Abstract: The present invention provides, inter alia, a multiply auxotrophic cell line that is deficient in genes encoding enzymes that catalyze steps in the de novo synthesis of the pyrimidine and purine pathways, such as, e.g., uridine monophosphate synthetase (UMPS) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), respectively, for the production of recombinant proteins such as recombinant monoclonal and bispecific antibodies. Methods for preparing the multiply auxotrophic, in particular the doubly auxotrophic and octa-auxotrophic cell lines disclosed herein, methods for selecting a cell expressing a protein of interest, methods for producing a protein of interest, methods for optimizing the activity of a protein of interest, and kits for selecting a cell expressing a protein of interest, are also provided. In addition, recombinant proteins such as antibodies, including monoclonal and bispecific antibodies, made by the methods of the present disclosure are also provided.

Abstract: A method and apparatus include preparing a library of molecules that can be sequenced. The library includes multiple instances of each possible member of a k-mer. The library is sequenced to determine the relative frequency of each member of the k-mer in the library. The library is contacted with a biochemical system. A population of output molecules is sequenced to determine the relative frequency of each member of the k-mer in the population of output molecules. Each output molecule is related to a product of a process of the biochemical system and carries a k-mer related to a corresponding k-mer of a library molecule involved in the process. Effectiveness of each member of the k-mer is determined based on the relative frequency of each member of the k-mer in the population of output molecules and the relative frequency of the corresponding k-mer in the library.

Abstract: An internal combustion barrel engine having rotating cylinders and pistons which together form combustion spaces. The combustion spaces are maintained at a substantially constant volume while a compressed air-fuel mixture is combusted therein.

Abstract: The present invention relates to compositions that can detect the presence of specific entities or substances in an environment, and provide an amplified response to the detection as manifested by release of enzymes, reporter signals or drugs. The detection and response is based on nucleic acid functionalities, such as aptamer regions that are designed to specifically bind almost any entity or ligand, and enzymatic regions that can cleave nucleic acids at specific sequences. The response can be amplified on a first order through creating an allosteric relationship between the different nucleic acid functionalities present on the same nucleic acid molecule and on a second order through the release of active cargo molecules capable of generating molecules detectable by their color, fluorescence, luminescence, or ability to modulate an electric signal.

Abstract: This invention concerns a method for recovering mutant cells which produce a substance in a quantifiably reduced amount relative to wild type cells, and the mutant cells so recovered. The method involves contacting the mutant cells under suitable conditions with a suitable amount of an appropriate detectable compound capable of binding to the substance when it is present in the cells so as to permit the detectable compound to bind to the substance. The amount of the detectable compound bound to the substance in the cells is then detected, and the cells which produce the substance in the quantifiably reduced amount are thereby detected. Such cells which produce the quantifiably reduced amount of the substance are then recovered. This invention is applicable to a wide variety of cell types of various genetic characteristics and should therefore be useful in providing a wide range of useful mutant cells.