132157 Results for: "cell+culture+serum&pageNo=10&view=easy"

Supplier: Beckman Coulter

The Avanti™ J-15 series of benchtop centrifuges (refrigerated or ventilated) leverage the ultra harmonic technology, designed to protect your sample and increase workflow time efficiencies.

Supplier: Prosci

GTF2 is encoded by a gene that is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This gene is within the telomeric copy of the duplication. Deletion of this gene sometimes accompanies deletion of the neighboring SMN1 gene in spinal muscular atrophy (SMA) patients but it is unclear if deletion of this gene contributes to the SMA phenotype. This gene encodes the 44 kDa subunit of RNA polymerase II transcription initiation factor IIH which is involved in basal transcription and nucleotide excision repair. Transcript variants for this gene have been described, but their full length nature has not been determined. A second copy of this gene within the centromeric copy of the duplication has been described in the literature. It is reported to be different by either two or four base pairs; however, no sequence data is currently available for the centromeric copy of the gene.

Supplier: Peprotech

BMPs (Bone Morphogenetic Proteins) belong to the TGF-β superfamily of structurally related signaling proteins. BMP-2 is a potent osteoinductive cytokine, capable of inducing bone and cartilage formation in association with osteoconductive carriers such as collagen and synthetic hydroxyapatite. In addition to its osteogenic activity, BMP-2 plays an important role in cardiac morphogenesis, and is expressed in a variety of tissues, including lung, spleen, brain, liver, prostate ovary and small intestine. The functional form of BMP-2 is a 26 kDa protein composed of two identical 114 amino acid polypeptide chains linked by a single disulfide bond. Each BMP-2 monomer is expressed as the C-terminal part of a precursor polypeptide, which also contains a 23 amino acid signal sequence for secretion, and a 259 amino acid propeptide. After dimerization of this precursor, the covalent bonds between the propeptide (which is also a disulfide-linked homodimer) and the mature BMP-2 ligand are cleaved by a furin-type protease. Recombinant Human BMP-2 is a 26.0 kDa homodimeric protein consisting of two 115 amino acid polypeptide chains. Manufactured using all Animal-Free reagents.

Supplier: Peprotech

The three mammalian isoforms of TGF-β, TGF-β1, β2, and β3, signal through the same receptor and elicit similar biological responses. They are multifunctional cytokines that regulate cell proliferation, growth, differentiation and motility, as well as synthesis and deposition of the extracellular matrix. They are involved in various physiological processes, including embryogenesis, tissue remodeling and wound healing. They are secreted predominantly as latent complexes, which are stored at the cell surface and in the extracellular matrix. The release of the biologically active TGF-β isoform from a latent complex involves proteolytic processing of the complex and /or induction of conformational changes by proteins such as thrombospondin-1. TGF-β2 has been shown to exert suppressive effects on IL-2-dependent T-cell growth, and may also have an autocrine function in enhancing tumor growth by suppressing immuno-surveillance of tumor development. Recombinant Human TGF-β2 is a 25.0 kDa protein composed of two identical 112 amino acid polypeptide chains linked by a single disulfide bond.

Supplier: Prosci

In humans, multiple isoforms of Cytokeratin 6 (6A-6F), encoded by several highly homologous genes, have distinct tissue expression patterns, and Cytokeratin 6A is the dominant form in epithelial tissue. The gene encoding human Cytokeratin 6A maps to chromosome 12q13, and mutations in this gene are linked to several inheritable hair and skin pathologies. Keratins 6 and 16 are expressed in keratinocytes, which are undergoing rapid turnover in the suprabasal region (also known as hyper-proliferation-related keratins). Keratin 6 is found in hair follicles, suprabasal cells of a variety of internal stratified epithelia, in epidermis, in both normal and hyper-proliferative situations. Epidermal injury results in activation of keratinocytes, which express CK6 and CK16. CK6 is strongly expressed in about 75% of head and neck squamous cell carcinomas. Expression of CK6 is particularly associated with differentiation.

Supplier: Prosci

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S12P family. The encoded protein is a key component of the ribosomal small subunit and controls the decoding fidelity and susceptibility to aminoglycoside antibiotics. The gene for mitochondrial seryl-tRNA synthetase is located upstream and adjacent to this gene, and both genes are possible candidates for the autosomal dominant deafness gene (DFNA4). Splice variants that differ in the 5' UTR have been found for this gene; all three variants encode the same protein.

Supplier: Prosci

This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined.

Supplier: Prosci

It recognizes a polypeptide of 6.5kDa, identified as pS2 estrogen-regulated protein. pS2 is a trefoil peptide. Trefoil peptides are protease resistant molecules secreted throughout the gut that play a role in mucosal healing. These peptides contain three intra-chain disulfide bonds, forming the trefoil motif, or P-domain. pS2 is known to form dimers and this dimerization is thought to play a role in its protective and healing properties. About 60% of breast carcinomas are positive for pS2. Staining is cytoplasmic, often with localization to the Golgi apparatus. It is shown to be localized in normal stomach mucosa, gastric fluid, goblet cells in the colon and small intestine, and in ulcerations of the gastrointestinal tract. Several studies have shown that pS2 is primarily expressed in estrogen receptor-positive breast tumors and it may define a subset of estrogen-dependent tumors that displays an increased likelihood of response to endocrine therapy.

Supplier: Prosci

Mucosa associated lymphoid tissue lymphoma translocation gene 1 is found in extranodal low-grade B cell lymphomas. It encodes two Ig-like C2-type domains and fuses with an API2 gene, which is highly expressed in adult lymphoid tissue. The translocation of the MALT1 gene, which maps to human chromosome 18q21, and the apoptosis-inhibiting API2 gene results in an increased development of MALT lymphomas and apoptosis inhibition. Sites at which this API2-MALT1 (11;18)(q21;q21) translocation commonly occurs are within human lung and kidney tissue. MALT lymphoma expresses nuclear Bcl10, which mediates the oligomerization and activation of a caspase-like domain. MALT1 mRNA is found in pre-B cells, mature B cells and plasma cells.

Supplier: YMC America,Inc

YMC-Triart C18, 5 µm semi-preparative and preparative columns are packed with a novel, organic/inorganic hybrid silica particles derivatized with C18. Triart C18 columns feature chemical stability and mechanical strength, operation over a wide pH range of 1 to 12, high loading capacity, narrow particle and pore size distributions, and the ability to operate in 100% aqueous environments. Triart C18 5 µm semi-preparative and preparative columns are available in many column geometries.

Supplier: Prosci

This antibody is specific to the rod domain of human Cytokeratin 19 (CK19), a polypeptide of 40kDa. Its epitope maps between amino acid 312-335. Cytokeratin 19 is expressed in sweat gland, mammary gland ductal and secretory cells, bile ducts, gastrointestinal tract, bladder urothelium, oral epithelia, esophagus, and ectocervical epithelium. Cytokeratin 19 antibody reacts with a wide variety of epithelial malignancies including adenocarcinomas of the colon, stomach, pancreas, biliary tract, liver, and breast. Perhaps the most useful application is the identification of thyroid carcinoma of the papillary type, although 50%-60% of follicular carcinomas are also labeled. Cytokeratin 19 antibody is a useful marker for detection of tumor cells in lymph nodes, peripheral blood, bone marrow and breast cancer.

Supplier: Prosci

The transcription factor Forkhead-box A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha, is a member of the FOX class of transcription factors. HNF-1 (alpha and beta), HNF-3 (alpha, beta and gamma), HNF-4 (alpha and gamma), and HNF-6 compose, in part, a homeoprotein family designated the hepatocyte nuclear factor family. The various HNF-1 isoforms regulate transcription of genes in the liver as well as in other tissues such as kidney, small intestine and thymus. FOXA1 is expressed in normal breast ductal epithelium and other epithelium in different organs, such as lung, pancreas, bladder, prostate, and colon. Recently, FOXA1 has been shown to be a major determinant of estrogen-ER activity and endocrine response in breast cancer cells. FOXA1 expression correlates with estrogen receptor (ER)-positivity, especially in luminal subtype A breast cancers, which is associated with favorable prognosis. FOXA1 is useful in the sub-classification of breast carcinomas.

Supplier: MP Biomedicals

Murashige and Skoog Medium is widely used plant tissue culture growth medium. It has been proven effective in the culture of tissue derived from moncotyledons and dicotyledons. This medium, originally formulated to support tobacco callus, has been used to support callus initiation and growth, the growth of cells in suspension culture and the regeneration of shoots and plantlets from explants. More recently, it has been used for micropropagation of ornamental, vegetable and fruit plants in research and commercial enterprises.

Supplier: Prosci

This mAb recognizes a protein of 130kDa, identified as Ksp-cadherin. Cadherins form a superfamily of related glycoproteins that mediate calcium-dependent cell adhesion and transmit signals from the extracellular matrix to the cytoplasm. Cadherins have been implicated in embryogenesis, tissue morphogenesis, tissue structure maintenance, cell polarization, neoplastic invasiveness and metastasis, and membrane transport. It is suggested that Ksp-cadherin is a marker for terminal differentiation of the basolateral membranes of renal tubular epithelial cells. Within the kidney, Ksp-Cadherin is found exclusively in the basolateral membrane of renal tubular epithelial cells and collecting duct cells, and not in glomeruli, renal interstitial cells, or blood vessels. Ksp-Cadherin has been suggested to distinguish Chromophobe Renal-Cell Carcinoma from Oncocytoma.

Supplier: Prosci

Recognizes a protein of 42-46kDa, identified as MAGE-1. This mAb does not cross-react with other members of MAGE-family. Human malignant neoplasms carry rejection antigens that are recognized by the patients' autologous, tumor directed and specific, cytolytic, CD8+ T lymphocyte clones (CTL). The MAGE family of genes codes an important group of antigens. It was identified that melanomas and primary glial brain tumors express common melanoma associated antigens (MAAs). Because MAGE-1 is expressed on a significant proportion of human neoplasms of various histological types (melanoma, brain tumors of glial origin, neuroblastoma, non-small cell lung cancer, breast, gastric, colorectal, ovarian, renal cell carcinomas) and not on normal tissues, the encoded antigen may serve as a marker of early detection and target for cancer immunotherapy.

Supplier: Prosci

ACTH (or Corticotropin) is a 39 amino acid active peptide produced by the anterior pituitary. This mAb is specific to CLIP (aa 25-39) and does not react with Synacthen (aa 1-24). POMC (pro-opiomelanocortin or corticotropin-lipotropin) is a 267 amino acid polypeptide hormone precursor that goes through extensive, tissue-specific posttranslational processing by convertases. POMC is cleaved into ten hormone chains named NPP, ACTH, alpha-MSH (Melanocyte Stimulating Hormone), beta-MSH, gamma-MSH, CLIP (corticotropin-like intermediary peptide), Lipotropin-beta, Lipotropin-gamma, beta-endorphin and Met-enkephalin. ACTH is also produced by cells of immune system (T-cells, B-cells, and macrophages) in response to stimuli associated with stress. Anti-ACTH is a useful marker in classification of pituitary tumors and the study of pituitary disease. It reacts with ACTH-producing cells (corticotrophs). It also may react with other tumors (e.g. some small cell carcinomas of the lung) causing paraneoplastic syndromes by secreting ACTH.

Supplier: Prosci

T-Cell Intracellular Antigen-1 is a cytoplasmic granule-associated protein expressed in lymphocytes processing cytolytic potential. It is a member of an RNA-binding protein family and possesses nucleolytic activity against cytotoxic lymphocyte (CTL) target cells. It has been suggested that this protein may be involved in the induction of apoptosis as it preferentially recognizes poly(A) homopolymers and induces DNA fragmentation in CTL targets. The major granule-associated species is a 15kDa protein thought to be derived from the carboxyl terminus of the 40kDa product by proteolytic processing. TIA-1 antibody labels cytotoxic T cells and natural killer cells (NK cells). It is also expressed in T-cell lymphoma, large granular lymphocyte (LGL) leukemia and hairy cell leukemia. TIA1 expression in T-cell malignancies may help in differentiating LGL leukemia (high expression) from T-cell lymphocytosis and other T-cell diseases (low expression). TIA1 may also be used to label tumor-infiltrating lymphocytes in the study of immune response to malignancies.

Supplier: Rockland Immunochemical

Adhesion to extracellular matrix regulates cell survival through both integrin engagement and appropriate cell spreading. Anoikis is the molecular mechanism of apop-tosis induced by integrin detachment. Bit1 (Bcl-2 inhibitor of transcription 1) was recently identified as being involved in this process. Bit1 is a mitochondrial protein that is released into the cytoplasm upon onset of apoptosis where it forms a complex with AES, a small Groucho/transducin-like enhancer of split (TLE) protein and induces caspase-independent apoptosis. Both AES and TLE proteins are transcriptional co-repressors that play important roles in neurogenesis, segmentation, and sex determination. It has been suggested that Bit1-AES complexes turn off a survival-promoting gene transcription program controlled by TLE. Interestingly, apoptosis of cells transfected with Bit1 and AES could be inhibited if the cells were allowed to attach to fibronectin through the alpha5beta1 integrin suggesting that the Bit1-AES pathway contributing to anoikis is regulated by integrins, and in particular, the alpha5beta1 integrin.

Supplier: Invitrogen

Thermo Scientific Pierce EDC is a carboxyl- and amine-reactive zero-length crosslinker. EDC reacts with a carboxyl group first and forms an amine-reactive O-acylisourea intermediate that quickly reacts with an amino group to form an amide bond with release of an isourea by-product. The intermediate is unstable in aqueous solutions and so two-step conjugation procedures rely on N-hydroxysuccinimide (NHS) for stabilization. Failure to react with an amine will result in hydrolysis of the intermediate, regeneration of the carboxyl, and release of an N-substituted urea. A side reaction is the formation of an N-acylurea, which is usually restricted to carboxyls located in hydrophobic regions of proteins.

Supplier: Peprotech

CD30 ligand (CD30L) is a type-II membrane-associated glycoprotein belonging to the TNF superfamily and is expressed primarily on certain B cells, T cells, and monocytes. CD30L binds specifically to CD30 (receptor), which is expressed on activated, but not resting, B and T cells, in lymphomas and various chronically inflamed tissues. CD30L/CD30 interactions initiate a signaling cascade that can ultimately lead to the activation of NF-κB. CD30L/CD30 signaling exerts pleiotropic effects on normal cells, including cell death, differentiation, and cell division. Certain diseases, including Hodgkin’s lymphoma, allergic inflammation, diabetes (in NOD mice), and mycobacterial infection can also be affected by CD30L/CD30 signaling. The CD30L gene encodes for a 234 amino acid type II transmembrane protein, which contains a 37 amino acid cytoplasmic sequence, a 25 amino acid transmembrane domain and a 172 amino acid extracellular domain. Recombinant Human soluble CD30L (sCD30L) is a 188 amino acid polypeptide corresponding to the extracellular domain, and contains an 8 residue N-terminal His-Tag. The calculated molecular weight of Recombinant Human sCD30 Ligand is 21.3 kDa.

Supplier: Prosci

UGT1A4 is an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This enzyme has some glucuronidase activity towards bilirubin, although is is more active on amines, steroids, and sapogenins.This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. This enzyme has some glucuronidase activity towards bilirubin, although is is more active on amines, steroids, and sapogenins.

Supplier: Prosci

CAPN10 is the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM) and located within the NIDDM1 region. Multiple alternative transcript variants encoding different isoforms have been described for this gene.

Supplier: Sartorius

These MCE series essential user interface balance was a large, high-contrast touch display with factory-installed essential weighing applications for easy operation.

Supplier: MP Biomedicals

Human chorionic gonadotropin (HCG), a polypeptide hormone produced by the human placenta, is composed of an alpha and a beta sub-unit. The alpha sub-unit is essentially identical to the alpha sub-units of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to the alpha sub-unit of human thyroid-stimulating hormone (TSH). The beta sub-units of these hormones differ in amino acid sequence
The action of HCG is virtually identical to that of pituitary LH, although HCG appears to have a small degree of FSH activity as well. It stimulates production of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce androgens and the corpus luteum of the ovary to produce progesterone. Androgen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent is present. This descent is usually reversible when HCG is discontinued. During the normal menstrual cycle, LH participates with FSH in the development and maturation of the normal ovarian follicle, and the mid-cycle LH surge triggers ovulation. HCG can substitute for LH in this function

Supplier: Adipogen

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. AMG-47 is one of two optimized chemical compounds that has been shown to be extremely effective in vivo and in vitro in inhibiting Lck as well as a number of other receptor tyrosine kinases. In an anti-CD3/ IL-2 mouse model system AMG-47 has been shown to be effective in inhibiting the Lck mediated anti-inflammatory activity (ED50 11 mg/kg; 630nM) in vivo. In multiple other in vitro assays, AMG-47 exhibits subnanomolar inhibition against Lck, and low (10nM) inhibition against other hard to inhibit kinases such as KDR and SRC and MAPK alpha (p38alpha). Moreover at slightly higher doses but well under 10µM, AMG-47 effectively inhibits the JNK family of kinases including TYK2 at ~ 1.2µM.

Supplier: Prosci

The transcription factor Forkhead-box A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha, is a member of the FOX class of transcription factors. HNF-1 (alpha and beta), HNF-3 (alpha, beta and gamma), HNF-4 (alpha and gamma), and HNF-6 compose, in part, a homeoprotein family designated the hepatocyte nuclear factor family. The various HNF-1 isoforms regulate transcription of genes in the liver as well as in other tissues such as kidney, small intestine and thymus. FOXA1 is expressed in normal breast ductal epithelium and other epithelium in different organs, such as lung, pancreas, bladder, prostate, and colon. Recently, FOXA1 has been shown to be a major determinant of estrogen-ER activity and endocrine response in breast cancer cells. FOXA1 expression correlates with estrogen receptor (ER)-positivity, especially in luminal subtype A breast cancers, which is associated with favorable prognosis. FOXA1 is useful in the sub-classification of breast carcinomas.

Supplier: Prosci

The transcription factor Forkhead-box A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha, is a member of the FOX class of transcription factors. HNF-1 (alpha and beta), HNF-3 (alpha, beta and gamma), HNF-4 (alpha and gamma), and HNF-6 compose, in part, a homeoprotein family designated the hepatocyte nuclear factor family. The various HNF-1 isoforms regulate transcription of genes in the liver as well as in other tissues such as kidney, small intestine and thymus. FOXA1 is expressed in normal breast ductal epithelium and other epithelium in different organs, such as lung, pancreas, bladder, prostate, and colon. Recently, FOXA1 has been shown to be a major determinant of estrogen-ER activity and endocrine response in breast cancer cells. FOXA1 expression correlates with estrogen receptor (ER)-positivity, especially in luminal subtype A breast cancers, which is associated with favorable prognosis. FOXA1 is useful in the sub-classification of breast carcinomas.

Supplier: Rockland Immunochemical

Human immunodeficiency virus (HIV) and related viruses require coreceptors, in addition to CD4, to infect target cells. Some G protein-coupled receptors including CCR5, CXCR4, CCR3, CCR2b and CCR8 in the chemokine receptor family, and four new human molecules GPR15, STRL33, GPR1 and V28 were recently identified as HIV coreceptors. Among them, CXCR4 is a principal coreceptor for T-cell tropic strains of HIV-1 fusion and entry of human white blood cells. CXCR4 is also required for the infection by dual-tropic strains of HIV-1 and mediates CD-4 independent infection by HIV-2. The alpha-chemokine SDF-1 is the ligand for CXCR4 and prevents infection by T-tropic HIV-1. CXCR4 associates with the surface CD4-gp120 complex before HIV enters target cells. CXCR4 messenger RNA levels correlated with HIV-1 permissiveness in diverse human cell types. Antibodies to CXCR4 block HIV-1 and HIV-2 fusion and infection of human target cells. The amino-terminal domain and the second extracellular loop of CXCR4 serve as HIV binding sites.

Supplier: Prosci

This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined.

Supplier: Stirling Ultracold

Ultra-low temperature freezer featuring a free-piston Stirling engine.