157 research outputs found
CORPORATIONS-MEMBERSHIP CORPORATIONS-VOTING RIGHTS UNDER CALIFORNIA LAW
The original owner of a subdivision recorded a declaration of restrictions which provided that the majority of the property owners within the subdivision may form . . . a non-profit cooperative corporation without capital stock, but with one share thereof appurtenant to each of the lots in such subdivision,\u27\u27 to approve plans for building on these lots. Defendants acquired 133 lots and commenced construction of homes in spite of the disapproval of their plans by the association organized under the authority of the declaration. The two defendants claimed to have acquired majority control of the association, claiming 133 votes as owners of 133 lots, being opposed by the votes of 39 persons owning 39 lots. On appeal from a decree denying an injunction against defendants\u27 construction, held, reversed. Each member has only one vote regardless of number of lots owned. Green Gables Home Owners\u27 Assn. v. Sunlite Homes, Inc., (Cal. 1949) 202 P. (2d) 143
Actuator fault-tolerant control based on set separation
In this paper, an actuator fault-tolerant control (FTC) strategy based on set separation is presented. The proposed scheme employs a standard configuration consisting of a bank of observers which match the different fault situations that can occur in the plant. Each of these observers has an associated estimation error with a distinctive behaviour when a estimator matches the current fault situation of the plant. With this information from each observer, a fault diagnosis and isolation (FDI) module is able to reconfigure the control loop by selecting the appropriate stabilising controller from a bank of precomputed control laws, each of them related to one of the considered fault models. The control law consists of a reference feedforward term and a feedback gain multiplying the state estimate provided by the matching observer. A novel feature of the proposed scheme resides in the decision criteria of the FDI, which is based on the computation of sets towards which the output estimation errors related to each fault scenario and for each control configuration converge. Conditions for the design of the FDI module and for fault tolerant closed-loop stability are given, and the effectiveness of the approach is illustrated by means of a numerical examplePostprint (published version
Computational Analysis of Organic Anion Transport Proteins
This project will use ancestral sequence reconstruction and computational modeling to inform the design of novel function in human OATP proteins with the dual goal of enhanced uptake of MRI contrast agents and non-immunogenic properties. These new functions will allow cells introduced into the body, such as stem cells or immunotherapies to be accurately tracked. This design will also lend insight into the sequence-structure-function connections in OATPs, which is invaluable for a number of therapies. In this study, to discover specific domains or positions that confer activity, we will compare ancestral sequences with a selection of extant sequences to discover the evolutionary changes within the family. That evolutionary data will inform mutational information such that any OATP could be given intentional, designed mutations for any desired functionality
Directed evolution of a biterminal bacterial display scaffold enhances the display of diverse peptides
Bacterial cell-surface display systems coupled with quantitative screening methods offer the potential to expand protein engineering capabilities. To more fully exploit this potential, a unique bacterial surface display scaffold was engineered to display peptides more efficiently from the surface exposed C- and N-termini of a circularly permuted outer membrane protein. Using directed evolution, efficient membrane localization of a circularly permuted OmpX (CPX) display scaffold was rescued, thereby improving the presentation of diverse passenger peptides on the cell surface. Random and targeted mutagenesis directed towards linkers joining the native N- and C-termini of OmpX coupled with screening by FACS yielded an enhanced CPX (eCPX) variant which localized to the outer membrane as efficiently as the non-permuted parent. Interestingly, enhancing substitutions coincided with a C-terminal motif conserved in outer membrane proteins. Surface localization of various passenger peptides and mini-proteins was expedited using eCPX relative to that achieved with the parent scaffold. The new variant also permitted simultaneous display and labeling of distinct peptides on structurally adjacent C- and N-termini, thus enabling display level normalization during library screening and the display of bidentate or dimeric peptides. Consequently, the evolved scaffold, eCPX, expands the range of applications for bacterial display. Finally, this approach provides a route to improve the performance of cell-surface display vectors for protein engineering and design
Peak-to-peak exponential direct learning of continuous-time recurrent neural network models: a matrix inequality approach
DNA-ENCODED PEPTIDE LIBRARIES AND DRUG DISCOVERY
Over the past decade, several methods have been developed
for the construction of DNA-encoded peptide libraries.
The common principle behind all these methods is the establishment
of a physical linkage between a displayed peptide
and its encoding DNA. Vast libraries can be generated, binding
peptides can be isolated with simple selections, and the
sequences of selected peptides can be rapidly determined
from the sequence of the linked DNA. As a result, DNAencoded
libraries can provide specific ligands for essentially
any protein. These ligands can be used to determine the natural
binding specificities of protein–protein interactions, and
this information can be used to identify natural binding partners
or to aid the design of organic mimics. Binding peptides
can also be used for target validation and the development of
high-throughput screens for small-molecule libraries. Finally,
binding peptides themselves could prove useful as drugs
A mammalian cell based FACS-panning platform for the selection of HIV-1 envelopes for vaccine development
An increasing number of broadly neutralizing monoclonal antibodies (bnMAb) against the HIV-1 envelope (Env) protein has been discovered recently. Despite this progress, vaccination efforts with the aim to re-elicit bnMAbs that provide protective immunity have failed so far. Herein, we describe the development of a mammalian cell based FACS-panning method in which bnMAbs are used as tools to select surface-exposed envelope variants according to their binding affinity. For that purpose, an HIV-1 derived lentiviral vector was developed to infect HEK293T cells at low multiplicity of infection (MOI) in order to link Env phenotype and genotype. For proof of principle, a gp145 Env model-library was established in which the complete V3 domain was substituted by five strain specific V3 loop sequences with known binding affinities to nMAb 447-52D, respectively. Env genes were recovered from selected cells by PCR, subcloned into a lentiviral vector (i) to determine and quantify the enrichment nMAb binders and (ii) to generate a new batch of transduction competent particles. After 2 selection cycles the Env variant with highest affinity was enriched 20-fold and represented 80% of the remaining Env population. Exploiting the recently described bnMAbs, this procedure might prove useful in selecting Env proteins from large Env libraries with the potential to elicit bnMAbs when used as vaccine candidates
First order optimality conditions for mathematical programs with semidefinite cone complementarity constraints
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