Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology

Multitarget design offers access to bioactive small molecules with potentially superior efficacy and safety. Particularly multifactorial chronic inflammatory diseases demand multiple pharmacological interventions for stable treatment. By minor structural changes, we have developed a close analogue of the cysteinyl-leukotriene receptor antagonist zafirlukast that simultaneously inhibits soluble epoxide hydrolase and activates peroxisome proliferator-activated receptor \u3b3. The triple modulator exhibits robust anti-inflammatory activity in vivo and highlights the therapeutic potential of designed multitarget agents

Optical Arbitrary Waveform Measurement (OAWM) on the Silicon Photonic Platform

We demonstrate optical arbitrary waveform measurement (OAWM) using a silicon pho-tonic spectral slicer. Exploiting maximal-ratio combining (MRC), we demonstrate the viability of the scheme by reconstructing 100-GBd 64QAM signals with high quality

Perturbations of Noise: The origins of Isothermal Flows

We make a detailed analysis of both phenomenological and analytic background for the "Brownian recoil principle" hypothesis (Phys. Rev. A 46, (1992), 4634). A corresponding theory of the isothermal Brownian motion of particle ensembles (Smoluchowski diffusion process approximation), gives account of the environmental recoil effects due to locally induced tiny heat flows. By means of local expectation values we elevate the individually negligible phenomena to a non-negligible (accumulated) recoil effect on the ensemble average. The main technical input is a consequent exploitation of the Hamilton-Jacobi equation as a natural substitute for the local momentum conservation law. Together with the continuity equation (alternatively, Fokker-Planck), it forms a closed system of partial differential equations which uniquely determines an associated Markovian diffusion process. The third Newton law in the mean is utilised to generate diffusion-type processes which are either anomalous (enhanced), or generically non-dispersive.Comment: Latex fil

Rapid Detection Of Brca1/2 Recurrent Mutations In Chinese Breast And Ovarian Cancer Patients With Multiplex Snapshot Genotyping Panels

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Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood-brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P-gp/BCRP function in vivo but also highlight some challenges associated with this strategy

The Process That is Due: Preponderance of the Evidence as the Standard of Proof for University Adjudications of Student-on-Student Sexual Assault Complaints

In April 2011, the U.S. Department of Education Office for Civil Rights issued a “Dear Colleague Letter” to colleges and universities clarifying their obligation, as a condition of the receipt of federal funding under Title IX, to respond promptly and effectively to complaints of student-on-student sexual assault. The Letter explained that schools must, among other requirements, use the “preponderance of the evidence” standard of proof in campus disciplinary proceedings for student sexual assault complaints. Commentators quickly criticized the use of the preponderance of the evidence standard as violating accused students\u27 due process rights. This Note examines the history of the due process rights of public school students and applies the Supreme Court’s Mathews v. Eldridge procedural due process balancing test to demonstrate that the preponderance of the evidence standard adequately protects accused students’ rights. When the accused students’ individual interests are balanced against a realistic assessment of the risk of erroneous findings and the significant competing interests of colleges and universities in the particular context of student-on-student sexual assault, it becomes clear that schools may comply with Title IX without jeopardizing the rights of accused students