Send your good work in the knowledge base is simple. Use the form below
Students, graduate students, young scientists who use the knowledge base in their studies and work will be very grateful to you.
Posted on http://www.allbest.ru/
Provisions of the cell theory of Schleiden-Schwann
1. Main provisions of modern cell theory
2. Purkinje School
3. The Müller school and the work of Schwann
4. Development of cell theory in the second half of the 19th century
1. The main provisions of modern cell theory
1. A cell is an elementary, functional unit of the structure of all living things. (Except for viruses that do not have a cellular structure)
2. A cell is a single system, it includes many elements that are naturally interconnected, representing a holistic formation, consisting of conjugated functional units - organelles.
3. Cells of all organisms are homologous.
4. The cell occurs only by dividing the mother cell.
5. A multicellular organism is a complex system of many cells united and integrated into systems of tissues and organs connected to each other.
6. Cells of multicellular organisms are totipotent.
7. A cell can only arise from a previous cell.
Additional Provisions of Cell Theory
In order to bring the cellular theory more fully into line with the data of modern cell biology, the list of its provisions is often supplemented and expanded. In many sources, these additional provisions differ, their set is quite arbitrary.
1. Cells of prokaryotes and eukaryotes are systems of different levels of complexity and are not completely homologous to each other.
2. The basis of cell division and reproduction of organisms is the copying of hereditary information - nucleic acid molecules ("each molecule from a molecule"). The provisions on genetic continuity apply not only to the cell as a whole, but also to some of its smaller components - to mitochondria, chloroplasts, genes and chromosomes. microscopic organ cell theory
3. A multicellular organism is a new system, a complex ensemble of many cells united and integrated in a system of tissues and organs connected to each other by means of chemical factors, humoral and nervous (molecular regulation).
4. Cells of multicellular are totipotent, that is, they have the genetic potencies of all cells of a given organism, are equivalent in genetic information, but differ from each other in different expression (work) of various genes, which leads to their morphological and functional diversity - to differentiation.
17th century
1665 -- English physicist R. Hooke in the work "Micrographia" describes the structure of cork, on thin sections of which he found correctly located voids. Hooke called these voids "pores, or cells." The presence of a similar structure was known to him in some other parts of plants.
1670s -- Italian physician and naturalist M. Malpighi and English naturalist N. Gru described different organs of plants "sacs, or vesicles" and showed a wide distribution of cellular structure in plants. Cells were depicted in their drawings by a Dutch microscopist A. Levenguk. He was the first to discover the world of unicellular organisms - he described bacteria and ciliates.
The researchers of the 17th century, who showed the prevalence of the "cellular structure" of plants, did not appreciate the significance of the discovery of the cell. They imagined cells as voids in a continuous mass of plant tissues. Grew considered cell walls as fibers, so he introduced the term "tissue", by analogy with textile fabric. Studies of the microscopic structure of animal organs were of a random nature and did not provide any knowledge about their cellular structure.
18th century
In the 18th century, the first attempts were made to compare the microstructure of plant and animal cells. K.F. wolf in his Theory of Generation (1759) he tries to compare the development of the microscopic structure of plants and animals. According to Wolf, the embryo, both in plants and animals, develops from a structureless substance in which movements create channels (vessels) and voids (cells). The facts cited by Wolff were erroneously interpreted by him and did not add new knowledge to what was known to the seventeenth-century microscopists. However, his theoretical ideas largely anticipated the ideas of the future cell theory.
19th century
In the first quarter of the 19th century, there was a significant deepening of ideas about the cellular structure of plants, which is associated with significant improvements in the design of the microscope (in particular, the creation of achromatic lenses).
Link and Moldenhower establish that plant cells have independent walls. It turns out that the cell is a kind of morphologically isolated structure. In 1831, Mol proves that even seemingly non-cellular plant structures, like aquifers, develop from cells.
In 1831 Robert Brown describes the nucleus and suggests that it is a permanent part of the plant cell.
2. Purkinje School
In 1801, Vigia introduced the concept of animal tissues, but he isolated tissues on the basis of anatomical preparation and did not use a microscope. The development of ideas about the microscopic structure of animal tissues is associated primarily with the research of Purkinje, who founded his school in Breslau. Purkinje and his students (G. Valentin should be especially noted) revealed in the first and most general form the microscopic structure of tissues and organs of mammals (including humans). Purkinje and Valentin compared individual plant cells with individual microscopic animal tissue structures, which Purkinje most often called "seeds" (for some animal structures, the term "cell" was used in his school). In 1837, Purkinje delivered a series of reports in Prague. In them, he reported on his observations on the structure of the gastric glands, nervous system etc. In the table attached to his report, clear images of some cells of animal tissues were given. However, Purkinje could not establish the homology of plant cells and animal cells. Purkinje compared plant cells and animal "seeds" in terms of analogy, not homology of these structures (understanding the terms "analogy" and "homology" in the modern sense).
3. Müller school and Schwann's work
The second school where the microscopic structure of animal tissues was studied was the laboratory of Johannes Müller in Berlin. Müller studied the microscopic structure of the dorsal string (chord); his student Henle published a study on the intestinal epithelium, in which he gave a description of its various types and their cellular structure.
Here the classic studies of Theodor Schwann were carried out, laying the foundation for the cell theory. Schwann's work was strongly influenced by the Purkinje school and Henle. Schwann found the correct principle for comparing plant cells and the elementary microscopic structures of animals. Schwann was able to establish homology and prove correspondence in the structure and growth of the elementary microscopic structures of plants and animals.
The significance of the nucleus in the Schwann cell was prompted by the research of Matthias Schleiden, who in 1838 published the work Materials on Phylogeny. Therefore, Schleiden is often called a co-author of the cell theory. The basic idea of the cell theory - the correspondence of plant cells and the elementary structures of animals - was alien to Schleiden. He formulated the theory of new cell formation from a structureless substance, according to which, first, the nucleolus condenses from the smallest granularity, and a nucleus is formed around it, which is the cell's former (cytoblast). However, this theory was based on incorrect facts. In 1838, Schwann published 3 preliminary reports, and in 1839 his classic work “Microscopic studies on the correspondence in the structure and growth of animals and plants” appeared, in the very title of which the main idea of the cell theory is expressed:
4. Development of cell theory in the second half of the 19th century
Since the 1840s, the study of the cell has been at the center of attention of all biology and has been rapidly developing, turning into an independent branch of science - cytology. For the further development of the cellular theory, its extension to protozoa, which were recognized as free-living cells, was essential (Siebold, 1848). At this time, the idea of the composition of the cell changes. The secondary importance of the cell membrane, which was previously recognized as the most essential part of the cell, is clarified, and the importance of the protoplasm (cytoplasm) and the nucleus of cells is brought to the fore, which found its expression in the definition of the cell given by M. Schulze in 1861:
A cell is a lump of protoplasm with a nucleus contained inside.
In 1861, Brucco puts forward a theory about the complex structure of the cell, which he defines as an "elementary organism", clarifies the theory of cell formation from a structureless substance (cytoblastema) further developed by Schleiden and Schwann. It was found that the method of formation of new cells is cell division, which was first studied by Mole on filamentous algae. In the refutation of the theory of cytoblastema on botanical material, the studies of Negeli and N. I. Zhele played an important role.
The division of tissue cells in animals was discovered in 1841 by Remarque. It turned out that the fragmentation of blastomeres is a series of successive divisions. The idea of the universal spread of cell division as a way to form new cells is fixed by R. Virchow in the form of an aphorism: Every cell from a cell.
In the development of cellular theory in the 19th century, sharp contradictions arise, reflecting the dual nature of the cellular theory that developed within the framework of a mechanistic conception of nature. Already in Schwann there is an attempt to consider the organism as a sum of cells. This trend is especially developed in Virchow's "Cellular Pathology" (1858). Virchow's work had an ambiguous impact on the development of cellular science:
20th century
From the second half of the 19th century, cell theory acquired an increasingly metaphysical character, reinforced by Ferworn's Cellular Physiology, who considered any physiological process occurring in the body as a simple sum of the physiological manifestations of individual cells. At the end of this line of development of the cellular theory, the mechanistic theory of the "cellular state" appeared, which was supported by Haeckel, among others. According to this theory, the body is compared with the state, and its cells - with citizens. Such a theory contradicted the principle of the integrity of the organism.
In the 1950s, a Soviet biologist O. B. Lepeshinskaya, based on the data of her research, put forward a "new cellular theory" as opposed to "Virchowianism". It was based on the idea that in ontogenesis cells can develop from some non-cellular living substance. A critical verification of the facts put by O. B. Lepeshinskaya and her adherents as the basis of the theory put forward by her did not confirm the data on the development of cell nuclei from a nuclear-free “living substance”.
Modern cell theory
Modern cellular theory proceeds from the fact that the cellular structure is the main form of existence of life, inherent in all living organisms, except viruses. The improvement of the cellular structure was the main direction of evolutionary development in both plants and animals, and the cellular structure was firmly held in most modern organisms.
Hosted on Allbest.ru
...Similar Documents
The unity of the principle of structure and development of the world of plants and the world of animals. The first stages of the formation and development of ideas about the cell. Basic provisions of the cell theory. The Müller school and the work of Schwann. The development of cell theory in the second half of the 19th century.
presentation, added 04/25/2013
History of development, subject of cytology. The main provisions of modern cell theory. Cell structure of living organisms. Life cycle cells. Comparison of the processes of mitosis and meiosis. Unity and diversity of cell types. The value of cell theory.
abstract, added 09/27/2009
Biological works of Schwann - German cytologist, histologist and physiologist, author of the cell theory. Development of principles of cell structure and development of living organisms. Microscopic studies on conformity in the structure and growth of animals and plants.
presentation, added 12/10/2014
Cytology as a science that studies the structure, functions and evolution of cells. The history of the study of the cell, the appearance of the first microscopes. Opening of a workshop of optical instruments in Russia. The history of the development of cell theory, its main provisions in modern biology.
presentation, added 03/23/2010
History of the study of the cell. Discovery and main provisions of the cell theory. The main provisions of the Schwann-Schleiden theory. Methods for studying cells. Prokaryotes and eukaryotes, their Comparative characteristics. Principle of compartmentation and cell surface.
presentation, added 09/10/2015
Positions of the cellular theory. Features of electron microscopy. A detailed description of the structure and function of cells, their connections and relationships in organs and tissues in multicellular organisms. Gravity hypothesis by Robert Hooke. The essence of the structure of the eukaryotic cell.
presentation, added 04/22/2015
Invention of the primitive microscope by Zachary Jansen. Study of sections of plant and animal tissues by Robert Hooke. The discovery by Karl Maksimovich Baer of the egg of mammals. Creation of the cell theory. The process of cell division. The role of the cell nucleus.
presentation, added 11/28/2013
presentation, added 11/25/2015
The chemical composition of cells, the functions of intracellular structures, the functions of cells in the body of animals and plants, the reproduction and development of cells, the adaptation of cells to environmental conditions. Provisions of the cell theory according to M. Schleiden and T. Schwann.
presentation, added 12/17/2013
Study of the main stages in the development of cell theory. Analysis of the chemical composition, structure, functions and evolution of cells. The history of the study of the cell, the discovery of the nucleus, the invention of the microscope. Characterization of cell forms of unicellular and multicellular organisms.
Chapter USE: 2.1. Modern cellular theory, its main provisions, role in the formation of the modern natural-science picture of the world. Development of knowledge about the cell. …
Cell- the basic structural and functional unit of all living organisms, the smallest living system. It is at the level of the cell that everything manifests itself. properties of life . It can exist as a separate organism (bacteria, unicellular plants, animals and fungi) or be part of the tissues of multicellular organisms.
Scientific theory is a generalization of scientific data about the object of study. This fully applies cell theory, created by two German researchers M. Schleiden and T. Schwann in 1839
Development of knowledge about the cell.
At the beginning of the XIX century. botanist M. Schleiden, summarizing the observations of his predecessors, came to the conclusion that all plants consist of cells. Zoologist T. Schwann discovered the similarity of plant and animal cells and in 1839 formulated cell theory.
The cellular theory was based on the work of many researchers who were looking for an elementary structural unit of the living. The creation and development of cell theory was facilitated by the emergence in the 16th century. and further development microscopy .
Here are the main events that became the forerunners of the creation of the cell theory:
- 1590 - the creation of the first microscope (Jansen brothers);
- 1665 Robert Hooke - the first description of the microscopic structure of the cork of the elderberry branch (in fact, these were cell walls, but Hooke introduced the name "cell");
- 1695 - the publication of Antony Leeuwenhoek about microbes and other microscopic organisms that he saw through a microscope;
- 1833 R. Brown described the nucleus of a plant cell;
- 1839 M. Schleiden and T. Schwann discovered the nucleolus.
Cell theory has evolved thanks to new discoveries. In 1880, Walter Flemming described chromosomes and the processes that take place in mitosis. Since 1903, genetics began to develop. Beginning in 1930, electron microscopy began to develop rapidly, which allowed scientists to study the finest structure of cellular structures. The 20th century was the heyday of biology and such sciences as cytology, genetics, embryology, biochemistry, and biophysics. Without the creation of the cell theory, this development would have been impossible.
The main provisions of modern cell theory:
1. All simple and complex organisms consist of cells capable of exchanging with environment substances, energy, biological information.
2. A cell is an elementary structural, functional and genetic unit of the living.
3. A cell is an elementary unit of reproduction and development of living things.
4. In multicellular organisms, cells are differentiated in structure and function. They are combined into tissues, organs and organ systems.
5. A cell is an elementary, open living system capable of self-regulation, self-renewal and reproduction.
Although imperfect in many respects, the cell theory has proved unity of living nature and gave a powerful impetus to further research and development of cytology as an independent biological science. At the current stage, our knowledge of the cell is extensive, but not always sufficient to understand the mechanisms of its functioning.
This is a synopsis on the topic. Choose next steps:
- Go to the next abstract:
- View abstract: (Grade 6)
- View abstract: (Grade 7)
Discovery and study cells made possible by the invention of the microscope and the improvement of microscopic examination methods.
In 1665, the Englishman Robert Hooke was the first to observe the division of cork oak bark tissue into cells (cells) using magnifying lenses. Although it turned out that he did not discover cells (in his own concept of the term), but only the outer shells of plant cells. Later, the world of unicellular organisms was discovered by A. Leeuwenhoek. He was the first to see animal cells (erythrocytes). Later, F. Fontana described animal cells, but these studies at that time did not lead to the concept of the universality of the cellular structure, because there were no clear ideas about what a cell is.
R. Hooke believed that cells are voids or pores between plant fibers. Later, M. Malpighi, N. Gru and F. Fontana, observing plant objects under a microscope, confirmed the data of R. Hooke, calling the cells “bubbles”. A. Levenguk made a significant contribution to the development of microscopic studies of plant and animal organisms. He published the data of his observations in the book "Secrets of Nature".
The illustrations for this book clearly demonstrate the cellular structures of plant and animal organisms. However, A. Leeuwenhoek did not represent the described morphological structures as cellular formations. His research was random, not systematized. G. Link, G. Travenarius and K. Rudolph at the beginning of the $19th century showed by their research that cells are not voids, but independent formations limited by walls. It was found that the cells have contents that I called protoplasm Purkinje. R. Brown described the nucleus as a permanent part of the cells.
T. Schwann analyzed the literature data on the cellular structure of plants and animals, comparing them with his own research and published the results in his work. In it, T. Schwann showed that cells are elementary living structural units of plant and animal organisms. They have a common structural plan and are formed in a single way. These theses became the basis of the cell theory.
Researchers for a long time were engaged in the accumulation of observations of the structure of unicellular and multicellular organisms, before formulating the provisions of CT. It was during this period that various optical research methods were more developed and improved.
Cells are divided into nuclear (eukaryotic) and non-nuclear (prokaryotic). Animals are built from eukaryotic cells. Only mammalian red blood cells (erythrocytes) do not have nuclei. They lose them in the course of their development.
The definition of a cell has changed depending on the knowledge of their structure and function.
Definition 1
According to modern data, cell - this is a structurally ordered system of biopolymers limited by the active shell, which form the nucleus and cytoplasm, participate in a single set of metabolic processes and ensure the maintenance and reproduction of the system as a whole.
cell theory is a generalized idea of the structure of the cell as a unit of life, of the reproduction of cells and their role in the formation of multicellular organisms.
Progress in the study of cells is associated with the development of microscopy in the $19th century. At that time, the idea of the structure of the cell changed: not the cell membrane was taken as the basis of the cell, but its contents - protoplasm. At the same time, the nucleus was discovered as a permanent element of the cell.
Information about the fine structure and development of tissues and cells made it possible to generalize. Such a generalization was made in 1839 by the German biologist T. Schwann in the form of the cell theory formulated by him. He argued that the cells of both animals and plants are fundamentally similar. The German pathologist R. Virchow developed and generalized these ideas. He put forward an important position, which was that cells arise only from cells by reproduction.
Basic provisions of cell theory
T. Schwann in 1839, in his work “Microscopic studies on the correspondence in the structure and growth of animals and plants”, he formulated the main provisions of the cell theory (later they were refined and supplemented more than once.
The cell theory contains the following provisions:
- cell - the basic elementary unit of the structure, development and functioning of all living organisms, the smallest unit of life;
- cells of all organisms are homologous (similar) (homologous) in their own way chemical structure, the main manifestations of life processes and metabolism;
- cells multiply by division - a new cell is formed as a result of the division of the original (mother) cell;
- in complex multicellular organisms, cells specialize in the functions they perform and form tissues; organs are built from tissues, closely interconnected by intercellular, humoral and nervous forms of regulation.
The intensive development of cytology in the $XIX$ and $XX$ centuries confirmed the main provisions of CT and enriched it with new data on the structure and functions of the cell. During this period, some incorrect theses of the cellular theory of T. Schwann were discarded, namely, that a single cell of a multicellular organism can function independently, that a multicellular organism is a simple collection of cells, and the development of a cell occurs from a non-cellular “blastema”.
In its modern form, cell theory includes the following main provisions:
- A cell is the smallest unit of a living thing, which has all the properties that meet the definition of "living". These are metabolism and energy, movement, growth, irritability, adaptation, variability, reproduction, aging and death.
- The cells of various organisms have a common structural plan, which is due to the similarity of the general functions aimed at maintaining the life of the cells themselves and their reproduction. The diversity of cell forms is the result of the specificity of their functions.
- Cells multiply as a result of the division of the original cell with the previous reproduction of its genetic material.
- Cells are parts of an integral organism, their development, structural features and functions depend on the whole organism, which is a consequence of the interaction in the functional systems of tissues, organs, apparatuses and organ systems.
Remark 1
The cell theory, which corresponds to the current level of knowledge in biology, in many respects radically differs from the ideas about the cell not only at the beginning of the 19th century, when T. Schwann formulated it for the first time, but even in the middle of the 20th century. In our time, this is a system of scientific views, which has taken the form of theories, laws and principles.
The main provisions of CT have retained their significance to this day, although for more than 150 years new information has been obtained on the structure, vital activity and development of cells.
Significance of cell theory
The significance of the cell theory in the development of science lies in the fact that thanks to it it became clear that the cell is the most important component of all organisms, their main "building" component. Since the development of each organism begins with a single cell (zygote), the cell is also the embryonic basis of multicellular organisms.
The creation of the cell theory has become one of the decisive proofs of the unity of all living nature, the most important event in biological science.
Cell theory contributed to the development of embryology, histology and physiology. It provided the basis for the materialistic concept of life, for explaining the evolutionary interconnection of organisms, for the concept of the essence of ontogeny.
The main provisions of CT are still relevant today, although over a period of more than 100 years, natural scientists have received new information about the structure, development and life of the cell.
The cell is the basis of all processes in the body: both biochemical and physiological, since it is at the cellular level that all these processes occur. Thanks to the cellular theory, it became possible to come to the conclusion about the similarity in the chemical composition of all cells and once again to be convinced of the unity of the entire organic world.
The cell theory is one of the most important biological generalizations, according to which all organisms have a cellular structure.
Remark 2
The cellular theory, together with the law of energy transformation and the evolutionary theory of Charles Darwin, is one of the three greatest discoveries of natural science in the $19th century.
Cell theory has dramatically influenced the development of biology. She proved the unity of living nature and showed the structural unit of this unity, which is the cell.
The creation of the cell theory has become a major event in biology, one of the decisive proofs of the unity of all living nature. The cell theory had a significant and decisive influence on the development of biology, serving as the main foundation for the development of such disciplines as embryology, histology and physiology. It provided a basis for explaining the related relationships of organisms, for the concept of the mechanism of individual development.
Cell theory is perhaps the most important generalization of modern biology and is a system of principles and provisions. It is the scientific background for many biological disciplines that study the structure and life of living beings. The cell theory reveals the mechanisms of growth, development and reproduction of organisms.
cell theory- the most important biological generalization, according to which all living organisms are composed of cells. The study of cells became possible after the invention of the microscope. For the first time, the cellular structure in plants (a cork cut) was discovered by the English scientist, physicist R. Hooke, who also proposed the term "cell" (1665). The Dutch scientist Anthony van Leeuwenhoek was the first to describe vertebrate erythrocytes, spermatozoa, various microstructures of plant and animal cells, various unicellular organisms, including bacteria, etc.
In 1831, the Englishman R. Brown discovered the nucleus in the cells. In 1838, the German botanist M. Schleiden came to the conclusion that plant tissues are composed of cells. The German zoologist T. Schwann showed that animal tissues also consist of cells. In 1839, T. Schwann's book "Microscopic studies on the correspondence in the structure and growth of animals and plants" was published, in which he proves that cells containing nuclei are the structural and functional basis of all living beings. The main provisions of T. Schwann's cell theory can be formulated as follows.
- The cell is the elementary structural unit of the structure of all living beings.
- Cells of plants and animals are independent, homologous to each other in origin and structure.
M. Schdeiden and T. Schwann erroneously believed that the main role in the cell belongs to the membrane and new cells are formed from the intercellular structureless substance. Subsequently, refinements and additions made by other scientists were made to the cell theory.
Back in 1827, Academician of the Russian Academy of Sciences K.M. Baer, having discovered the eggs of mammals, found that all organisms begin their development with a single cell, which is a fertilized egg. This discovery showed that the cell is not only a unit of structure, but also a unit of development of all living organisms.
In 1855, the German physician R. Virchow came to the conclusion that a cell can only arise from a previous cell by dividing it.
At the present level of development of biology the main provisions of cell theory can be represented as follows.
- A cell is an elementary living system, a unit of structure, vital activity, reproduction and individual development of organisms.
- The cells of all living organisms are similar in structure and chemical composition.
- New cells arise only by dividing pre-existing cells.
- The cellular structure of organisms is proof of the unity of the origin of all living things.
Types of cell organization
There are two types of cellular organization: 1) prokaryotic, 2) eukaryotic. Common to both types of cells is that the cells are limited by a membrane, the internal contents are represented by the cytoplasm. The cytoplasm contains organelles and inclusions. Organelles- permanent, necessarily present, components of the cell that perform specific functions. Organoids can be limited to one or two membranes (membrane organoids) or not limited to membranes (non-membrane organoids). Inclusions- non-permanent components of the cell, which are deposits of substances temporarily removed from metabolism or its final products.
The table lists the main differences between prokaryotic and eukaryotic cells.
sign | prokaryotic cells | eukaryotic cells |
---|---|---|
Structurally designed core | Absent | Available |
genetic material | Circular non-protein bound DNA | Linear protein-bound nuclear DNA and circular non-protein-bound DNA of mitochondria and plastids |
Membrane organelles | Missing | Available |
Ribosomes | 70-S type | 80-S type (in mitochondria and plastids - 70-S type) |
Flagella | Not limited by membrane | Restricted by the membrane, inside the microtubule: 1 pair in the center and 9 pairs on the periphery |
Major component of the cell wall | Murein | Plants have cellulose, fungi have chitin |
Bacteria are prokaryotes, and plants, fungi, and animals are eukaryotes. Organisms can consist of a single cell (prokaryotes and unicellular eukaryotes) or multiple cells (multicellular eukaryotes). In multicellular organisms, specialization and differentiation of cells occurs, as well as the formation of tissues and organs.
Cell theory is one of the basic principles of biology. The first to formulate this theory were the German scientists Theodor Schwann, Matthias Schleiden and Rudolf Virchow.
The essence of the cell theory is the following points:
- All living organisms are made up of cells. They can be unicellular or multicellular.
- Cells is the main one.
- arise from pre-existing cells. (They do not come from spontaneous generation).
The modern version of the cell theory includes the following main provisions:
- The flow of energy takes place within the cells.
- Inheritance information (DNA) is passed from cell to cell.
- All cells have the same basic chemical composition.
In addition to cell theory, and constitute the main principles underlying the study of life.
Cell Basics
DNA replication and protein synthesis
The cellular process of DNA replication is important function, which is essential for several processes, including cell synthesis and division. DNA transcription and RNA translation enable the process of protein synthesis.