AIM To establish a model to enrich and characterize stemlike cells from murine normal liver and hepatocellular carcinoma(HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesench...AIM To establish a model to enrich and characterize stemlike cells from murine normal liver and hepatocellular carcinoma(HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition(EMT).METHODS In this study,we utilized a stem cell conditioned serumfree medium to enrich stem-like cells from mouse HCC and normal liver cell lines,Hepa 1-6 and AML12,respectively.We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating theRNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR(q RTPCR).Next,we examined the relationship between stem cells and EMT using q RT-PCR.RESULTS Three-dimensional spheres were enriched by culturing murine HCC and normal hepatocyte cell lines in stem cell conditioned serum-free medium supplemented with epidermal growth factor,basic fibroblast growth factor and heparin sulfate.The 3-dimensional spheres had enhanced stemness markers such as Klf4 and Bmi1 and hepatic cancer stem cell(CSC) marker Cd44 compared to parental cells grown as adherent cultures.We report that epithelial markers E-cadherin and ZO-1 were downregulated,while mesenchymal markers Vimentin and Fibronectin were upregulated in 3-dimensional spheres.The 3-dimensional spheres also exhibited changes in expression of Snai,Zeb and Twist family of EMT transcription factors.CONCLUSION Our novel method successfully enriched stem-like cells which possessed an EMT phenotype.The isolation and characterization of murine hepatic CSCs could establish a precise target for the development of more effective therapies for HCC.展开更多
Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed...Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed before accepting manuscripts for publication. In this report, post hoc power analysis for retrospective studies is examined and the informativeness of understanding the power for detecting significant effects of the results analysed, using the same data on which the power analysis is based, is scrutinised. Monte Carlo simulation is used to investigate the performance of posthoc power analysis.展开更多
SUMMARY The p value has been widely used as a way to summarise the significance in data analysis. However, misuse and misinterpretation of the p value is common in practice. Our result shows that if the model specific...SUMMARY The p value has been widely used as a way to summarise the significance in data analysis. However, misuse and misinterpretation of the p value is common in practice. Our result shows that if the model specification is wrong, the distribution of the p value may be inappropriate, which makes the decision based on the p value invalid.展开更多
Machine learning(ML)techniques have been widely used to address mental health questions.We discuss two main aspects of ML in psychiatry in this paper,that is,supervised learning and unsupervised learning.Examples are ...Machine learning(ML)techniques have been widely used to address mental health questions.We discuss two main aspects of ML in psychiatry in this paper,that is,supervised learning and unsupervised learning.Examples are used to illustrate how ML has been implemented in recent mental health research.展开更多
One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of...One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of astute observations by Sir Arthur Hurst in World War I. Additional descriptions followed from military and non-military practitioners adding the evidence which has transitioned this recognized condition from association to causation. While mechanistic understanding is an area of active pursuit, this historical accounting of a centuries progress highlights important advances and contributions of military medicine and scientists to advances benefiting global populations.展开更多
The possible intermittent impacts of a two-stage isolation system with rigid limiters have been investigated. The isolation system is under periodic external excitation disturbed by small stationary Gaussian white no...The possible intermittent impacts of a two-stage isolation system with rigid limiters have been investigated. The isolation system is under periodic external excitation disturbed by small stationary Gaussian white noise after shock. The maximal impact Poincaré map is proposed based on the multi-body dynamics with unilateral constrains. Then in the period after shock, the zero order approximate stochastic discrete model and the first order approximate stochastic model are developed. The real isolation system of an MTU diesel engine is used to evaluate the established model. After calculating of the numerical example, the effects of noise excitation on the isolation system are discussed. The results show that the property of the system is complicated due to intermittent impact. The difference between zero order model and the first order model may be great. The effect of small noise is obvious. The results may be expected useful to the naval designers.展开更多
Based on the concept of hydraulic dissipation of kinetic energy, a novel shock wave regulator, which is composed of a damper and an extemally triggered valve, is presented with thorough analyses on its working mechani...Based on the concept of hydraulic dissipation of kinetic energy, a novel shock wave regulator, which is composed of a damper and an extemally triggered valve, is presented with thorough analyses on its working mechanism. By establishing motion equations of each component of the regulator and simulating the dynamic behavior of the whole system, the shock wave regulator is demonstrated numerically to be able to change the width and amplitude of shock pulses. Prompt and easy adjustment can be achieved by changing the equivalent flow area of damping orifices and consequently the closing velocity of the flow area of a valve, which makes it applicable to different impact testing.展开更多
Background: Musculoskeletal injuries(MSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. MSkIs affect members of the military during...Background: Musculoskeletal injuries(MSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. MSkIs affect members of the military during initial training,operational training, and deployment and have a direct negative impact on overall troop readiness. Currently, a systematic overview of all risk factors for MSkIs in the military is not available.Methods: A systematic literature search was carried out using the PubMed, Ovid/Medline, and Web of Science databases from January 1, 2000 to September 10, 2019. Additionally, a reference list scan was performed(using the “snowball method”). Thereafter, an international, multidisciplinary expert panel scored the level of evidence per risk factor, and a classification of modifiable/non-modifiable was made.Results: In total, 176 original papers and 3 meta-analyses were included in the review. A list of 57 reported potential risk factors was formed. For 21 risk factors, the level of evidence was considered moderate or strong. Based on this literature review and an in-depth analysis, the expert panel developed a model to display the most relevant risk factors identified, introducing the idea of the “order of importance” and including concepts that are modifiable/nonmodifiable, as well as extrinsic/intrinsic risk factors.Conclusions: This is the qualitative systematic review of studies on risk factors for MSkIs in the military that has attempted to be all-inclusive. A total of 57 different potential risk factors were identified, and a new, prioritizing injury model was developed. This model may help us to understand risk factors that can be addressed, and in which order they should be prioritized when planning intervention strategies within military groups.展开更多
Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of t...Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness,and symptoms of depression, anxiety, and post-traumatic stress disorder(PTSD) in US service members(n=298).Although predominantly young males(who skew toward eveningness in civilian populations), these Sailors skewed toward morningness(35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and PTSD(P<0.01), less time in bed(P<0.05), more sleep disruption(P<0.01), and poorer daytime functioning and alertness(P<0.05). Evening types were less likely to consider sleep important for performance(P<0.05). To maximize service member readiness, schedules should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.展开更多
SAS and other popular statistical packages provide support for survey data with sampling weights. For example, PROC MEANS and PROC LOGISTIC in SAS have their counterparts PROC SURVEYMEANS and PROC SURVEYLOGISTIC to fa...SAS and other popular statistical packages provide support for survey data with sampling weights. For example, PROC MEANS and PROC LOGISTIC in SAS have their counterparts PROC SURVEYMEANS and PROC SURVEYLOGISTIC to facilitate analysis of data from complex survey studies. On the other hand, PROC MEANS and many other classic SAS procedures also provide an option for including weights and yield identical point estimates, but different standard errors (SEs), as their corresponding survey procedures. This paper takes an in-depth look at different types of weights and provides guidance on use of different SAS procedures.展开更多
Mental health questions can be tackled through machine learning(ML)techniques.Apart from the two ML methods we introduced in our previous paper,we discuss two more advanced ML approaches in this paper:support vector m...Mental health questions can be tackled through machine learning(ML)techniques.Apart from the two ML methods we introduced in our previous paper,we discuss two more advanced ML approaches in this paper:support vector machines and artificial neural networks.To illustrate how these ML methods have been employed in mental health,recent research applications in psychiatry were reported.展开更多
Cell-free systems contain many proteins and metabolites required for complex functions such as transcription and translation or multi-step metabolic conversions.Research into expanding the delivery of these systems by...Cell-free systems contain many proteins and metabolites required for complex functions such as transcription and translation or multi-step metabolic conversions.Research into expanding the delivery of these systems by drying or by embedding into other materials is enabling new applications in sensing,point-of-need manufacturing,and responsive materials.Meanwhile,silk fibroin from the silk worm,Bombyx mori,has received attention as a protective additive for dried enzyme formulations and as a material to build biocompatible hydrogels for controlled localization or delivery of biomolecular cargoes.In this work,we explore the effects of silk fibroin as an additive in cell-free protein synthesis(CFPS)reactions.Impacts of silk fibroin on CFPS activity and stability after drying,as well as the potential for incorporation of CFPS into hydrogels of crosslinked silk fibroin are assessed.We find that simple addition of silk fibroin increased productivity of the CFPS reactions by up to 42%,which we attribute to macromolecular crowding effects.However,we did not find evidence that silk fibroin provides a protective effects after drying as previously described for purified enzymes.Further,the enzymatic crosslinking transformations of silk fibroin typically used to form hydrogels are inhibited in the presence of the CFPS reaction mixture.Crosslinking attempts did not impact CFPS activity,but did yield localized protein aggregates rather than a hydrogel.We discuss the mechanisms at play in these results and how the silk fibroin-CFPS system might be improved for the design of cell-free devices.展开更多
基金Supported by The Gallipoli Medical Research Foundation,Australia,No.016092the Cyril Gilbert Foundation,Australia,No.017348
文摘AIM To establish a model to enrich and characterize stemlike cells from murine normal liver and hepatocellular carcinoma(HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition(EMT).METHODS In this study,we utilized a stem cell conditioned serumfree medium to enrich stem-like cells from mouse HCC and normal liver cell lines,Hepa 1-6 and AML12,respectively.We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating theRNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR(q RTPCR).Next,we examined the relationship between stem cells and EMT using q RT-PCR.RESULTS Three-dimensional spheres were enriched by culturing murine HCC and normal hepatocyte cell lines in stem cell conditioned serum-free medium supplemented with epidermal growth factor,basic fibroblast growth factor and heparin sulfate.The 3-dimensional spheres had enhanced stemness markers such as Klf4 and Bmi1 and hepatic cancer stem cell(CSC) marker Cd44 compared to parental cells grown as adherent cultures.We report that epithelial markers E-cadherin and ZO-1 were downregulated,while mesenchymal markers Vimentin and Fibronectin were upregulated in 3-dimensional spheres.The 3-dimensional spheres also exhibited changes in expression of Snai,Zeb and Twist family of EMT transcription factors.CONCLUSION Our novel method successfully enriched stem-like cells which possessed an EMT phenotype.The isolation and characterization of murine hepatic CSCs could establish a precise target for the development of more effective therapies for HCC.
文摘Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed before accepting manuscripts for publication. In this report, post hoc power analysis for retrospective studies is examined and the informativeness of understanding the power for detecting significant effects of the results analysed, using the same data on which the power analysis is based, is scrutinised. Monte Carlo simulation is used to investigate the performance of posthoc power analysis.
文摘SUMMARY The p value has been widely used as a way to summarise the significance in data analysis. However, misuse and misinterpretation of the p value is common in practice. Our result shows that if the model specification is wrong, the distribution of the p value may be inappropriate, which makes the decision based on the p value invalid.
文摘Machine learning(ML)techniques have been widely used to address mental health questions.We discuss two main aspects of ML in psychiatry in this paper,that is,supervised learning and unsupervised learning.Examples are used to illustrate how ML has been implemented in recent mental health research.
文摘One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of astute observations by Sir Arthur Hurst in World War I. Additional descriptions followed from military and non-military practitioners adding the evidence which has transitioned this recognized condition from association to causation. While mechanistic understanding is an area of active pursuit, this historical accounting of a centuries progress highlights important advances and contributions of military medicine and scientists to advances benefiting global populations.
基金Project supported by the National Natural Science Foundation of China (No. 10072040)
文摘The possible intermittent impacts of a two-stage isolation system with rigid limiters have been investigated. The isolation system is under periodic external excitation disturbed by small stationary Gaussian white noise after shock. The maximal impact Poincaré map is proposed based on the multi-body dynamics with unilateral constrains. Then in the period after shock, the zero order approximate stochastic discrete model and the first order approximate stochastic model are developed. The real isolation system of an MTU diesel engine is used to evaluate the established model. After calculating of the numerical example, the effects of noise excitation on the isolation system are discussed. The results show that the property of the system is complicated due to intermittent impact. The difference between zero order model and the first order model may be great. The effect of small noise is obvious. The results may be expected useful to the naval designers.
基金the Naval Warship Research Department of Defense(No05131/1046)
文摘Based on the concept of hydraulic dissipation of kinetic energy, a novel shock wave regulator, which is composed of a damper and an extemally triggered valve, is presented with thorough analyses on its working mechanism. By establishing motion equations of each component of the regulator and simulating the dynamic behavior of the whole system, the shock wave regulator is demonstrated numerically to be able to change the width and amplitude of shock pulses. Prompt and easy adjustment can be achieved by changing the equivalent flow area of damping orifices and consequently the closing velocity of the flow area of a valve, which makes it applicable to different impact testing.
文摘Background: Musculoskeletal injuries(MSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. MSkIs affect members of the military during initial training,operational training, and deployment and have a direct negative impact on overall troop readiness. Currently, a systematic overview of all risk factors for MSkIs in the military is not available.Methods: A systematic literature search was carried out using the PubMed, Ovid/Medline, and Web of Science databases from January 1, 2000 to September 10, 2019. Additionally, a reference list scan was performed(using the “snowball method”). Thereafter, an international, multidisciplinary expert panel scored the level of evidence per risk factor, and a classification of modifiable/non-modifiable was made.Results: In total, 176 original papers and 3 meta-analyses were included in the review. A list of 57 reported potential risk factors was formed. For 21 risk factors, the level of evidence was considered moderate or strong. Based on this literature review and an in-depth analysis, the expert panel developed a model to display the most relevant risk factors identified, introducing the idea of the “order of importance” and including concepts that are modifiable/nonmodifiable, as well as extrinsic/intrinsic risk factors.Conclusions: This is the qualitative systematic review of studies on risk factors for MSkIs in the military that has attempted to be all-inclusive. A total of 57 different potential risk factors were identified, and a new, prioritizing injury model was developed. This model may help us to understand risk factors that can be addressed, and in which order they should be prioritized when planning intervention strategies within military groups.
基金supported by the Department of Defense Congressionally Directed Medical Research Programs,Joint Program Committee-5 Early Assessment and Intervention Working Group(N1634)。
文摘Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness,and symptoms of depression, anxiety, and post-traumatic stress disorder(PTSD) in US service members(n=298).Although predominantly young males(who skew toward eveningness in civilian populations), these Sailors skewed toward morningness(35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and PTSD(P<0.01), less time in bed(P<0.05), more sleep disruption(P<0.01), and poorer daytime functioning and alertness(P<0.05). Evening types were less likely to consider sleep important for performance(P<0.05). To maximize service member readiness, schedules should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.
文摘SAS and other popular statistical packages provide support for survey data with sampling weights. For example, PROC MEANS and PROC LOGISTIC in SAS have their counterparts PROC SURVEYMEANS and PROC SURVEYLOGISTIC to facilitate analysis of data from complex survey studies. On the other hand, PROC MEANS and many other classic SAS procedures also provide an option for including weights and yield identical point estimates, but different standard errors (SEs), as their corresponding survey procedures. This paper takes an in-depth look at different types of weights and provides guidance on use of different SAS procedures.
文摘Mental health questions can be tackled through machine learning(ML)techniques.Apart from the two ML methods we introduced in our previous paper,we discuss two more advanced ML approaches in this paper:support vector machines and artificial neural networks.To illustrate how these ML methods have been employed in mental health,recent research applications in psychiatry were reported.
基金our funding sources:US Office of the Secretary of Defense Applied Research for the Advancement of S&T Priorities program Synthetic Biology for Military Environments and the US Army Combat Capabilities Development Command Chemical Biological Center Section 2363 Biological Engineering for Applied Materials Solutions program.This work was performed while Marilyn Lee held an NRC Research Associateship award at US Army CCDC CBC.
文摘Cell-free systems contain many proteins and metabolites required for complex functions such as transcription and translation or multi-step metabolic conversions.Research into expanding the delivery of these systems by drying or by embedding into other materials is enabling new applications in sensing,point-of-need manufacturing,and responsive materials.Meanwhile,silk fibroin from the silk worm,Bombyx mori,has received attention as a protective additive for dried enzyme formulations and as a material to build biocompatible hydrogels for controlled localization or delivery of biomolecular cargoes.In this work,we explore the effects of silk fibroin as an additive in cell-free protein synthesis(CFPS)reactions.Impacts of silk fibroin on CFPS activity and stability after drying,as well as the potential for incorporation of CFPS into hydrogels of crosslinked silk fibroin are assessed.We find that simple addition of silk fibroin increased productivity of the CFPS reactions by up to 42%,which we attribute to macromolecular crowding effects.However,we did not find evidence that silk fibroin provides a protective effects after drying as previously described for purified enzymes.Further,the enzymatic crosslinking transformations of silk fibroin typically used to form hydrogels are inhibited in the presence of the CFPS reaction mixture.Crosslinking attempts did not impact CFPS activity,but did yield localized protein aggregates rather than a hydrogel.We discuss the mechanisms at play in these results and how the silk fibroin-CFPS system might be improved for the design of cell-free devices.
