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J .theor .Biol .(2002)214,105}134
doi:10.1006/jtbi.2001.2444,available online at https://www.wendangku.net/doc/cc7614327.html,
on Putting Intentions into Cell Biochemistry:An Arti 5cial
Intelligence Perspective
C ATHOLIJN M.J ONKER *-,J ACKY L.S NOEP -A ,J AN T REUR *,H ANS V.W ESTERHOFF ?
AND W OUTER C.A.W IJNGAARDS *
*Department of Arti ,cial Intelligence , of Stellenbosch ,Private Bag X1,Matieland 7602,Stellenbosch ,South Africa (Received on 31July 2001,Accepted in revised form on 28August 2001) The living cell exists by virtue ofthousands ofnonlinearly interacting processes.This complex- ity greatly impedes its understanding.The standard approach to the calculation ofthe behaviour ofthe living cell,or part thereof ,integrates all the rate equations ofthe individual processes.If successful extremely intensive calculations often lead the calculation of coherent, apparently simple,cellular &&decisions ''taken in response to a signal:the complexity ofthe behavior ofthe cell is of ten smaller than it might have been.The &&decisions ''correspond to the activation ofentire f unctional units ofmolecular processes,rather than individual ones. The limited complexity ofsignal and response suggests that there might be a simpler way to model at least some important aspects ofcell f unction.In the "eld ofArti "cial Intelligence, such simpler modelling methods for complex systems have been developed.In this paper,it is shown how the Arti "cial Intelligence description method for deliberative agents functioning on the basis ofbelief s,desires and intentions as known in Arti "cial Intelligence,can be used successfully to describe essential aspects of cellular regulation.This is demonstrated for catabolite repression and substrate induction phenomena in the bacterium Escherichia coli . The method becomes highly e $cient when the computation is automated in a Prolog implementation.By de "ning in a qualitative way the food supply of the bacterium,the make-up ofits catabolic pathways is readily calculated f or cases that are su $ciently complex to make the traditional human reasoning tedious and error prone. 2001Academic Press 1.Introduction Thanks to the sequencing ofcomplete genomes, the complexity of the simplest forms of life is becoming delimited.The simplest life forms require some 300processes (encoded by genes).Simple organisms such as Escherichia coli and yeast use a few thousand processes to &&live ''.Due to nonlinear interactions the true complexity is ofcourse substantially higher,but limited (Westerho !et al .,2000).The most straightfor-ward way ofunderstanding cell f unction on the basis ofmolecular processes is to write the rate equation for each process explicitly and then in-tegrate all equations numerically.Only recently,0022}5193/01/010105#30$35.00/0 2001Academic Press F I G .2.The levels ofregulation in the cell. the intentional notions and their interdepen- dencies (see Fig.1)are delineated.The notions of Belief ,Desire and Intention are often used to model agents in the "eld ofArti "cial Intelligence, see Cohen &Levesque (1990)and Rao &Geor- ge !(1991).Agents are autonomous entities that sense and act on the world (Wooldridge &Jenn- ings,1995).The interdependencies between the notions (Fig.1),are based upon a number of simplifying assumptions on beliefs ,desires ,and intentions . The history ofthe agent leads to a set of desires by the agent.It is taken that the agent desires C, and this desire is labelled .Also,the history of the agent is relevant for the information obtained previously,and this information is stored as a set of beliefs .Some ofthe beliefs are reasons for the agent to pursue some B.The reason is labelled . As B realizes C,thus making B happen accom- plishes C as well,the agent derives that it intends B.The intention is labelled n .Based on the obser- vations in the past,the agent might come to believe that it has the opportunity to do action A. The opportunity is labelled the Greek letter o .As A realizes B,thus by doing A the agents gets the result B as well,the agent derives that it performs A.The performing ofan action is labelled . Assumptions on beliefs .In the simplest ap- proach,beliefs are just based on information the agent has received by observation.Beliefs are persistent by default:the agent keeps beliefs until the belief is overridden by more recent informa- tion.This entails the "rst assumption relevant for modelling the biological cell:ifthe agent has observed a world fact,then the agent creates a belief on the world fact.The second assumption is the converse:for every belief on a world fact, the agent observed this world fact. Assumptions on intentions and desires .In the "rst place,when an action is performed,the agent is assumed to have had an intention to do that. Moreover,the second assumption is that an agent who has an intention to perform an action will execute the action ifan opportunity in the external world (or in the cell 's own physical inter- nal state)occurs.Thirdly,it is assumed that every intention is based on a desire .An agent can have a desire for some state of the world as well as a desire for some action to be performed.When the agent has a set of desires ,it can choose to pursue some ofthem.A chosen desire can only lead to an intention to engage in an action ifan additional reason (Dretske,1991)is present:the third assumption is that for each intended action there is a reason and a desire as well.The fourth assumption is that ifboth the desire is present and the agent believes the reason to pursue the desire is present,then the intention to perform the action will be generated.3.Hierarchical Levels in E.coli A simple biological organism,the bacterium Escherichia coli ,was chosen as the biological model system.E .coli is the best studied bacterium (Neidhardt et al .,1996).It is often challenged by changes in the environment and versatile in its responses to these changes.The complete cycle ofimport,metabolic processing and growth is covered in this paper.For reasons ofpresentation,the principles are explained using a restricted part ofthe example (f ood import),see Section https://www.wendangku.net/doc/cc7614327.html,ter,the more complex model is pre-sented in Section 7.With respect to the selection of food,the known preference of glucose over lactose (catabolite or glucose repression)will be considered.The nutrition import processes are regulated metabolically but also at the levels oftranscrip-tion and translation.In Fig.2,four levels of regulation are depicted.The DNA may change through evolution but remains the same within one individual.The DNA is read at the transcrip-tion level,assembling ribonucleotides into mRNA when metabolic substances from the metabolism level bind indirectly to speci "c parts ofthe DNA.The mRNA molecules are unstable and are read by the translation process (at the translation level).The translation process creates INTENTIONS INTO CELL BIOCHEMISTRY 107 F I G .3.Relationships between the chemical perspective and the logical perspective.enzymes from amino acids.Most enzymes decay rather slowly.At the lowest,metabolic level in the diagram,the processes perform the major cell functions.The catabolic processes release Gibbs energy from food,synthesizing ATP molecules from ADP and inorganic phosphate.The anabolic processes build complex molecules.The transport processes e !ect the import ofsources and an export ofwaste across the cell membrane. Although the living cell depend on thousands ofprocesses,it is less than maximally complex, because it is organized in a number ofways.One such organizational principle was made explicit in hierarchical control analysis (Kahn &Wester- ho !,1991;Hofmeyr &Westerho !,2001)and is re #ected in Fig.2.Chemistry in the living cell occurs at di !erent levels,at the transcription level,the translation level and the metabolism level.Essentially,there is no chemistry between these levels (this chemistry is neglected)in the sense that substances at the one level are con- verted to substances at another level.There is, however,in #uence ofchemical substances ofone level on processes at other levels.This in #uence is indicated by dashed lines.Within each level bio- chemical conversions occur,indicated by full-line arrows.At the mRNA levels this is mRNA syn- thesis,mRNA processing and mRNA degrada- tion.The levels are not identical in function.The metabolic level is where the primary functions of the cell are e !ected.The other two levels serve to regulate that metabolic level. Thus,there are di !erent regulation levels in the bacterium.The metabolism level,the translation level,and the transcription level together control the cell 's processes.Substances and process from these regulation levels need to be interpreted in conceptual terms in order to capture the regula- tion in the cell in a logical perspective. 4.Inte rpre tation ofRe gulation in BDI Conce pts The notions ofbelief ,desire and intention are used to create a logical perspective ofthe bac- terium.The chemical perspective is the model of a bacterium in terms ofsubstances and chemical reactions (cf.Fig.3).Two relations are intro- duced,which are each other 's inverse:a repre - sentation relation,connecting the notions from the logical perspective to the notions from the chemical perspective and an interpretation relation,connecting the notions from the chem-ical perspective to the notions from the logical perspective.The logical belief concepts are also the interpretation ofchemical notions.They are the result ofthe observation ofthe external world (i.e.the growth medium)by the cell.This ob-served state ofthe external world is represented inside the cell by a speci "c con "guration ofthe internal chemistry,for example the cAMP (cycli-cal AMP)concentration (change)e !ected by the presence or the absence ofglucose in the external world.In this manner,the observation of(ex-ternal)physical circumstances leads to beliefs in the cell.The easiest case for a cell should be the obser-vation ofa substance that passes f reely through the cell membrane,the internal concentration of the substance being a clear indication ofthe ex-ternal concentration ofthe substance.In most cells,most external substances may require more subtle means ofdetection,such as through active transport.In E .coli ,for many substances the external concentration a !ects the importing pro-cess,by changing the concentration ofan inducer substance inside the cell.This inducer then binds to a repressor protein,which then loses its a $nity for DNA.The absence of the repressor activates an operon in the DNA,enabling the operon for transcription.The transcription produces mRNA,which will be translated to enzymes,which will change the functioning of the cell.Having acquired these internal con "gurations representing the external world,the cell can mod-ify its behaviour to act accordingly.Sometimes more than one option exists for the representation ofa belief .The question then is which substance is the most appropriate 108 C.M.JONKER E 1A ?. F I G .5.The transcriptional regulation and corresponding intentional concepts.Only information #ow is shown.Leg-end: desire; reason;n intention;o beliefin opportunity; action.representation ofthe belief .In the literature (Godfrey-Smith,1996;Ballim &Wilks,1991),an external condition is related to an internal sub- stance that represents the belief that the external condition is present.The mechanism that pro- duces the belief is not considered.Instead,the belief is analysed in relation to the chosen inter- nal substance,even though an organism as small as a single cell has elaborate mechanisms for performing observation and establishing beliefs . All the other internal substances involved in the observation mechanism may have some bearing on the external substance that is observed as well, and thus also give some indication ofthe external world state.For example,the external glucose concentration becomes known during its uptake via the phosphotransferase system.One of the components ofthis uptake system,GlcIIA is pre- dominantly present in its dephosphorylated state when glucose is taken up,while in the absence of glucose it is phosphorylated to GlcIIA-P.The phosphorylated form of GlcIIA activates the ad- enylyl cyclase enzyme leading to an increase of CRPcAMP levels in the cell necessary for expres- sion ofthe lac operon.Here,low concentrations ofboth GlcIIA-P and CRP-cAMP indicate that glucose is outside,but in our model a choice has been made as to which substance represents the belief .In our model,the last substance from the mechanism,i.e.the signal that regulates the deci- sive processes is taken as the belief .The reason for this is that a !ecting these substances directly a !ects the decision processes.In the example of glucose import,changing the CRPcAMP con- centration will cause the cell to make a di !erent decision,but changing the IIAglcP concentration will only cause di !erent behaviour indirectly through a change ofCRPcAMP. 4.1.REGULATION IN BACTERIA The enzyme complement that is present in a living cell can be altered by changes in gene expression,or by changes in protein degradation rates.Adaptation to altered environmental con- ditions often involves the former.The best- documented cases ofregulated gene expression consist ofalterations ofthe f requency oftran- scription ofsets ofgenes (operons)into mRNA. This is called transcriptional regulation (Fig.4).In the "gure only information #ow is given,the material #ow is not depicted.Thus,the material e !ects ofthe chemical reactions are not shown,but the regulatory information e !ects are.Rep-ressors and activation proteins can bind to the DNA.Chemical substances that are substrates,intermediaries or products ofmetabolic path-ways can bind to such repressors and a !ect the a $nities ofthe latter f or the corresponding DNA.Thus,although all DNA is always present,not all possible mRNAs are synthesized at any moment,but a selection is made.This selection is made during transcription.The mRNA is translated to a polypeptide chain during translation,but again this can be a !ected by (co)factors.Once mRNA is INTENTIONS INTO CELL BIOCHEMISTRY 109 E XAMPLE.1ranscriptional control of the lac-operon Biological facts Intentional interpretation The lac-operon coding for the transport and the"rst steps in the catabolism oflactose is under both negative and positive control.The lac-operon is part ofthe DNA,and thus it is a desire( ) f or the transport and start ofcatabolism oflactose.There is a reason( )a!ecting the creation ofan intention(n )from it. Negative control is mediated by the lac gene product.This lac repressor is constitutively expressed and its binding to the operator site ofthe operon prevents binding ofRNA polymerase to the promoter https://www.wendangku.net/doc/cc7614327.html,ctose binds to the rep-ressor thereby decreasing its a$nity for the operator site.The belief( )represented by the lacI gene product being not present is a part ofthe reason( )The lacI gene product being present denotes that the bacterium believes there is no lactose outside.When lacI is bound to lactose,the bacterium believes there is lactose outside. For e$cient transcription ofthe operon also the cAMP-receptor protein(CRP)needs to be bound near the lac promoter.CRP mediates the positive control,it is activated by binding ofcAMP.When E.coli is growing on lactose the intracellular concentration ofcAMP is high enough to f orm the CRP.In addition,lactose binds to the lac repressor.In the presence ofCRP and inducer bound to the repressor the lac operon is transcribed.When glucose is added to such a cell culture growing on lactose the constitutive expression ofthe PTS enzymes ensure its uptake.Furthermore,glucose uptake leads to a decreased activity ofadenylate cyclase causing the cAMP levels to drop.Thus,the CRP concentra-tions decrease and the lac operon is no longer transcribed although lactose is still present.Another part ofthe reason( )needed for making the intention(n )to import lactose is the belief represented by CRP.The cAMP level is high when no glucose is used,thus CRP represents the belief that no glucose is present outside. When glucose is present the cAMP level drops,and the belief that there is no glucose disappears.And so the reason for having the intention to import lactose disappears,and the intention will be removed. This preference for the cell to use glucose above other free energy sources is termed catabolite repression.The term catabolite repression used in biology is modelled by the knowledge that the intention(n )to import lactose is only created when there is a belief( )that no glucose is present,which is represented by the presence ofCRPcAMP. Similar reasons for other energy sources exist. translated to polypeptide chains,the latter are assembled into enzymes during further process-ing.The enzymes catalyse metabolic conversions. Inhibitors can modify the enzyme e!ect,called metabolic control. 4.2.BDI MODEL FOR BACTERIAL REGULATION In this paper,the BDI model is used to inter-pret the regulation in bacteria.In order to"t the BDI model to the bacterial regulation model two levels of intentions are identi"ed.Thus,a desire with an appropriate reason gives rise to an inten-tion,which in turn when combined with another appropriate reason gives rise to another intention, and only the latter intention when combined with a belief in an opportunity is capable of causing an action to be concluded.This double layer of intentions is a small extension ofthe BDI model. Figure5depicts the transcriptional regulation process(taken from Fig.4)annotated with an intentional interpretation.The intentional con-cepts are taken from Fig.1in Section2.Each type ofdepicted material or process is associated with an intentional notion. The DNA encodes for masses of unrealized potential substances,and thus chemical reactions and thus things the bacterium can do.Since some ofthose things may be in con#ict with each other, the DNA is interpreted as a desire( ).The in- ducers and active proteins that bind to the DNA to enable or hamper the transcription ofmRNA are decisive factors,and are interpreted as the beliefs( )constituting the reason( )to pursue the desire encoded by the operon being tran- scribed. The obtained mRNA is interpreted as an inten- tion n )to prepare to execute an action.Depend-ing on cofactors that can in#uence the translation ofthe mRNA to enzymes,the action actually is prepared.These cofactors are interpreted as be-liefs( )constituting the reason( )to prepare for the action.The produced enzymes are interpreted as intentions(n )to perform the actions.When the cell believes that the opportunity arises(N), 110 C.M.JONKER E1A?. T ABLE1 ?ogical notions and their chemical criteria ?ogical notion Chemical criterion Informal reading glucose–externally–present Glucose concentration outside the cell at least0.1mmol l\ In the external world glucose is present. lactose–externally–present Lactose concentration outside the cell at least0.1mmol l\ In the external world lactose is present. glucose–internally–present Glucose-6-phosphate concentration inside the cell at least0.1mmol l\ Inside the cell glucose is present. lactose–internally–present Lactose concentration inside the cell at least0.1mmol l\ Inside the cell lactose is present. deoxyglucose–internally–present Deoxyglucose-6-phosphate concen- tration inside the cell at least 0.1mmol l\ Inside the cell deoxyglucose is present. deoxyglucose–externally–present Deoxyglucose concentration outside the cell at least0.1mmol l\ In the external world deoxyglucose is present. some–nutrition–outside Glucose or lactose concentration out- side at least0.1mmol l\ At least one source ofnutrition is present outside the cell. some–nutrition–inside Glucose-6-phosphate or lactose con- centration inside at least0.1mmol l\ At least one source ofnutrition is present inside the cell. meaning(represented by)no inhibitors are pres- ent,the metabolic reactions can take place.The metabolic reactions happening together consti- tute the action( ). In the next example,an intentional interpreta- tion ofthe transcriptional control ofthe lac-oper- on is given.Since it is about the control of transcription ofa piece ofDNA to mRNA,reason ,intention n ,opportunity o and action will not be needed in the interpretation.The use of belief , desire ,reason and intention n su$ces. 5.A Logical Description for Steady States In order to reason with the BDI model for bacterial regulation,described in Section4,and to enable further formal analysis of steady-state behaviour of E.coli,a logical description has been developed for it.This logical description is not expressed in terms ofchemicals or the chemical reactions between chemical substances.The logi- cal description consists oflogical f ormalizations ofthe intentional notions and logical relation- ships between these logical notions.These no- tions and relationships are then used to describe control in bacteria. Note that propositional predicate logic is used here,with , ,n and as predicates.The logical symbols used are: which means not, mean- ing and,R denoting or,P meaning implies and which is the bi-implication(ifand only if). Bacteria have many complex chemical reac- tions inside them,but for constant environmental circumstances(a world state,growth medium) these reactions reach the so-called steady states where the#uxes through the reactions remain constant.For each growth medium the steady state can be determined in terms ofintermediary concentrations and reaction#uxes.A growth me- dium can be the basis on which a logical reason- ing process can derive the interpretations in terms ofBDI notions.This logical reasoning pro- cess can be automated and analysed using some rigorous formalization. For reasons ofpresentation,a simple model is discussed in this section.In Sections5.1and5.2, the concepts used to describe the material and intentional views on the bacterium are de"ned, "rst the growth medium description(Section5.1) then the intentional notions(Section5.2).The chemical criteria and logical notations for con- cepts used are summarized in Tables1and2. INTENTIONS INTO CELL BIOCHEMISTRY111 T ABLE2 A concise listing of the concepts and their chemical criteria and logical notations Belief Chemical criterion?ogical notation Glucose externally present belief CRPcAMP not internally present, concentration at most0.01mmol l\ (glucose–externally–present,pos) Lactose externally present belief Lactose internally present,concen- tration above0.1mmol l\ (lactose–externally–present,pos) Glucose not externally present be-lief CRPcAMP internally present,con- centration above0.01mmol l\ (glucose–externally–present,neg) Lactose not externally present be-lief Lactose internally absent,concen- tration at most0.1mmol l\ (lactose–externally–present,neg) Desire Growth desire DNA is present (grow) Nutrition import desire Lactose and glucose import oper- ons present in DNA (food–import) Glucose import desire Glucose import operon internally present in DNA (glucose–import) Lactose import desire Lactose import operon internally present in DNA (lactose–import) Reason for creation of Prepare glucose import intention None true Prepare lactose import intention Beliefthat no glucose is present outside,beliefthat lactose is present outside (glucose–externally–present,neg) (lactose–externally–present,pos) Perform glucose import intention Beliefthat glucose is present out- side (glucose–externally–present,pos) Perform lactose import intention Beliefthat lactose is present outside (lactose–externally–present,pos) Intention Prepare glucose import intention Glucose import mRNA internally present,concentration above 0.1mmol l\ n(prepare–glucose–import) Prepare lactose import intention Lactose import mRNA internally present,concentration above 0.1mmol l\ n(prepare–lactose–import) Perform glucose import intention Glucose import enzymes internally present,concentration above 0.1mmol l\ n(perform–glucose–import) Perform lactose import intention Lactose import enzymes internally present,concentration above 0.1mmol l\ n(perform–lactose–import) Opportunity for activity Glucose import action None true Lactose import action Beliefthat no glucose is externally present (glucose–externally–present,neg) Action Glucose import action Glucose import enzymes are catalysing reactions,#ux above 0.1mmol s\ . (glucose–import) 112 C.M.JONKER E1A?. T ABLE2 (Continued) Belief Chemical criterion?ogical notation Lactose import action Lactose import enzymes are cataly- sing reactions,#ux above 0.1mmol s\ . (lactose–import) At least one nutrition import action Lactose or glucose import enzymes are catalysing reactions,#ux above 0.1mmol s\ . some–nutrition–import These concepts used with propositional predicate logic form a logical language with which the logical description can be formally described.In Section 5.3,the logical relationships between these concepts are then given,enabling deriva-tion. 5.1.GROWTH MEDIUM DESCRIPTION The statements glucose–externally–pre-sent and lactose–externally–present denote external world state statements expressing that in the external world glucose is present,resp. lactose is present(see Table1).The statement deoxyglucose–externally–present denotes that deoxyglucose,a glucose look-alike,is present outside,also an external world state statement.The statement some–nutrition–outside denotes that at least one nutrition source is present outside the cell,and the state-ment some–nutrition–inside denotes that at least one nutrition source is present inside the cell. The reaction ofthe cell to the substance deoxyglucose(2-deoxyglucose)has been model-led in this paper.The reaction ofthe cell to deoxyglucose is similar to the reaction to glucose. The e!ect ofdeoxyglucose on the phosphotran-sferase system that imports glucose seems to be by way ofthe mannose(a sugar)import system and the HPR substance shared by the glucose and the mannose import system.The reaction of the cell to the sugar alpha-methyl-glucoside is similar to that ofdeoxyglucose,see Stock et al. (1982).The alpha-methyl glucoside is imported directly using the glucose import system,which is a slightly more direct mimicking ofglucose.In this paper,the model is restricted to the reaction ofthe cell to deoxyglucose. The statement lactose–internally–pre-sent denotes that lactose is present inside the bacterium and the statement glucose–intern-ally–present denotes that glucose is present inside the bacterium.Since the glucose import pathway,the phosphotransferase system,deposi-ts the glucose inside the cell as glucose-6-phos-phate,the concentration ofglucose-6-phosphate is taken as indicating that glucose is present inside the cell.Also,deoxyglucose is phos-phorylated on import,resulting in deoxyglucose-6-phosphate inside the cell,denoted as deoxyglucose–internally-present.These statements denote internal world state state-ments.Together with the external world state statements,these denote the world state state-ments. The necessary situations have already been informally explained,but more rigorous criteria can be applied,making the notions well-de"ned, see Table1.The logical notions are taken to hold when the internal chemical state has crossed a particular threshold value,so that glucose–externally–present holds when glucose out-side the cell has a concentration of0.1mmol l\ or above.Similar chemical criteria are given for the other notions. In Table1,the logical notions are listed to-gether with the chemical criterion,stated using chemical notions.This de"nes the representation and interpretation relations between the logical and chemical notions,see Fig.3.When the chem-ical criterion holds,the logical notion is true, and conversely.To explain the notions an infor-mal reading is added as well. INTENTIONS INTO CELL BIOCHEMISTRY113 5.2.INTENTIONAL NOTIONS AND CHEMICAL REPRESENTATIONS The following intentional notions are used. 5.2.1.Belief Statements The logical statement (glucose–exter-nally–present,pos)denotes that the bac-terium has the(positive)belief that in the external world glucose is present,i.e.the belief that the world fact glucose–externally–present holds,see Table 2.Moreover, (glucose–externally–present,neg)denotes the belief that in the external world glucose is not present, i.e.the belief that the world fact glucose–externally–present is not true in the world.Similarly, (lactose–externally–present,pos)and (lactose–externally–present,neg)denote the beliefs about the presence oflactose. The positive belief in glucose (glucose–externally–present,pos)is the interpreta-tion ofCRPcAMP having a very low concentra-tion,below a threshold of0.01mmol l\ ,see Table 2.The positive belief in lactose (lactose–externally–present,pos)is the interpretation ofthe lactose concentration being elevated,above a threshold of 0.1mmol l\ .The beliefs in the negation ofthe world facts are interpretations of the reverse of these situations. The cell does not have any indication ofthe presence ofonly glucose outside,without con-fusing glucose and deoxyglucose.The cell cannot distinguish glucose from deoxyglucose,and the belief that the glucose is present holds for the presence ofeither glucose or deoxyglucose.Ra-tionally,the import ofglucose would only be expected when glucose is present,but because the cell cannot distinguish glucose from deoxyglu-cose,it will import when either is present.When neither the belief that a world fact holds nor the belief that it does not hold is true,this means the bacterium has no knowledge about the world fact.Notice that the belief that a fact both holds and not holds is expressible,i.e.a belief may contradict other beliefs.This is not problematic, for the formalization at least,since a belief does not always describe the way the world actually is. The bacterium may encounter severe di$culties though ifit were to hold such contradictory be-liefs,as it may readily take the wrong actions. 5.2.2.Desire Statements The logical statement (grow)denotes that the bacterium has the desire to grow.The more speci"c statement (food–import)states that the bacterium would like to import nutritious substances.The statement (glucose–import) denotes the more speci"c desire for the bacterium to import glucose.Similarly, (lactose–import)denotes the desire to import lactose. The desire (grow)is linked to the chemical criterion that the DNA is present in the cell.The desire for food import is the interpretation of the part ofthe DNA that concerns nutrition import-ing,and the glucose and lactose import desires are the interpretation ofthe glucose and lactose operons. 5.2.3.Intention Statements The statement n(prepare–glucose–import) denotes that the bacterium has the intention to prepare the import ofglucose.Similarly, n(prepare–lactose–import),n(perform–glucose–import)and n(perform–lactose–import)denote their corresponding intentions. The material counterpart of n(prepare–glucose–import)is the existence ofmRNA transcribed from the glucose operon.The state-ment n(prepare–lactose–import)is the inter-pretation ofthe mRNA encoding f or lactose import enzymes.The n(perform–glucose–import)is the interpretation ofthe glucose import enzymes and n(perform–lactose–import)is the interpretation ofthe lactose import enzymes. 5.2.4.Reason Statements Statements for reasons to choose an intention are speci"c belief statements.A reason can be represented by a complex statement using several beliefs,connected with , and R.No reason for intending to prepare the import ofglucose is needed;it is denoted as true.The reason for intending to prepare to import lactose is that the cell believes that both lactose is present outside and no glucose is present outside the cell,denoted 114 C.M.JONKER E1A?. as (lactose–externally–present,pos) (glucose–externally–present,neg). The reason for intending to perform lactose im-port is the belief in the presence oflactose, (lactose–externally–present,pos)and the reason for intending to perform glucose import is the belief in the presence ofglucose outside,denoted as (glucose–externally–present,pos). 5.2.5.Opportunity Statements Opportunities for the execution of an action are world states that will enable the action to suc-ceed.The cell needs to believe in the opportunity being present to conclude to actually perform the action.This belief can be a complex belief.Per-forming an action when there is no opportunity for it will not engender the e!ect aimed for,per-haps no e!ect at all.The opportunity for the import ofglucose activity is true,as no oppor-tunity is needed.The opportunity for the import of lactose is that no glucose is available,thus the belief (glucose–externally–present,neg) is needed to conclude and to actually perform the lactose import action. 5.2. 6.Action Statements The statement (glucose–import)denotes that the bacterium is performing the action of importing glucose.Similarly, (lactose–import)denotes that the bacterium is perform-ing the action ofimporting lactose.And some–nutrition–import denotes that the bac-terium is performing at least one nutrition import action.They are the interpretations ofthe glu-cose,https://www.wendangku.net/doc/cc7614327.html,ctose,import reactions.Thus,the intentional notions of action have not the inter-pretation ofa material substance,but ofa pro-cess.The actions refer to metabolic processes. 5.3.LOGICAL RELATIONS The assumptions discussed in Section2lead to the following relations(equivalences)assumed between the representations discussed in the pre-vious section. glucose–externally–present R lactose–externally–present some–nutrition–outside glucose–internally–present R lactose–internally–present some–nutrition–inside glucose–externally–present R deoxyglucose–externally–present (glucose–externally–present,pos) lactose–externally–present (lactose–externally–present,pos) glucose–externally–present deoxyglucose–externally–present (glucose–externally–present,neg) lactose–externally–present (lactose–externally–present,neg) In the above logical relationships,the observa-tion by the bacterium is de"ned.Thus,the history ofthe agent is used to conclude beliefs(see Fig.1 in Section2),here the very recent history when perception has taken place.The belief that glu-cose is present outside is derived when glucose is present outside or deoxyglucose is present out-side;ifthis does not hold,the belief does not hold either.The presence oflactose outside leads to the conclusion ofthe belief that lactose is present outside.When both glucose is absent and deoxyglucose is absent,the belief that glucose is not present can be derived.Also,from the belief that glucose is not present it can be derived that glucose is absent as well as that deoxyglucose is absent.When no lactose is present outside the belief that no lactose is present outside can be derived,and conversely.Also,when glucose or lactose is present outside,it can be derived that there is some nutrition outside. (grow) (grow) (food–import) (food–import) (lactose–import) (glucose–import) (lactose–import) 1.1 n(prepare–lactose–import) (glucose–import) 1.2 n(prepare–glucose–import) 1.1"def (lactose–externally–present,pos) (lactose–externally–present,neg). 1.2"def true. The statements are beliefs for the reasons. The reasons are beliefs about the external world. Here,the desires ofthe cell can be used f or derivation.The desire to grow is always present, INTENTIONS INTO CELL BIOCHEMISTRY115 and can always be derived.The desire to grow implies the desire to import food and the desire to import food implies the desire to grow,since that is the part ofthe cell behaviour that has been modelled.The desire to import food implies the desire to import lactose and the desire to import glucose,and conversely.The desires in the"rst three lines are from the history of the agent(see Fig.1in Section2).A desire to import lactose and su$cient reason gives rise to the intention to prepare the import oflactose.Conversely,the intention to prepare the import oflactose leads to the desire to import lactose and the reason to do so(it is assumed that this is the only way to derive the intention to prepare the import oflactose). The desire to import glucose with su$cient rea-son also gives rise to the intention to prepare to import it and vice versa.In the last two relation-ships a desire is combined with a reason to imply an intention(see Fig.1in Section2again),and conversely. n(prepare–lactose–import) 2.1 n(perform–lactose–import) n(prepare–glucose–import) 2.2 n(perform–glucose–import) n(perform–lactose–import) o1 (lactose–import) n(perform–glucose–import) o2 (glucose–import) 2.1"def (lactose–externally–present,pos). 2.2"def (glucose–externally–present,pos). o1"def (glucose–externally–present,neg). o2"def true. The statements o are the beliefs in opportuni-ties. In the"rst two lines,the intentions to prepare the import ofa substance combined with a reason to do so lead to intentions to perform the import ofthe substance,and conversely.The intention to perform the import combined with beliefs in the opportunity to do so gives rise to the actual action to import the substance(see Fig.1in Section2).It is assumed that these relationships are the only options to conclude the action to import a sub-stance. (lactose–import)P (lactose–externally–present P lactose–internally–present) (glucose–import)P( (glucose–externally–present P glucose–internally–present) (deoxyglucose–externally–present P deoxyglucose–internally–present)) (glucose–import)R (lactose–import) P some–nutrition–import The e!ects of actions can be derived using these lines.The lactose import action will cause the presence oflactose outside to imply the pre-sence oflactose inside.The glucose import action means that glucose outside implies that glucose will be present inside the cell and that deoxyglu-cose outside implies that deoxyglucose will be present inside the cell.For our logical descrip-tion,it can be assumed that these are the only possibilities to achieve these e!ects.Ifthe glucose or the lactose import action is taken,it can be said that some nutrition import is happening. In the logical description as given above,the cell can be fooled into falsely believing that glu-cose is present outside by presenting it with deoxyglucose.The cell will also import deoxyglu-cose with its glucose import mechanism.After prolonged exposure to deoxyglucose,the cell will eventually die.This e!ect has not been modelled above,as the cell ceases to function when it dies. The logical description represents the behaviour ofthe cell when it is alive. This concludes the presentation ofthe logical description.The representations,from Tables1 and2,together with propositional predicate logic form the language to express these relations.The logical notions used in the relations have mater-ial representations,linking the logical description to the chemical description.The relations also allow for the derivation of consequences given a growth medium,making an implementation possible. 6.Imple me ntation ofthe Logical De scription In Arti"cial Intelligence in the past decades, techniques and tools have been developed to automate reasoning processes.As an example, the logic programming language,Prolog,has been developed(Bratko,2001;Clocksin& Mellish,1987)that can be used for such 116 C.M.JONKER E1A?. T ABLE 3 A set of Prolog rules to derive intentions ,actions and e +ects for a growth medium 01 belief(glucose –externally –present,pos):-world –state(glucose –externally –present,pos).02 belief(glucose –externally –present,pos):-world –state(deoxyglucose –externally –present,pos).03 belief(lactose –externally –present,pos):-world –state(lactose –externally –present,pos).04belief(glucose –externally –present,neg):-world –state(glucose –externally –present,neg). world –state(deoxyglucose –externally –present,neg). 05belief(lactose –externally –present,neg):-world –state(lactose –externally –present,neg).06 desire(grow)07 desire(food –import):-desire(grow).08 desire(lactose –import):-desire(food –import).08desire(glucose –import):-desire(food –import). 10intention(prepare –lactose –import):-desire(lactose –import), belief(lactose –externally –present,pos),belief(glucose –externally –present,neg).11intention(prepare –glucose –import):-desire(glucose –import). 12intention(perform –lactose –import):-intention(prepare –lactose –import), belief(lactose –externally –present,pos). 13intention(perform –glucose –import):-intention(prepare –glucose –import), belief(glucose –externally –present,pos). 14performs(lactose –import):-intention(perform –lactose –import), belief(glucose –externally –present,neg). 15performs(glucose –import):-intention(perform –glucose –import). 16world –state(lactose –internally –present,pos):-performs(lactose –import), world –state(lactose –externally –present,pos). 17world –state(glucose –internally –present,pos):-performs(glucose –import), world –state(glucose –externally –present,pos). 18world –state(deoxyglucose –internally –present,pos):-performs(glucose –import), world –state(deoxyglucose –externally –present,pos). automated derivation.A computer program has been implemented in this logic programming lan- guage Prolog for the logical formalization.This program is able,for example,to automatically derive the actions and steady state predicted by the logical description given any growth condi- tion.The program has been used to reason from a growth medium towards subsequently deter- mining the beliefs ,desires ,intentions ,actions and their e !ects.In Section 6.1,the Prolog program is presented,followed by an example ofautomated derivation in Section 6.2. An overview ofthe derivation results,f or the di !erent speci "c growth conditions,is given in Section 6.3. 6.1.THE PROLOG PROGRAM In the Prolog code the operator :-is used.It signi "es an if }then,an implication,with the conclusion at the front and the conditions afterwards.Thus,the rule conclusion:-condition1,condition2will lead to the conclusion whenever both condition1and condition2have been derived.When no condi-tions are listed,the conclusion is always derived.The rules implementing the logical formaliz-ation ofSection 5.3are shown in Table 3.The rules in the program are grouped by the type ofintentional concept they are to conclude.A growth medium has to be given.Contrary to the notation used in Section 5.3,in the INTENTIONS INTO CELL BIOCHEMISTRY 117 implementation the predicate world–state is used to denote the growth conditions,for clarity. Furthermore,in the program is denoted as belief, as desire,n as intention and as performs. The"rst rules,line1}5,take a world state and conclude the corresponding belief.Lines1}5 show observation ofthe environment,which is not hindered in any way.Ifobservations were to be hindered,then for each belief the rule can be given that concludes the belief only ifit has been successfully observed.Glucose can be observed correctly,but also it can falsely be observed by concluding the belief that glucose is present, based on the fact that deoxyglucose is present.As can be seen in lines1and2,the belief that glucose is present can be concluded when glucose is pre-sent outside(as in line1)or when deoxyglucose is present outside(as in line2).Line4concludes the belief that no glucose is present,because deoxy-glucose and glucose are both absent outside. Lines3and5conclude the beliefs that lactose is present or absent,depending on the situation outside the cell. The growth desire is stated as a fact that is always derived,since it is always true,in line6.It implies a food importing desire in line7,which in turn implies lactose and glucose uptake desires in lines8and9,respectively. No reasons are needed to derive the intention to prepare to import glucose from the desire in line11.For deriving the intention to prepare to import lactose the reasons that lactose is believed present and glucose is believed absent are needed, see line10.The intentions to perform the import ofglucose and lactose are only derived when the preparation for importing is intended and the glucose or lactose is believed present in lines12 and13. To derive the action ofimporting lactose,the intention to perform it must be there and an opportunity to do so,here the fact that no glucose is present outside,see line14.The action ofim-porting glucose is derived when the intention to perform it exists and no deoxyglucose is present outside,see line15. The e!ects to the world state are derived as well in lines16,https://www.wendangku.net/doc/cc7614327.html,ctose becomes present inside when the import is performed and lactose is present outside.Glucose becomes pre-sent inside the cell when the import is performed ofglucose together with the f act that glucose is present outside.Deoxyglucose becomes present inside the cell when the glucose import action is attempted and deoxyglucose is present out-side.Ifboth glucose and deoxyglucose are pres-ent,the glucose import action will import some ofboth. 6.2.EXAMPLE OF AN AUTOMATED DERIVATION USING THE PROLOG PROGRAM Thus far,a formalization and implementation for steady states has been discussed.In this sec-tion,an example derivation using the Prolog rules given in Table3,and an overview ofthe results is discussed after that in Section6.3. In this example the growth condition is the fol-lowing. Facts on the external world state: glucose–externally–present, lactose–externally–present, deoxyglucose–externally–present. This is denoted as input for the Prolog program as follows: world–state(glucose–externally–present, pos). world–state(lactose–externally–present, neg). world–state(deoxyglucose–externally–present,neg). First,it will be shown how the actions to per-form are derived,these are our goals for the reasoning.Along the way all interesting parts of the program will be visited in this manner. As Prolog reasons in a goal-directed manner, the"rst question is whether the statement performs(lactose–import)can be derived, see Fig.6.Note that the numbers given in the picture refer to the program lines in Table3. A large X means that the goal is considered underivable,a'means that a goal can be derived successfully.Line14in Table3is considered,and the conditions are examined. Whatever the result for intention(perform–lactose–import),the condition belief (glucose–externally–present,neg)is not ful"lled,since that would have to be concluded 118 C.M.JONKER E1A?. F IG.6.The derivation depicted as an AND/OR graph with line numbers(an arc means and). by line4,requiring world–state(glucose–externally–present,neg),and world–s t a t e(d e o x y g l u c o s e–e x t e r n a l l y–present,neg),ofwhich only world–state(deoxyglucose–externally–present ,neg)can be derived.Thus,the conclusion is not derived. Next,a look is taken at the other goal,namely performs(glucose–import)see Fig.6.This leads to examining line15ofTable3.The state-ment intention(perform–glucose–import) must be derived.For the intention a look is taken at line13,and it will turn out that intention (prepare–glucose–import)can be derived as well as belief(glucose–externally–present,pos).The belief can be derived using line1.For the statement intention(prepare–glucose–import)take a look at line11. To derive intention(prepare–glucose–import)the statement desire(glucose–import)should be derived. The statement desire(glucose–import) can be derived using line9.It needs that desire(food–import)is derived,which can be derived via line7,needing desire(grow)in turn.The statement desire(grow)is stated as a fact,not needing any conditions to be derived, using line6. At this point,enough lines ofcode have been examined and the conclusion can be drawn that the cell performs glucose import.The Prolog interpreter performed these derivations auto-matically for each intentional notion,as well as the importing e!ects,to make Table6in the next section. 7.Extended Model and Results from the Implementation for Di4erent Growth Conditions In this section,a more complex example is built,as an extension ofthe smaller example.This increased complexity results in predictions made by experts for the e!ects ofa certain growth medium being tedious and often wrong.First,the notions used in the more complex example are presented.Then,the intentional notions used in this extended example are discussed.Finally,the results obtained from a set of computer calcu-lations are explained,showing that they are correct and proving that the model is ofvalue for making predictions. 7.1.GROWTH MEDIUM DESCRIPTION This example builds upon the smaller example, describing the cell regulation in more detail and complexity.The situations described and pre-dicted by this model are hard to derive by means other than by a computer.Biologists are often wrong when trying to assess these situations,as the complexity is getting larger.First,the set of external world state statements are described, then the internal world state statements.Then the intentional notions are described,and the logical INTENTIONS INTO CELL BIOCHEMISTRY119 relationships are given.These logical relation-ships then enable the use ofa computer as a calculator,in order to predict states. The external world state statements describe the situation in the external world,the growth conditions.The presence or absence ofnutrition sources,inhibitors and growth resources can be stated. The statements glucose–low–externally–present,glucose–medium–externally–pre-sent and glucose–high–externally–pre-sent denote the amount ofglucose present outside the cell.The three categories are used in order to distinguish the behaviour ofthe cell in the di!erent cases.The statement lactose–externally–present denotes the presence of lactose. The presence ofthe inhibitors2-deoxyglucose and6-deoxyglucose can be denoted using the statements2-deoxyglucose–externally–present and6-deoxyglucose–externally–present.The e!ect ofthese inhibitors is the same as in the smaller example. The presence ofoxygen outside the cell can be denoted using the statement oxygen–exter-nally–present.The presence ofthe carbon providing buildingblocks,ofthe sources f or ni-trogen,phosphor and sulphur are denoted using the statements buildingblocks–externally–present,nitrogen–externally–present, phosphor–externally–present and sulphur–externally–present. The internal state statements ofthe cell con-cern the physical situation inside the cell.The nutrition sources are denoted by the statements glucose–internally–present and lactose–internally–present.The discrimination be-tween several levels ofglucose presence is not needed when glucose has been imported for the description ofthe regulation behaviour. The oxygen present inside is denoted by the statement oxygen–internally–present. The sources for carbons in the buildingblocks, the sources for nitrogen,phosphor and sulphur are denoted using the statements building-blocks–internally–present,nitrogen–in-ternally–present,phosphor–internally–present and sulphur–internally–present. The energy in the cell is described using the statements energy–low,energy–medium and energy–high.These statements describe the ATP concentration in the cell. In Table4,the logical notions are listed to- gether with the chemical criterion,stated using chemical notions for the world state statements. This de"nes the representation and interpreta- tion relations for the world state statements and the chemical conditions inside and outside the cell.An informal reading is added in the table for explanation. All the intentional notions used are presented here,sorted by intention. 7.1.1.Belief Statements The logical statement (glucose–exter-nally–present,pos)holds when the bac-terium believes that glucose is present outside, which is an interpretation ofthe concentration of the substance CRPcAMP.When the CRPcAMP concentration is at most0.01mmol l\ the belief holds,as glucose is detected.When the CRPcAMP contraction is above0.01mmol l\ , then the belief will not hold.The logical state- ment (glucose–externally–present,neg) is another interpretation ofthe concentration of CRPcAMP,which holds when no glucose is de- tected.Similarly,there are beliefs for the lactose, oxygen,buildingblocks,nitrogen,phosphor and sulphur presence outside,see Table5.These be- liefs also are interpretations ofsubstances in the cell,see Table5. 7.1.2.Desire Statements The logical statement (grow)denotes that the bacterium has the desire to grow.This is the interpretation ofthe f act that the cell has DNA. More speci"c parts ofthe DNA code f or more speci"c desires.When the nutrition import ope- rons are present in the DNA, (food–import) holds.When the glucose import operon is present in the DNA, (glucose–import)holds.When the lactose import operon is present in the DNA, (lactose–import)holds. When the energy production operons,the catabolism operons,are present in the DNA, (energy)holds.When the respiration operon and fermentation operon are present, (respiration)and (fermentation)hold. When the anabolism operons are present in the 120 C.M.JONKER E1A?. T ABLE4 ?ogical notions and their chemical criteria ?ogical notion Chemical criterion Informal reading glucose–low–externally–present Glucose concentration outside the cell below0.01mmol l\ In the external world there is almost no glucose present. glucose–medium–externally–present Glucose concentration outside the cell at least0.01mmol l\ but below 0.1mmol l\ In the external world some glucose is present. glucose–high–externally–present Glucose concentration outside the cell at least0.1mmol l\ In the external world a lot ofglucose is present. lactose–externally–present Lactose concentration outside the cell at least0.1mmol l\ In the external world lactose is present. 2-deoxyglucose–externally–present2-Deoxyglucose concentration out- side the cell at least0.1mmol l\ In the external world2-deoxyglucose is present. 6-deoxyglucose–externally–present6-Deoxyglucose concentration out- side the cell at least0.1mmol l\ In the external world6-deoxyglucose is present. oxygen–externally–present Oxygen concentration outside the cell at least0.1mmol l\ In the external world oxygen is present. buildingblocks–externally–present The building blocks'concentration outside the cell is at least0.1mmol l\ Building blocks are present outside the cell. nitrogen–externally–present Nitrogen concentration outside the cell is at least0.1mmol l\ Nitrogen is present outside the cell. phosphor–externally–present Phosphor concentration outside the cell is at least0.1mmol l\ Phosphor is present outside the cell. sulphur–externally–present Sulphur concentration outside the cell is at least0.1mmol l\ Sulphur is present outside the cell. glucose–internally–present Glucose-6-phosphate concentration inside the cell at least0.1mmol l\ Inside the cell glucose is present. lactose–internally–present Lactose concentration inside the cell at least0.1mmol l\ Inside the cell lactose is present. 2-deoxyglucose–internally–present2-Deoxyglucose-6-phosphate concen- tration inside the cell at least 0.1mmoll\ Inside the cell2-deoxyglucose is present. oxygen–internally–present Oxygen concentration inside the cell at least0.1mmol l\ Inside the cell oxygen is present. buildingblocks–internally–present The building blocks'concentration inside the cell is at least0.1mmol l\ Building blocks are present inside the cell. nitrogen–internally–present Nitrogen concentration inside the cell is at least0.1mmol l\ Nitrogen is present inside the cell. phosphor–internally–present Phosphor concentration inside the cell is at least0.1mmol l\ Phosphor is present inside the cell. sulphur–internally–present Sulphur concentration inside the cell is at least0.1mmol l\ Sulphur is present inside the cell. energy–low Inside the cell the ATP concentration is below0.1mmol l\ Little energy is available inside the cell. energy–medium Inside the cell the ATP concentration is at least0.1mmol l\ but below 0.15mmol l\ Some energy is available inside the cell. energy–high Inside the cell the ATP concentration is at least0.15mmol l\ Much energy is available inside the cell. INTENTIONS INTO CELL BIOCHEMISTRY121 T ABLE5 A concise listing of the concepts and their chemical criteria and logical notations BeliefChemical criterion Logical notation Glucose externally present belief CRPcAMP not internally present, concentration at most0.01mmol l\ (glucose–externally–present,pos) Glucose not externally present belief CRPcAMP internally present con- centration above0.01mmol l\ (glucose–externally–present,neg) Lactose externally present belief Lactose internally present concen- tration above0.1mmol l\ (lactose–externally–present,pos) Lactose not externally present belief Lactose internally absent concen- tration at most0.1mmol l\ (lactose–externally–present,neg) Oxygen externally present belief Oxygen internally present concen- tration above0.1mmol l\ (oxygen–externally–present,pos) Oxygen not externally present belief Oxygen internally absent concen- tration at most0.1mmol l\ (oxygen–externally–present,neg) Buildingblocks externally present belief Buildingblocks internally present concentration above0.1mmol l\ (buildingblocks–externally–present, pos) Buildingblocks not externally pres-ent belief Buildingblocks internally absent concentration at most0.1mmol l\ (buildingblocks–externally–present, neg) Nitrogen externally present belief Nitrogen internally present concen- tration above0.1mmol l\ (nitrogen–externally–present,pos) Nitrogen not externally present belief Nitrogen internally absent concen- tration at most0.1mmol l\ (nitrogen–externally–present,neg) Phosphor externally present belief Phosphor internally present con- centration above0.1mmol l\ (phosphor–externally–present,pos) Phosphor not externally present belief Phosphor internally absent concen- tration at most0.1mmol l\ (phosphor–externally–present,neg) Sulphur externally present belief Sulphur internally present concen- tration above0.1mmol l\ (sulphur–externally–present,pos) Sulphur not externally present belief Sulphur internally absent concen- tration at most0.1mmol l\ (sulphur–externally–present,neg) Desire Growth desire DNA is present (grow) Nutrition import desire Lactose and glucose import operons present in DNA (food–import) Glucose import desire Glucose import operon internally present in DNA (glucose–import) Lactose import desire Lactose import operon internally present in DNA (lactose–import) Energy desire Respiration and fermentation operon internally present in DNA (energy) Respiration desire Respiration operon internally present in DNA (respiration) Fermentation desire Fermentation operon internally present in DNA (fermentation) 122 C.M.JONKER E1A?. Anabolism desire Anabolism operons internally present in DNA (anabolism) Resources import desire Resources import operon internally present in DNA (resources) Buildingblocks import desire Buildingblocks import operon internally present in DNA (buildingblocks–import) Nitrogen import desire Nitrogen import operon internally present in DNA (nitrogen–import) Phosphor import desire Phosphor import operon internally present in DNA (phosphor–import) Sulphur import desire Sulphur import operon internally present in DNA (sulphur–import) Reason for creation of Prepare glucose import intention None true Prepare lactose import intention Belief that no glucose is present outside,belief that lactose is present outside (glucose–externally–present,neg) (lactose–externally–present,pos) Prepare anabolism intention Belief that buildingblocks are pres- ent outside,belief that nitrogen is present outside,belief that phos- phor is present outside,belief that sulphur is present outside (buildingblocks–externally–present, pos) (nitrogen–externally–present,pos) (phosphor–externally–present,pos) (sulphur–externally–present,pos) Prepare respiration intention Belief that oxygen is present outside (oxygen–externally–present,pos) Prepare fermentation intention Belief that no oxygen is present outside (oxygen–externally–present,neg) Prepare buildingblocks import intention Belief that buildingblocks are present outside (buildingblocks–externally–present, pos) Prepare nitrogen import intention Belief that nitrogen is present outside, (nitrogen–externally–present,pos) Prepare phosphor import intention Belief that phosphor is present outside, (phosphor–externally–present,pos) Prepare sulphur import intention Belief that sulphur is present outside (sulphur–externally–present,pos) Perform glucose import intention Belief that glucose is present outside (glucose–externally–present,pos) Perform lactose import intention Belief that lactose is present outside (lactose–externally–present,pos) Perform anabolism intention None true Perform respiration intention None true Perform fermentation intention None true Perform buildingblocks import intention None true Perform nitrogen import intention None true Perform phosphor import intention None true Perform sulphur import intention None true Intention Prepare glucose import intention Glucose import mRNA internally present,concentration above 0.1mmol l\ n(prepare–glucose–import) INTENTIONS INTO CELL BIOCHEMISTRY123 T ABLE5 (Continued) BeliefChemical criterion Logical notation Prepare lactose import intention Lactose import mRNA internally present,concentration above 0.1mmol l\ n(prepare–lactose–import) Prepare anabolism intention Anabolism mRNA internally present,concentration above 0.1mmol l\ n(prepare–anabolism) Prepare respiration intention Respiration mRNA internally present,concentration above 0.1mmol l\ n(prepare–respiration) Prepare fermentation intention Fermentation mRNA internally present,concentration above 0.1mmol l\ n(prepare–fermentation) Prepare buildingblocks import intention Buildingblocks import mRNA internally present,concentration above0.1mmol l\ n(prepare–buildingblocks–import) Prepare nitrogen import intention Nitrogen import mRNA internally present,concentration above 0.1mmol l\ n(prepare–nitrogen–import) Prepare phosphor import intention Phosphor import mRNA internally present,concentration above 0.1mmol l\ n(prepare–phosphor–import) Prepare sulphur import intention Sulphur import mRNA internally present,concentration above 0.1mmol l\ n(prepare–sulphur–import) Perform glucose import intention Glucose import enzymes internally present,concentration above 0.1mmol l\ n(perform–glucose–import) Perform lactose import intention Lactose import enzymes internally present,concentration above 0.1mmol l\ n(perform–lactose–import) Perform anabolism intention Anabolism enzymes internally present,concentration above 0.1mmol l\ n(perform–anabolism) Perform respiration intention Respiration enzymes internally present,concentration above 0.1mmol l\ n(perform–respiration) Perform fermentation intention Fermentation enzymes internally present,concentration above 0.1mmol l\ n(perform–fermentation) Perform buildingblocks import intention Buildingblocks import enzymes internally present,concentration above0.1mmol l\ n(perform–buildingblocks–import) Perform nitrogen import intention Nitrogen import enzymes inter- nally present,concentration above 0.1mmol l\ n(perform–nitrogen–import) 124 C.M.JONKER E1A?.