In this paper we report a kind of fast-scale instability occurring in the single-ended primary inductance converter （SEPIC） power factor pre-regulator, which is designed to operate in discontinuous conduction mode. ...In this paper we report a kind of fast-scale instability occurring in the single-ended primary inductance converter （SEPIC） power factor pre-regulator, which is designed to operate in discontinuous conduction mode. Main results are given by exact cycle-by-cycle computer simulations as well as theoretical analysis. It is found that the instability phenomenon manifests itself as a fast-scale bifurcation at the switching period, which implies the occurrence of border collision bifurcation, or is related to the transition of the regular operating mode of the SEPIC. According to the theoretical analysis and simulation results, the effects of parameters on system stability, and the locations of the bifurcation points are confirmed. Moreover, the effects of such an instability on power factor and switching stress are also discussed. Finally, the occurrence of the asymmetric bifurcation locations is investigated. The results show that this work provides a convenient means of predicting stability boundaries which can facilitate the selection of the practical parameters.展开更多
AIM To determine the association of human antigen R(HuR) and inhibitors of apoptosis proteins(IAP1, IAP2) and prognosis in pancreatic cancer.METHODS Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreat...AIM To determine the association of human antigen R(HuR) and inhibitors of apoptosis proteins(IAP1, IAP2) and prognosis in pancreatic cancer.METHODS Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreatic ductal adenocarcinoma(PDAC) were compared with normal pancreatic tissue. The correlations among IAP1/IAP2 and HuR as well as their respective correlations with clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for survival analysis. Immunoprecipitation assay was performed to demonstrate HuR binding to IAP1, IAP2 mRNA. PANC1 cells were transfected with either anti-HuR siRNA or control siRNA for 72 h and quantitative reverse transcription polymerase chain reaction(RT-PCR), western blot analysis was carried out.RESULTS RT-PCR analysis revealed that HuR, IAP1, IAP2 mRNA expression were accordingly 3.3-fold, 5.5-fold and 8.4 higher in the PDAC when compared to normal pancreas(P < 0.05). Expression of IAP1 was positively strongly correlated with HuR expression(P < 0.05, r = 0.783). Western blot analysis confirmed RTPCR results. High IAP1 expression, tumor resection status, T stage, lymph-node metastases, tumor differentiation grade, perineural and lymphatic invasion were identified as significant factors for shorter survival in PDAC patients(P < 0.05).Immunohistological analysis showed that HuR was mainly expressed in the ductal cancer cell's nucleus and less so in cytoplasm. RNA immunoprecipitation analysis confirmed IAP1 and IAP2 post-transcriptional regulation by HuR protein. Following siHuR transfection, IAP1 mRNA and protein levels were decreased, however IAP2 expression levels were increased.CONCLUSION HuR mediated overexpression of IAP1 significantly correlates with poor outcomes and early progression of pancreatic cancer. Further studies are needed to assess the underlying mechanisms.展开更多
Post-traumatic stress disorder(PTSD) is a disabling, potentially chronic disorder that is characterized by re-experience and hyperarousal symptoms as well as the avoidance of trauma-related stimuli. The distress exper...Post-traumatic stress disorder(PTSD) is a disabling, potentially chronic disorder that is characterized by re-experience and hyperarousal symptoms as well as the avoidance of trauma-related stimuli. The distress experienced by many veterans of the Vietnam War and their partners prompted a strong interest in developing conjoint interventions that could both alleviate the core symptoms of PTSD and strengthen family bonds. We review the evolution of and evidence base for conjoint PTSD treatments from the Vietnam era through the post-911 era. Our review is particularly focused on the use of treatment strategies that are designed to address the emotions that are generated by the core symptoms of the disorder to reduce their adverse impact on veterans, their partners and the relationship. We present a rationale and evidence to support the direct incorporation of emotion-regulation skills training into conjoint interventions for PTSD. We begin by reviewing emerging evidence suggesting that high levels of emotion dysregulation are characteristic of and predict the severity of both PTSD symptoms and the level of interpersonal/marital difficulties reported by veterans with PTSD and their family members. In doing so, we present a compelling rationale for the inclusion of formal skills training in emotional regulation in couple–/family-based PTSD treatments. We further argue that increased exposure to trauma-related memories and emotions in treatments based on learning theory requires veterans and their partners to learn to manage the uncomfortable emotions that they previously avoided. Conjoint treatments that were developed in the last 30 years all acknowledge the importance of emotions in PTSD but vary widely in their relative emphasis on helping participants to acquire strategies to modulate them compared to other therapeutic tasks such as learning about the disorder or disclosing the trauma to a loved one. We conclude our review by describing two recent innovative treatments for PTSD that incorporate a special emphasis on emotion-regulation skills training in the dyadic context: structured approach therapy(SAT) and multi-family group for military couples(MFG-MC). Although the incorporation of emotion-regulation skills into conjoint PTSD therapies appears promising, replication and comparison to cognitive-behavioral approaches is needed to refine our understanding of which symptoms and veterans might be more responsive to one approach versus others.展开更多
Ikaros (also known as Lyf-1) was initially described as a lymphoid-specific transcription factor.Although Ikaros has been shown to regulate hematopoietic stem cell renewal,as well as the development and function of ce...Ikaros (also known as Lyf-1) was initially described as a lymphoid-specific transcription factor.Although Ikaros has been shown to regulate hematopoietic stem cell renewal,as well as the development and function of cells from multiple hematopoietic lineages,including the myeloid lineage,Ikaros has primarily been studied in context of lymphoid development and malignancy.This review focuses on the role of Ikaros in myeloid cells.We address the importance of post-transcriptional regulation of Ikaros function;the emerging role of Ikaros in myeloid malignancy;Ikaros as a regulator of myeloid differentiation and function;and the selective expression of Ikaros isoform-x in cells with myeloid potential.We highlight the challenges of dissecting Ikaros function in lineage commitment decisions among lymphoidmyeloid progenitors that have emerged as a major myeloid differentiation pathway in recent studies,which leads to reconstruction of the traditional map of murine and human hematopoiesis.展开更多
Background:Large numbers of post-deployment U.S.veterans are diagnosed with post-traumatic stress disorder(PTSD)and/or traumatic brain injury(TBI),leading to an urgent need for effective interventions to reduce sympto...Background:Large numbers of post-deployment U.S.veterans are diagnosed with post-traumatic stress disorder(PTSD)and/or traumatic brain injury(TBI),leading to an urgent need for effective interventions to reduce symptoms and increase veterans’coping.PTSD includes anxiety,flashbacks,and emotional numbing.The symptoms increase health care costs for stress-related illnesses and can make veterans’civilian life difficult.Methods:We used a randomized wait-list controlled design with repeated measures of U.S.military veterans to address our specific aim to test the efficacy of a 6-week therapeutic horseback riding(THR)program for decreasing PTSD symptoms and increasing coping self-efficacy,emotion regulation,social and emotional loneliness.Fiftyseven participants were recruited and 29 enrolled in the randomized trial.They were randomly assigned to either the horse riding group(n=15)or a wait-list control group(n=14).The wait-list control group experienced a 6-week waiting period,while the horse riding group began THR.The wait-list control group began riding after 6 weeks of participating in the control group.Demographic and health history information was obtained from all the participants.PTSD symptoms were measured using the standardized PTSD Checklist-Military Version(PCL-M).The PCL-M as well as other instruments including,The Coping Self Efficacy Scale(CSES),The Difficulties in Emotion Regulation Scale(DERS)and The Social and Emotional Loneliness Scale for Adults-short version(SELSA)were used to access different aspects of individual well-being and the PTSD symptoms.Results:Participants had a statistically significant decrease in PTSD scores after 3 weeks of THR(P≤0.01)as well as a statistically and clinically significant decrease after 6 weeks of THR(P≤0.01).Logistic regression showed that participants had a 66.7%likelihood of having lower PTSD scores at 3 weeks and 87.5%likelihood at 6 weeks.Under the generalized linear model(GLM),our ANOVA findings for the coping self-efficacy,emotion regulation,and social and emotional loneliness did not reach statistical significance.The results for coping self-efficacy and emotion regulation trended in the predicted direction.Results for emotional loneliness were opposite the predicted direction.Logistic regression provided validation that outcome effects were caused by riding longer.Conclusion:The findings suggest that THR may be a clinically effective intervention for alleviating PTSD symptoms in military veterans.展开更多
BACKGROUND Tubulins,building blocks of microtubules,are modified substrates of diverse post-translational modifications including phosphorylation,polyglycylation and polyglutamylation.Polyglutamylation of microtubules...BACKGROUND Tubulins,building blocks of microtubules,are modified substrates of diverse post-translational modifications including phosphorylation,polyglycylation and polyglutamylation.Polyglutamylation of microtubules,catalyzed by enzymes from the tubulin tyrosine ligase-like(TTLL)family,can regulate interactions with molecular motors and other proteins.Due to the diversity and functional importance of microtubule modifications,strict control of the TTLL enzymes has been suggested.AIM To characterize the interaction between never in mitosis gene A-related kinase 5(NEK5)and TTLL4 proteins and the effects of TTLL4 phosphorylation.METHODS The interaction between NEK5 and TTLL4 was identified by yeast two-hybrid screening using the C-terminus of NEK5(a.a.260–708)as bait and confirmed by immunoprecipitation.The phosphorylation sites of TTLL4 were identified by mass spectrometry and point mutations were introduced.RESULTS Here,we show that NEK5 interacts with TTLL4 and regulates its polyglutamylation activity.We further show that NEK5 can also interact with TTLL5 and TTLL7.The silencing of NEK5 increases the levels of polyglutamylation of proteins by increasing the activity of TTLL4.The same effects were observed after the expression of the catalytically inactive form of NEK5.This regulation of TTLL4 activity involves its phosphorylation at Y815 and S1136 amino acid residues.CONCLUSION Our results demonstrate,for the first time,the regulation of TTLL activity through phosphorylation,pointing to NEK5 as a potential effector kinase.We also suggest a general control of tubulin polyglutamylation through NEK family members in human cells.展开更多
文摘In this paper we report a kind of fast-scale instability occurring in the single-ended primary inductance converter （SEPIC） power factor pre-regulator, which is designed to operate in discontinuous conduction mode. Main results are given by exact cycle-by-cycle computer simulations as well as theoretical analysis. It is found that the instability phenomenon manifests itself as a fast-scale bifurcation at the switching period, which implies the occurrence of border collision bifurcation, or is related to the transition of the regular operating mode of the SEPIC. According to the theoretical analysis and simulation results, the effects of parameters on system stability, and the locations of the bifurcation points are confirmed. Moreover, the effects of such an instability on power factor and switching stress are also discussed. Finally, the occurrence of the asymmetric bifurcation locations is investigated. The results show that this work provides a convenient means of predicting stability boundaries which can facilitate the selection of the practical parameters.
文摘AIM To determine the association of human antigen R(HuR) and inhibitors of apoptosis proteins(IAP1, IAP2) and prognosis in pancreatic cancer.METHODS Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreatic ductal adenocarcinoma(PDAC) were compared with normal pancreatic tissue. The correlations among IAP1/IAP2 and HuR as well as their respective correlations with clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for survival analysis. Immunoprecipitation assay was performed to demonstrate HuR binding to IAP1, IAP2 mRNA. PANC1 cells were transfected with either anti-HuR siRNA or control siRNA for 72 h and quantitative reverse transcription polymerase chain reaction(RT-PCR), western blot analysis was carried out.RESULTS RT-PCR analysis revealed that HuR, IAP1, IAP2 mRNA expression were accordingly 3.3-fold, 5.5-fold and 8.4 higher in the PDAC when compared to normal pancreas(P < 0.05). Expression of IAP1 was positively strongly correlated with HuR expression(P < 0.05, r = 0.783). Western blot analysis confirmed RTPCR results. High IAP1 expression, tumor resection status, T stage, lymph-node metastases, tumor differentiation grade, perineural and lymphatic invasion were identified as significant factors for shorter survival in PDAC patients(P < 0.05).Immunohistological analysis showed that HuR was mainly expressed in the ductal cancer cell's nucleus and less so in cytoplasm. RNA immunoprecipitation analysis confirmed IAP1 and IAP2 post-transcriptional regulation by HuR protein. Following siHuR transfection, IAP1 mRNA and protein levels were decreased, however IAP2 expression levels were increased.CONCLUSION HuR mediated overexpression of IAP1 significantly correlates with poor outcomes and early progression of pancreatic cancer. Further studies are needed to assess the underlying mechanisms.
文摘Post-traumatic stress disorder(PTSD) is a disabling, potentially chronic disorder that is characterized by re-experience and hyperarousal symptoms as well as the avoidance of trauma-related stimuli. The distress experienced by many veterans of the Vietnam War and their partners prompted a strong interest in developing conjoint interventions that could both alleviate the core symptoms of PTSD and strengthen family bonds. We review the evolution of and evidence base for conjoint PTSD treatments from the Vietnam era through the post-911 era. Our review is particularly focused on the use of treatment strategies that are designed to address the emotions that are generated by the core symptoms of the disorder to reduce their adverse impact on veterans, their partners and the relationship. We present a rationale and evidence to support the direct incorporation of emotion-regulation skills training into conjoint interventions for PTSD. We begin by reviewing emerging evidence suggesting that high levels of emotion dysregulation are characteristic of and predict the severity of both PTSD symptoms and the level of interpersonal/marital difficulties reported by veterans with PTSD and their family members. In doing so, we present a compelling rationale for the inclusion of formal skills training in emotional regulation in couple–/family-based PTSD treatments. We further argue that increased exposure to trauma-related memories and emotions in treatments based on learning theory requires veterans and their partners to learn to manage the uncomfortable emotions that they previously avoided. Conjoint treatments that were developed in the last 30 years all acknowledge the importance of emotions in PTSD but vary widely in their relative emphasis on helping participants to acquire strategies to modulate them compared to other therapeutic tasks such as learning about the disorder or disclosing the trauma to a loved one. We conclude our review by describing two recent innovative treatments for PTSD that incorporate a special emphasis on emotion-regulation skills training in the dyadic context: structured approach therapy(SAT) and multi-family group for military couples(MFG-MC). Although the incorporation of emotion-regulation skills into conjoint PTSD therapies appears promising, replication and comparison to cognitive-behavioral approaches is needed to refine our understanding of which symptoms and veterans might be more responsive to one approach versus others.
文摘Ikaros (also known as Lyf-1) was initially described as a lymphoid-specific transcription factor.Although Ikaros has been shown to regulate hematopoietic stem cell renewal,as well as the development and function of cells from multiple hematopoietic lineages,including the myeloid lineage,Ikaros has primarily been studied in context of lymphoid development and malignancy.This review focuses on the role of Ikaros in myeloid cells.We address the importance of post-transcriptional regulation of Ikaros function;the emerging role of Ikaros in myeloid malignancy;Ikaros as a regulator of myeloid differentiation and function;and the selective expression of Ikaros isoform-x in cells with myeloid potential.We highlight the challenges of dissecting Ikaros function in lineage commitment decisions among lymphoidmyeloid progenitors that have emerged as a major myeloid differentiation pathway in recent studies,which leads to reconstruction of the traditional map of murine and human hematopoiesis.
文摘Background:Large numbers of post-deployment U.S.veterans are diagnosed with post-traumatic stress disorder(PTSD)and/or traumatic brain injury(TBI),leading to an urgent need for effective interventions to reduce symptoms and increase veterans’coping.PTSD includes anxiety,flashbacks,and emotional numbing.The symptoms increase health care costs for stress-related illnesses and can make veterans’civilian life difficult.Methods:We used a randomized wait-list controlled design with repeated measures of U.S.military veterans to address our specific aim to test the efficacy of a 6-week therapeutic horseback riding(THR)program for decreasing PTSD symptoms and increasing coping self-efficacy,emotion regulation,social and emotional loneliness.Fiftyseven participants were recruited and 29 enrolled in the randomized trial.They were randomly assigned to either the horse riding group(n=15)or a wait-list control group(n=14).The wait-list control group experienced a 6-week waiting period,while the horse riding group began THR.The wait-list control group began riding after 6 weeks of participating in the control group.Demographic and health history information was obtained from all the participants.PTSD symptoms were measured using the standardized PTSD Checklist-Military Version(PCL-M).The PCL-M as well as other instruments including,The Coping Self Efficacy Scale(CSES),The Difficulties in Emotion Regulation Scale(DERS)and The Social and Emotional Loneliness Scale for Adults-short version(SELSA)were used to access different aspects of individual well-being and the PTSD symptoms.Results:Participants had a statistically significant decrease in PTSD scores after 3 weeks of THR(P≤0.01)as well as a statistically and clinically significant decrease after 6 weeks of THR(P≤0.01).Logistic regression showed that participants had a 66.7%likelihood of having lower PTSD scores at 3 weeks and 87.5%likelihood at 6 weeks.Under the generalized linear model(GLM),our ANOVA findings for the coping self-efficacy,emotion regulation,and social and emotional loneliness did not reach statistical significance.The results for coping self-efficacy and emotion regulation trended in the predicted direction.Results for emotional loneliness were opposite the predicted direction.Logistic regression provided validation that outcome effects were caused by riding longer.Conclusion:The findings suggest that THR may be a clinically effective intervention for alleviating PTSD symptoms in military veterans.
基金Fundação de AmparoàPesquisa do Estado São Paulo(FAPESP,São Paulo,Brazil)through Grant Temático,No.2017/03489-1.
文摘BACKGROUND Tubulins,building blocks of microtubules,are modified substrates of diverse post-translational modifications including phosphorylation,polyglycylation and polyglutamylation.Polyglutamylation of microtubules,catalyzed by enzymes from the tubulin tyrosine ligase-like(TTLL)family,can regulate interactions with molecular motors and other proteins.Due to the diversity and functional importance of microtubule modifications,strict control of the TTLL enzymes has been suggested.AIM To characterize the interaction between never in mitosis gene A-related kinase 5(NEK5)and TTLL4 proteins and the effects of TTLL4 phosphorylation.METHODS The interaction between NEK5 and TTLL4 was identified by yeast two-hybrid screening using the C-terminus of NEK5(a.a.260–708)as bait and confirmed by immunoprecipitation.The phosphorylation sites of TTLL4 were identified by mass spectrometry and point mutations were introduced.RESULTS Here,we show that NEK5 interacts with TTLL4 and regulates its polyglutamylation activity.We further show that NEK5 can also interact with TTLL5 and TTLL7.The silencing of NEK5 increases the levels of polyglutamylation of proteins by increasing the activity of TTLL4.The same effects were observed after the expression of the catalytically inactive form of NEK5.This regulation of TTLL4 activity involves its phosphorylation at Y815 and S1136 amino acid residues.CONCLUSION Our results demonstrate,for the first time,the regulation of TTLL activity through phosphorylation,pointing to NEK5 as a potential effector kinase.We also suggest a general control of tubulin polyglutamylation through NEK family members in human cells.
