Gastrin and cholecystokinin peptide-based radiopharmaceuticals: an in vivo and in vitro comparison

The development of suitable radioligands for targeting CCK-2 receptor expressing tumors, such as medullary thyroid carcinoma, is of great clinical interest. In the search for the best CCK-2R binding peptides, we have synthesized, evaluated and compared the CCK8 peptide (Asp-Tyr-Met-Gly-Trp-Met-Asp-PheNH(2) ) and two gastrin analogs commonly referred to as MG0 (DGlu-Glu(5)-Ala-Tyr-Gly-Trp-Met-Asp-PheNH(2) ) and MG11 (DGlu(1)-Ala-Tyr-Gly-Trp-Met-Asp-PheNH(2) ). The N-terminal portion of the three peptide sequences was derivatized by introducing the DTPAGlu or DOTA chelators to allow radiolobeling with (111) In(III) and (68) Ga(III), respectively. Saturation binding and cellular internalization experiments were performed on A431 cells overexpressing CCK2R (A431-CCK2R). All compounds showed Kd values in the nM range and were internalized with similar rates in CCK2 receptor overexpressing cells. Biodistribution experiments showed higher specific uptake of both MG0-based compounds compared to conjugates containing the CCK8 and MG11 peptide sequences. The higher retention levels of MG0-based peptides were associated with markedly elevated and undesired kidney uptake compared to the other compounds. Current indications suggest that the 5 Glu N-terminal residues while improving peptide stability and receptor-mediated tumor uptake cause unacceptably high kidney retention. Although displaying lower absolute tumor uptake values, the DOTA-coupled CCK8 peptide provided the best tumor to kidney uptake ratio and appears more suitable as lead compound for improvement of radiopharmaceutical properties

Protein amyloid fibrils as template for the synthesis of silica nanofibers, and their use to prepare superhydrophobic, lotus-like surfaces

In this work, amyloid fibrils are used as a template for the preparation of long silica fibers, with a variety of aspect ratios and surface roughness. Starting with β‐ lactoglobulin fibrils with typical diameters of about 20 nm and a length of several micrometers, two different strategies are followed to grow silica: either in water at acidic pH values, or in ethanol–water mixtures under Stöber conditions and an excellent control of both the thickness and the roughness of the silica layer has been achieved. Silica nanofibers with a thickness ranging from a few nanometers to hundreds of nanometers are prepared. As an application, the rough silica nanotubes are used to create superhydrophobic surfaces by mimicking the structure of the lotus leaf. The papillary structure of the lotus leaf is replicated by depositing 10 μm colloidal particles in either a single colloidal crystal, or in a binary colloidal crystal made with smaller sub‐micrometer particles. Then, silica nanofibers are deposited on the binary colloidal crystal surfaces through a layer‐by‐layer deposition procedure to replicate the nanoscale roughness provided by wax nanotubes. Upon hydrophobization of the silica nanotubes, the final surfaces are highly superhydrophobic, with a water contact angle of 165.5°

Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg) mouse models that examined each inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or 'double' tg). GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the 'double' tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy

RGB-D camera-based quadrotor navigation in GPS-denied and low light environments using known 3D markers

This paper presents an original approach for autonomous navigation based on RGB-D data and known 3D markers, where the basic concept is to detect and recognize the markers and then to use them for a straightforward pose estimation solution. The developed algorithms can allow a quadrotor to autonomously fly in (cooperative) GPS denied environments and/or when there is no natural or artificial illumination of the scene, by following a predetermined path consisting of successive targets having a well defined shape and/or color. Algorithms for target detection and recognition based on depth data are described which are optimized for real time use, paying particular attention to the on-board computational load. Experimental tests have been carried out by integrating a RGB-Depth sensor (ASUS Xtion Pro Live) on-board a custom-built quadrotor. First results confirm the potential of the proposed approach. The technique can be applied to different types of unmanned aerial vehicles (UAVs), as well as unmanned ground vehicles (UGVs)

Implementation of a Distributed Flocking Algorithm with Obstacle Avoidance Capability for UAV Swarming

An implementation of a distributed flocking algorithm with obstacle avoidance capability for a swarm of UAVs is presented. Aim of the algorithm is to produce the accelerations to guide the flock in reaching its destination while avoiding obstacles and each other. The distributed nature of the algorithm consists in the capability of each component of the swarm to calculate its own acceleration while having only partial measurements, such as position and velocity, of only neighbouring vehicles. A limitation related to the strong assumptions that have to be made about the obstacles shape has been individuated in literature. The root cause has been identified and a possible solution has been investigated to overcome the restriction