Some homogenization and corrector results for nonlinear monotone operators

This paper deals with the limit behaviour of the solutions of quasi-linear equations of the form \ \ds -\limfunc{div}\left(a\left(x, x/{\varepsilon _h},Du_h\right)\right)=f_h on $\Omega$ with Dirichlet boundary conditions. The sequence $(\varepsilon _h)$ tends to $0$ and the map $a(x,y,\xi )$ is periodic in $y$, monotone in $\xi$ and satisfies suitable continuity conditions. It is proved that $u_h\rightarrow u$ weakly in $H_0^{1,2}(\Omega )$, where $u$ is the solution of a homogenized problem \ -\limfunc{div}(b(x,Du))=f on $\Omega$. We also prove some corrector results, i.e. we find $(P_h)$ such that $Du_h-P_h(Du)\rightarrow 0$ in $L^2(\Omega ,R^n)$

Management of Hepatitis C Antiviral Therapy Adverse Effects

Hepatitis C is one of the leading causes of liver disease in the United States, affecting more than 4 million individuals. The current treatment regimen involves pegylated interferon in combination with ribavirin. Although antiviral treatment has been associated with a greater than 50% sustained viral response rate, the adverse effects have proven to be detrimental to quality of life and therapy adherence, and consequently lead to lower sustained viral response rates. This article identifies the most frequently described complications associated with pegylated interferon and ribavirin. The active management of these complications is discussed, including both preventive and empiric treatments

Improving trafficking and kinetics of a synthetic light-gated Potassium channel

BLINK1 is a synthetic light-gated potassium (K+) channel reversibly activated by blue light, encoded by a single gene, whose activity does not need the addition of cofactors. Transient ectopic expression of BLINK1 reversibly inhibits the escape response in light-exposed two-days-old Zebrafish larvae, confirming in vivo applicability of BLINK1 as a single-component optogenetic tool that can establish sustained, physiological hyperpolarization of cells at K+ electrochemical potential (EK). In HEK293 cells, we record a measurable BLINK1 current in less than 10% of the transfected cells. Immunolocalization experiments confirmed a very low frequency of BLINK1-specific signal on the plasma membrane (PM) of transfected cells and retention of the protein in inner cellular compartments. To fix this problem, we have added to the channel C-terminal region diacidic ER export signals from other K+ channels (mKir2.1, KAT1), plasma membrane trafficking sequences (YXX\u3a6 motifs) and mode III 14-3-3 binding sites found in other channels and pumps (TASK channels, MHA2 H+-ATP-ase, KAT1). In most cases, addition of trafficking motifs increased BLINK1 presence at the PM up to 30-40 % (cells with measurable current on the total of transfected cells) but the channel lost its light regulation. The best results were obtained with the clone renamed BLINK2, that shows a moderate improvement of expression rate (26% of transfected HEK 293T cells) but intact light regulation of the current. However, BLINK2 has slower kinetics (t1/2 on= 5 min; t1/2 off= 8 min) than the parental channel BLINK1 (\uf074on= 87s; \uf074off 168 s) and a 60 to 90 s delay in opening after light on. To improve channel kinetics, we have introduced mutations known to tune the LOV domain photocycle: BLINK2 Q513D shows indeed a reduced delay in opening (30 sec). BLINK2 and BLINK2 Q513D are currently under investigation for optogenetic applicability in vivo, both in zebrafish and mouse models