The present invention provides, among other things, improved methods for purifying I2S protein produced recombinantly for enzyme replacement therapy. The present invention is, in part, based on the surprising discovery that recombinant I2S protein can be purified from unprocessed biological materials, such as, I2S-containing cell culture medium, using a process involving as few as four chromatography columns.

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. As a preferred example, the present disclosure relates to fusion polypeptides comprising (a) a first polypeptide comprising a first secretion signal, a first multimerization domain, a first transmembrane domain, and an actuator domain, (b) a viral self-cleaving polypeptide, and (c) a second polypeptide comprising a second secretion signal, a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand, a second multimerization domain, and a second transmembrane domain.

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. As a preferred example, the present disclosure relates to fusion polypeptides comprising (a) a first polypeptide comprising a first secretion signal, a first multimerization domain, a first transmembrane domain, and an actuator domain, (b) a viral self-cleaving polypeptide, and (c) a second polypeptide comprising a second secretion signal, a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand, a second multimerization domain, and a second transmembrane domain.

Enzyme-immobilizing MOFs and methods for their use in enzymatically catalyzed reactions are provided. The MOFs are channel-type MOFs that present a hierarchical pore structure comprising a first set of large channels sized for enzyme immobilization and a second set of smaller channels running alongside of the large channels that remain enzyme-free and allow for reactant delivery to the enzymes and product expulsion from the larger channels.

Enzyme-immobilizing MOFs and methods for their use in enzymatically catalyzed reactions are provided. The MOFs are channel-type MOFs that present a hierarchical pore structure comprising a first set of large channels sized for enzyme immobilization and a second set of smaller channels running alongside of the large channels that remain enzyme-free and allow for reactant delivery to the enzymes and product expulsion from the larger channels.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

The present disclosure relates to microbial stem cell technology that enables a growing microbial culture to stably maintain two or more distinct cell types in a ratio that can be genetically programmed and/or dynamically controlled during cultivation. It is contemplated that embodiments described herein can be utilized to increase product yield in microbial fermentations and advanced engineering of biomaterials using genetically engineered microbial cells, among others.

An improved data intake and query system that can perform and display ingest-time and search-time field extraction, redaction, copy, and/or categorization is described herein. As described herein, ingest-time field extraction, redaction, copy, and/or categorization may refer to field or field value extraction, redaction, copy, and/or categorization that is performed by a log observer system of the data intake and query system on raw machine data as the raw machine data is ingested or received from a publisher. As described herein, search-time field extraction, redaction, copy, and/or categorization may refer to field or field value extraction, redaction, copy, and/or categorization that is performed by the log observer system and/or other components of the improved data intake and query system on historical raw machine data that has already been ingested and indexed by the improved data intake and query system.

Provided herein are methods, compositions, and non-naturally occurring microbial organism for preparing compounds such as α-butanol, butyric acid, succinic acid, 1,4-butanediol, 1-pentanol, pentanoic acid, glutaric acid, 1,5-pentanediol, 1-hexanol, hexanoic acid, adipic acid, 1,6-hexanediol, 6-hydroxy hexanoic acid, ε-Caprolactone, 6-amino-hexanoic acid, ε-Caprolactam, hexamethylenediamine, linear fatty acids and linear fatty alcohols that are between 7-25 carbons long, linear alkanes and linear α-alkenes that are between 6-24 carbons long, sebacic acid and dodecanedioic acid comprising: a) converting a C.sub.N aldehyde and pyruvate to a C.sub.N+3 β-hydroxyketone intermediate through an aldol addition; and b) converting the C.sub.N+3 β-hydroxyketone intermediate to the compounds through enzymatic steps, or a combination of enzymatic and chemical steps.