Abstract: Disclosed is a novel microorganism which has a malate dehydrogenase activity higher than that of a wild-type. Also, a recombinant vector which has the structure shown in the cleavage map of FIG. 1, a Corynebacteria strain transformed therewith, and a method of producing 5?-xanthosine monophosphate by culturing the transformed strain are disclosed.

Abstract: The present invention relates to a novel N-acetylglucosamine-2-epimerase and a method for preparing CMP-N-acetylneuraminic acid, more specifically, relates to a N-acetylglucosamine-2-epimerase derived from Bacteroides fragilis NCTC 9343, and a method for preparing CMP-N-acetylneuraminic acid using said N-acetylglucosamine-2-epimerase. According to the present invention, CMP-N-acetylneuraminic acid can be produced economically in a large amount through a one-step reaction using cytidine monophosphate and N-acetyl-D-glucosamine which are inexpensive substrates.

Abstract: Methods for manipulating carbohydrate processing pathways in cells of interest are provided. Methods are directed at manipulating multiple pathways involved with the sialylation reaction by using recombinant DNA technology and substrate feeding approaches to enable the production of sialylated glycoproteins in cells of interest. These carbohydrate engineering efforts encompass the implementation of new carbohydrate bioassays, the examination of a selection of insect cell lines and the use of bioinformatics to identify gene sequences for critical processing enzymes. The compositions comprise cells of interest producing sialylated glycoproteins. The methods and compositions are useful for heterologous expression of glycoproteins.

Abstract: The present invention is directed to a process for producing CMP-N-acetylneuraminic acid (CMP-NeuAc), characterized in that the process includes adding yeast cells, N-acetylglucosamine-6-phosphate 2-epimerase (GlcNAc-6P 2-epimerase), N-acetylneuraminic acid lyase (NeuAc lyase), and CMP-N-acetylneuraminic acid synthase (CMP-NeuAc synthase) to a reaction system containing N-acetylglucosamine (GlcNAc), pyruvate, and cytidine 5?-monophosphate (CMP), and inducing reaction of the mixture. The present invention is also directed to a process for producing CMP-N-acetylneuraminic acid (CMP-NeuAc), characterized in that the process includes adding yeast cells, N-acetylglucosamine-6-phosphate 2-epimerase (GlcNAc-6P 2-epimerase), N-acetylneuraminic acid synthase (NeuAc synthase), and CMP-N-acetylneuraminic acid synthase (CMP-NeuAc synthase) to a reaction system containing N-acetylglucosamine (GlcNAc) and cytidine 5?-monophosphate (CMP), and inducing reaction of the mixture.

Abstract: The invention relates to methods and devices for analyzing single molecules, i.e. nucleic acids. Such single molecules may be derived from natural samples, such as cells, tissues, soil, air and water without separating or enriching individual components. In certain aspects of the invention, the methods and devices are useful in performing nucleic acid sequence analysis by probe hybridization.

Abstract: The present invention provides a method for enzymatically producing uridine 5?-diphospho-N-acetylgalactosamine (UDP-GalNAc) (which is an important substrate for oligosaccharide synthesis) from uridine 5?-triphosphate (UTP) and N-acetylgalactosamine 1-phosphate (GalNAc 1-P), the method including using, as an enzyme, uridine 5?-diphospho-N-acetylglucosamine pyrophosphorylase (UDP-GlcNAc pyrophosphorylase) derived from a microorganism (exclusive of a pathogenic microorganism). The GalNAc 1-P employed can be prepared from N-acetylgalactosamine and a phosphate donor in a reaction system by use of N-acetylgalactosamine kinase. According to the present invention, uridine 5?-diphospho-N-acetylgalactosamine can be efficiently produced by use of a relatively inexpensive substrate.

Abstract: The invention relates to a method for altering a protein X such as to modify the characteristics thereof by a) obtaining the mutants X* of the sequence coding for protein X, by means of aleatory mutagenesis, b) transformation of cells with a phenotype [P-] with vectors comprising the mutated nucleic acids obtained in step (a) which code for proteins X*, where P-signifies that said cells are auxotrophic for substance P, P begin the product of the action of X on the natural substrate thereof S, c) culturing said cells in a medium comprising a substrate S*, S* being an analogue of the natural substrate S of the protein X, d) selection of the cells [P-:: X*] which have survived step c) in which the proteins X* can biosynthesise the product P from the substrate S*.

Abstract: The present invention relates to a method for manufacturing an aqueous glucose solution from the starch components of Triticeae grains, for example from rye, triticale or in particular wheat grains. The invention also relates to a glucose-based fermentation method for manufacturing organic compounds in which the glucose manufactured for fermentation is produced from the starch components of Triticeae grains by way of a method according to the invention.

Abstract: A polypeptide having a novel endoribonuclease activity; a nucleic acid encoding the polypeptide; recombinant DNA having the nucleic acid therein; a transformant transformed with the recombinant DNA; a process for producing the polypeptide comprising the steps of cultivating the transformant and collecting the polypeptide from the culture; a process for producing a digest of single-stranded RNA comprising the step of reacting the polypeptide with the single-stranded RNA; and a method for the digestion of single-stranded RNA.

Abstract: Nucleotide analogues comprising a reactive hydrazide function (formula II) used as initial synthons for preparing compounds (formula I) capable of inducing mutations or capable of inhibiting a DNA polymerase or a kinase provided. Nucleic acids comprising the nucleotide and nucleoside analogues are also provided. Methods of using the compounds are also provided.

Abstract: The present invention relates to eukaryotic host cells which have been modified to produce sialylated glycoproteins by the heterologous expression of a set of glycosyltransferases, including sialyltransferase and/or trans-sialidase, to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. Novel eukaryotic host cells expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities (such as those involved in sialylation) to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation.

Abstract: The N-acetyl-D-galactosamine transferase protein of the present invention is characterized by transferring N-acetyl-D-galactosamine to N-acetyl-D-glucosamine with ?1,3 linkage, and it preferably has the amino acid sequence shown in SEQ ID NO: 2 or 4. The canceration assay according to the present invention uses a nucleic acid for measurement which hybridizes under stringent conditions to the nucleotide sequence shown in SEQ ID NO: 1 or 3 or a nucleotide sequence complementary to at least one of them.

Abstract: The invention relates to coryneform bacteria which, instead of the singular copy of an open reading frame (ORF), gene or allele naturally present at the particular desired site (locus), have at least two copies of the open reading frame (ORF), gene or allele in question, preferably in tandem arrangement, and optionally at least a third copy of the open reading frame (ORF), gene or allele in question at a further gene site, and processes for the preparation of chemical compounds by fermentation of these bacteria.

Abstract: The present invention describes compositions and methods showing that the spatial proximity of intracellular components may be related to their ability to cooperate in intracellular biochemical reactions. In some embodiments, the present invention contemplates a variety of nucleic acid barcoded binding partners capable of determining the spatial proximity of intracellular components as determined by ligation of their respective nucleotide barcodes. As such, an intracellular component contact map may be constructed to fingerprint specific physiological and/or pharmacological intracellular conditions.

Abstract: The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. Specifically, the present invention relates to expression of PUMP-1 protease (matrix metalloprotease 7). The detected proteases are themselves specifically over-expressed in certain cancers, and their presence may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment.

Abstract: The present invention relates to a process for the production of an aqueous glucose solution from maize or maize kernels. The invention also relates to a glucose solution obtainable by this process, and to its use for the production of organic compounds. The process according to the invention comprises: a) fractionating dry milling of maize kernels, where the maize kernels are separated into a maize-starch-comprising endosperm fraction and a high-oil germ fraction and, if appropriate, a bran fraction; b) enzymatic liquefaction and saccharification of the maize starch in an aqueous suspension of the endosperm fraction, which gives an aqueous glucose solution comprising maize gluten; and c) depletion of the maize gluten and, if appropriate, any bran present from the aqueous glucose solution.

Abstract: The present invention relates to preparation of nucleotide compositions and uses thereof for conducting nucleic acid analyses. The compositions and methods embodied in the present invention are particularly useful for nucleic acid analyses that require high-resolution detection of labeled nucleotides or labeled nucleic acid targets.

Abstract: The invention relates to coryneform bacteria which have, in addition to at least one copy, present at the natural site (locus), of an open reading frame (ORF), gene or allele which codes for the synthesis of a protein or an RNA, in each case a second, optionally third or fourth copy of this open reading frame (ORF), gene or allele at in each case a second, optionally third or fourth site in a form integrated into the chromosome and processes for the preparation of chemical compounds by fermentation of these bacteria.

Abstract: Provided are mutant strains derived from Escherichia sp. GPU1114 (Accession No. KCCM-10536), having cumulative inactivation of deoD, aphA, appA, and hprt genes, and methods of using the same.

Abstract: The present invention relates to a polypeptide having a modified amino acid sequence of 6-phosphogluconate dehydrogenase (hereinafter abbreviated as GND) derived from a microorganism belonging to the genus Corynebacterium, said modification being substitution of the amino acid residue(s) at the position(s) corresponding to the 158th and/or the 361st amino acid(s) of the amino acid sequence shown in SEQ ID NO: 1, and having GND activity; DNA encoding the polypeptide; a recombinant DNA comprising the DNA; a transformant carrying the recombinant DNA; a microorganism carrying the DNA on the chromosome; and a process for producing a useful substance which comprises culturing the transformant or the microorganism in a medium.

Abstract: A polypeptide having a novel endoribonuclease activity; a nucleic acid encoding the polypeptide; recombinant DNA having the nucleic acid therein; a transformant transformed with the recombinant DNA; a process for producing the polypeptide comprising the steps of cultivating the transformant and collecting the polypeptide from the culture; a process for producing a digest of single-stranded RNA comprising the step of reacting the polypeptide with the single-stranded RNA; and a method for the digestion of single-stranded RNA.

Abstract: The present invention provides TLR9 agonists comprising, as an active ingredient, a compound represented by formula (I): (wherein a represents 0 or 1; n represents an integer of 0 to 2; m represents an integer of 0 to 5; X1 and X2 each independently represent a hydrogen atom or hydroxy; Y represents an oxygen atom or a sulfur atom; -Q1-represents —O— or the like; -Q2- represents —O— or the like; -Z- represents —O— or the like; R1, R3 and R4 each independently represent hydroxy or the like; R2 and R5 each independently represent a hydrogen atom, hydroxy or the like; and A represents 6-aminopurin-9-yl or the like) or a pharmaceutically acceptable salt thereof, and the like.

Abstract: The present invention relates to methods of treating viral disease using mutagenic nucleoside analogs. In particular, the invention provides isoguanosine nucleosides and derivatives thereof as well a method of increasing the mutation rate of a virus such as bovine viral diarrhea virus (BVDV) and hepatitis C virus (HCV).

Abstract: This invention pertains to the discovery that an amplification of the CYP24 gene or an increase in CYP24 activity is a marker for the presence of, progression of, or predisposition to, a cancer (e.g., breast cancer). Using this information, this invention provides methods of detecting a predisposition to cancer in an animal. The methods involve (i) providing a biological sample from an animal (e.g. a human patient); (ii) detecting the level of CYP24 within the biological sample; and (iii) comparing the level of CYP24 with a level of CYP24 in a control sample taken from a normal, cancer-free tissue where an increased level of CYP24 in the biological sample compared to the level of CYP24 in the control sample indicates the presence of said cancer in said animal.

Abstract: Methods and kits for DNA repair are provided. The methods and kits described herein repair multiple types of DNA damage. The kit may include a plurality of enzymes to repair a greater variety of lesions than any single enzyme is capable of repairing. Repair of damaged DNA may include releasing damaged bases from the DNA strand, nicking the DNA at the damaged sites, translating the nicks via 5?-3? exonuclease activity, and sealing the nicks. The enzymes employed in the repair process may then be heat-inactivated, thereby obviating a purification process. The repaired DNA may then be analyzed using a variety of DNA analysis methods.

Abstract: Chromosomal abnormalities are responsible for a significant number of birth defects, including mental retardation. The present invention is related to methods for non-invasive and rapid, prenatal diagnosis of chromosomal abnormalities based on analysis of a maternal blood sample. The invention exploits the differences in DNA between the mother and fetus, for instance differences in their methylation states, as a means to enrich for fetal DNA in maternal plasma sample. The methods described herein can be used to detect chromosomal DNA deletions and duplications. In a preferred embodiment, the methods are used to diagnose chromosomal aneuploidy and related disorders, such as Down's and Turner's Syndrome.

Abstract: The invention provides a method for producing a cytosine nucleoside compound from pentose-1-phosphate and cytosine or a derivative thereof using a nucleoside phosphorylase reactive to cytosine or a bacterium having the enzyme activity. The invention also provides a method for specifically reducing an activity to degrade the substrates or the product, resulting in efficient production of the cytosine nucleoside compound. According to the invention, little by-product is produced in producing cytonucleocide compounds.

Abstract: Method of production of recombinant sucrose synthase, use thereof in the manufacture of kits for determination of sucrose, production of ADPglucose and production of transgenic plants whose leaves and storage organs accumulate high contents of ADPglucose and starch A method is described for efficient production of large quantities of soluble recombinant SS in its active form, by expression of the gene that encodes SS in a strain of Escherichia coli. The expression vector used means that the recombinant SS produced possesses a histidine tail which facilitates its quick purification. In addition it describes sequences of mutated versions of the gene of SS that encode isoforms of SS suitable for the production of ADPG. Making use of the “wild-type” and “mutated” versions of recombinant SS, an efficient method is described for production of ADPG and UDPG. It also describes the use of SS for the production of assay kits for the determination of sucrose.

Abstract: The invention provides a method of producing a chemical product through continuous fermentation which includes filtering a culture of a microorganism or cultured cells with a separation membrane to recover a product from a filtrate and simultaneously retaining a nonfiltered fluid in, or refluxing it to, the culture, and adding fermentation materials to the culture, wherein a porous membrane having an average pore size of 0.01 ?m or more to less than 1 ?m is used as the separation membrane and the filtration is conducted with a transmembrane pressure difference in the range of 0.1 to 20 kPa. According to this method, the fermentation productivity of the chemical product can be largely elevated at high stability and a low cost.

Abstract: The present invention relates to a method for the production of at least one nonvolatile microbial metabolite in solid form by sugar-based microbial fermentation, in which process a microorganism strain which produces the desired metabolites is grown using a sugar-containing liquid medium with a monosaccharide content of more than 20% by weight based on the total weight of the liquid medium, and the volatile constituents of the fermentation liquor are subsequently largely removed, the sugar-containing liquid medium being prepared by: a1) milling selected starch feedstock from cereal grains; and a2) liquefying the millbase in an aqueous liquid in the presence of at least one starch-liquefying enzyme, followed by saccharification using at least one saccharifying enzyme, where, for liquefaction purposes, at least a portion of the millbase is liquefied by continuous or batchwise addition to the aqueous liquid.

Abstract: The present invention provides a method for constructing recombinant translationally coupled operons, a method for producing useful metabolites using the bacterium containing the coupled operons, and a method for monitoring gene expression.

Abstract: The invention relates to a process for the production of at least one microbial metabolite having at least 3 carbon atoms or at least 2 carbon atoms and at least 1 nitrogen atom by means of sugar-based microbial fermentation, comprising: a) the preparation of a sugar-containing liquid medium with a monosaccharide content of more than 20% by weight from a starch feedstock, the sugar-containing liquid medium also comprising non-starchy solid constituents of the starch feedstock; b) the fermentation of the sugar-containing liquid medium for the production of the metabolite(s); and c) depletion or isolation of at least one metabolite from the fermentation liquor, wherein a microorganism strain which produces the desired metabolite(s) is cultivated with the sugar-containing liquid medium, said liquid medium being obtained by: a1) milling the starch feedstock; and a2) liquefying the millbase in an aqueous liquid in the presence of at least one starch-liquefying enzyme, followed by saccharification using at lea

Abstract: The present invention describes a process to produce a composition containing 5?-ribonucleotides wherein a microorganism is subjected to autolysis under conditions at which a substantial part of the RNA remains in a form degradable into 5?-ribonucleotides and at which a substantial part of the RNA remains associated with the cell wall fraction. Said cell wall fraction is recovered by a solid/liquid separation method and the RNA associated with said wall fraction is converted into 5?-ribonucleotides. The present invention also describes compositions containing 5?-ribonucleotides and their use in food or feed.

Abstract: A method for the production of fungus resistant transgenic plants, plant cells or plant tissue comprising the introduction of an Ab, rAb, rAb fragment or fusion or vector of the invention or the vectors of the composition of the invention into the genome of a plant, plant cell or plant cell tissue and a transgenic plant cell comprising stably integrated into the genome a polynucleotide or vector of the invention or the vectors of the composition of the invention.

Abstract: The present invention provides materials and methods for enhancing aptamers. More specifically, the materials and methods of the present invention are directed toward the modification of aptamers by the identification of one or more cleavage sites, and introduction of a chemical substitution at a position proximal to the cleavage site(s). Such aptamers are useful for the treatment of disease, in diagnostic and detection applications, and/or research, e.g., target validation.

Abstract: Improved methods and compounds to control insects, involving a biological control method to induce toxicity in targeted insects using iridoptin. The present invention induces high levels of apoptosis and inhibition of host protein synthesis in insect cells. It is the first viral toxin against non-lepidopteran insects and is distinct from existing bacterial toxins, such as Bacillus thuringiensis toxins, which are not effective against most beetles, including the boll weevil, and the Baculoviridae, which is the main group of viruses currently used as biological control agents. Iridoptin will have use in the control of agricultural pests. It will increase productivity and reduce disease transfer by vectors and household pests. By extension it has application in cancer therapy and other medical treatments where apoptosis is critical to removal of certain cells.

Abstract: An isolated nucleic acid molecule encoding a human DNA repair enzyme, MED1, is disclosed. Like other mismatch repair genes which are mutated in certain cancers, MED1, encoding nucleic acids, proteins and antibodies thereto may be used to advantage in genetic or cancer screening assays. MED1, which recognizes and cleaves DNA, may also be used for the diagnostic detection of mutations and genetic variants.

Abstract: The present invention is directed to, for example, an oligosaccharide having at an end thereof a 4-position halogenated galactose residue represented by formula (I): (wherein X represents a halogen atom, and R represents a monosaccharide, an oligosaccharide, or a carrier), a transferase inhibitor containing the oligosaccharide, and a method for inhibiting sugar chain elongation reaction in the presence of glycosyltransferase, the method including employing the inhibitor. The invention also provides a method for producing a 4-position halogenated galactose sugar nucleotide represented by formula (II): (wherein each of R1 to R3 represents a hydroxyl group, an acetyl group, a halogen atom, or a hydrogen atom; X represents a halogen atom; and M represents a hydrogen ion or a metal ion), wherein the method employs bacterium-derived galactokinase and bacterium-derived hexose-1-phosphate uridylyltransferase.

Abstract: Disclosed herein are ammonia-specific 5?-XMP aminase mutants and a method for preparing the same. A mutation is introduced into the active site of glutamine-dependent catalysis in 5?-XMP aminase. The resulting 5?-XMP aminase mutant is devoid of the glutamine-dependent activity and specifically reacts with external ammonia in converting 5?-XMP into 5?-GMP. Thus, the ammonia-specific 5?-XMP aminase mutant is stabler within cells compared to the wild type, and can be useful in the industrial conversion of 5?-XMP into 5?-GMP.

Abstract: Provided are mutant strains derived from Escherichia sp. GPU1114 (Accession No. KCCM-10536), having cumulative inactivation of deoD, aphA, appA, and hprt genes, and methods of using the same.

Abstract: The invention relates to a method for altering a protein X such as to modify the characteristics thereof by a) obtaining the mutants X* of the sequence coding for protein X, by means of aleatory mutagenesis, b) transformation of cells with a phenotype [P-] with vectors comprising the mutated nucleic acids obtained in step (a) which code for proteins X*, where P-signifies that said cells are auxotrophic for substance P, P begin the product of the action of X on the natural substrate thereof S, c) culturing said cells in a medium comprising a substrate S*, S* being an analogue of the natural substrate S of the protein X, d) selection of the cells [P-:: X*] which have survived step c) in which the proteins X* can biosynthesise the product P from the substrate S*.

Abstract: A process for the fermentative production of at least one organic compound having at least 3 C atoms or having at least 2 C atoms and at least one 1 N atom, comprising the following steps: a1) milling a starch feedstock, thus obtaining a millbase which comprises at least part of the nonstarchy solid constituents of the starch feedstock; a2) suspending the millbase in an aqueous liquid and hydrolysis of the starch portion in the millbase by enzymatic liquefaction and, if appropriate, subsequent saccharification, whereby a first liquid (1) which comprises mono- or oligosaccharides is obtained; and b) addition of the liquid (1) which comprises mono- or oligosaccharides together with metabolizable mono-, di- or oligosaccharides or together with a composition which comprises metabolizable mono-, di- or oligosaccharide in a concentration of at least 50% by weight and which is essentially free from solids which are insoluble in water to a fermentation medium comprising a microorganism which is capable of overproduc

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The present invention provides mutant Rm1A enzymes possessing an increased purine/pyrimidine bias in nucleotide triphosphate substrate specificity as compared to a corresponding non-mutated Rm1A enzyme. Such enzymes expand the types of substrates that can be used in enzymatic glycorandomization methods thereby increasing diversity of chemical libraries.

Abstract: Methods for producing purine nucleosides, and purine nucleotides, such as inosine and 5?-inosinic acid are provided which include using a bacterium belonging to the genus Bacillus or to the genus Escherichia wherein the purine nucleoside productivity of said bacterium is enhanced by increasing an activity of the YdhL protein. Also disclosed is the amino acid sequence of the YdhL protein from Bacillus amyloliquefaciens and the gene encoding it.

Abstract: The ATP amplification method of the present invention is a method for amplifying and detecting a very trace amount of exogenous ATP by allowing a fusion protein (PPK-ADK) of a polyphosphate kinase and an adenylate kinase, the fusion protein not containing ADP, to act on a mixture of ATP, AMP, and a polyphosphate compound. The present invention also provides an ultrasensitive ATP amplification method by which ATP at a single cell level can be amplified and detected, and an ultrasensitive microbial assay based on this ATP amplification method.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: A fluid processing device and method of using the device are provided. The fluid processing device can include a substrate with a fluid processing pathway at least partially formed in or on the substrate. The fluid processing pathway can include an input end, at least one output end, a first input opening, a plurality of reaction sites each in fluid communication with the first input opening and arranged between the first input opening and the at least one output end. The fluid processing pathway can include a plurality of second input openings including two or more in fluid communication respectively with each of the reaction sites, the second input openings being arranged with the reaction site disposed between the at least one output end and the second input openings. The fluid processing device can include one or more output openings in fluid communication with one or more of the plurality of reaction sites and arranged at the at least one output end of the fluid processing pathway.

Abstract: A method for generating a Drosophila clipped FRT (cFRT) chromosome is provided, wherein the chromosome is insensitive to a P transposase but remains functional to a yeast site-specific flippase recombinase (FLP). The method includes steps of: (a) exposing a FRT chromosome to the P transposase for occurring a local and imprecise transposition, wherein the FRT chromosome contains a P[FRT] insertion with a selection marker gene, (b) screening the P[FRT] insertion insensitive to the P transposase to obtain screened products, (c) selecting candidate products from the screened products by further examinations, and (d) exposing the candidate products by the P transposase and selecting a desired product by the further examinations to obtain the Drosophila clipped FRT (cFRT) chromosome insensitive to the P transposase but remaining functional to the yeast site-specific flippase recombinase. The cFRT2L2R chromosome can be used as the direct target in the direct P-transposon-induced mutagenesis.

Abstract: A target substance is produced by culturing a bacterium which has the ability to produce the target substance in a medium to cause accumulation of said target substance in the medium and collecting the target substance from the medium, wherein the bacterium is modified so that a system for uptake of a byproduct of the target substance or a substrate for a biosynthesis system of the target substance into the bacterial cell.