Drug design and synthesis of first in class PDZ1 targeting NHERF1 inhibitors as anticancer agents

Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents

Mid-Infrared Plasmonic Platform Based on n-Doped Ge-on-Si: Molecular Sensing with Germanium Nano-Antennas on Si

CMOS-compatible, heavily-doped semiconductor films are very promising for applications in mid-infrared plasmonic devices because the real part of their dielectric function is negative and broadly tunable in this wavelength range. In this work we investigate n-type doped germanium epilayers grown on Si substrates. We design and realize Ge nanoantennas on Si substrates demonstrating the presence of localized plasmon resonances, and exploit them for molecular sensing in the mid-infrared

Dual-tip-enhanced ultrafast CARS nanoscopy

Coherent anti-Stokes Raman scattering (CARS) and, in particular, femtosecond adaptive spectroscopic techniques (FAST CARS) have been successfully used for molecular spectroscopy and microscopic imaging. Recent progress in ultrafast nanooptics provides flexibility in generation and control of optical near fields, and holds promise to extend CARS techniques to the nanoscale. In this theoretical study, we demonstrate ultrafast subwavelentgh control of coherent Raman spectra of molecules in the vicinity of a plasmonic nanostructure excited by ultrashort laser pulses. The simulated nanostructure design provides localized excitation sources for CARS by focusing incident laser pulses into subwavelength hot spots via two self-similar nanolens antennas connected by a waveguide. Hot-spot-selective dual-tip-enhanced CARS (2TECARS) nanospectra of DNA nucleobases are obtained by simulating optimized pump, Stokes and probe near fields using tips, laser polarization- and pulse-shaping. This technique may be used to explore ultrafast energy and electron transfer dynamics in real space with nanometre resolution and to develop novel approaches to DNA sequencing.Comment: 11 pages, 6 figure

Optical properties of highly n-doped germanium obtained by in situ doping and laser annealing

High n-type doping in germanium is essential for many electronic and optoelectronic applications especially for high performance Ohmic contacts, lasing and mid-infrared plasmonics. We report on the combination of in situ doping and excimer laser annealing to improve the activation of phosphorous in germanium. An activated n-doping concentration of 8.8  ×  1019 cm−3 has been achieved starting from an incorporated phosphorous concentration of 1.1  ×  1020 cm−3. Infrared reflectivity data fitted with a multi-layer Drude model indicate good uniformity over a 350 nm thick layer. Photoluminescence demonstrates clear bandgap narrowing and an increased ratio of direct to indirect bandgap emission confirming the high doping densities achieved

Conceptual design of electron beam diagnostics for high brightness plasma accelerator

A design study of the diagnostics of a high brightness linac, based on X-band structures, and a plasma accelerator stage, has been delivered in the framework of the EuPRAXIA@SPARC_LAB project. In this paper, we present a conceptual design of the proposed diagnostics, using state of the art systems and new and under development devices. Single shot measurements are preferable for plasma accelerated beams, including emittance, while $\mu$m level and fs scale beam size and bunch length respectively are requested. The needed to separate the driver pulse (both laser or beam) from the witness accelerated bunch imposes additional constrains for the diagnostics. We plan to use betatron radiation for the emittance measurement just at the end of the plasma booster, while other single-shot methods must be proven before to be implemented. Longitudinal measurements, being in any case not trivial for the fs level bunch length, seem to have already a wider range of possibilities

Longitudinal phase-space manipulation with beam-driven plasma wakefields

The development of compact accelerator facilities providing high-brightness beams is one of the most challenging tasks in field of next-generation compact and cost affordable particle accelerators, to be used in many fields for industrial, medical and research applications. The ability to shape the beam longitudinal phase-space, in particular, plays a key role to achieve high-peak brightness. Here we present a new approach that allows to tune the longitudinal phase-space of a high-brightness beam by means of a plasma wakefields. The electron beam passing through the plasma drives large wakefields that are used to manipulate the time-energy correlation of particles along the beam itself. We experimentally demonstrate that such solution is highly tunable by simply adjusting the density of the plasma and can be used to imprint or remove any correlation onto the beam. This is a fundamental requirement when dealing with largely time-energy correlated beams coming from future plasma accelerators

Diabetic Ketoacidosis Complicated With Previously Unknown Gitelman Syndrome in a Tunisian Child

Gitelman syndrome (GS) is an auto- somal recessive disease characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. In the great majority of cases, GS is caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive NaCl co- transporter (NCCT), which is specifically expressed in the apical membrane of cells along the distal convoluted tubul

Estudo comparativo da imuno-antigenicidade de 8 amostras de Paracoccidioides brasiliensis

Para se detectar diferenças imuno-antigênicas entre 8 amostras de P. brasiliensis isoladas de diferentes áreas endêmicas (Botucatu: Pb 1, 2 e 3; São Paulo: Pb: 18, 192 e 265; Venezuela: Pb 9 e 73), esutdaram-se: 1. A reatividade antigênica de cada amostra nas reações de imunofluorescência indireta (II) e de imunodifusão dupla em gel de agar (ID) contra painel de 20 soros controles positivos para paracoccidioidomicose; 2. A capacidade de induzir resposta imune humoral (medida por imunodifusão) e celular (medida pelo teste de coxim plantar) em camundongos imunizados com an-tígenos de cada amostra. Observamos: 1. As amostras Pb 265 e Pb 9 mostraram-se mais reativas na II; 2. Os antígenos das amostras Pb 192 e Pb 73 foram significativamente mais reativas na ID; 3. Estes dados demonstram diferenças de antigenicidade entre estas amostras; 4. A amostra Pb 18 mostrou baixo poder indutor de resposta imune celular e alta capacidade de indução de resposta imune humoral em camundongos imunizados, revelando dissociação de sua imunogenicidade. Estas diferenças podem indicar a existência de cepas distintas do fungo ou refletir modificações do parasita no hospedeiro ou du rante seu cultivo

Focusing of high-brightness electron beams with active-plasma lenses

Plasma-based technology promises a tremendous reduction in size of accelerators used for research, medical, and industrial applications, making it possible to develop tabletop machines accessible for a broader scientific community. By overcoming current limits of conventional accelerators and pushing particles to larger and larger energies, the availability of strong and tunable focusing optics is mandatory also because plasma-accelerated beams usually have large angular divergences. In this regard, active-plasma lenses represent a compact and affordable tool to generate radially symmetric magnetic fields several orders of magnitude larger than conventional quadrupoles and solenoids. However, it has been recently proved that the focusing can be highly nonlinear and induce a dramatic emittance growth. Here, we present experimental results showing how these nonlinearities can be minimized and lensing improved. These achievements represent a major breakthrough toward the miniaturization of next-generation focusing devices

Mid-Infrared Bloch Surface Waves for biosensing applications

We report on the design, fabrication, and spectroscopic characterization of a 1D Photonic Cristal (1DPC) sustaining Bloch Surface Waves (BSWs) in the mid-infrared. The reported all-dielectric 1DPC structure shows potential for label-free biosensing applications to medical diagnostics