Optimization of Continuous Bioconversion Process of Glycerol to 1,3-Propanediol

This paper addresses the optimization of continuous bioconversion process of glycerol to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae. The studied bioprocess is a complex nonlinear system that involves the gene regulation for dha regulon, enzyme-catalytic kinetics on the reductive pathway, the active transport of glycerol and (passive) diffusion of 1,3-PD across the cell membrane, and the inhibition of glycerol dehydratase (GDHt) and 1,3-propanediol oxidoreductase (PDOR) by 3-hydroxypropionaldehy (3-HPA). We first propose a nonlinear optimization model that can maximize the production rate of 1,3-PD. Then the optimal solution of this optimization problem is obtained by using an interior point method. In this approach a sequence of barrier problems are solved iteratively. We finally obtain the maximum production rate of 1,3-PD increased more than 22.86 times its initial value

Glucocorticoid-Induced TNF Receptor Family-Related Protein Ligand is Requisite for Optimal Functioning of Regulatory CD4+ T Cells

Glucocorticoid-induced tumor necrosis factor receptor family-related protein (TNFRSF18, CD357) is constitutively expressed on regulatory T cells (Tregs) and is inducible on effector T cells. In this report, we examine the role of glucocorticoid-induced TNF receptor family-related protein ligand (GITR-L), which is expressed by antigen presenting cells, on the development and expansion of Tregs. We found that GITR-L is dispensable for the development of naturally occurring FoxP3+ Treg cells in the thymus. However, the expansion of Treg in GITR-L−/− mice is impaired after injection of the dendritic cells (DCs) inducing factor Flt3 ligand. Furthermore, DCs from the liver of GITR-L−/− mice were less efficient in inducing proliferation of antigen-specific Treg cells in vitro than the same cells from WT littermates. Upon gene transfer of ovalbumin into hepatocytes of GITR-L−/−FoxP3(GFP) reporter mice using adeno-associated virus (AAV8-OVA) the number of antigen-specific Treg in liver and spleen is reduced. The reduced number of Tregs resulted in an increase in the number of ovalbumin specific CD8+ T effector cells. This is highly significant because proliferation of antigen-specific CD8+ cells itself is dependent on the presence of GITR-L, as shown by in vitro experiments and by adoptive transfers into GITR-L−/−Rag−/− and Rag−/− mice that had received AAV8-OVA. Surprisingly, administering αCD3 significantly reduced the numbers of FoxP3+ Treg cells in the liver and spleen of GITR-L−/− but not WT mice. Because soluble Fc-GITR-L partially rescues αCD3 induced in vitro depletion of the CD103+ subset of FoxP3+CD4+ Treg cells, we conclude that expression of GITR-L by antigen presenting cells is requisite for optimal Treg-mediated regulation of immune responses including those in response during gene transfer

Non-Interactive Zero-Knowledge Functional Proofs

In this paper, we consider to generalize NIZK by empowering a prover to share a witness in a fine-grained manner with verifiers. Roughly, the prover is able to authorize a verifier to obtain extra information of witness, i.e., besides verifying the truth of the statement, the verifier can additionally obtain certain function of the witness from the accepting proof using a secret functional key provided by the prover. To fulfill these requirements, we introduce a new primitive called \emph{non-interactive zero-knowledge functional proofs (fNIZKs)}, and formalize its security notions. We provide a generic construction of fNIZK for any $\textsf{NP}$ relation $\mathcal{R}$, which enables the prover to share any function of the witness with a verifier. For a widely-used relation about set membership proof (implying range proof), we construct a concrete and efficient fNIZK, through new building blocks (set membership encryption and dual inner-product encryption), which might be of independent interest

LHCA4 residues surrounding red chlorophylls allow for fine-tuning of the spectral region for photosynthesis in Arabidopsis thaliana

Improving far-red light utilization could be an approach to increasing crop production under suboptimal conditions. In land plants, only a small part of far-red light can be used for photosynthesis, which is captured by the antenna proteins LHCAs of photosystem I (PSI) through the chlorophyll (Chl) pair a603 and a609. However, it is unknown how the energy level of Chls a603–a609 is fine-tuned by the local protein environment in vivo. In this study, we investigated how changing the amino acid ligand for Chl a603 in LHCA4, the most red-shifted LHCA in Arabidopsis thaliana, or one amino acid near Chl a609, affected the energy level of the resulting PSI-LHCI complexes in situ and in vitro. Substitutions of the Chl a603 ligand N99 caused a blue shift in fluorescence emission, whereas the E146Q substitution near Chl a609 expanded the emission range to the red. Purified PSI-LHCI complexes with N99 substitutions exhibited the same fluorescence emission maxima as their respective transgenic lines, while the extent of red shift in purified PSI-LHCI with the E146Q substitution was weaker than in the corresponding transgenic lines. We propose that substituting amino acids surrounding red Chls can tune their energy level higher or lower in vivo, while shifting the absorption spectrum more to the red could prove more difficult than shifting to the blue end of the spectrum. Here, we report the first in vivo exploration of changing the local protein environment on the energy level of the red Chls, providing new clues for engineering red/blue-shifted crops

A novel isoform of the Ly108 gene ameliorates murine lupus

Studies of human systemic lupus erythematosus patients and of murine congenic mouse strains associate genes in a DNA segment on chromosome 1 with a genetic predisposition for this disease. The systematic analysis of lupus-prone congenic mouse strains suggests a role for two isoforms of the Ly108 receptor in the pathogenesis of the disease. In this study, we demonstrate that Ly108 is involved in the pathogenesis of lupus-related autoimmunity in mice. More importantly, we identified a third protein isoform, Ly108-H1, which is absent in two lupus-prone congenic animals. Introduction of an Ly108-H1–expressing transgene markedly diminishes T cell–dependent autoimmunity in congenic B6.Sle1b mice. Thus, an immune response–suppressing isoform of Ly108 can regulate the pathogenesis of lupus.Peer Reviewe

A novel isoform of the Ly108 gene ameliorates murine lupus

The expression of the new Ly108 isoform H1 weakens lupus-like disease of C57BL/6.Sle1b mice

An Improved Geometric Programming Approach for Optimization of Biochemical Systems

This paper proposes an improved geometric programming approach to address the optimization of biochemical systems. In the proposed method we take advantage of a special and interesting class of nonlinear kinetic models known as generalized mass action (GMA) models. In most situations optimization problems with GMA models are nonconvex and difficult problems to solve for global optimality. To deal with this difficulty, in this work, some transformation strategy is first used to convert the optimization problem with GMA models into an equivalent problem. Then a convexification technique is applied to transform this resulting optimization problem into a series of standard geometric programming problems that can be solved to reach a global solution. Two case studies are presented to demonstrate the advantages of the proposed method in terms of computational efficiency