 So let us continue this morning with, again, my honor and privilege to receive my, we've been knowing each other for many years now. We're not that young anymore. Rilin Chen from Zhang Chen University that will give us a talk called scientific exploration of causation and biomedical research. The case of gene targeting on mouse embryonic stem cells. Ladies and gentlemen, it's my honor to take part in this workshop. Many thanks for Alessandro and Charlie's organization. My talk is scientific exploration of causation in biomedical research. The case of gene targeting on mouse embryonic stem cells. I have a hard feeling my friend will help write down your question in the comments. Maybe I answer you by typing because my pronunciation is not smooth. This paper, arms to explore scientific exploration of causation in biomedical research. By scientific exploration I mean search for new information, data or analogy beyond what is known about stem objective by plural mean. I use this concept in construction to scientific explanation because a scientific exploration does not answer a quite question. A scientific exploration answers a question of whether there is new information, data or analogy or not. A scientific exploration of causation, arms to discover new information, data or analogy about a particular coral relationship. It can also determine whether a supposed coral relationship between a breath and a monument is this or not. Hence, a scientific exploration of causation involves the establishment of criteria of causation, which by a medical scientist frequently appear to robot-conference, postulates. Thus, prior to a scientific exploration of causation, I offer a case study of gene targeting on mouse embryonic stem cells, in particular employing this technique to produce gene-collapsing out mice that express the symptoms of cystic fibrosis and do establish a mouse model for human disease of cystic fibrosis. The main goal of a biomedical scientist concerned with causation is to search for coral relationship between some causes of factors and some effects of ingest. So, whether they can solve problems or eliminate undesirable effects, rather than explain those one manner. How do we find a coral relationship between a specific cause and a specific effect? Coming to what criteria of causation do let the lab or the lab claim that a specific factor is the real cause of an effect of ingest. I call the general action of medical scientists come back for their goal and practice scientific exploration of causation. A scientific exploration of causation is the compound action that integrates exploratory experiments that can grant knowledge and ideas about the production of research tools. The standard is operational procedures that are based on searches and more modeling than the relation of structure and the logical reason. The kind of action is best executed by using gene targeting a mouse ear cells to produce gene-collapsing out mice to investigate functions or dysfunctions of specific gene. Investigating a function or dysfunctions of a specific gene is following the coral relationship between the targeted gene and some unknown expression. For example, a proper function or dysfunctions of mice to explore such a kind of coral relationship, biomedical scientists have forced to select a doable gene in a mouse genome from such a public database or by means of gene sequence and the lab produced gene-collapsing out mice by means of homologous, the combination together. In producing gene-collapsing out mice and observing the expression of the produced mice, biomedical scientists may identify a coral relationship between a function future and the targeted genes. An actual case is the establishment of the mouse model was created by gene targeting in 1992. The established coral relationship is reliable and this investigation is the standard of exploration of concentration. Why can such a coral relationship be established reliable? The key is the method of gene targeting for carcass. A gene carcass refers to the technique according to which a targeted gene in an organism is deleted from or made inactive in a genome of an organism. The technique offers sufficient evidence for judgments of concentration which biomedical scientists frequently appear to co-host less concentration in order to justify. To feed with the requirements of the particular cases of the new development, biomedical scientists also revise co-host original postulates once again. I will discuss some revisions. Scientific exploration is the concept extended from letter of exploratory experimentation in the philosophy of science, the conception and the practice of exploratory experimentation has been discussed since Brian understand. Gelfall's aesthetic concept is progression to modeling and Matic suggests a general concept of exploration. As he said, the exploration is a key scientific practice and percolates all scientific fields and methods. Up below, I will provide general characterization of scientific exploration. I use scientific exploration to review the action of search for new information, data or knowledge beyond what is known about some adjectives by plural scientific means. The adjectives include fundamental, regularities, properties, relations, structures, mechanisms, concepts, instruments, methods, and there may be others. The scientific means involve experimentation, observation, measurement, modeling, hypothesis, and so on. Hence, scientific exploration involves discovery or findings. Scientific discoveries are the end of scientific explorations and scientific explorations in terms of the means action and our process of scientific discoveries. Section 3 of my paper discusses the gene targeting technique and then using the technique we can track a mouse model for human shape disease due to the limited time or ice cave detail. A scientific exploration of concepts is usually performed to answer the question whether or not there is a common relationship between a factor and a fundamental. Sometimes the factor is known and the fundamental is unknown or undetermined. Sometimes the factor is unknown or undetermined and the fundamental is unknown. Sometimes both are unknown or undetermined. In all situations, the supposed common relationship is unknown or undetermined. Scientific exploration is less used to determine whether or not a supposed common relationship really exists. Hence, a scientific exploration, concentration always involves establishment of a criterion of concentration. In many cases, a criterion of concentration is embedded in its broader masses or procedures used to discover the supposed common relationship. The key action of the gene collecting out mice out of CF by the technique of gene targeting disease is the research of animal experiment. This mouse experiment presupposes the following background assumptions. There is a gene equivalent to the human cystis fibrosis transport regulator's gene in mice, which is possible for the production of the marine CFTR protein. The marine CFTR regulates the transport of chloride ions into and out of cells in mice. Other in or in activity, the marine CFTR gene was result in the abnormal CFTR and the abnormal transport of chloride. The abnormalities further result in the disease of CF in mice, which would be displayed on the ship-tended Shimano to letter of the human CF. The four background assumptions imply two groups of common relationship. A1 and A2 imply the first group of common relationship between the CFTR gene and its multiple effects, including the products of the normal CFTR protein and the normal chloride transport. S3 and A4 imply the second group of common relationship between the other read CFTR gene and its multiple effects, including the abnormal CFTR protein products and the abnormal chloride transport. All these assumptions in turn stem from the background knowledge of the human CF disease. The ship-tended disease is an autosomal, the excessive disease, the partially pathological mechanism that I derived. The reaction of the genetic factors that is the CFTR gene, the location of the CFTR gene, the mutation that is now in the abnormal CFTR protein, that identify the reactions of the mutations. Under the closing background knowledge and assumptions, the scientist Oliver Smith and his team conducted the experiment of CFM mice by the technique of gene targeting. This experiment derived from the following three outcomes. The fourth outcome is the realization of the four background assumptions, offering A1 to A4 at the lowest determination of the function and dysfunction of the marine CFTR and their genetic factors. A marine gene that is equivalent to the human CFTR gene was discovered by gene sequencing in 1991. The second is the production of experimental animals as tools for the investigation of the pathological mechanism of CFM mice. The third is the construction of a mouse model for the human CF and the N. The logical inference from the mouse model of CF to the human CF are all outcomes and consequences of Santibis prognosis. One man wants to say that Smith's experiment of CFM mice conformed the hypothesis about the pathological mechanism of the human CF because the hypothesis guides the experiment and derives the assumption. By saying such, it may be too hasty. In fact, the assumptions will not derive from the hypothesis about the disease because the experimental objects are mice rather than humans. There are only assumptions about what might happen in mice given the background knowledge about the psychological similarity of mice to humans and about the human CF. People did not know whether or not the equivalent CFTR gene in mice would function as the human CFTR gene before Smith's experiment. People did not even know whether or not there is a marine gene equivalent to the human CFTR gene till the discovery by means of gene sequence in 1991. The nature of Smith's experiment is to create or realize the CFTCs in mice and investigate the coral pathway of the disease from the marine CFTR gene to the symptoms of the experimental mice. That is the chloride transport rather than to conform a given hypothesis of the human CF other than for Smith's research is the Santibis prognosis in the volume for sexes. Therefore, the experiment provides new data and knowledge about the marine CFTCs by realizing the background assumption that data and knowledge are part of or knowledge about CF helping part of outer conflict managing the CFTCs in human and mouse. In this sense, the experiment is exploratory. Two, in the experiment, the scientist in the one specific factor comes that has been targeted. That is the marine CFTR gene and observe what effects would be resulted by this intervention. If a soon effect occurs, then the assumption about the coral relationship between the factor and the effects is realized and a new coral relationship in mice is discovered. Hence, the arm of the experiment is not to provide a coral explanation for a given phenomenon. In fact, the effect was unknown before the experiment. It is not a given phenomenon. And whether we do this experiment, in this sense, it is exploratory. Third, the research of CF offers a coral inference and a coral pathway from the abnormal regulation of the chloride transport to the shipments of the human CFTCs. However, the inference is analogical because it infuses the mouse model to the human conditions. In other words, the hypothesis that the CFTR neglected the chloride transport in human bodies is not conformed because this research did not experiment on human subjects. And the hypothesis established by the mouse model was waiting to be tested by some experiment on human cells or subjects. In this sense, it is exploratory, but not only an exploratory experiment. It also messes modeling, analogically reasoning, and hadithic philosophy behind the experiment. Fourth, the research of CF mice establishes a standard method for other seminar investigations. To add to help develop a new therapy technique or a method in the future, a scientist who discovered the marine CFTR gene said that an animal model of a cystic nerve fibrosis would be useful in elucidating the role of CFTR in the normal and the tissue status and for testing new treatment modelities. All arms are exploratory, rather than exploratory. Finally, scientists judge that there is a common relationship between a targeted, modified gene and a specific future in experimenting. Mice are connected to hard criteria or conditions, can scientists do such a judgment? Biomedical scientists frequently visit the biological cohorts postulate of concentration. Discussion and revising cohorts are originally postulated to feed with new development. In biomedical sense, although one of the conditions of exploration and concentration. The original cause of postulate can be familiarized as follows. Okay one, the person that occurs in every case of the disease in question and under circumstances which can account for the physiological change and the clinical cause of the disease. Okay two, the person that occurs in no other disease as a fortuitous and non-testogenic person. After being fully isolated from the body and repeatedly grown in poor culture, the person can induce the disease anew. I propose a set of more curable cohorts of postulate for the demands of treasure of common relationship between genetic evaluations and the disease. In Femininity, the following five guidelines. Everyone, the final type of properties and the investigation should be associated with pathogenic members of a genus or pathogenic chain of a species. Specific in activation of the gene associated with the suspected. Revenants should lead to a memorable loss in pathogenicity or valueless. Reversion or elivic displacement of the mutati gene should lead to restoration of the pathogenicity. Let's see, guidelines revise the cause of original combinations that involve the method of gene manipulation. However, how further suggest the following to alternative? The gene associated with the supposed relationship should be isolated by molecular method. Specific in activation or deletion of the gene should lead to loss of the function in the car. The placement of the mutati gene for its elivic part in the shape or engine should lead to loss of function and loss of pathogenicity or valueless. Restoration of the pathogenicity should accompany the introduction of the weird type gene. The revision called postulation should show that the establishment standard procedure variation in the scientific exploration of the procession. In the case of cystic fibroces, however, scientists in equity will learn no more gene to make the disease observed in the experimented mice. As a human entity, the guidelines for such cases as CF and the other cases in which express function or features are not deceased by difference from molecular postulates of the procession. M1 loss of a function or future associated with the mutation of a gene should be discovered in some individuals of a kind of organism. Specific in active action or deletion of the normal gene should lead to loss of the function future in the experimented organism. For example, the cracker of mice. The specific function or difference between the individuals with the modified gene and the individual with the normal gene should be observed. I call the combination of M1 and M2 the intervention version of the procession lens. It offers a strong criterion of concentration. If one finds that a specific gene and a specific future satisfy the three conditions, then one won't believe that there is a coral relationship between the gene and the future. The criterion is embedded in the standards, procedures of the gene, characteristics of the basis of the gene targeting again. In the final part of this section, let me provide a preliminary analysis of the intervention version from a philosophical perspective of concentration. M1 implies the condition of correlation because it has layers and statistics. Correlation between a loss of a function and a mortality gene. M2 implies the condition of a kind of vector intervention because it states an intervention is meant to realize a kind of vector situation. M3 implies the condition of difference making by intervention because it states the difference between the intervening objects and the non-intervening objects. By the intervention, I have no conclusion. Thank you for listening. You are welcome to email me at teleconference. Okay, so for a long question, it's better that you e-mail the repeat of your name. For a short question, Jonathan is a volunteer to write a interview. My question has to be asked here, so we can see the dramatic effect. If I want to say great, argue against Michelle. Okay, so the question is, I wonder what Rayden thinks about his account in relation to Michelle's comment that he thinks the causal reason principle is to make neutral. Because Rayden's account, he presents this case, and then he tried to show that oh, this method, you know, then during this mind model, he showed that there is this criterion of causality embedded in the method, in this case, inside it. Are you okay, Jonathan? Because it seems a long question. Okay, so your question, do you agree or not with this domain neutral of causal reasoning principle? That's all I wrote on the screen. And then Rayden started answering. Good, good, good. Go for it. I guess while Rayden is typing, I could take another question and write it down. Maybe more efficiently. He's really thinking for the answer. In all cases, if you have questions, Rayden usually prefer that we send it to anybody. Okay. If there are no questions, this makes my job so... It's so much better. I'm already formulating an email that I want to send. So my question is, would you say that in this case I just have established causation in mice but not in humans? Second question. Okay, next question. Yes. Thank you. Yes, okay. Because I know it's not easy to translate. I've got some of you. Shaw, are you typing your email up question? Right now. I'm literally doing it right now. So maybe we should go that direction. So normally, could you put your email again, email address again? And of course in the program you can have access to the Union's email address to ask a question and receive a more elaborated answer. So now it's time for the coffee break. We will start again at 11.30. We should thank our speaker again.