BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatoria...BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.展开更多
Quadratic 0-1 problems with linear inequality constraints are briefly considered in this paper.Global optimality conditions for these problems,including a necessary condition and some sufficient conditions,are present...Quadratic 0-1 problems with linear inequality constraints are briefly considered in this paper.Global optimality conditions for these problems,including a necessary condition and some sufficient conditions,are presented.The necessary condition is expressed without dual variables.The relations between the global optimal solutions of nonconvex quadratic 0-1 problems and the associated relaxed convex problems are also studied.展开更多
In this paper,quadratic 0-1 programming problem (I) is considered, in terms of its features quadratic 0-1 programming problem is solved by linear approxity heurstic algrothm and a developed tabu search ahgrothm .
The purpose of this research is to implement an IT-based education program in order to promote cervical cancer screenings for women aged 20 - 29 years, as well as to examine the results of said program. This is a long...The purpose of this research is to implement an IT-based education program in order to promote cervical cancer screenings for women aged 20 - 29 years, as well as to examine the results of said program. This is a longitudinal/comparative study of two groups, one for which the program was implemented (the intervention group), and the other for which it was not (the control group). The program consisted of attending a health lecture and encouragement to be screened one month, six months, and one year later sent through IT-based methods. The target was unmarried women aged 20 - 29 who had neither previously given birth nor had been screened for cervical cancer in a period one year prior. They were divided into two groups, the intervention group (n = 142) and control group (n = 145). The effectiveness of the program was assessed via an initial survey and further surveys six months and one year later. Results were based on the Japanese version of the Health Belief Model Scale for Cervical Cancer and the Pap Smear Test (HBMSCCPST), knowledge scores in the categories of Healthy Lifestyles, Cervical Cancer, Cervical Cancer Screening, and screening behavior. A two-way ANOVA of the HBMSCCPST subscales and knowledge scores in the initial, six-month, and one-year surveys was performed, showing interaction in Cervical Cancer (p = 0.00). Main effects were observed in Cervical Cancer Screening (p = 0.00) and Healthy Lifestyles (p = 0.00). Regarding the amount of change from the initial survey, knowledge scores in the Cervical Cancer (p = 0.027) and Cervical Cancer Screening (p = 0.016) categories were significantly higher in the intervention group than in the control group. There was no significant difference in cervical cancer screening rates (p = 0.26) between the two groups. However, a small-degree effect size was observed for Benefits, Seriousness, and Susceptibility subscales in both examinees and non-examinees. Although the educational program of this study was effective in improving the knowledge of women in their twenties, there was little improvement in HBMSCCPST and it did not lead to the promotion of cervical cancer screening. In order to raise interest in cervical cancer screening, it is necessary to consider useful content to guide women to consult with healthcare professionals, a long-term population approach, and organizational structure of consultation.展开更多
To relax convexity assumptions imposed on the functions in theorems on sufficient conditions and duality,new concepts of generalized dI-G-type Ⅰ invexity were introduced for nondifferentiable multiobjective programmi...To relax convexity assumptions imposed on the functions in theorems on sufficient conditions and duality,new concepts of generalized dI-G-type Ⅰ invexity were introduced for nondifferentiable multiobjective programming problems.Based upon these generalized invexity,G-Fritz-John （G-F-J） and G-Karnsh-Kuhn-Tucker （G-K-K-T） types sufficient optimality conditions were established for a feasible solution to be an efficient solution.Moreover,weak and strict duality results were derived for a G-Mond-Weir type dual under various types of generalized dI-G-type Ⅰ invexity assumptions.展开更多
Jointly published by 14 Department headed by Standardization Administraion ofChina(SAC) Subtitle: China will formulate and reformulate 926 standards for energy conservation andcomprehensive u-tilization during 2005 an...Jointly published by 14 Department headed by Standardization Administraion ofChina(SAC) Subtitle: China will formulate and reformulate 926 standards for energy conservation andcomprehensive u-tilization during 2005 and 2007. In the past few days, 14 departments jointlypublished the Development Program of Energy Conservation and Comprehensive Utilization 2005-2007,(Program for short). They are Standardization Administration of China, National Development andReform Commission, Ministry of Land and Resources, Ministry of Establishment, Ministry ofCommunications, Ministry of Information Industry, Ministry of Waster Resources, Ministry ofAgriculture, Ministry of Commerce, General Administration of Quality Supervision, Inspection andQuarantine of the PRC, State Environmental Protection Administration, State Forestry Bureau, StateOceanic Administration and China Meteorological Bureau.展开更多
The Agulhas Current is a major western boundary current flowing polewards on the southeast coast of South Africa.This analysis assesses its characteristics and suitability to generate power as a source of clean renewa...The Agulhas Current is a major western boundary current flowing polewards on the southeast coast of South Africa.This analysis assesses its characteristics and suitability to generate power as a source of clean renewable energy.On a section of coastline some 400 km long,over a period spanning more than 5 years an extensive set of current measurements was obtained.These data confirmed that south-westward currents with a speed greater than 1.2 m s^(-1)occurred over more than 60%of the recorded time;such ocean current speeds compare very favourably to winds required for energy generation.These currents occurred at the continental shelf break in water depths around 100 m,in the upper 50 m of the water column.Occasional current slowdowns and reversals did occur,with the major influence coming from‘Natal Pulses’,which are large-scale meanders in the Current that temporarily reversed the currents at the measurement sites.However,because of the surface temperature structure of the relevant water masses,such meanders can be identified in satellite imagery giving a few days advance warning of such current reversals.The characteristics of western boundary currents have been known for many years,but at Present,there is no operational system where this source of power is being utilised.It has tremendous potential for renewable energy generation,but is symptomatic of the many engineering challenges that still have to be solved to make such generation economically viable.展开更多
Obnoxious facilities are those crucial to human living, yet antagonistic to the public or environment. However, the interactions between obnoxious facilities and their clients have been less frequently investigated. A...Obnoxious facilities are those crucial to human living, yet antagonistic to the public or environment. However, the interactions between obnoxious facilities and their clients have been less frequently investigated. A state-of-the-art model for this problem involves numerous 0 - 1 variables, rendering it difficult to solve. This study aims at removing most of these 0 - 1 variables to enhanced model efficiency. A compact model is presented in this study, with the equivalence between the new and original models proved. Additionally, numerical tests were conducted to show that the proposed compact model is more efficient than the original one.展开更多
Java programming language is a major . new development which involves object-oriented programming and computer networking. Here, several examples of Java programs are presented. These examples show some major features...Java programming language is a major . new development which involves object-oriented programming and computer networking. Here, several examples of Java programs are presented. These examples show some major features that Java language provides, such as multi-thread, exception handling, network application writing, and the usage of Java applets. This article also shows some ways of setting up a Java language programming environment. All these examples are correct and ready to run.展开更多
Concave resource allocation problem is an integer programming problem of minimizing a nonincreasing concave function subject to a convex nondecreasing constraint and bounded integer variables. This class of problems a...Concave resource allocation problem is an integer programming problem of minimizing a nonincreasing concave function subject to a convex nondecreasing constraint and bounded integer variables. This class of problems are encountered in optimization models involving economies of scale. In this paper, a new hybrid dynamic programming method was proposed for solving concave resource allocation problems. A convex underestimating function was used to approximate the objective function and the resulting convex subproblem was solved with dynamic programming technique after transforming it into a 0-1 linear knapsack problem. To ensure the convergence, monotonicity and domain cut technique was employed to remove certain integer boxes and partition the revised domain into a union of integer boxes. Computational results were given to show the efficiency of the algorithm.展开更多
Background：Paraoxonase 1（PON1） is an antioxidant enzyme that protects high-density lipoprotein（HDL） and low-density lipoprotein against oxidation.Limited studies have addressed the influenc of exercise on PON1 ac...Background：Paraoxonase 1（PON1） is an antioxidant enzyme that protects high-density lipoprotein（HDL） and low-density lipoprotein against oxidation.Limited studies have addressed the influenc of exercise on PON1 activity and its relationship with PON1 phenotypes.We investigated relationships between PON1-192 phenotypes,PON1 activity,aerobic exercise,and blood lipid and lipoprotein concentrations in middle-aged women.Methods：An exercise group（n=50） engaging in regular aerobic exercise and a control group（n=41） were selected from a subset of 300 Caucasian women that met the inclusion criteria.Serum PON1,salt-stimulated PON1（SSPON1）,and arylesterase（ARE） activities;cholesterol levels and ARE activities of total HDL and HDL subgroups（HDLs）（supernatants obtained by polyethylene glycol）;and blood lipid and lipoprotein concentrations were determined by standardized enzymatic methods.PON1-192 QQ（low activity）,QR（moderate activity）,and RR（high activity） phenotype groups were define using serum SSPON1/ARE activity ratios.The R-carries（RC） phenotype group consisted of the QR and RR groups combined.Results：All lipid and lipoprotein concentrations were greater in the exercise group than in the control group.Regardless of phenotype,no significan differences were observed between the exercise and control groups in terms of serum PON1,SSPON1,or ARE activity associated with HDLs（p〉 0.05）,whereas PON1 activities in QQ-phenotyped women in the exercise group were significant y higher than those in the control group（p〈0.01）,but not the RC group.A statistically significan interaction between PON1 phenotypes（QQ and RC groups） and exercise（exercise and control groups） on PON1 activity was found.Conclusion：These results showed that a regular aerobic exercise program can improve PON1 activity depending on PON1-192 phenotype,but not on lipid and lipoprotein levels,in middle-aged Turkish women.展开更多
To meet the development trend of multi-bar warp knit-ting machine towards high-speed,advanced technologyand computer control and the requirements of variousproducts with small quantity,there are many researcheson the ...To meet the development trend of multi-bar warp knit-ting machine towards high-speed,advanced technologyand computer control and the requirements of variousproducts with small quantity,there are many researcheson the computer-aided pattern design of multi-barwarp knitted fabrics.In terms of the special propertiesof the computer-aided pattern design of multi-barwarp knitted fabrics,the Object Oriented Program(OOP)programming-Object Windows class Library(OWL)programming is selected.According to thecharacters of the OWL programming,various functionsare defined.Pattern design and technical parameters canbe output,which offers a great convenience for the fac-tory.展开更多
文摘BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.
文摘Quadratic 0-1 problems with linear inequality constraints are briefly considered in this paper.Global optimality conditions for these problems,including a necessary condition and some sufficient conditions,are presented.The necessary condition is expressed without dual variables.The relations between the global optimal solutions of nonconvex quadratic 0-1 problems and the associated relaxed convex problems are also studied.
文摘In this paper,quadratic 0-1 programming problem (I) is considered, in terms of its features quadratic 0-1 programming problem is solved by linear approxity heurstic algrothm and a developed tabu search ahgrothm .
文摘The purpose of this research is to implement an IT-based education program in order to promote cervical cancer screenings for women aged 20 - 29 years, as well as to examine the results of said program. This is a longitudinal/comparative study of two groups, one for which the program was implemented (the intervention group), and the other for which it was not (the control group). The program consisted of attending a health lecture and encouragement to be screened one month, six months, and one year later sent through IT-based methods. The target was unmarried women aged 20 - 29 who had neither previously given birth nor had been screened for cervical cancer in a period one year prior. They were divided into two groups, the intervention group (n = 142) and control group (n = 145). The effectiveness of the program was assessed via an initial survey and further surveys six months and one year later. Results were based on the Japanese version of the Health Belief Model Scale for Cervical Cancer and the Pap Smear Test (HBMSCCPST), knowledge scores in the categories of Healthy Lifestyles, Cervical Cancer, Cervical Cancer Screening, and screening behavior. A two-way ANOVA of the HBMSCCPST subscales and knowledge scores in the initial, six-month, and one-year surveys was performed, showing interaction in Cervical Cancer (p = 0.00). Main effects were observed in Cervical Cancer Screening (p = 0.00) and Healthy Lifestyles (p = 0.00). Regarding the amount of change from the initial survey, knowledge scores in the Cervical Cancer (p = 0.027) and Cervical Cancer Screening (p = 0.016) categories were significantly higher in the intervention group than in the control group. There was no significant difference in cervical cancer screening rates (p = 0.26) between the two groups. However, a small-degree effect size was observed for Benefits, Seriousness, and Susceptibility subscales in both examinees and non-examinees. Although the educational program of this study was effective in improving the knowledge of women in their twenties, there was little improvement in HBMSCCPST and it did not lead to the promotion of cervical cancer screening. In order to raise interest in cervical cancer screening, it is necessary to consider useful content to guide women to consult with healthcare professionals, a long-term population approach, and organizational structure of consultation.
基金National Natural Science Foundation of China(No.11071110)
文摘To relax convexity assumptions imposed on the functions in theorems on sufficient conditions and duality,new concepts of generalized dI-G-type Ⅰ invexity were introduced for nondifferentiable multiobjective programming problems.Based upon these generalized invexity,G-Fritz-John （G-F-J） and G-Karnsh-Kuhn-Tucker （G-K-K-T） types sufficient optimality conditions were established for a feasible solution to be an efficient solution.Moreover,weak and strict duality results were derived for a G-Mond-Weir type dual under various types of generalized dI-G-type Ⅰ invexity assumptions.
文摘Jointly published by 14 Department headed by Standardization Administraion ofChina(SAC) Subtitle: China will formulate and reformulate 926 standards for energy conservation andcomprehensive u-tilization during 2005 and 2007. In the past few days, 14 departments jointlypublished the Development Program of Energy Conservation and Comprehensive Utilization 2005-2007,(Program for short). They are Standardization Administration of China, National Development andReform Commission, Ministry of Land and Resources, Ministry of Establishment, Ministry ofCommunications, Ministry of Information Industry, Ministry of Waster Resources, Ministry ofAgriculture, Ministry of Commerce, General Administration of Quality Supervision, Inspection andQuarantine of the PRC, State Environmental Protection Administration, State Forestry Bureau, StateOceanic Administration and China Meteorological Bureau.
文摘The Agulhas Current is a major western boundary current flowing polewards on the southeast coast of South Africa.This analysis assesses its characteristics and suitability to generate power as a source of clean renewable energy.On a section of coastline some 400 km long,over a period spanning more than 5 years an extensive set of current measurements was obtained.These data confirmed that south-westward currents with a speed greater than 1.2 m s^(-1)occurred over more than 60%of the recorded time;such ocean current speeds compare very favourably to winds required for energy generation.These currents occurred at the continental shelf break in water depths around 100 m,in the upper 50 m of the water column.Occasional current slowdowns and reversals did occur,with the major influence coming from‘Natal Pulses’,which are large-scale meanders in the Current that temporarily reversed the currents at the measurement sites.However,because of the surface temperature structure of the relevant water masses,such meanders can be identified in satellite imagery giving a few days advance warning of such current reversals.The characteristics of western boundary currents have been known for many years,but at Present,there is no operational system where this source of power is being utilised.It has tremendous potential for renewable energy generation,but is symptomatic of the many engineering challenges that still have to be solved to make such generation economically viable.
文摘Obnoxious facilities are those crucial to human living, yet antagonistic to the public or environment. However, the interactions between obnoxious facilities and their clients have been less frequently investigated. A state-of-the-art model for this problem involves numerous 0 - 1 variables, rendering it difficult to solve. This study aims at removing most of these 0 - 1 variables to enhanced model efficiency. A compact model is presented in this study, with the equivalence between the new and original models proved. Additionally, numerical tests were conducted to show that the proposed compact model is more efficient than the original one.
文摘Java programming language is a major . new development which involves object-oriented programming and computer networking. Here, several examples of Java programs are presented. These examples show some major features that Java language provides, such as multi-thread, exception handling, network application writing, and the usage of Java applets. This article also shows some ways of setting up a Java language programming environment. All these examples are correct and ready to run.
基金Project supported by the National Natural Science Foundation oChina (Grant os.79970107 and 10271073)
文摘Concave resource allocation problem is an integer programming problem of minimizing a nonincreasing concave function subject to a convex nondecreasing constraint and bounded integer variables. This class of problems are encountered in optimization models involving economies of scale. In this paper, a new hybrid dynamic programming method was proposed for solving concave resource allocation problems. A convex underestimating function was used to approximate the objective function and the resulting convex subproblem was solved with dynamic programming technique after transforming it into a 0-1 linear knapsack problem. To ensure the convergence, monotonicity and domain cut technique was employed to remove certain integer boxes and partition the revised domain into a union of integer boxes. Computational results were given to show the efficiency of the algorithm.
基金supported by the Ege University Scientifi Research Projects Directorate(2006-BESYO-004)
文摘Background：Paraoxonase 1（PON1） is an antioxidant enzyme that protects high-density lipoprotein（HDL） and low-density lipoprotein against oxidation.Limited studies have addressed the influenc of exercise on PON1 activity and its relationship with PON1 phenotypes.We investigated relationships between PON1-192 phenotypes,PON1 activity,aerobic exercise,and blood lipid and lipoprotein concentrations in middle-aged women.Methods：An exercise group（n=50） engaging in regular aerobic exercise and a control group（n=41） were selected from a subset of 300 Caucasian women that met the inclusion criteria.Serum PON1,salt-stimulated PON1（SSPON1）,and arylesterase（ARE） activities;cholesterol levels and ARE activities of total HDL and HDL subgroups（HDLs）（supernatants obtained by polyethylene glycol）;and blood lipid and lipoprotein concentrations were determined by standardized enzymatic methods.PON1-192 QQ（low activity）,QR（moderate activity）,and RR（high activity） phenotype groups were define using serum SSPON1/ARE activity ratios.The R-carries（RC） phenotype group consisted of the QR and RR groups combined.Results：All lipid and lipoprotein concentrations were greater in the exercise group than in the control group.Regardless of phenotype,no significan differences were observed between the exercise and control groups in terms of serum PON1,SSPON1,or ARE activity associated with HDLs（p〉 0.05）,whereas PON1 activities in QQ-phenotyped women in the exercise group were significant y higher than those in the control group（p〈0.01）,but not the RC group.A statistically significan interaction between PON1 phenotypes（QQ and RC groups） and exercise（exercise and control groups） on PON1 activity was found.Conclusion：These results showed that a regular aerobic exercise program can improve PON1 activity depending on PON1-192 phenotype,but not on lipid and lipoprotein levels,in middle-aged Turkish women.
文摘To meet the development trend of multi-bar warp knit-ting machine towards high-speed,advanced technologyand computer control and the requirements of variousproducts with small quantity,there are many researcheson the computer-aided pattern design of multi-barwarp knitted fabrics.In terms of the special propertiesof the computer-aided pattern design of multi-barwarp knitted fabrics,the Object Oriented Program(OOP)programming-Object Windows class Library(OWL)programming is selected.According to thecharacters of the OWL programming,various functionsare defined.Pattern design and technical parameters canbe output,which offers a great convenience for the fac-tory.
