains under Moving Block Signalling System

In the moving block signalling (MBS) system where the tracking target point of the following train is moving forward with its leading train, overload of the substations occurs when a dense queue of trains starts (or restarts) in very close distance interval. This is the peak power demand problem. Several methods have been attempted in the literature to deal with this problem through changing train’s operation strategies. However, most existing approaches reduce the service quality. In this paper, two novel approaches—“Service Headway Braking” (SHB) and “Extending Stopping Distance Interval” (ESDI)—are proposed according to available and unavailable extra station dwell times, respectively. In these two methods, the restarting times of the trains are staggered and traction periods are reduced, which lead to the reduction of peak power demand and energy consumption. Energy efficient control switching points are seen as the decision parameters. Nonlinear programming method is used to model the process. Simulation results indicate that, compared with ARL, peak power demands are reduced by 40% and 20% by applying SHB and ESDI without any arrival time delay, respectively. At the same time, energy consumptions are also reduced by 77% and 50% by applying SHB and ESDI, respectively

Quantitative Proteomic Study of Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Acquired by Laser Capture Microdissection

Objective. To investigate the differential protein profile of human lung squamous carcinoma (HLSC) and normal bronchial epithelium (NBE) and provide preliminary results for further study to explore the carcinogenic mechanism of HLSC. Methods. Laser capture microdissection (LCM) was used to purify the target cells from 10 pairs of HLSC tissues and their matched NHBE, respectively. A stable-isotope labeled strategy using iTRAQ, followed by 2D-LC/Q-STAR mass spectrometry, was performed to separate and identify the differential expression proteins. Results. A total of 96 differential expression proteins in the LCM-purified HLSC and NBE were identified. Compared with NBE, 49 proteins were upregulated and 47 proteins were downregulated in HLSC. Furthermore, the expression levels of the differential proteins including HSPB1, CKB, SCCA1, S100A8, as well as S100A9 were confirmed by western blot and tissue microarray and were consistent with the results of quantitative proteomics. Conclusion. The different expression proteins in HLSC will provide scientific foundation for further study to explore the carcinogenic mechanism of HLSC

Prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation

OBJECTIVE: The aim of this study was to evaluate the prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation (AF). METHODS: A cohort of 136 unrelated patients with idiopathic atrial fibrillation and 200 unrelated, ethnically matched healthy controls were enrolled. The coding exons and splice junctions of the Nkx2.5 gene were sequenced in 136 atrial fibrillation patients, and the available relatives of mutation carriers and 200 controls were subsequently genotyped for the identified mutations. The functional characteristics of the mutated Nkx2.5 gene were analyzed using a dual-luciferase reporter assay system. RESULTS: Two novel heterozygous Nkx2.5 mutations (p.N19D and p.F186S) were identified in 2 of the 136 unrelated atrial fibrillation cases, with a mutational prevalence of approximately 1.47%. These missense mutations co-segregated with atrial fibrillation in the families and were absent in the 400 control chromosomes. Notably, 2 mutation carriers also had congenital atrial septal defects and atrioventricular block. Multiple alignments of the Nkx2.5 protein sequences across various species revealed that the altered amino acids were completely conserved evolutionarily. Functional analysis demonstrated that the mutant Nkx2.5 proteins were associated with significantly reduced transcriptional activity compared to their wild-type counterpart. CONCLUSION: These findings associate the Nkx2.5 loss-of-function mutation with atrial fibrillation and atrioventricular block and provide novel insights into the molecular mechanism involved in the pathogenesis of atrial fibrillation. These results also have potential implications for early prophylaxis and allele-specific therapy of this common arrhythmia

PITX2C loss-of-function mutations responsible for idiopathic atrial fibrillation

OBJECTIVE: This study aimed to identify novel PITX2c mutations responsible for idiopathic atrial fibrillation. METHODS: A cohort of 210 unrelated patients with idiopathic atrial fibrillation and 200 unrelated, ethnically matched healthy individuals used as controls were recruited. The whole coding exons and splice junctions of the PITX2c gene, which encodes a paired-like homeobox transcription factor required for normal cardiovascular morphogenesis, were sequenced in 210 patients and 200 control subjects. The causative potentials of the identified mutations were automatically predicted by MutationTaster and PolyPhen-2. The functional characteristics of the PITX2c mutations were explored using a dual-luciferase reporter assay system. RESULTS: Two novel heterozygous PITX2c mutations (p.Q105L and p.R122C) were identified in 2 of the 210 unrelated patients with idiopathic atrial fibrillation. These missense mutations were absent in the 400 control chromosomes and were both predicted to be pathogenic. Multiple alignments of PITX2c protein sequences across various species showed that the altered amino acids were highly evolutionarily conserved. A functional analysis demonstrated that the mutant PITX2c proteins were both associated with significantly reduced transcriptional activity compared with their wild-type counterparts. CONCLUSION: The findings of this study associate PITX2c loss-of-function mutations with atrial fibrillation, supporting the hypothesis that dysfunctional PITX2c confers enhanced susceptibility to atrial fibrillation and suggesting potential implications for early prophylaxis and allele-specific therapy for this common arrhythmia

Zhi-Bai-Di-Huang-Wan, a classic Chinese medicinal formula in relieving menopausal symptoms: A multi-centre and controlled trial from UK and China

Background: To explore the effects of Zhi-Bai-Di-Huang-Wan (ZBDHW), a classic formula of Chinese  medicinal herbs in relieving menopausal symptoms in British and Chinese women.Methods and Materials: Between May 2011 and May 2013, 224 Chinese and British women were  divided into a ZBDHW group with 115 cases and a control group with 109 cases. The clinical menopausal  symptoms were assessed by the modified Kupperman Index Scale. The serum levels of follicle stimulating hormone (FSH) and estradiol (E2) were respectively detected before and after the treatment. Results: After 12 weeks of treatment, both groups’ Kupperman index scores markedly decreased  (P<0.05) and no significant difference existed between them (P>0.05). The serum levels of FSH did not change  significantly after the treatment (P>0.05) and no significant difference existed between them (P>0.05). The  serum levels of E2 significantly increased in both of the two groups (P<0.05) and it increased more in the comparison group (P<0.05). No side-effect of the treatment was reported in both of the two groups during the  period of the treatment.Conclusion: The classic Chinese medicinal formula, ZBDHW, showed promise in relieving menopausal  symptoms.Key words: Chinese medicinal herb; Zhi-Bai-Di-Huang-Wan (ZBDHW); menopausal symptom

LSDP5 Enhances Triglyceride Storage in Hepatocytes by Influencing Lipolysis and Fatty Acid β-Oxidation of Lipid Droplets

Lipid storage droplet protein 5 (LSDP5) is a lipid droplet-associated protein of the PAT (perilipin, adipophilin, and TIP47) family that is expressed in the liver in a peroxisome proliferator-activated receptor alpha (PPARα)-dependent manner; however, its exact function has not been elucidated. We noticed that LSDP5 was localized to the surface of lipid droplets in hepatocytes. Overexpression of LSDP5 enhanced lipid accumulation in the hepatic cell line AML12 and in primary hepatocytes. Knock-down of LSDP5 significantly decreased the triglyceride content of lipid droplets, stimulated lipolysis, and modestly increased the mitochondrial content and level of fatty-acid β-oxidation in the mitochondria. The expression of PPARα was increased in LSDP5-deficient cells and required for the increase in the level of fatty acid β-oxidation in LSDP5-deficient cells. Using serial deletions of LSDP5, we determined that the lipid droplet-targeting domain and the domain directing lipid droplet clustering overlapped and were localized to the 188 amino acid residues at the N-terminus of LSDP5. Our findings suggest that LSDP5, a novel lipid droplet protein, may contribute to triglyceride accumulation by negatively regulating lipolysis and fatty acid oxidation in hepatocytes

Therapeutic effect of Rho kinase inhibitor FSD-C10 in a mouse model of Alzheimer\u27s disease.

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer\u27s disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of its action. The results showed that FSD-C10 effectively improved learning and memory impairment, accompanied by reduced expression of amyloid-β1-42 (Aβ 1-42 ), Tau protein phosphorylation (P-tau) and β-site APP-cleaving enzyme in the hippocampus and cortex area of brain. In addition, FSD-C10 administration boosted the expression of synapse-associated proteins, such as postynaptic density protein 95, synaptophsin, α-amino 3-hydroxy-5-methyl-4-isoxa-zolep-propionate receptor and neurotrophic factors, e,g., brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Taken together, our results demonstrate that FSD-C10 has therapeutic potential in the AD mouse model, possibly through inhibiting the formation of Aβ 1-42 and P-tau, and promoting the generation of synapse-associated proteins and neurotrophic factors

Electrophysiological Characteristics in Depressive Personality Disorder: An Event-Related Potential Study

This study aimed to investigate the neurophysiological characteristics of young people with depressive personality disorder using event-related potentials (ERP). To explore the effects of visual-emotional words on ERP, mainly N350, we recruited 19 individuals with a depressive personality disorder and 10 healthy controls. ERP were recorded while the subjects took decisions on target words that were classified into three categories: emotionally positive, negative, and neutral. The ERP signals were then separately averaged according to the subjects’ classifications. Data analysis showed that the amplitude of N350 was larger in response to positive and negative words than to neutral words. The latency of N350 was longer in negative words, in contrast with positive and neutral words. However, no difference was found between the two groups. These results suggest that neurophysiological characteristics of young people with a depressive personality disorder in visual-emotional word processing have not yet been influenced by their personality traits. To some extent, N350 reflected semantic processes and was not sensitive to participants’ mood state

STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells

Background: Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated.Methods: Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors.Results: Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth.Conclusions: Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response

High-Mobility Semiconducting Polymers With Different Spin Ground States

Organic semiconductors with high-spin ground states are fascinating because they could enable fundamental understanding on the spin-related phenomenon in light element and provide opportunities for organic magnetic and quantum materials. Although high-spin ground states have been observed in some quinoidal type small molecules or doped organic semiconductors, semiconducting polymers with high-spin at their neutral ground state are rarely reported. Here we report three high-mobility semiconducting polymers with different spin ground states. We show that polymer building blocks with small singlet-triplet energy gap (ΔES-T) could enable small ΔES-T gap and increase the diradical character in copolymers. We demonstrate that the electronic structure, spin density, and solid-state interchain interactions in the high-spin polymers are crucial for their ground states. Polymers with a triplet ground state (S = 1) could exhibit doublet (S = 1/2) behavior due to different spin distributions and solid-state interchain spin-spin interactions. Besides, these polymers showed outstanding charge transport properties with high hole/electron mobilities and can be both n- and p-doped with superior conductivities. Our results demonstrate a rational approach to obtain high-mobility semiconducting polymers with different spin ground states